bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Labyrinth Microfluidic Device Detects Circulating Tumor Cells Expressing Cancer Stem Cell Marker and Circulating Tumor Microemboli in Hepatocellular Carcinoma
Authors: Wan Shanshan , Kim Tae Hyun , Smith Kaylee J. , Delaney Ryan , Park G-Su , Guo Hui , Lin Eric , Plegue Thomas , Kuo Ning , Steffes John , Leu Christopher , Simeone Diane M. , Razimulava Nataliya , Parikh Neehar D. , Nagrath Sunitha , Welling Theodore H. 
Published: December 2019

AbstractHepatocellular Carcinoma (HCC) is one of the most lethal cancers with a high mortality and recurrence rate. Circulating tumor cell (CTC) detection offers various opportunities to advance early detection and monitoring of HCC tumors which is crucial for improving patient outcome. We developed and optimized a novel Labyrinth microfluidic device to efficiently isolate CTCs from peripheral blood of HCC patients. CTCs were identified in 88.1% of the HCC patients over different tumor stages. The CTC positivity rate was significantly higher in patients with more advanced HCC stages. In addition, 71.4% of the HCC patients demonstrated CTCs positive for cancer stem cell marker, CD44, suggesting that the major population of CTCs could possess stemness properties to facilitate tumor cell survival and dissemination. Furthermore, 55% of the patients had the presence of circulating tumor microemboli (CTM) which also correlated with advanced HCC stage, indicating the association of CTM with tumor progression. Our results show effective CTC capture from HCC patients, presenting a new method for future noninvasive screening and surveillance strategies. Importantly, the detection of CTCs with stemness markers and CTM provides unique insights into the biology of CTCs and their mechanisms influencing metastasis, recurrence and therapeutic resistance.
Interaction of human hemoglobin and semi-hemoglobins with the Staphylococcus aureus hemophore IsdB: a kinetic and mechanistic insight
Authors: Gianquinto Eleonora , Moscetti Ilaria , De Bei Omar , Campanini Barbara , Marchetti Marialaura , Luque F. Javier , Cannistraro Salvatore , Ronda Luca , Bizzarri Anna Rita , Spyrakis Francesca , Bettati Stefano 
Published: December 2019

AbstractAmong multidrug-resistant bacteria, methicillin-resistant Staphylococcus aureus is emerging as one of the most threatening pathogens. S. aureus exploits different mechanisms for its iron supply, but the preferred one is acquisition of organic iron through the expression of hemoglobin (Hb) receptors. One of these, IsdB, belonging to the Isd (Iron-Regulated Surface Determinant) system, was shown to be essential for bacterial growth and virulence. Therefore, interaction of IsdB with Hb represents a promising target for the rational design of a new class of antibacterial molecules. However, despite recent investigations, many structural and mechanistic details of complex formation and heme extraction process are still elusive. By combining site-directed mutagenesis, absorption spectroscopy, surface plasmon resonance and molecular dynamics simulations, we tackled most of the so far unanswered questions: (i) the exact complex stoichiometry, (ii) the microscopic kinetic rates of complex formation, (iii) the IsdB selectivity for binding to, and extracting heme from, α and β subunits of Hb, iv) the role of specific amino acid residues and structural regions in driving complex formation and heme transfer, and (v) the structural/dynamic effect played by the hemophore on Hb.
Developing a preoperative serum metabolome-based recurrence-predicting nomogram for patients with resected pancreatic ductal adenocarcinoma
Authors: Rho Seoung Yoon , Lee Sang-Guk , Park Minsu , Lee Jinae , Lee Sung Hwan , Hwang Ho Kyoung , Lee Min Jung , Paik Young-Ki , Lee Woo Jung , Kang Chang Moo 
Published: December 2019

