An Evaluation of Avian Influenza Virus Whole-Genome Sequencing Approaches Using Nanopore Technology

As exemplified by the global response to the SARS-CoV-2 pandemic, whole-genome sequencing played an important role in monitoring the evolution of novel viral variants and provided guidance on potential antiviral treatments. The recent rapid and extensive introduction and spread of highly pathogenic avian influenza virus in Europe, North America, and elsewhere raises the need for similarly rapid sequencing to aid in appropriate response and mitigation activities. To facilitate this objective, we investigate a next-generation sequencing platform that uses a portable nanopore sequencing device to generate and present data in real time. This platform offers the potential to extend in-house sequencing capacities to laboratories that may otherwise lack resources to adopt sequencing technologies requiring large benchtop instruments. We evaluate this platform for routine use in a diagnostic laboratory. In this study, we evaluate different primer sets for the whole genome amplification of influenza A virus and evaluate five different library preparation approaches for sequencing on the nanopore platform using the MinION flow cell. A limited amplification procedure and a rapid procedure are found to be best among the approaches taken

Capecitabine as Salvage Treatment for Lymphoepithelioma-Like Carcinoma of Lung

AbstractLymphoepithelioma-like carcinoma (LELC) of lung has previously demonstrated good clinical response to 5-fluorouracil containing chemotherapy regimen, similar to the observation in undifferentiated nasopharyngeal carcinoma. Capecitabine, which is converted into active 5-fluorouracil within tumor cells, has been found effective in colorectal, breast, and recently nasopharyngeal carcinomas. We report our experience in five patients with advanced or metastatic LELC of lung who were treated with single agent capecitabine as salvage chemotherapy. The finding of disease control in three of five patients, especially with exceptionally durable stable disease (14.8 months) in one patient, suggests the potential clinical activity of capecitabine in LELC of lung. Future studies on capecitabine-containing chemotherapy regimens in LELC of lung are warranted

Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants, United States, 2014–2015

Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses

Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants, United States, 2014–2015

Asian highly pathogenic avian influenza A(H5N8) viruses spread into North America in 2014 during autumn bird migration. Complete genome sequencing and phylogenetic analysis of 32 H5 viruses identified novel H5N1, H5N2, and H5N8 viruses that emerged in late 2014 through reassortment with North American low-pathogenicity avian influenza viruses

Elevated plasma TGF-β1 levels in patients with chronic obstructive pulmonary disease

SummaryBackgroundTransforming growth factor-β1 (TGF-β1), a multifunctional cytokine, has been implicated to be responsible for the increased deposition of extracellular matrix in the airways, and increased submucosal collagen expression in chronic obstructive pulmonary disease (COPD). We determined plasma TGF-β1 levels in patients with COPD and explored its association with common functional polymorphisms of TGF-β1 gene at C-509T and T869C in the development of COPD in a case–control study.MethodsStable COPD patients who were ever smokers, and age and pack-years smoked matched healthy controls (n = 205 in each group) were recruited for measurement of plasma TGF-β1 levels using commercially available ELISA kit, and genotyped at C-509T and T869C functional polymorphisms of TGF-β1 gene using polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP).ResultsCOPD patients had significantly elevated plasma TGF-β1 levels in comparison to healthy controls irrespective of the genotypes. Allele frequencies and genotype distributions at both polymorphic sites were not different among COPD patients or controls. TGF-β1 levels were inversely correlated (Pearson's correlation analysis) with FEV1 (% predicted) (p < 0.001) and FVC (% predicted) (p < 0.001).ConclusionThe findings of elevated plasma TGF-β1 levels in patients with COPD suggest that TGF-β1 may play a role in COPD pathogenesis. The C-509T and T869C functional polymorphisms of TGF-β1 gene do not represent a genetic predisposition to COPD susceptibility in Hong Kong Chinese patients

Induced Pluripotent Stem Cells-Derived Mesenchymal Stem Cells Attenuate Cigarette Smoke-Induced Cardiac Remodeling and Dysfunction

