Improving the Likelihood of Identifying Alpha-1 Antitrypsin Deficiency Among Patients With COPD: A Novel Predictive Model Using Real-world Data.

Background: Despite guideline recommendations, most patients with COPD do not undergo alpha-1 antitrypsin deficiency (AATD) testing and approximately 90% of people with AATD in the US remain undiagnosed. This study sought to develop a predictive model using real-world data to improve detection of AATD-positive patients in the general COPD population.

Methods: A predictive model using XGBoost was developed using the EVERSANA database, including longitudinal, patient-level medical claims, prescription claims, AATD-specific testing data, and electronic health records (EHR).

Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments.

Mitochondria regulate several physiological functions through mitochondrial Ca2+ dynamics. However, role of mitochondrial Ca2+ signaling in melanosome biology remains unknown. Here, we show that pigmentation requires mitochondrial Ca2+ uptake.

Steering research on mRNA splicing in cancer towards clinical translation.

Splicing factors are affected by recurrent somatic mutations and copy number variations in several types of haematologic and solid malignancies, which is often seen as prima facie evidence that splicing aberrations can drive cancer initiation and progression. However, numerous spliceosome components also 'moonlight' in DNA repair and other cellular processes, making their precise role in cancer difficult to pinpoint. Still, few would deny that dysregulated mRNA splicing is a pervasive feature of most cancers.

SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function.

In this study, we characterize a novel lncRNA-producing gene locus that we name Syntenic Cardiovascular Conserved Region-Associated lncRNA-6 (scar-6) and functionally validate its role in coagulation and cardiovascular function. A 12-bp deletion of the scar-6 locus in zebrafish (scar-6) results in cranial hemorrhage and vascular permeability. Overexpression, knockdown and rescue with the scar-6 lncRNA modulates hemostasis in zebrafish.

An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia.

Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer-related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B-ALL patients, suggesting additional mechanisms of resistance. By mining RNA sequencing datasets of paired diagnostic/relapse pediatric B-ALL samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers of resistance to glucocorticoids, antifolates, and thiopurines.