AbstractWe investigated the potential application of preoperative serum metabolomes in predicting recurrence in patients with resected pancreatic cancer. From November 2012 to June 2014, patients who underwent potentially curative pancreatectomy for pancreatic ductal adenocarcinoma were examined. Among 57 patients, 32 were men; 42 had pancreatic head cancers. The 57 patients could be clearly categorized into two main clusters using 178 preoperative serum metabolomes. Patients within cluster 2 showed earlier tumor recurrence, compared with those within cluster 1 (p = 0.034). A nomogram was developed for predicting the probability of early disease-free survival in patients with resected pancreatic cancer. Preoperative cancer antigen (CA) 19–9 levels and serum metabolomes PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful preoperative clinical variables with which to predict 6-month and 1-year cancer recurrence-free survival after radical pancreatectomy, with a Harrell’s concordance index of 0.823 (95% CI: 0.750–0.891) and integrated area under the curve of 0.816 (95% CI: 0.736–0.893). Patients with resected pancreatic cancer could be categorized according to their different metabolomes to predict early cancer recurrence. Preoperative detectable parameters, serum CA 19–9, PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful predictors of early recurrence of pancreatic cancer.
Applied Veterinary Informatics: Development of a Semantic and Domain-Specific Method to Construct a Canine Data Repository
Authors: Boland Mary Regina , Casal Margret L. , Kraus Marc S. , Gelzer Anna R. 
Published: December 2019

AbstractAnimals are used to study the pathogenesis of various human diseases, but typically as animal models with induced disease. However, companion animals develop disease spontaneously in a way that mirrors disease development in humans. The purpose of this study is to develop a semantic and domain-specific method to enable construction of a data repository from a veterinary hospital that would be useful for future studies. We developed a two-phase method that combines semantic and domain-specific approaches to construct a canine data repository of clinical data collected during routine care at the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania (PennVet). Our framework consists of two phases: (1) a semantic data-cleaning phase and (2) a domain-specific data-cleaning phase. We validated our data repository using a gold standard of known breed predispositions for certain diseases (i.e., mitral valve disease, atrial fibrillation and osteosarcoma). Our two-phase method allowed us to maximize data retention (99.8% of data retained), while ensuring the quality of our result. Our final population contained 84,405 dogs treated between 2000 and 2017 from 194 distinct dog breeds. We observed the expected breed associations with mitral valve disease, atrial fibrillation, and osteosarcoma (P < 0.05) after adjusting for multiple comparisons. Precision ranged from 60.0 to 83.3 for the three diseases (avg. 74.2) and recall ranged from 31.6 to 83.3 (avg. 53.3). Our study describes a two-phase method to construct a clinical data repository using canine data obtained during routine clinical care at a veterinary hospital.
Interaction between androgen receptor and coregulator SLIRP is regulated by Ack1 tyrosine kinase and androgen
Authors: De Silva Dinuka , Zhang Zhentao , Liu Yuanbo , Parker Joel S. , Xu Chenxi , Cai Ling , Wang Gang Greg , Earp H. Shelton , Whang Young E. 
Published: December 2019

AbstractAberrant activation of the androgen receptor (AR) may play a critical role in castration resistant prostate cancer. After ligand binding, AR is recruited to the androgen responsive element (ARE) sequences on the DNA where AR interaction with coactivators and corepressors modulates transcription. We demonstrated that phosphorylation of AR at Tyr-267 by Ack1/TNK2 tyrosine kinase results in nuclear translocation, DNA binding, and androgen-dependent gene transcription in a low androgen environment. In order to dissect downstream mechanisms, we searched for proteins whose interaction with AR was regulated by Ack1. SLIRP (SRA stem-loop interacting RNA binding protein) was identified as a candidate protein. Interaction between AR and SLIRP was disrupted by Ack1 kinase activity as well as androgen or heregulin treatment. The noncoding RNA, SRA, was required for AR-SLIRP interaction. SLIRP was bound to ARE’s of AR target genes in the absence of androgen. Treatment with androgen or heregulin led to dissociation of SLIRP from the ARE. Whole transcriptome analysis of SLIRP knockdown in androgen responsive LNCaP cells showed that SLIRP affects a significant subset of androgen-regulated genes. Our data suggest that Ack1 kinase and androgen regulate interaction between AR and SLIRP and that SLIRP functions as a coregulator of AR with properties of a corepressor in a context-dependent manner.
Use of different RT-QuIC substrates for detecting CWD prions in the brain of Norwegian cervids
Authors: Bistaffa Edoardo , Vuong Tram Thu , Cazzaniga Federico Angelo , Tran Linh , Salzano Giulia , Legname Giuseppe , Giaccone Giorgio , Benestad Sylvie L. , Moda Fabio 
Published: December 2019

