PD-0458: AFP response as a predictor of clinical outcome after stereotactic body radiotherapy (SBRT) for advanced HCC

POSTER DISCUSSION: YOUNG SCIENTISTS 2: LUNG AND GASTROINTESTINAL TUMOURSpublished_or_final_version2nd ESTRO Forum, Geneva, Switzerland, 19-23 April 2013, In Radiotherapy & Oncology, 2013, v. 106, p. S17

Specific TATAA and bZIP requirements suggest that HTLV-I Tax has transcriptional activity subsequent to the assembly of an initiation complex

BACKGROUND: Human T-cell leukemia virus type I (HTLV-I) Tax protein is a transcriptional regulator of viral and cellular genes. In this study we have examined in detail the determinants for Tax-mediated transcriptional activation. RESULTS: Whereas previously the LTR enhancer elements were thought to be the sole Tax-targets, herein, we find that the core HTLV-I TATAA motif also provides specific responsiveness not seen with either the SV40 or the E1b TATAA boxes. When enhancer elements which can mediate Tax-responsiveness were compared, the authentic HTLV-I 21-bp repeats were found to be the most effective. Related bZIP factors such as CREB, ATF4, c-Jun and LZIP are often thought to recognize the 21-bp repeats equivalently. However, amongst bZIP factors, we found that CREB, by far, is preferred by Tax for activation. When LTR transcription was reconstituted by substituting either κB or serum response elements in place of the 21-bp repeats, Tax activated these surrogate motifs using surfaces which are different from that utilized for CREB interaction. Finally, we employed artificial recruitment of TATA-binding protein to the HTLV-I promoter in "bypass" experiments to show for the first time that Tax has transcriptional activity subsequent to the assembly of an initiation complex at the promoter. CONCLUSIONS: Optimal activation of the HTLV-I LTR by Tax specifically requires the core HTLV-I TATAA promoter, CREB and the 21-bp repeats. In addition, we also provide the first evidence for transcriptional activity of Tax after the recruitment of TATA-binding protein to the promoter

A Smartphone Application for Skin Lesion Detection and Classification with Deep Learning Algorithms

The Skin Lesion (SL) classification has recently received a lot of attention. Because of the significant resemblance between these skin lesions, physicians spend a lot of time analyzing them. A Deep Learning (DL) based automated categorization system can help clinicians recognize the type of SL and improve the patient's health. In this research, DL approaches such as VGG-16, ResNet-50 and customized model are employed to detect the SL using a smartphone application. These models are trained on the SL classification dataset from the International Skin Imaging Collaboration (ISIC) 2019. The customized model over fits the other two models with a validation accuracy of 86.21%, whereas the validation accuracy of VGG-16 and ResNet-50 is 85.15% and 84.82%, respectively. Physicians will save time and have a higher precision rate in the automatic classification of SL utilizing DL

Exploiting physico-chemical properties in string kernels

<p>Abstract</p> <p>Background</p> <p>String kernels are commonly used for the classification of biological sequences, nucleotide as well as amino acid sequences. Although string kernels are already very powerful, when it comes to amino acids they have a major short coming. They ignore an important piece of information when comparing amino acids: the physico-chemical properties such as size, hydrophobicity, or charge. This information is very valuable, especially when training data is less abundant. There have been only very few approaches so far that aim at combining these two ideas.</p> <p>Results</p> <p>We propose new string kernels that combine the benefits of physico-chemical descriptors for amino acids with the ones of string kernels. The benefits of the proposed kernels are assessed on two problems: MHC-peptide binding classification using position specific kernels and protein classification based on the substring spectrum of the sequences. Our experiments demonstrate that the incorporation of amino acid properties in string kernels yields improved performances compared to standard string kernels and to previously proposed non-substring kernels.</p> <p>Conclusions</p> <p>In summary, the proposed modifications, in particular the combination with the RBF substring kernel, consistently yield improvements without affecting the computational complexity. The proposed kernels therefore appear to be the kernels of choice for any protein sequence-based inference.</p> <p>Availability</p> <p>Data sets, code and additional information are available from <url>http://www.fml.tuebingen.mpg.de/raetsch/suppl/aask</url>. Implementations of the developed kernels are available as part of the Shogun toolbox.</p

A Comparison Between Chinese Children Infected with Coronavirus Disease-2019 and with Severe Acute Respiratory Syndrome 2003

