bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standards of care and educational gaps in adult cystic fibrosis units: a European Respiratory Society survey
Authors: Felipe Montiel Almudena , Álvarez Fernández Antonio , Culebras Amigo Mario , Blasi Francesco , Gramegna Andrea , Elborn Stuart , Horsley Alexander , Madge Susan , Stolz Daiana , Tabin Nathalie , Pannetier Carine , Polverino Eva 
Published: April 2024

BackgroundSignificant progress in the field of cystic fibrosis (CF) has substantially extended the life expectancy of patients with CF (pwCF). Consequently, the population of adult pwCF has outnumbered paediatric patients in most developed countries. Ageing is a new factor that can contribute to disease complexity and can require adaptation of CF units. Therefore, the necessity for standardised, specialised and multidisciplinary care is imperative. Concerns arise regarding the adequacy of current healthcare, therapeutic and educational offerings.MethodsTo address these concerns, a multinational survey was conducted to assess the current state of care in specialised multidisciplinary adult and paediatric CF units and identify areas for improvement. Responses were collected from 44 centres providing regular care to CF patients.ResultsThe survey unveiled considerable disparities in the availability of critical resources, including diagnostic access, supplementary testing, treatment modalities, transplant and transition programmes, and healthcare professionals’ training.ConclusionThis study underscores the urgent need to standardise care across these centres in order to minimise disparities in terms of available resources and training with a particular emphasis on adult pwCF who are becoming more numerous and showing different needs with ageing. The changing landscape of CF in adulthood will require constant monitoring to ensure proper adaptation of the current model of care.
Genomic epidemiology ofMycobacterium abscessusat an adult cystic fibrosis programme reveals low potential for healthcare-associated transmission
Authors: Gross Jane E. , Finklea James D. , Caceres Silvia M. , Poch Katie R. , Hasan Nabeeh A. , Jia Fan , Epperson L. Elaine , Lipner Ettie M. , Vang Charmie K. , Honda Jennifer R. , Strand Matthew J. , Nogueira de Moura Vinicius Calado , Daley Charles L. , Strong Michael , Nick Jerry A. 
Published: April 2024

RationaleNontuberculous mycobacteria (NTM) has been reported to be transmitted between people with cystic fibrosis (CF) attending CF centres. A suspectedMycobacterium abscessusoutbreak was investigated at the University of Texas Southwestern (UTSW) Adult CF Program using a combination of pathogen genomic sequencing and epidemiologic methods. The objectives of the present study were to apply the Healthcare-Associated Links in Transmission of NTM (HALT NTM) study to investigate the occurrence of potential healthcare-associated transmission and/or acquisition of NTM among people with CF infected with genetically similar NTM isolates.MethodsWhole-genome sequencing of respiratoryM. abscessusisolates from 50 people with CF receiving care at UTSW was performed to identify genetically similar isolates. Epidemiologic investigation, comparison of respiratory and environmental isolates, and home residence watershed mapping were studied.Measurements and main resultsWhole-genome sequencing analysis demonstrated seven clusters of genetically similarM. abscessus(four ssp. abscessusand three ssp.massiliense). Epidemiologic investigation revealed potential opportunities for healthcare-associated transmission within three of these clusters. Healthcare environmental sampling did not recoverM. abscessus, but did recover four human disease-causing species of NTM. No subjects having clustered infections lived in the same home residence watershed. Some subjects were infected with more than oneM. abscessusgenotype, both within and outside of the dominant circulating clones.ConclusionsHealthcare-associated person-to-person transmission ofM. abscessusappears to be rare at this centre. However, polyclonal infections ofM. abscessusspecies and subspecies, not originating from the endemic hospital environment, suggest multiple shared modes of acquisition outside the healthcare setting.
Environmental, healthcare and societal impacts of asthma: a UK model-based assessment
Authors: Orlovic Martina , Tzelis Dimitrios , Guerra Inês , Bar-Katz Vladislava , Woolley Nicholas , Bray Hannah , Hanslot Mohammed , Usmani Omar , Madoni Alessandra 
Published: April 2024

