Effects of HA and NA glycosylation pattern changes on the transmission of avian influenza A(H7N9) virus in guinea pigs

AbstractAvian influenza H7N9 virus has posed a concern of potential human-to-human transmission by resulting in seasonal virus-like human infection cases. To address the issue of sustained human infection with the H7N9 virus, here we investigated the effects of hemagglutinin (HA) and neuraminidase (NA) N-linked glycosylation (NLG) patterns on influenza virus transmission in a guinea pig model. Based on the NLG signatures identified in the HA and NA genetic sequences of H7N9 viruses, we generated NLG mutant viruses using either HA or NA gene of a H7N9 virus, A/Anhui/01/2013, by reverse genetics on the 2009 pandemic H1N1 virus backbone. For the H7 HA NLG mutant viruses, NLG pattern changes appeared to reduce viral transmissibility in guinea pigs. Intriguingly, however, the NLG changes in the N9 NA protein, such as a removal from residue 42 or 66 or an addition at residue 266, increased transmissibility of the mutant viruses by more than 33%, 50%, and 16%, respectively, compared with a parental N9 virus. Given the effects of HA-NA NLG changes with regard to viral transmission, we then generated the HA-NA NLG mutant viruses harboring the H7 HA of double NLG addition and the N9 NA of various NLG patterns. As seen in the HA NLG mutants above, the double NLG-added H7 HA decreased viral transmissibility. However, when the NA NLG changes occurred by a removal of residue 66 and an addition at 266 were additionally accompanied, the HA-NA NLG mutant virus recovered the transmissibility of its parental virus. These demonstrate the effects of specific HA-NA NLG changes on the H7N9 virus transmission by highlighting the importance of a HA-NA functional balance

Measurement Variability in Treatment Response Determination for Non-Small Cell Lung Cancer: Improvements using Radiomics

Multimodality imaging measurements of treatment response are critical for clinical practice, oncology trials, and the evaluation of new treatment modalities. The current standard for determining treatment response in non-small cell lung cancer (NSCLC) is based on tumor size using the RECIST criteria. Molecular targeted agents and immunotherapies often cause morphological change without reduction of tumor size. Therefore, it is difficult to evaluate therapeutic response by conventional methods. Radiomics is the study of cancer imaging features that are extracted using machine learning and other semantic features. This method can provide comprehensive information on tumor phenotypes and can be used to assess therapeutic response in this new age of immunotherapy. Delta radiomics, which evaluates the longitudinal changes in radiomics features, shows potential in gauging treatment response in NSCLC. It is well known that quantitative measurement methods may be subject to substantial variability due to differences in technical factors and require standardization. In this review, we describe measurement variability in the evaluation of NSCLC and the emerging role of radiomics. © 2019 Wolters Kluwer Health, Inc. All rights reserved

Compositional assessment of carotenoid-biofortified rice using substantial equivalence

One important aspect in assessing the safety of genetically modified (GM) crops for human consumption is characterizing their nutrient composition. A β-carotene-biofortified rice was generated by inserting phytoene synthase (Psy) and carotene desaturase (Crtl) genes isolated from Capsicum and Pantoea into the genome of a conventional variety of rice (Nakdongbyeo). Nutrients (proximates, amino acids, fatty acids, minerals, and vitamins), anti-nutritive components (trypsin inhibitors and phytic acid), and ferulic acid in GM rice were compared with those in the parent line Nakdongbyeo. Statistical comparisons to test for equivalence showed that all of the analyzed components in the GM plants were equivalent to those in its non-transgenic counterpart, and most nutritional components fell within the range of values reported for other commercial lines, indicating the safety of the GM plant.Key words: Genetically modified crop, β-Carotene, Transgenic rice, Nutrient, Substantial equivalence

Differential Methylation Pattern of ID4, SFRP1, and SHP1 between Acute Myeloid Leukemia and Chronic Myeloid Leukemia