AbstractChronic wasting disease (CWD) is a highly contagious prion disease affecting captive and free-ranging cervid populations. CWD has been detected in United States, Canada, South Korea and, most recently, in Europe (Norway, Finland and Sweden). Animals with CWD release infectious prions in the environment through saliva, urine and feces sustaining disease spreading between cervids but also potentially to other non-cervids ruminants (e.g. sheep, goats and cattle). In the light of these considerations and due to CWD unknown zoonotic potential, it is of utmost importance to follow specific surveillance programs useful to minimize disease spreading and transmission. The European community has already in place specific surveillance measures, but the traditional diagnostic tests performed on nervous or lymphoid tissues lack sensitivity. We have optimized a Real-Time Quaking-Induced Conversion (RT-QuIC) assay for detecting CWD prions with high sensitivity and specificity to try to overcome this problem. In this work, we show that bank vole prion protein (PrP) is an excellent substrate for RT-QuIC reactions, enabling the detection of trace-amounts of CWD prions, regardless of prion strain and cervid species. Beside supporting the traditional diagnostic tests, this technology could be exploited for detecting prions in peripheral tissues from live animals, possibly even at preclinical stages of the disease.
Cinnamaldehyde and Phenyl Ethyl Alcohol promote the entrapment of intermediate species of HEWL, as revealed by structural, kinetics and thermal stability studies
Authors: Seraj Zahra , Groves Matthew R. , Seyedarabi Arefeh 
Published: December 2019

AbstractNumerous efforts have been directed towards investigating the different stages leading to the fibrillation process in neurodegenerative diseases and finding the factors modulating it. In this study, using a wide range of molecular techniques as well as fibrillation kinetics coupled with differential scanning fluorimetry (DSF) and crystal structure determination of HEWL treated with cinnamaldehyde (Cin) and Phenyl ethyl alcohol (PEA) in their aroma form during fibrillation, we were able to identify the binding positions of Cin and PEA in HEWL. Additionally, crystal structures were used to suggest residues Thr43, Asn44, Arg45 and Arg68 as a plausible ‘hotspot’ promoting entrapment of intermediate species in the process of fibril formation in HEWL. We were also able to use DSF to show that Cin can significantly decrease the thermal stability of HEWL, promoting the formation of partially unfolded intermediate species. In conclusion, our data led us to emphasize that compounds in their ‘aroma form’ can influence the structure and stability of protein molecules and suggest reconsideration of HEWL as a model protein for fibrillation studies related to neurodegenerative diseases based on the initial structure of the proteins, whether globular (HEWL) or intrinsically disordered.
Genome investigations show host adaptation and transmission of LA-MRSA CC398 from pigs into Danish healthcare institutions
Authors: Sieber Raphael Niklaus , Larsen Anders Rhod , Urth Tinna Ravnholt , Iversen Søren , Møller Camilla Holten , Skov Robert Leo , Larsen Jesper , Stegger Marc 
Published: December 2019

AbstractOver the last decade, an increasing number of infections with livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (LA-MRSA CC398) in persons without contact to livestock has been registered in Denmark. These infections have been suggested to be the result of repeated spillover of random isolates from livestock into the community. However, other studies also found emerging sub-lineages spreading among humans. Based on genome-wide SNPs and genome-wide association studies (GWAS), we assessed the population structure and genomic content of Danish LA-MRSA CC398 isolates from healthcare-associated infections from 2014 to 2016 (n = 73) and compared these to isolates from pigs in Denmark from 2014 (n = 183). Phylogenetic analyses showed that most human isolates were closely related to and scattered among pig isolates showing that the majority of healthcare-associated infections are the result of repeated spillover from pig farms, even though cases of human-to-human transmission also were identified. GWAS revealed frequent loss of antimicrobial resistance genes and acquisition of human-specific virulence genes in the human isolates showing adaptation in response to changes in selective pressures in different host environments, which over time could lead to the emergence of LA-MRSA CC398 lineages more adapted to human colonization and transmission.
Chronic voluntary alcohol consumption causes persistent cognitive deficits and cortical cell loss in a rodent model
Authors: Charlton Annai J. , May Carlos , Luikinga Sophia J. , Burrows Emma L. , Hyun Kim Jee , Lawrence Andrew J. , Perry Christina J. 
Published: December 2019

AbstractChronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies.
A Biogeographic Barrier Test Reveals a Strong Genetic Structure for a Canopy-Emergent Amazon Tree Species
Authors: Nazareno Alison G. , Dick Christopher W. , Lohmann Lúcia G. 
Published: December 2019

AbstractWallace’s (1854) Riverine Barrier hypothesis is one of the earliest explanations for Amazon biotic diversification. Despite the importance of this hypothesis for explaining speciation in some animal groups, it has not been studied extensively for plant species. In this study we use a prominent Amazon tree, Buchenavia oxycarpa (Mart.) Eichler (Combretaceae), to evaluate Wallace’s hypothesis along the Rio Negro, a major Amazon tributary that has driven allopatric speciation for several animal taxa. We sampled six individuals from sixteen localities along both river banks, and used a modified ddRADseq protocol to identify SNP markers. Our population genomic data revealed strong genetic structure for B. oxycarpa sampled across banks of the Rio Negro (ϕCT = 0.576, P < 0.001), supporting the hypothesis that the Rio Negro acted as a significant genetic barrier for B. oxycarpa. Our study shows that gene flow for this large and well-dispersed Amazon tree is impeded by riverine barriers, though this has not yet resulted in speciation. Future studies focused on species with different life histories, including species restricted to non-flooded forests, are needed to further advance our understanding of Amazon rivers as drivers of biotic diversification.
Expression of Metazoan Annexins in Yeast Provides Protection Against Deleterious Effects of the Biofuel Isobutanol
Authors: Creutz Carl E. 
Published: December 2019

AbstractThe ability of microorganisms to produce biofuels by fermentation is adversely affected by the perturbing effects of the hydrophobic biofuel on plasma membrane structure. It is demonstrated here that heterologous expression of metazoan, calcium-dependent, membrane-binding proteins of the annexin class can reduce deleterious effects of isobutanol on Saccharomyces cerevisiae viability and complex membrane functions. Therefore, expression of annexins in industrial strains of yeast or bacteria may prove beneficial in biofuel production.
Antifungal potential of secondary metabolites involved in the interaction between citrus pathogens
Authors: Costa Jonas Henrique , Wassano Cristiane Izumi , Angolini Célio Fernando Figueiredo , Scherlach Kirstin , Hertweck Christian , Pacheco Fill Taícia 
Published: December 2019

AbstractNumerous postharvest diseases have been reported that cause substantial losses of citrus fruits worldwide. Penicillium digitatum is responsible for up to 90% of production losses, and represent a problem for worldwide economy. In order to control phytopathogens, chemical fungicides have been extensively used. Yet, the use of some artificial fungicides cause concerns about environmental risks and fungal resistance. Therefore, studies focusing on new approaches, such as the use of natural products, are getting attention. Co-culture strategy can be applied to discover new bioactive compounds and to understand microbial ecology. Mass Spectrometry Imaging (MSI) was used to screen for potential antifungal metabolites involved in the interaction between Penicillium digitatum and Penicillium citrinum. MSI revealed a chemical warfare between the fungi: two tetrapeptides, deoxycitrinadin A, citrinadin A, chrysogenamide A and tryptoquialanines are produced in the fungi confrontation zone. Antimicrobial assays confirmed the antifungal activity of the investigated metabolites. Also, tryptoquialanines inhibited sporulation of P. citrinum. The fungal metabolites reported here were never described as antimicrobials until this date, demonstrating that co-cultures involving phytopathogens that compete for the same host is a positive strategy to discover new antifungal agents. However, the use of these natural products on the environment, as a safer strategy, needs further investigation. This paper aimed to contribute to the protection of agriculture, considering health and ecological risks.
First identification of mammalian orthoreovirus type 3 by gut virome analysis in diarrheic child in Brazil
Authors: Rosa Ulisses Alves , Ribeiro Geovani de Oliveira , Villanova Fabiola , Luchs Adriana , Milagres Flávio Augusto de Pádua , Komninakis Shirley Vasconcelos , Tahmasebi Roozbeh , Lobato Márcia Cristina Alves Brito Sayão , Brustulin Rafael , Chagas Rogério Togisaki das , Abrão Maria de Fátima Neves dos Santos , Soares Cassia Vitória de Deus Alves , Tinker Rory J , Pandey Ramendra Pati , Raj V. Samuel , Sabino Ester Cerdeira , Deng Xutao , Delwart Eric , Costa Antonio Charlys da , Leal Élcio 
Published: December 2019