BackgroundThis study aimed to assess the broader environmental, healthcare and societal impacts across the entire asthma pathway from diagnosis to treatment in the UK.MethodsA comprehensive cost-of-illness framework was developed considering the effects of the full asthma patient pathway, including greenhouse gas emissions generated from inhalers, National Health Service (NHS) costs, health-related quality of life and productivity losses. The model was based on published literature and clinical expert opinion to accurately estimate, in monetary terms, the net present value of the asthma pathway impacts for 2022–2031.ResultsThe estimated net present value of the environmental, healthcare and societal impacts of the asthma pathway was £47 billion over the 2022–2031 period in the UK. Loss of disease control was a key contributor to higher greenhouse gas emissions and NHS costs. In 2022, a patient with non-severe uncontrolled asthma was estimated to incur 22% higher NHS costs than a patient with controlled asthma, while generating 0.1 t more of CO2equivalent emissions. In the same year, the total direct impacts per patient with severe asthma were four times higher than for a patient with non-severe controlled asthma, with 0.54 t CO2equivalent of greenhouse gas emissions. Moreover, as much as 77% of the total economic impact was driven by worsening health-related quality of life and productivity impacts occurring when patients’ symptoms were uncontrolled.ConclusionsUncontrolled asthma significantly impacts patients, the economy and the environment in the UK. Our results emphasise the need for a holistic approach in controlling asthma and should be carefully considered when developing policies to mitigate the overall burden of the disease.
Untargeted metabolomic analysis reveals different metabolites associated with response to mepolizumab and omalizumab in asthma
Authors: Nopsopon Tanawin , Chen Yulu , Chen Qingwen , Wheelock Craig E. , Weiss Scott. T. , McGeachie Michael , Lasky-Su Jessica , Akenroye Ayobami 
Published: April 2024

BackgroundThere is limited evidence on biomarkers associated with response to the monoclonal antibodies currently approved for asthma treatment. We sought to identify circulatory metabolites associated with response to treatment with mepolizumab or omalizumab.MethodsWe conducted global metabolomic profiling of pre-treatment plasma samples from 100 patients with moderate-to-severe asthma who initiated mepolizumab (n=31) or omalizumab (n=69). The primary outcome was the change in exacerbations within 12 months of therapy. Negative binomial models were used to assess the association between each metabolite and exacerbations, adjusting for age, sex, body mass index, baseline exacerbations and inhaled corticosteroid use. Chemical similarity enrichment analysis (ChemRICH) was conducted to identify chemical subclasses associated with treatment response.ResultsThe mean age of the mepolizumab group was 58.7 years with on average 2.9 exacerbations over the year prior to initiation of biologic therapy. The mean age in the omalizumab group was 48.8 years with 1.5 exacerbations in the preceding year. Patients with higher levels of two tocopherol metabolites were associated with more exacerbations on mepolizumab (δ-carboxyethyl hydroxychroman (CEHC) (p=2.65E-05, false discovery rate (FDR=0.01) and δ-CEHC glucuronide (p=2.47E-06, FDR=0.003)). Higher levels of six androgenic steroids, three carnitine metabolites and two bile acid metabolites were associated with decreased exacerbations in the omalizumab group. In enrichment analyses, xanthine metabolites (cluster FDR=0.0006) and tocopherol metabolites (cluster FDR=0.02) were associated with worse mepolizumab response, while androgenic steroids (cluster FDR=1.9E-18), pregnenolone steroids (cluster p=3.2E-07, FDR=1.4E-05) and secondary bile acid metabolites (cluster p=0.0003, FDR=0.006) were the top subclasses associated with better omalizumab response.ConclusionThis study identifies distinct metabolites associated with response to mepolizumab and omalizumab, with androgenic steroids associated with response to both mepolizumab and omalizumab.
Control of false discoveries in grouped hypothesis testing for eQTL data
Authors: Rudra Pratyaydipta , Zhou Yi-Hui , Nobel Andrew , Wright Fred A. 
Published: April 2024

AbstractBackgroundExpression quantitative trait locus (eQTL) analysis aims to detect the genetic variants that influence the expression of one or more genes. Gene-level eQTL testing forms a natural grouped-hypothesis testing strategy with clear biological importance. Methods to control family-wise error rate or false discovery rate for group testing have been proposed earlier, but may not be powerful or easily apply to eQTL data, for which certain structured alternatives may be defensible and may enable the researcher to avoid overly conservative approaches.ResultsIn an empirical Bayesian setting, we propose a new method to control the false discovery rate (FDR) for grouped hypotheses. Here, each gene forms a group, with SNPs annotated to the gene corresponding to individual hypotheses. The heterogeneity of effect sizes in different groups is considered by the introduction of a random effects component. Our method, entitled Random Effects model and testing procedure for Group-level FDR control (REG-FDR), assumes a model for alternative hypotheses for the eQTL data and controls the FDR by adaptive thresholding. As a convenient alternate approach, we also propose Z-REG-FDR, an approximate version of REG-FDR, that uses only Z-statistics of association between genotype and expression for each gene-SNP pair. The performance of Z-REG-FDR is evaluated using both simulated and real data. Simulations demonstrate that Z-REG-FDR performs similarly to REG-FDR, but with much improved computational speed.ConclusionOur results demonstrate that the Z-REG-FDR method performs favorably compared to other methods in terms of statistical power and control of FDR. It can be of great practical use for grouped hypothesis testing for eQTL analysis or similar problems in statistical genomics due to its fast computation and ability to be fit using only summary data.
HOXA9 gene inhibits proliferation and differentiation and promotes apoptosis of bovine preadipocytes
Authors: He Lixia , Feng Xue , Hu Chunli , Liu Shuang , Sheng Hui , Cai Bei , Ma Yun 
Published: April 2024

Abstract
Background
Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function.

