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Triple treatment with elexacaftor, tezacaftor, and ivacaftor in patients with cystic fibrosis who had one Phe508del allele and a minimal-function mutation resulted in sustained improvement in FEV 1 , sweat chloride concentration, and the number of pulmonary exacerbations.

Cystic fibrosis (CF) is a genetic disorder that occurs in people of all genetic ancestries. CF is caused by variants in the CF transmembrane conductance regulator (CFTR) gene that result in decreased, absent, or nonfunctional CFTR protein at the cell surface of the mucous membranes. Clinical manifestations include chronic respiratory disease, malabsorption, and decreased fertility. Historically, therapies for CF were focused on the signs and symptoms of the disease. However, more recently, CFTR modulators, therapies directed at the basic defect, are improving the quality and duration of the lives of people with CF. The predicted survival of people with CF in the United States is now 53 years of age. With the hope of longer, healthier lives, female individuals with CF (fwCF) are expressing the desire to discuss fertility, pregnancy, and parenthood. Furthermore, pregnancy rates are increasing substantially. Understanding the impact of use or discontinuation of highly effective modulator therapy on the reproductive health of fwCF is critical. Finally, fwCF and their providers must consider preventative cancer screening.

IntroductionTherapeutic advances have markedly increased life expectancy for those with cystic fibrosis (CF), resulting in a median predicted survival over 50 years. Consequently, people with CF (pwCF) are living through their reproductive years and the rate of pregnancy is rapidly rising. Despite the increased relevance of this topic, multicentre studies investigating the association between maternal health and choices made during pregnancy on maternal and fetal outcomes do not exist. Furthermore, there are very limited data on the outcomes following CF transmembrane conductance regulator (CFTR) modulator use during pregnancy and lactation.Methods and analysisMaternal and Fetal Outcomes in the Era of Modulators (MAYFLOWERS) is a prospective, multicentre observational clinical trial which will enrol approximately 285 pregnant pwCF including those who are modulator ineligible and those who choose to continue or discontinue CFTR modulator therapy during pregnancy and lactation. The primary aim of this 35-month study is to assess whether lung function changes during pregnancy differ based on the continued use of modulators or other factors such as pre-existing comorbid conditions. Secondary objectives include evaluation of pregnancy related and obstetrical complications and changes in mental health.Ethics and disseminationThe design of this study required special consideration of study burden on pregnant and lactating people with chronic illness in the setting of a substantial number of unanswered questions under these conditions. MAYFLOWERS is the first prospective clinical trial examining pregnancy in CF; the outcomes will guide providers on pregnancy management in pwCF and others with chronic respiratory disease.

Endothelin-1 (ET-1) is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), but the cellular mechanisms underlying the role it plays in this disease are not well characterized. Epithelial–mesenchymal transition (EMT), which was recently demonstrated in alveolar epithelial cells (AEC), may play an important role in the pathogenesis of IPF and other forms of pulmonary fibrosis. Whether ET-1 contributes to the induction of EMT in AEC is unknown. The aims of this study were to evaluate AEC production of ET-1 and to determine if ET-1 induces EMT in AEC. We demonstrate that ET-1 is produced at physiologically relevant levels by primary AEC and is secreted preferentially toward the basolateral surface. We also demonstrate that AEC express high levels of endothelin type A receptors (ET-A) and, to a lesser extent, type B receptors (ET-B), suggesting autocrine or paracrine function for alveolar ET-1. In addition, ET-1 induces EMT through ET-A activation. Furthermore, TGF-β1 synthesis is increased by ET-1, ET-1 induces Smad3 phosphorylation, and ET-1–induced EMT is attenuated by a TGF-β1–neutralizing antibody. Thus, ET-1 is an important mediator of EMT in AEC, acting through ET-A–mediated TGF-β1 production. These findings increase our basic understanding of the role of ET-1 in pulmonary fibrosis and suggest potential roles for AEC-derived ET-1 in the pathogenesis of other alveolar epithelial–mediated lung diseases.

Background Data Envelopment Analysis (DEA) methodology is considered the most suitable approach for relative performance efficiency calculation for banks as it is believed to be superior to traditional ratio-based analysis and other conventional performance evaluations. This study provides statistical evidence on the sampling error that can creep into performance evaluation studies using the DEA methodology. Inferences are drawn based on samples, and various preventive measures must be taken to eliminate or avoid sampling errors and misleading results. This study demonstrates the possibility of sampling error in DEA with the secondary data available in financial statements and reports from a sample set of banks. Methods The samples included 15 public sectors and five leading private sector banks in India based on their market share, and the data for calculating efficiencies were retrieved from the published audited reports. The sample data was collected from 2014 to 2017 because the banking sector in India witnessed a series of mergers of public sector banks post-2017, and the data after that would be skewed and not comparable due to the demonetization policy implementation and merger process-related consolidation implemented by the Government of India. The efficiency measures thus computed are further analyzed using non-parametric statistical tests. Results We found statistically significant discrepancies in the efficiency score calculations using DEA approach when specific outlier values. Evidence is provided on statistically significant differences in the efficiencies due to the inclusion and exclusion of particular samples in the DEA. Conclusion The study offers a novel contribution along with statistical evidence on the possible sampling error that can creep into the performance evaluation of organizations while applying the DEA methodology.