To gain insight into the differential mechanism of gene promoter hypermethylation in acute and chronic leukemia, we identified the methylation status on one part of 5'CpG rich region of 8 genes, DAB2IP, DLC-1, H-cadherin, ID4, Integrin α4, RUNX3, SFRP1, and SHP1 in bone marrows from acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Also, we compared the methylation status of genes in AML and CML using methylation-specific PCR (MSP). The frequencies of DNA methylation of ID4, SFRP1, and SHP1 were higher in AML patients compared to those in CML patients. In contrast, no statistical difference between AML and CML was detected for other genes such as DLC-1, DAB2IP, H-cadherin, Integrin α4, and RUNX3. Taken together, these results suggest that these methylation-controlled genes may have different roles in AML and CML, and thus, may act as a biological marker of AML

Delayed Diagnosis of an Intraurethral Foreign Body Causing Urosepsis and Penile Necrosis

Cases of self-inserted foreign bodies in the male urethra and urinary bladder are unusual. In most cases, the type of foreign body can be identified by taking a history or from radiological findings; sometimes, however, it is difficult to identify the foreign body because of decreased mental capacity of the patient or unknown radiological characteristics of the foreign body. We experienced a chronic alcoholic patient with septicemia and penile necrosis in whom a fragment of mirror glass had passed through the urethra into the bladder. The glass, 2 cm in length and 0.7 cm in diameter, was detected by cystoscopy and was removed by using a resectosope

Effect of Pumpkin Seed Oil on Hair Growth in Men with Androgenetic Alopecia: A Randomized, Double-Blind, Placebo-Controlled Trial

Pumpkin seed oil (PSO) has been shown to block the action of 5-alpha reductase and to have antiandrogenic effects on rats. This randomized, placebo-controlled, double-blind study was designed to investigate the efficacy and tolerability of PSO for treatment of hair growth in male patients with mild to moderate androgenetic alopecia (AGA). 76 male patients with AGA received 400 mg of PSO per day or a placebo for 24 weeks. Change over time in scalp hair growth was evaluated by four outcomes: assessment of standardized clinical photographs by a blinded investigator; patient self-assessment scores; scalp hair thickness; and scalp hair counts. Reports of adverse events were collected throughout the study. After 24 weeks of treatment, self-rated improvement score and self-rated satisfaction scores in the PSO-treated group were higher than in the placebo group ( = 0.013, 0.003). The PSOtreated group had more hair after treatment than at baseline, compared to the placebo group ( < 0.001). Mean hair count increases of 40% were observed in PSO-treated men at 24 weeks, whereas increases of 10% were observed in placebo-treated men ( < 0.001). Adverse effects were not different in the two groups

A Hybrid Approach of Data-driven and Physics-based Methods for Estimation and Prediction of Fatigue Crack Growth

Lamb-wave-based nondestructive testing and evaluation (NDT/E) methods have drawn much attention due to their potential to inspect plate-like structures in a variety of industrial applications. To estimate and/or predict fatigue crack growth, many research efforts have been made to develop data-driven or physics-based methods. Data-driven methods show high predictive capability without the need for physical domain knowledge; however, fewer data can lead to overfitting in the results. On the other hand, physics-based methods can provide reliable results without the need for measured data; however, small amounts of physical information can worsen their predictive capability. In real applications, both the measurable data and the physical information of systems may be considerably limited; it is thus challenging to estimate and/or predict the crack length using either the data-driven or physics-based method alone. To make use of the advantages and minimize the disadvantages of each method, the work outlined in this paper aims to develop a hybrid approach that combines the data-driven and the physics-based methods for estimation and prediction of fatigue crack growth with and without Lamb wave signals. First, with Lamb wave signals, a data-driven method based on signal processing and the random forest model can be used estimate crack lengths. Second, in the absence of Lamb wave signals, a physics-based method based on an ensemble prognostics approach and Walker’s equation can be used to predict crack lengths with the help of the previously estimated crack lengths. To demonstrate the validity of the proposed approach, a case study is presented using datasets provided in the 2019 PHM Conference Data Challenge by the PHM Society. The case study confirms that the proposed method shows high accuracy; the RMSEs for specimens T7 and T8 are calculated as 0.2021 and 0.551, respectively. A penalty score is calculated as 7.63; this result led to a 2nd place finish in the Data Challenge. To the best of the authors’ knowledge, this is the first attempt to propose a hybrid approach for estimation and prediction of fatigue crack growth