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Objective: Patients with diffuse cutaneous systemic sclerosis (dcSSc) frequently show spontaneous improvement of skin fibrosis. Our aim was to examine whether an improvement in skin fibrosis predicts lower likelihood of visceral organ progression and better survival., Methods: Patients from the European Scleroderma Trials and Research (EUSTAR) cohort with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, and valid mRSS at 12±3 months follow up were included. Regression/progression of skin fibrosis was defined as a decrease/increase in mRSS >5 points and ≥25% from baseline to follow up. The outcomes included progression of lung, renal, cardiac and gastrointestinal manifestations using consensus derived definitions and all-cause death. Regressive, stable and progressive patients were compared by univariate, Kaplan-Meier survival curve and Cox regression analysis., Results: Of 1257 included patients, 883 (70.2%) were stable, 282 (22.4%) regressive, and 92 (7.3%) progressive. Regressive patients, adjusted for baseline mRSS, baseline immunosuppression, baseline FVC, and disease duration, showed a significantly lower probability of FVC decline ≥10% than progressive patients (p=0.00003), lower probability of all-cause mortality during follow up (p=0.035) compared to progressive patients. .Improvement of skin fibrosis was not associated with progression of other organ manifestations., Conclusion: We found that regression of skin fibrosis is associated with a lower probability of lung progression and better survival at follow up. The link between the disease course of skin and lung fibrosis in SSc can help to better stratify patients in clinical practice and enrich for ILD progressive patients in clinical trials., (© 2024. The Author(s).)

Background: Karat (Musa troglodytarum L.) is an autotriploid Fe'i banana of the Australimusa section. Karat was domesticated independently in the Pacific region, and karat fruit are characterized by a pink sap, a deep yellow-orange flesh colour, and an abundance of β-carotene. Karat fruit showed non-climacteric behaviour, with an approximately 215-day bunch filling time. These features make karat a valuable genetic resource for studying the mechanisms underlying fruit development and ripening and carotenoid biosynthesis. Results: Here, we report the genome of M. troglodytarum, which has a total length of 603 Mb and contains 37,577 predicted protein-coding genes. After divergence from the most recent common ancestors, M. troglodytarum (T genome) has experienced fusion of ancestral chromosomes 8 and 9 and multiple translocations and inversions, unlike the high synteny with few rearrangements found among M. schizocarpa (S genome), M. acuminata (A genome) and M. balbisiana (B genome). Genome microsynteny analysis showed that the triplication of MtSSUIIs due to chromosome rearrangement may lead to the accumulation of carotenoids and ABA in the fruit. The expression of duplicated MtCCD4s is repressed during ripening, leading to the accumulation of α-carotene, β-carotene and phytoene. Due to a long terminal repeat (LTR)-like fragment insertion upstream of MtERF11, karat cannot produce large amounts of ethylene but can produce ABA during ripening. These lead to non-climacteric behaviour and prolonged shelf-life, which contributes to an enrichment of carotenoids and riboflavin. Conclusions: The high-quality genome of M. troglodytarum revealed the genomic basis of non-climacteric behaviour and enrichment of carotenoids, riboflavin, flavonoids and free galactose and provides valuable resources for further research on banana domestication and breeding and the improvement of nutritional and bioactive qualities. [ABSTRACT FROM AUTHOR]

Background: Musaceae is an economically important family consisting of 70-80 species. Elucidation of the interspecific relationships of this family is essential for a more efficient conservation and utilization of genetic resources for banana improvement. However, the scarcity of herbarium specimens and quality molecular markers have limited our understanding of the phylogenetic relationships in wild species of Musaceae. Aiming at improving the phylogenetic resolution of Musaceae, we analyzed a comprehensive set of 49 plastomes for 48 species/subspecies representing all three genera of this family. Results: Musaceae plastomes have a relatively well-conserved genomic size and gene content, with a full length ranging from 166,782 bp to 172,514 bp. Variations in the IR borders were found to show phylogenetic signals to a certain extent in Musa. Codon usage bias analysis showed different preferences for the same codon between species and three genera and a common preference for A/T-ending codons. Among the two genes detected under positive selection (dN/dS > 1), ycf2 was indicated under an intensive positive selection. The divergent hotspot analysis allowed the identification of four regions (ndhF-trnL, ndhF, matK-rps16, and accD) as specific DNA barcodes for Musaceae species. Bayesian and maximum likelihood phylogenetic analyses using full plastome resulted in nearly identical tree topologies with highly supported relationships between species. The monospecies genus Musella is sister to Ensete, and the genus Musa was divided into two large clades, which corresponded well to the basic number of n = x = 11 and n = x =10/9/7, respectively. Four subclades were divided within the genus Musa. A dating analysis covering the whole Zingiberales indicated that the divergence of Musaceae family originated in the Palaeocene (59.19 Ma), and the genus Musa diverged into two clades in the Eocene (50.70 Ma) and then started to diversify from the late Oligocene (29.92 Ma) to the late Miocene. Two lineages (Rhodochlamys and Australimusa) radiated recently in the Pliocene /Pleistocene periods. Conclusions: The plastome sequences performed well in resolving the phylogenetic relationships of Musaceae and generated new insights into its evolution. Plastome sequences provided valuable resources for population genetics and phylogenetics at lower taxon. [ABSTRACT FROM AUTHOR]