In recent times, macroeconomic factors have become a central focus of interest in international trade research. The economic environment in international trade directly affects trade performance and the global market. The study analyzes the export performance of Indian textile exports and the macroeconomic factors influencing them from the perspective of export destinations. The study incorporates the key macroeconomic variables, including exchange rate, interest rate, Gross Domestic Product (GDP) per capita, the inflation rates of export destination countries, and crude oil prices. The study includes secondary data gathered on a monthly basis, employing the vector auto-regressive (VAR) model and the Granger causality test to analyze the dynamic linkages and causal relationships between the variables in the study. The Granger causality test results revealed that Japan’s and South Africa’s GDP (p < 0.05) impacts India’s textile exports to these countries. Additionally, the inflation in Japan (p < 0.05) affects the performance of Indian textile exports. The VAR model further revealed that the USA’s and China’s interest rate, Japan’s exchange rate, GDP, and interest rate, as well as South Africa’s GDP, significantly influence the export performance of Indian textiles.

Background Nearly all males with cystic fibrosis (MwCF) are infertile and, thus, require the use of assisted reproductive technology (ART) to have biologic children. This study aims to describe the fertility and family-building knowledge, experiences, and care utilization of this population and to compare these findings to the general United States (US) population. Methods We conducted an anonymous cross-sectional study of self-reported survey data compared to data from the 2017–2019 US National Survey for Family Growth (NSFG). We recruited MwCF age 15 years and older at seven US cystic fibrosis (CF) centers. Results A total of 532 MwCF (mean age 35.3 ± 11.6 years) completed the survey. 83% knew that almost all MwCF are infertile and 84% were aware that MwCF can have biological children. 71% correctly identified the most common cause of male CF infertility. One third of MwCF stated they had never been told by anyone they were infertile due to their CF (mean age of discussion 19.3 ± 8.8 years). 31% reported being a parent. Among parents, 66% were a parent to a biological child born of a partner’s pregnancy, 20% via step-parenthood, 15% adoption, 4.3% surrogacy, and 0.6% foster parenthood. Compared to 44% of NSFG males, 18% of MwCF age 15–49 years reported being a parent to a biological child born of their partner’s pregnancy ( p  < 0.001). Among all MwCF, 82% with a biological child reported that they required medical assistance. Among those age 15–49 years, 87% of MwCF with a biological child required medical assistance compared to 9.4% of NSFG males ( p  < 0.001). Nearly three-quarters (73%) of MwCF who were biological parents underwent sperm retrieval via a variety of extraction techniques. 91% of those utilizing ART underwent in vitro fertilization and 9% intrauterine insemination of their partner. Conclusions MwCF face significant disease-related fertility and family-building implications with suboptimal counseling. Most MwCF who are parents pursue biological parenthood via a variety of ART services, but one-third chose alternative paths to parenthood. Further research is needed to best understand and support the family-building of MwCF. Clinical trial number Not applicable.

Cilia are traditionally classified as motile or primary. Motile cilia are restricted to specific populations of well-differentiated epithelial cells, including those in the airway, brain ventricles, and oviducts. Primary cilia are nonmotile, solitary structures that are present in many cell types, and often have sensory functions such as in the retina and renal tubules. Primary cilia were also implicated in the regulation of fundamental processes in development. Rare depictions of primary cilia in embryonic airways led us to hypothesize that primary cilia in airway cells are temporally related to motile ciliogenesis. We identified primary cilia in undifferentiated, cultured airway epithelial cells from mice and humans and in developing lungs. The solitary cilia in the airways express proteins considered unique to primary cilia, including polycystin-1 and polycystin-2. A temporal analysis of airway epithelial cell differentiation showed that cells with primary cilia acquire markers of motile ciliogenesis, suggesting that motile ciliated cells originate from primary ciliated cells. Whereas motile ciliogenesis requires Foxj1, primary ciliogenesis does not, and the expression of Foxj1 was associated with a loss of primary cilia, just before the appearance of motile cilia. Primary cilia were not found in well-differentiated airway epithelial cells. However, after injury, they appear in the luminal layer of epithelium and in basal cells. The transient nature of primary cilia, together with the temporal and spatial patterns of expression in the development and repair of airway epithelium, suggests a critical role of primary cilia in determining outcomes during airway epithelial cell differentiation.

The performance of bank stocks exhibits a country's overall financial health and signals economic growth. Therefore, understanding the interaction of macroeconomic factors on bank stock returns is crucial for the valuation of financial assets, especially in a highly volatile stock market. Although macroeconomic factors and their impact on bank stock returns have been extensively investigated, there is still a dearth of comprehensive review articles in this domain. To address this lacuna, we conducted a systematic review to identify the macroeconomic determinants driving bank stock returns. Through a systematic search, 64 articles were identified from two electronic databases for literature synthesis based on inclusion and exclusion criteria from 1980-2023. The review posits valuable insights into the macroeconomic factors that influence bank stock returns, the nuances of the variables' effects and the methodologies employed in these studies. The key macroeconomic factors identified include interest and exchange rate sensitivity, which has been studied extensively; however, the impact of monetary policies, gold prices and oil prices needs further investigation. Subsequently, the study documents various bank-specific characteristics that influence the relationship between macroeconomic factors and bank stock returns.

[...]in a recent analysis using the CFFPR, investigators reported 10- and 15-year survival rates of 76% and 65%, respectively, in adult-diagnosed patients, as opposed to the 88% and 86% rates reported in this study (7). Additional work needs to done to evaluate the factors preceding the diagnosis of CF in these adult-diagnosed patients to better understand how we can achieve earlier detection, particularly in individuals who have normal sweat tests and do not have pancreatic insufficiency or other features that may not be captured with newborn screening programs. [...]additional behavioral-science studies need to be conducted to determine how to best communicate this type of diagnosis to an adult patient who may have had symptoms for years that were misclassified (10). Pulmonary and Critical Care Medicine University of Texas Southwestern Medical Center Dallas, Texas References 1 Cystic Fibrosis Foundation Patient Registry. 2016 Annual Data Report.