AbstractDiarrhea remains one of the most common causes of deaths in children. Although many studies have investigated the prevalence of enteric pathogens around the globe some diarrheal episodes remain unexplained. It is possible that some yet-unidentified viral agents could be related to these cases of gastroenteritis. By using viral metagenomics techniques, we screened 251 fecal samples of children between 0.5 to 2.5-year-old with acute diarrhea not associated with common pathogens. These children live in rural areas and have different levels of contact with animals such as pigs, cows and bats. Here we report a complete genome of one mammalian orthoreovirus (MRV) type 3, denoted TO-151/BR, detected in a female child in the state of Tocantins (north of Brazil). Brazilian TO-151/BR strain was classified as MRV-3 based on S1 phylogeny and was closely related to porcine Asian strains. Phylogenetic analyses showed that other segments were more similar to MRV-3s of different geographic locations and hosts, including human and bats, highlighting genome reassortment and lack of host-specific barriers. This is the first report of MRV-3 in South America and a hypothesis of a silent long-term circulation of this virus in Brazil has been raised.
Electrospray patterning of yeast cells for applications in alcoholic fermentation
Authors: Jeong Sang Bin , Chong Eui-seok , Heo Ki Joon , Lee Gun Woong , Kim Hyung Joo , Lee Byung Uk 
Published: December 2019

AbstractYeast cells patterned by pulsed jet electrospray showed a high alcoholic fermentation rate. Multi-dimensional patterns of individual yeast cells were produced by varying the experimental parameters of the electrospray system. The electrospray process, which employed a vibrational electric field, could control patterns of viable yeast cells at a cellular resolution. This novel system for electrospraying viable cells can be applied to biological process engineering including whole cell biochip techniques and micro fermentation processes for biochemical studies.
Bottom Sediments Reveal Inter-Annual Variability of Interaction between the Ob and Yenisei Plumes in the Kara Sea
Authors: Osadchiev A. A. , Asadulin En. E. , Miroshnikov A. Yu. , Zavialov I. B. , Dubinina E. O. , Belyakova P. A. 
Published: December 2019

AbstractRiver discharge is the main source of terrigenous sediments in many coastal areas adjacent to estuaries and deltas of large rivers. Spreading and mixing dynamics of river plumes governs transport of suspended sediments and their deposition at sea bottom at these areas. Generally river plumes have very large synoptic and seasonal variability, which cannot be reconstructed from structure of bottom sediments due to their small accumulation velocity. However, bottom sediments can be indicative of variability of river plumes on inter-annual and decadal time scales. In this study we focus on the large Ob and Yenisei buoyant plumes formed in the central part of the Kara Sea. These plumes interact and mix in the area adjacent to the closely located Ob and Yenisei gulfs. Suspended sediments carried by these river plumes have significantly different geochemical characteristics that can be used to detect Ob or Yenisei origin of bottom sediments. Using new geochemical methods we revealed dependence between spreading patterns of these plumes and spatial distribution and vertical structure of bottom sediments in the study area. This relation is confirmed by a good agreement between local wind and discharge conditions reconstructed for 1948–2001 and vertical structure of bottom sediments.