The use of biologic-based therapeutics has revolutionized our ability to treat complex diseases such as cancer- and autoimmune-related disorders. Biologic-based therapeutics are known to generate anti-drug immune responses or immunogenicity in clinical patients which can lead to altered pharmacokinetics, decreased drug efficacy, and unwanted adverse clinical events. Assays designed to detect and assess anti-drug immune responses are used to help monitor patients and improve drug safety. Utilizing a tiered approach, screening assays are developed first to identify patients that are potentially positive for anti-drug-specific antibodies. Patients that screen positive are subjected to additional tiers of testing that include a confirmation assay to confirm the presence of expected anti-drug-specific antibodies, a titer assay to assess relative levels of anti-drug-specific antibodies, and, depending on the drug's mechanism of action or concerns of adverse clinical reactions, further characterization such as drug neutralization and anti-drug antibody isotyping. selleck This tiered approach can prove to be detrimental to clinical samples from exposure to multiple cycles of testing, freeze thaws, and repeated handling by lab personnel. Multiplexing some of these assays together may streamline the characterization of anti-drug immune responses and help reduce the repeated usage of clinical samples. In this study, we combined a screening assay and anti-drug isotyping assays into one multiplexed assay using the Luminex® xMAP® Technology. The multiplexed assay was developed and validated to meet the FDA recommended guidelines for immunogenicity assessments. These results show that multiplexed assays perform comparably to industry standards. This study should encourage labs to explore the use of multiplexing immunogenicity assays to characterize anti-drug antibody responses quickly, with less repeat testing and reduced sample handling. We have developed multiplex genome editing toolkits for citrus that significantly improve citrus genome editing efficacy. CRISPR/Cas systems have been engineered for genome editing in many organisms, including plants. However, the gene editing efficiency in citrus via CRISPR technology remains too low to be implemented for genetic improvement in practice. Moreover, it is very difficult to obtain homozygous or biallelic knockout mutants in citrus. Here, we have developed multiplex genome editing toolkits for citrus including PEG-mediated protoplast transformation, a GFP reporter system that allows the rapid assessment of CRISPR constructs, citrus U6 promoters with improved efficacy, and tRNA-mediated or Csy4-mediated multiplex genome editing. Using the toolkits, we successfully conducted genome modification of embryogenic protoplast cells and epicotyl tissues. We have achieved a biallelic mutation rate of 44.4% and a homozygous mutation rate of 11.1%, representing a significant improvement in citrus genome e.4% and a homozygous mutation rate of 11.1%, representing a significant improvement in citrus genome editing efficacy. In addition, our study lays the foundation for nontransgenic genome editing of citrus. Mechanical thrombectomy (MT) in posterior circulation large vessel occlusion (LVO), including posterior cerebral artery (PCA), has not been validated since all five major MT trials excluded such patients. To evaluate the feasibility and preliminary safety and efficacy of MT in isolated PCA occlusion stroke patients with new-generation MT devices. Endovascularly treated acute ischemic stroke (AIS) patients were identified from a prospectively collected database and their baseline characteristics were noted. Clinical outcomes were angiographic recanalization, a favorable clinical outcome at 3months on modified Rankin Scale (mRS) and visual field (VF) deficit improvement on confrontation test, rate of intracranial hemorrhage (ICH), and mortality at 3months. A total of 355 AIS patients underwent MT from January 2018 to December 2019. Isolated PCA MT was performed in 15 consecutive patients. The mean age was 64 ± 17years, and 9(60%) were women. Median presentation NIHSS was 9 (interquartile range 5-15). MT devices used were stent retrievers in 6 patients and combined aspiration and stent retriever in 9 patients. Complete revascularization (TICI 2c or 3) was achieved in 12/15 patients. 3-month VF normalization was seen in 7/12 of the patients. Post-procedure symptomatic ICH occurred in 1/15 of patients. mRS score of 0-2 was achieved in 9/15 of patients but one patient was dead at 3months post procedure. MT is feasible and can achieve successful reperfusion in isolated PCA occlusions and resulted in favorable motor and visual outcomes in this small series of ischemic stroke patients.MT is feasible and can achieve successful reperfusion in isolated PCA occlusions and resulted in favorable motor and visual outcomes in this small series of ischemic stroke patients.Dysregulated RNA metabolism is emerging as a crucially important mechanism underpinning the pathogenesis of frontotemporal dementia (FTD) and the clinically, genetically and pathologically overlapping disorder of amyotrophic lateral sclerosis (ALS). Heterogeneous nuclear ribonucleoproteins (hnRNPs) comprise a family of RNA-binding proteins with diverse, multi-functional roles across all aspects of mRNA processing. The role of these proteins in neurodegeneration is far from understood. Here, we review some of the unifying mechanisms by which hnRNPs have been directly or indirectly linked with FTD/ALS pathogenesis, including their incorporation into pathological inclusions and their best-known roles in pre-mRNA splicing regulation. We also discuss the broader functionalities of hnRNPs including their roles in cryptic exon repression, stress granule assembly and in co-ordinating the DNA damage response, which are all emerging pathogenic themes in both diseases. We then present an integrated model that depicts how a broad-ranging network of pathogenic events can arise from declining levels of functional hnRNPs that are inadequately compensated for by autoregulatory means. Finally, we provide a comprehensive overview of the most functionally relevant cellular roles, in the context of FTD/ALS pathogenesis, for hnRNPs A1-U.