The strong relationship between cigarette smoking and cardiovascular disease (CVD) has been well-documented, but the mechanisms by which smoking increases CVD risk appear to be multifactorial and incompletely understood. Mesenchymal stem cells (MSCs) are regarded as an important candidate for cell-based therapy in CVD. We hypothesized that MSCs derived from induced pluripotent stem cell (iPSC-MSCs) or bone marrow (BM-MSCs) might alleviate cigarette smoke (CS)-induced cardiac injury. This study aimed to investigate the effects of BM-MSCs or iPSC-MSCs on CS-induced changes in serum and cardiac lipid profiles, oxidative stress and inflammation as well as cardiac function in a rat model of passive smoking. Male Sprague-Dawley rats were randomly selected for exposure to either sham air (SA) as control or 4% CS for 1 h per day for 56 days. On day 29 and 43, human adult BM-MSCs, iPSC-MSCs or PBS were administered intravenously to CS-exposed rats. Results from echocardiography, serum and cardiac lipid profiles, cardiac antioxidant capacity, cardiac pro- and anti-inflammatory cytokines and cardiac morphological changes were evaluated at the end of treatment. iPSC-MSC-treated group showed a greater effect in the improvement of CS-induced cardiac dysfunction over BM-MSCs-treated group as shown by increased percentage left ventricular ejection fraction and percentage fractional shortening, in line with the greater reversal of cardiac lipid abnormality. In addition, iPSC-MSCs administration attenuated CS-induced elevation of cardiac pro-inflammatory cytokines as well as restoration of anti-inflammatory cytokines and anti-oxidative markers, leading to ameliorate cardiac morphological abnormalities. These data suggest that iPSC-MSCs on one hand may restore CS-induced cardiac lipid abnormality and on the other hand may attenuate cardiac oxidative stress and inflammation via inhibition of CS-induced NF-κB activation, leading to improvement of cardiac remodeling and dysfunction. Thus, iPSC-MSCs may be a promising candidate in cell-based therapy to prevent cardiac complications in smokers

H5N1 highly pathogenic avian influenza clade 2.3.4.4b in wild and domestic birds: Introductions into the United States and reassortments, December 2021–April 2022

Highly pathogenic avian influenza viruses (HPAIVs) of the A/goose/Guangdong/1/1996 lineage H5 clade 2.3.4.4b continue to have a devastating effect on domestic and wild birds. Full genome sequence analyses using 1369 H5N1 HPAIVs detected in the United States (U.S.) in wild birds, commercial poultry, and backyard flocks from December 2021 to April 2022, showed three phylogenetically distinct H5N1 virus introductions in the U.S. by wild birds. Unreassorted Eurasian genotypes A1 and A2 entered the Northeast Atlantic states, whereas a genetically distinct A3 genotype was detected in Alaska. The A1 genotype spread westward via wild bird migration and reassorted with North American wild bird avian influenza viruses. Reassortments of up to five internal genes generated a total of 21 distinct clusters; of these, six genotypes represented 92% of the HPAIVs examined. By phylodynamic analyses, most detections in domestic birds were shown to be point-source transmissions from wild birds, with limited farm-to-farm spread

Baseline Predictors of Visual Acuity and Retinal Thickness Outcomes in Patients with Retinal Vein Occlusion. SCORE Study Report 10

To investigate baseline factors significantly associated with visual acuity and central retinal thickness outcomes in patients with macular edema secondary to retinal vein occlusion in the Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study

Novel Eurasian Highly Pathogenic Avian Influenza A H5 Viruses in Wild Birds, Washington, USA, 2014

The novel Eurasian lineage clade 2.3.4.4 highly pathogenic avian influenza (HPAI) A(H5N8) virus (http://www.who.int/influenza/gisrs_laboratory/h5_nomenclature_clade2344/en/) spread rapidly and globally during 2014, substantially affecting poultry populations. The first outbreaks were reported during January 2014 in chickens and domestic ducks in South Korea and subsequently in China and Japan (1–4), reaching Germany, the Netherlands, and the United Kingdom by November 2014 and Italy in early December 2014 (5). Also in November 2014, a novel HPAI H5N2 virus was reported in outbreaks on chicken and turkey farms in Fraser Valley, British Columbia, Canada (5). This H5N2 influenza virus is a reassortant that contains the Eurasian clade 2.3.4.4 H5 plus 4 other Eurasian genes (polymerase acidic protein subunit, matrix protein, polymerase basic protein subunit [PB] 2, nonstructural protein) and 3 North American wild bird lineage genes (neuraminidase [NA], nucleoprotein, PB1) (5). Taiwan has recently reported novel reassortants of the H5 clade 2.3.4.4 with other Eurasian viruses (H5N2, H5N3)