OBJECTIVES: To compare the clinical and laboratory features of severe acute respiratory syndrome 2003 (SARS) and coronavirus disease 2019 (COVID-19) in two Chinese pediatric cohorts, given that the causative pathogens and are biologically similar. , STUDY DESIGN: This is a cross-sectional study reviewing paediatric patients with SARS (n = 43) and COVID-19 (n=244) who were admitted to the Princess Margaret Hospital in Hong Kong and Wuhan Children's Hospital in Wuhan, respectively. Demographics, hospital length of stay, clinical and laboratory features were compared RESULTS: Overall, 97.7% of patients with SARS and 85.2% of patients with COVID-19 had epidemiological associations with known cases. Significantly more patients with SARS developed fever, chills, myalgia, malaise, coryza, sore throat, sputum production, nausea, headache, and dizziness than patients COVID-19. No SARS patients were asymptomatic at the time of admission. 29.1% and 20.9% COVID-19 patients were asymptomatic on admission and throughout their hospital stay, respectively. More SARS patients required oxygen supplementation than COVID-19 patients (18.6 vs. 4.7%, P = 004). Only 1.6% COVID-19 and 2.3% SARS patients required mechanical ventilation. Leukopenia (37.2% vs. 18.6%, p=0.008), lymphopenia (95.4% versus 32.6%, p<0.01), and thrombocytopenia (41.9% vs 3.8%, p<0.001) were significantly more common in SARS than COVID-19 patients. The duration between positive and negative nasopharyngeal aspirate and the length in hospital stay were similar in COVID-19 patients regardless of whether they were asymptomatic or symptomatic, suggesting a similar duration of viral shedding. CONCLUSIONS: Children with COVID-19 were less symptomatic and had more favorable hematological findings than children with SARS

A method to improve protein subcellular localization prediction by integrating various biological data sources

<p>Abstract</p> <p>Background</p> <p>Protein subcellular localization is crucial information to elucidate protein functions. Owing to the need for large-scale genome analysis, computational method for efficiently predicting protein subcellular localization is highly required. Although many previous works have been done for this task, the problem is still challenging due to several reasons: the number of subcellular locations in practice is large; distribution of protein in locations is imbalanced, that is the number of protein in each location remarkably different; and there are many proteins located in multiple locations. Thus it is necessary to explore new features and appropriate classification methods to improve the prediction performance.</p> <p>Results</p> <p>In this paper we propose a new predicting method which combines two key ideas: 1) Information of neighbour proteins in a probabilistic gene network is integrated to enrich the prediction features. 2) Fuzzy k-NN, a classification method based on fuzzy set theory is applied to predict protein locating in multiple sites. Experiment was conducted on a dataset consisting of 22 locations from Budding yeast proteins and significant improvement was observed.</p> <p>Conclusion</p> <p>Our results suggest that the neighbourhood information from functional gene networks is predictive to subcellular localization. The proposed method thus can be integrated and complementary to other available prediction methods.</p

Clinical Characteristics and Transmission of COVID-19 in Children and Youths During 3 Waves of Outbreaks in Hong Kong

IMPORTANCE: Schools were closed intermittently across Hong Kong to control the COVID-19 outbreak, which led to significant physical and psychosocial problems among children and youths. OBJECTIVE: To compare the clinical characteristics and sources of infection among children and youths with COVID-19 during the 3 waves of outbreaks in Hong Kong in 2020. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study involved children and youths aged 18 years or younger with COVID-19 in the 3 waves of outbreaks from January 23 through December 2, 2020. Data were analyzed from December 2020 through January 2021. MAIN OUTCOMES AND MEASURES: Demographic characteristics, travel and contact histories, lengths of hospital stay, and symptoms were captured through the central electronic database. Individuals who were infected without recent international travel were defined as having domestic infections. RESULTS: Among 397 children and youths confirmed with COVID-19 infections, the mean (SD) age was 9.95 (5.34) years, 220 individuals (55.4%) were male, and 154 individuals (38.8%) were asymptomatic. There were significantly more individuals who were infected without symptoms in the second wave (59 of 118 individuals [50.0%]) and third wave (94 of 265 individuals [35.5%]) than in the first wave (1 of 14 individuals [7.1%]) (P = .001). Significantly fewer individuals who were infected in the second and third waves, compared with the first wave, had fever (first wave: 10 individuals [71.4%]; second wave: 22 individuals [18.5%]; third wave: 98 individuals [37.0%]; P < .001) or cough (first wave: 6 individuals [42.9%]; second wave: 15 individuals [12.7%]; third wave: 52 individuals [19.6%]; P = .02). Among all individuals, 394 individuals (99.2%) had mild illness. One patient developed chilblains (ie, COVID toes), 1 patient developed multisystem inflammatory syndrome in children, and 1 patient developed post–COVID-19 autoimmune hemolytic anemia. In all 3 waves, 204 patients with COVID-19 (51.4%) had domestic infections. Among these individuals, 186 (91.2%) reported having a contact history with another individual with COVID-19, of which most (183 individuals [90.0%]) were family members. In the third wave, 18 individuals with domestic infections had unknown contact histories. Three schoolmates were confirmed with COVID-19 on the same day and were reported to be close contacts. CONCLUSIONS AND RELEVANCE: his cross-sectional study found that nearly all children and youths with COVID-19 in Hong Kong had mild illness. These findings suggest that household transmission was the main source of infection for children and youths with domestic infections and that the risk of being infected at school was small

