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The article discusses the management of patent ductus arteriosus (PDA) in extreme preterm infants. PDA is a common condition in these infants and its treatment is a subject of debate. The article presents the findings of the Baby-OSCAR trial, which compared early treatment with ibuprofen to placebo. The trial found that early treatment with ibuprofen did not reduce the risk of death or bronchopulmonary dysplasia. The article concludes that there is no evidence to support early treatment with ibuprofen for PDA in extreme preterm infants and that it may be more harmful than the condition itself. [Extracted from the article]

The article discusses a randomized controlled trial that compared the use of higher versus standard nasal continuous positive airway pressure (nCPAP) for extubation of extremely preterm infants. The study found that using a higher nCPAP level of 10cmH2O reduced the rate of extubation failure compared to standard nCPAP. However, there was no significant difference in rates of bronchopulmonary dysplasia (BPD) between the two groups. The authors suggest that further research is needed to evaluate the safety and efficacy of higher post-extubation nCPAP levels on important outcomes for clinicians and families. [Extracted from the article]

Background: Long noncoding RNAs (lncRNAs) have surpassed the number of protein-coding genes, yet the majority have no known function. We previously discovered 844 lncRNAs that were genetically linked to breast cancer through genome-wide association studies (GWAS). Here, we show that a subset of these lncRNAs alter breast cancer risk by modulating cell proliferation, and provide evidence that a reduced expression on one lncRNA increases breast cancer risk through aberrant DNA replication and repair. Methods: We performed pooled CRISPR-Cas13d-based knockdown screens in breast cells to identify which of the 844 breast cancer-associated lncRNAs alter cell proliferation. We selected one of the lncRNAs that increased cell proliferation, KILR, for follow-up functional studies. KILR pull-down followed by mass spectrometry was used to identify binding proteins. Knockdown and overexpression studies were performed to assess the mechanism by which KILR regulates proliferation. Results: We show that KILR functions as a tumor suppressor, safeguarding breast cells against uncontrolled proliferation. The half-life of KILR is significantly reduced by the risk haplotype, revealing an alternative mechanism by which variants alter cancer risk. Mechanistically, KILR sequesters RPA1, a subunit of the RPA complex required for DNA replication and repair. Reduced KILR expression promotes breast cancer cell proliferation by increasing the available pool of RPA1 and speed of DNA replication. Conversely, KILR overexpression promotes apoptosis in breast cancer cells, but not normal breast cells. Conclusions: Our results confirm lncRNAs as mediators of breast cancer risk, emphasize the need to annotate noncoding transcripts in relevant cell types when investigating GWAS variants and provide a scalable platform for mapping phenotypes associated with lncRNAs. [ABSTRACT FROM AUTHOR]

Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research. [ABSTRACT FROM AUTHOR]

A letter published in the Annals of Hematology discusses the need for a diagnostic test with a short turnaround time for acute promyelocytic leukemia (APL). The authors conducted a proteomic analysis to identify a unique protein biomarker in APL. They found that cystatin F, a secretory protein found in extracellular space and body fluids, was significantly overexpressed in APL cells compared to other types of leukemia and healthy control cells. The authors suggest that cystatin F could be a potential biomarker for the rapid diagnosis of APL and the initiation of appropriate therapies. [Extracted from the article]