Background: Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) are commonly used drug-delivering devices for patients with chronic airway diseases. Appropriate peak inhalation flow rate (PIFR) and inhaler technique is essential for effective therapy. We aimed at optimizing inhalation therapy through the analysis of PIFRs in patients with chronic obstructive pulmonary disease (COPD) or asthma as well as the effect of technique training using In-Check DIAL® to help patients to achieve their optimal inspiratory flow rates.Methods: The study continuously enrolled patients who were diagnosed as COPD or asthma from respiratory clinics. PIFRs were described and analyzed between the newly-diagnosed and follow-up patients, and the stable and acute exacerbation patients, respectively. Every participant was trained inhaler technique using In-Check DIAL®. PIFRs before and after training was compared by self-control analysis.Results: Among a total of 209 patients, the average age was 56.9 years. For DPIs users, 10.8% patients had a PIFR < 30 L/min and 44.1% patients had a PIFR ≥ 60 L/min before technique training. After technique training, scarcely patient (1.5%) had a PIFR < 30 L/min, and 60.5% patients had a PIFR ≥ 60 L/min. The patient's average PIFR increased by 5.6L/min after training. The increase in PIFR before and after training was significant (p < 0.001) for most patients, but no significant variation was found in patients with acute exacerbation (p = 0.822).Conclusions: A considerable number of patients with COPD or asthma were not able to achieve the minimum or optimal PIFR for DPIs. Inhaler training can increase patients' PIFRs and improve their ability to use DPIs. Trail registration The study has registered in chictr.org.cn (ChiCTR1900024707) and been approved by the Ethics Committee of Zhongshan Hospital of Fudan University (B2019-142). [ABSTRACT FROM AUTHOR]

Background: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression., Methods: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient's lifetime., Results: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p <  0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p <  0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p <  0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc., Conclusions: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting β2-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol. They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated. Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD. A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twicedaily LABAs, and the once-daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs. A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators. Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in humans. The introduction of once-daily LABAs also provides the opportunity to develop combination inhalers of two or more classes of once-daily long-acting bronchodilators, which may be advantageous for COPD patients through simplification of treatment regimens as well as improvements in efficacy. Once-daily LABAs used both alone and in combination with long-acting muscarinic antagonists represent a promising advance in the treatment of COPD, and are likely to further improve outcomes for patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this project was to analyze and compare the educational experience in rheumatology specialty training programs across European countries, with a focus on self-reported ability., Method: An electronic survey was designed to assess the training experience in terms of self-reported ability, existence of formal education, number of patients managed and assessments performed during rheumatology training in 21 core competences including managing specific diseases, generic competences and procedures. The target population consisted of rheumatology trainees and recently certified rheumatologists across Europe. The relationship between the country of training and the self-reported ability or training methods for each competence was analyzed through linear or logistic regression, as appropriate., Results: In total 1079 questionnaires from 41 countries were gathered. Self-reported ability was high for most competences, range 7.5-9.4 (0-10 scale) for clinical competences, 5.8-9.0 for technical procedures and 7.8-8.9 for generic competences. Competences with lower self-reported ability included managing patients with vasculitis, identifying crystals and performing an ultrasound. Between 53 and 91 % of the trainees received formal education and between 7 and 61 % of the trainees reported limited practical experience (managing ≤10 patients) in each competence. Evaluation of each competence was reported by 29-60 % of the respondents. In adjusted multivariable analysis, the country of training was associated with significant differences in self-reported ability for all individual competences., Conclusion: Even though self-reported ability is generally high, there are significant differences amongst European countries, including differences in the learning structure and assessment of competences. This suggests that educational outcomes may also differ. Efforts to promote European harmonization in rheumatology training should be encouraged and supported.

Objective: COPD patients have challenges for effective use of inhalers due to advanced age, fixed airflow obstruction and comorbid medical conditions. Published clinical trials investigate drug efficacy but rarely consider the inhaler device. This trial investigates device efficacy, comparing clinical outcomes for the same medication via two different devices. Our intention was to communicate the results and to critically appraise the study protocol to inform planning of future device comparison research. Subjects with spirometry confirming at least moderate COPD were randomly assigned to inhaler sequence; starting with Accuhaler or metered dose inhaler and spacer (MDI/s). After baseline testing, subjects were assigned to fluticasone propionate/salmeterol xinafoate (SFC) 500/50 mcg twice daily via the first device for 6 weeks' duration, then changed to the alternate device for the following 6 weeks. Subjects were reassessed in terms of health-related quality of life (HRQL), exercise endurance and lung function after each exposure period. Results: The recruitment target was not achieved due to unanticipated developments within the pharmaceutical industry, potentially compromising the study's power. Study outcomes did not differ significantly according to the allocated inhaler device even after adjusting for baseline lung function or inhaler technique. Recommendations for future device comparison protocols are offered. Trial registration Australia and New Zealand Clinical Trials Registry, Current Controlled Trials ACTRN12618000075280, date of registration: 18.01.2018. Retrospectively registered [ABSTRACT FROM AUTHOR]