Poor Reproducibility of Allergic Rhinitis SNP Associations

10.1371/journal.pone.0053975PLoS ONE81

Carotid Body AT4 Receptor Expression and its Upregulation in Chronic Hypoxia

Hypoxia regulates the local expression of angiotensin-generating system in the rat carotid body and the me-tabolite angiotensin IV (Ang IV) may be involved in the modulation of carotid body function. We tested the hypothesis that Ang IV-binding angiotensin AT4 receptors play a role in the adaptive change of the carotid body in hypoxia. The expression and localization of Ang IV-binding sites and AT4 receptors in the rat carotid bodies were studied with histochemistry. Specific fluorescein-labeled Ang IV binding sites and positive staining of AT4 immunoreactivity were mainly found in lobules in the carotid body. Double-labeling study showed the AT4 receptor was localized in glomus cells containing tyrosine hydroxylase, suggesting the expression in the chemosensitive cells. Intriguingly, the Ang IV-binding and AT4 immunoreactivity were more intense in the carotid body of chronically hypoxic (CH) rats (breathing 10% oxygen for 4 weeks) than the normoxic (Nx) control. Also, the protein level of AT4 receptor was doubled in the CH comparing with the Nx group, supporting an upregulation of the expression in hypoxia. To examine if Ang IV induces intracellular Ca2+ response in the carotid body, cytosolic calcium ([Ca2+]i) was measured by spectrofluorimetry in fura-2-loaded glomus cells dissociated from CH and Nx carotid bodies. Exogenous Ang IV elevated [Ca2+]i in the glomus cells and the Ang IV response was significantly greater in the CH than the Nx group. Hence, hypoxia induces an upregulation of the expression of AT4 receptors in the glomus cells of the carotid body with an increase in the Ang IV-induced [Ca2+]i elevation. This may be an additional pathway enhancing the Ang II action for the activation of chemoreflex in the hypoxic response during chronic hypoxia

Plio-Pleistocene sea level and temperature fluctuations in the northwestern Pacific promoted speciation in the globally-distributed flathead mullet Mugil cephalus

<p>Abstract</p> <p>Background</p> <p>The study of speciation in the marine realm is challenging because of the apparent absence of physical barriers to dispersal, which are one of the main drivers of genetic diversity. Although phylogeographic studies using mitochondrial DNA (mtDNA) information often reveal significant genetic heterogeneity within marine species, the evolutionary significance of such diversity is difficult to interpret with these markers. In the northwestern (NW) Pacific, several studies have emphasised the potential importance of sea-level regression during the most recent glaciations as a driver of genetic diversity in marine species. These studies have failed, however, to determine whether the period of isolation was long enough for divergence to attain speciation. Among these marine species, the cosmopolitan estuarine-dependent fish <it>Mugil cephalus </it>represents an interesting case study. Several divergent allopatric mtDNA lineages have been described in this species worldwide, and three occur in sympatry in the NW Pacific.</p> <p>Results</p> <p>Ten nuclear microsatellites were surveyed to estimate the level of genetic isolation of these lineages and determine the role of sea-level fluctuation in the evolution of NW Pacific <it>M. cephalus</it>. Three cryptic species of <it>M. cephalus </it>were identified within this region (NWP1, 2 and 3) using an assignment test on the microsatellite data. Each species corresponds with one of the three mtDNA lineages in the COI phylogenetic tree. NWP3 is the most divergent species, with a distribution range that suggests tropical affinities, while NWP1, with a northward distribution from Taiwan to Russia, is a temperate species. NWP2 is distributed along the warm Kuroshio Current. The divergence of NWP1 from NWP2 dates back to the Pleistocene epoch and probably corresponds to the separation of the Japan and China Seas when sea levels dropped. Despite their subsequent range expansion since this period of glaciation, no gene flow was observed among these three lineages, indicating that speciation has been achieved.</p> <p>Conclusions</p> <p>This study successfully identified three cryptic species in <it>M. cephalus </it>inhabiting the NW Pacific, using a combination of microsatellites and mitochondrial genetic markers. The current genetic architecture of the <it>M. cephalus </it>species complex in the NW Pacific is the result of a complex interaction of contemporary processes and historical events. Sea level and temperature fluctuations during Plio-Pleistocene epochs probably played a major role in creating the marine species diversity of the NW Pacific that is found today.</p