Result
It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P < 0.05). The mRNA expression level of CDK1, CDK2, PCNA, CCNA2, CCNB1, CCND1 and CCNE2, as well as the protein expression of CDK2 also significantly decreased. The decrease of lipid droplets content was the main characteristic of the phenotype (P < 0.01), which further supported the evidence that HOXA9 was a negative regulator of preadipocytes differentiation. The decrease of cell proliferation rate and EdU positive rate, as well as the limitation of transition of preadipocytes from G0/G1 phase to S phase also provided evidence for the inhibition of proliferation. Apart from this above, we noted an interesting phenomenon that overexpression of HOXA9 showed in a significant upregulation of both mRNA and protein level of apoptosis markers, accompanied by a significant increase in cell apoptosis rate. These data led us not to refute the fact that HOXA9 played an active regulatory role in apoptosis. HOXA9 loss-of-function experiments, however, yielded the opposite results. Considering that HOXA9 acts as a transcription factor, we predicted its target genes. Dual luciferase reporter assay system indicated that overexpression of HOXA9 inhibits activity of PCNA promoter.

Conclusion
Taken together, we demonstrated for the first time that HOXA9 played a role as a negative regulatory factor in the differentiation and proliferation of preadipocytes, but played a positive regulatory role in apoptosis, and it may play a regulatory role by targeting PCNA. This study provides basic data for further exploring the regulatory network of intramuscular fat deposition in bovine.
Developmentally dependent reprogramming of the Arabidopsis floral transcriptome under sufficient and limited water availability
Authors: Ma Xinwei , Wang Jun , Su Zhao , Ma Hong 
Published: April 2024

Abstract
Background
Environmental stresses negatively impact reproductive development and yield. Drought stress, in particular, has been examined during Arabidopsis reproductive development at morphological and transcriptomic levels. However, drought-responsive transcriptomic changes at different points in reproductive development remain unclear. Additionally, an investigation of the entire transcriptome at various stages during flower development is of great interest.

Results
Here, we treat Arabidopsis plants with well-watered and moderately and severely limiting water amounts when the first flowers reach maturity and generate RNA-seq datasets for early, middle, and late phases during flower development at 5, 6, and 7 days following treatment. Under different drought conditions, flowers in different developmental phases display differential sets of drought-responsive genes (DTGs), including those that are enriched in different GO functional categories, such as transcriptional regulation and response to stresses (early phase), lipid storage (middle phase), and pollen and seed development and metabolic processes (late phase). Some gene families have different members induced at different floral phases, suggesting that similar biochemical functions are carried out by distinct members. Developmentally-regulated genes (DVGs) with differential expression among the three floral phases belong to GO terms that are similar between water conditions, such as development and reproduction, metabolism and transport, and signaling and stress response. However, for different water conditions, such similar GO terms correspond to either distinct gene families or different members of a gene family, suggesting that drought affects the expression of distinct families or family members during reproductive development. A further comparison among transcriptomes of tissues collected on different days after treatment identifies differential gene expression, suggesting age-related genes (ARGs) might reflect the changes in the overall plant physiology in addition to drought response and development.

Conclusion
Together, our study provides new insights into global transcriptome reprogramming and candidate genes for drought response, flower development, aging and coordination among these complex biological processes.
Exploring the synergistic effects of indole acetic acid (IAA) and compost in the phytostabilization of nickel (Ni) in cauliflower rhizosphere
Authors: Khan Raheel , Sarwar Muhammad Junaid , Shabaan Muhammad , Asghar Hafiz Naeem , Zulfiqar Usman , Iftikhar Irfan , Aijaz Nazish , Haider Fasih Ullah , Chaudhary Talha , Soufan Walid 
Published: April 2024

