Baker's law is the observation that recently dispersed populations are more likely to be self-fertilizing than populations at the range core. The explanatory hypothesis is that dispersal favors self-fertilization due to reproductive assurance. Caenorhabditis elegans nematodes reproduce via either self-fertilization or outcrossing and frequently disperse in small numbers to new bacterial food sources.
View Article and Find Full Text PDFBackground: Computed tomography to body divergence (CTBD) is one of the main barriers to bronchoscopic techniques for the diagnosis of peripherally located lung nodules. Cone-beam CT (CBCT) guidance is being rapidly adopted to correct for this phenomenon and to potentially increase diagnostic outcomes. In this trial, we hypothesized that the addition of mobile CBCT (m-CBCT) could improve the rate of tool in lesion (TIL) and the diagnostic yield of shape-sensing robotic-assisted bronchoscopy (SS-RAB).
View Article and Find Full Text PDFKey Points: Lademirsen, an anti–microRNA-21 therapy, was generally well-tolerated in adults with Alport syndrome at risk of rapid disease progression. There were no significant differences between lademirsen-treated and placebo-treated participants in eGFR at any timepoint. The proportions of participants with prespecified reductions in eGFR at weeks 24 and 48 were not significantly different for lademirsen versus placebo.
View Article and Find Full Text PDFAberrant condensation and localization of the RNA-binding protein (RBP) fused in sarcoma (FUS) occur in variants of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Changes in RBP function are commonly associated with changes in axonal cytoskeletal organization and branching in neurodevelopmental disorders. Here, we asked whether branching defects also occur in vivo in a model of FUS-associated disease.
View Article and Find Full Text PDFWhile we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume.
View Article and Find Full Text PDF[F]Fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are indispensable components in modern medicine. Although PET can provide additional diagnostic value, it is costly and not universally accessible, particularly in low-income countries. To bridge this gap, we have developed a conditional generative adversarial network pipeline that can produce FDG-PET from diagnostic CT scans based on multi-center multi-modal lung cancer datasets (n = 1,478).
View Article and Find Full Text PDFBackground: Genes that encode synaptic proteins or messenger RNA targets of the RNA-binding protein FMRP (fragile X messenger ribonucleoprotein) have been linked to schizophrenia and autism spectrum disorder (ASD) through the enrichment of genetic variants that confer risk for these disorders. FMRP binds many transcripts with synaptic functions and is thought to regulate their local translation, a process that enables rapid and compartmentalized protein synthesis required for development and plasticity.
Methods: We used summary statistics from large-scale genome-wide association studies of schizophrenia (74,776 cases, 101,023 controls) and ASD (18,381 cases, 27,969 controls) to test the hypothesis that the subset of synaptic genes that encode localized transcripts is more strongly associated with each disorder than nonlocalized transcripts.
Aero-digestive fistulas (ADFs) are pathologic connections between the airways and gastrointestinal system. These most commonly occur between the central airways and esophagus. Fistulas may develop congenitally or be acquired from a benign or malignant process.
View Article and Find Full Text PDFPurpose: The aim of this study was to report a rare observation of corneal superficial plaque formation after topical recombinant human nerve growth factor (rhNGF) treatment for a nonhealing epithelial defect in a patient with advanced mucous membrane pemphigoid, limbal stem cell deficiency, and neurotrophic keratopathy.
Methods: This study was a case report.
Results: A 72-year-old man with a complex course of mucous membrane pemphigoid, leading to cicatrizing keratoconjunctivits, limbal stem cell deficiency, and neurotrophic keratopathy presented with a recurrent persistent epithelial defect in the right eye.
Background: Pleural infections related to indwelling pleural catheters (IPCs) are an uncommon clinical problem. However, management decisions can be complex for patients with active malignancies due to their comorbidities and limited life expectancies. There are limited studies on the management of IPC-related infections, including whether to remove the IPC or use intrapleural fibrinolytics.
View Article and Find Full Text PDFJ Bronchology Interv Pulmonol
January 2024
J Bronchology Interv Pulmonol
October 2023
Objectives: To identify cytokine signature clusters in patients with septic shock.
Design: Prospective observational cohort study.
Setting: Single academic center in the United States.
Peripheral blood mononuclear cells (PBMCs) are commonly isolated from whole blood samples in clinical trials. Isolated PBMCs can be cryopreserved for use in downstream assays such as flow cytometry, single-cell RNA sequencing (scRNA-seq) and enzyme-linked immunosorbent spot (ELISpot) assays to aid understanding of disease biology and treatment effects, and biomarker identification. However, due to logistical practicalities, delays from blood collection to PBMC processing may exceed 24 h, which can potentially affect PBMC function and, ultimately, downstream assay results.
View Article and Find Full Text PDFEnhanced expression of the cold-shock protein RNA binding motif 3 (RBM3) is highly neuroprotective both in vitro and in vivo. Whilst upstream signalling pathways leading to RBM3 expression have been described, the precise molecular mechanism of RBM3 cold induction remains elusive. To identify temperature-dependent modulators of RBM3, we performed a genome-wide CRISPR-Cas9 knockout screen using RBM3-reporter human iPSC-derived neurons.
View Article and Find Full Text PDFPulmonary toxicity from immune checkpoint inhibitor therapy is typically a severe and potentially fatal complication, but these observations are driven by the most common toxicity, pneumonitis. Rarer pulmonary immune related adverse events, like airway disease and sarcoidosis, may have a more benign course. In this case report, we present a patient in whom therapy with the PD-1 inhibitor pembrolizumab resulted in severe eosinophilic asthma and sarcoidosis.
View Article and Find Full Text PDFBackground Pleural infection is a common clinical problem resulting in prolonged hospitalization and increased mortality. In patients with active malignancy, management decisions are based on the need for further immunosuppressive therapies, the ability to tolerate surgery, and consideration of the limited life expectancy. Identifying patients at risk for death or poor outcomes is very important as it will guide care.
View Article and Find Full Text PDFLaceration of an intercostal artery is a rare but potentially catastrophic complication of pleural procedures such as thoracentesis. Recognition of this problem often occurs late in the bleeding process, only after hemodynamic decompensation has occurred. Aggressive and emergent measures are usually undertaken such as angiographic embolization or thoracotomy.
View Article and Find Full Text PDFIntroduction: Caplacizumab demonstrated efficacy and safety in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in the phase 3 HERCULES trial. However, data on long-term outcomes following caplacizumab treatment are limited.
Objectives: The post-HERCULES trial (NCT02878603) evaluated long-term outcomes of patients with iTTP treated with caplacizumab in HERCULES and safety and efficacy of repeated caplacizumab use.
In neurons, specific mRNAs are transported into axons, where their local translation supports essential cellular functions. Over the years, our knowledge of the molecular mechanisms underlying axonal mRNA translation has rapidly expanded. However, tools to study mRNA localization and translation in real time with high spatial precision were not available until recently.
View Article and Find Full Text PDFIn patients who are mechanically ventilated, diaphragm thinning on ultrasound is thought to correlate with diaphragm atrophy and has been associated with prolonged intubation. Factors other than atrophy, however, may cause changes in diaphragm thickness, which may confound studies examining changes in diaphragm thickness over time. To determine if changes in the mode of mechanical ventilation or an interruption of sedatives have immediate effects on diaphragm thickness measurements in adult patients in the intensive care unit who are mechanically ventilated.
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