AbstractHeavy metals (HMs) contamination, owing to their potential links to various chronic diseases, poses a global threat to agriculture, environment, and human health. Nickel (Ni) is an essential element however, at higher concentration, it is highly phytotoxic, and affects major plant functions. Beneficial roles of plant growth regulators (PGRs) and organic amendments in mitigating the adverse impacts of HM on plant growth has gained the attention of scientific community worldwide. Here, we performed a greenhouse study to investigate the effect of indole-3-acetic acid (IAA @ 10− 5 M) and compost (1% w/w) individually and in combination in sustaining cauliflower growth and yield under Ni stress. In our results, combined application proved significantly better than individual applications in alleviating the adverse effects of Ni on cauliflower as it increased various plant attributes such as plant height (49%), root length (76%), curd height and diameter (68 and 134%), leaf area (75%), transpiration rate (36%), stomatal conductance (104%), water use efficiency (143%), flavonoid and phenolic contents (212 and 133%), soluble sugars and protein contents (202 and 199%), SPAD value (78%), chlorophyll ‘a and b’ (219 and 208%), carotenoid (335%), and NPK uptake (191, 79 and 92%) as compared to the control. Co-application of IAA and compost reduced Ni-induced electrolyte leakage (64%) and improved the antioxidant activities, including APX (55%), CAT (30%), SOD (43%), POD (55%), while reducing MDA and H2O2 contents (77 and 52%) compared to the control. The combined application also reduced Ni uptake in roots, shoots, and curd by 51, 78 and 72% respectively along with an increased relative production index (78%) as compared to the control. Hence, synergistic application of IAA and compost can mitigate Ni induced adverse impacts on cauliflower growth by immobilizing it in the soil.
Mortality and its predictors in abdominal injury across sub-Saharan Africa: systematic review and meta-analysis
Authors: Endeshaw Destaw , Delie Amare Mebrat , Adal Ousman , Tareke Abiyu Abadi , Bogale Eyob Ketema , Anagaw Tadele Fentabel , Tiruneh Misganaw Guadie , Fenta Eneyew Talie 
Published: April 2024

Abstract
Background
Abdominal injuries exert a significant impact on global morbidity and mortality. The aggregation of mortality data and its determinants across different regions holds immense importance for designing informed healthcare strategies. Hence, this study assessed the pooled mortality rate and its predictors across sub-Saharan Africa.

Method
This meta-analysis employed a comprehensive search across multiple electronic databases including PubMed, Africa Index Medicus, Science Direct, and Hinari, complemented by a search of Google Scholar. Subsequently, data were extracted into an Excel format. The compiled dataset was then exported to STATA 17 statistical software for analysis. Utilizing the Dersimonian-Laird method, a random-effect model was employed to estimate the pooled mortality rate and its associated predictors. Heterogeneity was evaluated via the I2 test, while publication bias was assessed using a funnel plot along with Egger's, and Begg's tests.

Result
This meta-analysis, which includes 33 full-text studies, revealed a pooled mortality rate of 9.67% (95% CI; 7.81, 11.52) in patients with abdominal injuries across sub-Saharan Africa with substantial heterogeneity (I2 = 87.21%). This review also identified significant predictors of mortality. As a result, the presence of shock upon presentation demonstrated 6.19 times (95% CI; 3.70-10.38) higher odds of mortality, followed by ICU admission (AOR: 5.20, 95% CI; 2.38-11.38), blunt abdominal injury (AOR: 8.18, 95% CI; 4.97-13.45), post-operative complications (AOR: 8.17, 95% CI; 4.97-13.44), and the performance of damage control surgery (AOR: 4.62, 95% CI; 1.85-11.52).

Conclusion
Abdominal injury mortality is notably high in sub-Saharan Africa. Shock at presentation, ICU admission, blunt abdominal injury, postoperative complications, and use of damage control surgery predict mortality. Tailored strategies to address these predictors could significantly reduce deaths in the region.
Risk factors for COVID-19 associated pulmonary aspergillosis and outcomes in patients with acute respiratory failure in a respiratory sub-intensive care unit
Authors: Iacovelli Alessandra , Oliva Alessandra , Mirabelli Flavio Marco , Giannone Silvia , Laguardia Marianna , Morviducci Matteo , Nicolardi Maria Luisa , Repaci Emma , Sanzari Maria Teresa , Leanza Cristiana , Raponi Giammarco , Mastroianni Claudio , Palange Paolo 
Published: April 2024

Abstract
Background
COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients.

Materials and methods
This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients.

Results
Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155–314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12–31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75–4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12–4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19–5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p < 0.0001). CAPA resulted an independent risk factor for in-hospital mortality [OR 2.92 (95%CI 1.47–5.89), p = 0.0024]. Among CAPA patients, age > 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20–26.92), p = 0.035]. No differences were observed in hematological cohort.

Conclusion
CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia.