bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical utility of SMARCA4 testing by immunohistochemistry in rare ovarian tumours
Authors: Genestie Catherine , Blanc-Durand Félix , Auguste Aurélie , Pautier Patricia , Dunant Ariane , Scoazec Jean-Yves , Gouy Sébastien , Morice Philippe , Bentivegna Enrica , Maulard Amandine , LeFormal Audrey , Devouassoux-Shisheboran Mojgan , Leary Alexandra 
Published: December 2019

Abstract
Background
Ovarian small cell carcinoma, hypercalcaemic type (SCCOHT) is a rare and lethal disease affecting young women. As histological diagnosis is challenging and urgent, there is a clear need for a robust diagnostic test. While mutations in the chromatin-remodelling gene, SMARCA4, appear to be typical, it may not be feasible routinely to be clinically relevant.

Methods
Previous studies have described the value of SMARCA4 IHC to differentiate SCCOHT from ovarian neoplasms (ON), with similar histologic appearances. We aimed to evaluate its clinical utility among a cohort of 44 SCCOHT and 94 rare ON frequently misdiagnosed as SCCOHT.

Results
Forty-three percent (16/36) of SCCOHT had been classified locally as non-SCCOHT confirming the diagnosis challenge. Sensitivity and specificity of SMARCA4 IHC were excellent at 88% and 94%, respectively. In a community setting with a much lower prevalence of the disease, estimated PPV is 40% while NPV remained high at 99%. Finally, among the 16 SCCOHT misclassified locally, SMARCA4 IHC testing would have resulted in corrected diagnosis in 88% of cases.

Conclusions
SMARCA4 IHC is a highly sensitive, and specific test for the diagnosis of SCCOHT and is of huge clinical utility in providing a timely and accurate diagnosis of this challenging disease.
Physical disruption of intervertebral disc promotes cell clustering and a degenerative phenotype
Authors: Lama Polly , Claireaux Harry , Flower Luke , Harding Ian J. , Dolan Trish , Le Maitre Christine L. , Adams Michael A. 
Published: December 2019

AbstractTo test the hypothesis that physical disruption of an intervertebral disc disturbs cell-matrix binding, leading to cell clustering and increased expression of matrix degrading enzymes that contribute towards degenerative disc cell phenotype. Lumbar disc tissue was removed at surgery from 21 patients with disc herniation, 11 with disc degeneration, and 8 with adolescent scoliosis. 5 μm sections were examined with histology, and 30-µm sections by confocal microscopy. Antibodies were used against integrin α5beta1, matrix metalloproteinases (MMP) 1, MMP-3, caspase 3, and denatured collagen types I and II. Spatial associations were sought between cell clustering and various degenerative features. An additional, 11 non-herniated human discs were used to examine causality: half of each specimen was cultured in a manner that allowed free ‘unconstrained’ swelling (similar to a herniated disc in vivo), while the other half was cultured within a perspex ring that allowed ‘constrained’ swelling. Changes were monitored over 36 h using live-cell imaging. 1,9-Di-methyl methylene blue (DMMB) assay for glycosaminoglycan loss was carried out from tissue medium. Partially constrained specimens showed little swelling or cell movement in vitro. In contrast, unconstrained swelling significantly increased matrix distortion, glycosaminoglycan loss, exposure of integrin binding sites, expression of MMPs 1 and 3, and collagen denaturation. In the association studies, herniated disc specimens showed changes that resembled unconstrained swelling in vitro. In addition, they exhibited increased cell clustering, apoptosis, MMP expression, and collagen denaturation compared to ‘control’ discs. Results support our hypothesis. Further confirmation will require longitudinal animal experiments.
Twin-peak temporal regulation during human neocortical development
Authors: Wang Wei , Wang Guang-Zhong 
Published: December 2019

AbstractUnderstanding the temporal and spatial expression patterns of the human cerebral cortex is essential for expanding knowledge of its functionality. Previous analysis focused on the differentially expressed genes (DEGs) among cortical subregions revealed an hourglass model for interareal differences. However, the overall pattern of transcriptional differences during the development of every region remains to be fully explored. Here, analysing more than 800 neocortex samples from lifespan transcriptional profiles revealed that excitatory neurons are more regulated than inhibitory neurons in the foetal brain. Developmental DEGs tend to be resting state or memory encoding-related and are also involved in autism and Alzheimer’s disease. In addition, twin peaks of DEGs occur during the development of each neocortex region, with a first peak appearing in the perinatal period and an unexpected second peak appearing around childhood. Genes in these peaks have similar functions, but the second peak is more inhibitory neuron related. All these results emphasize the significance of this unique temporal regulatory pattern for human neocortical development.
Principal Component Analysis applied directly to Sequence Matrix
Authors: Konishi Tomokazu , Matsukuma Shiori , Fuji Hayami , Nakamura Daiki , Satou Nozomi , Okano Kunihiro 
Published: December 2019

AbstractSequence data is now widely used to observe relationships among organisms. However, understanding structure of the qualitative data is challenging. Conventionally, the relationships are analysed using a dendrogram that estimates a tree shape. This approach has difficulty in verifying the appropriateness of the tree shape; rather, horizontal gene transfers and mating can make the shape of the relationship as networks. As a connection-free approach, principal component analysis (PCA) is used to summarize the distance matrix, which records distances between each combination of samples. However, this approach is limited regarding the treatment of information of sequence motifs; distances caused by different motifs are mixed up. This hides clues to figure out how the samples are different. As any bases may change independently, a sequence is multivariate data essentially. Hence, differences among samples and bases that contribute to the difference should be observed coincidentally. To archive this, the sequence matrix is transferred to boolean vector and directly analysed by using PCA. The effects are confirmed in diversity of Asiatic lion and human as well as environmental DNA. Resolution of samples and robustness of calculation is improved. Relationship of a direction of difference and causative nucleotides has become obvious at a glance.
Re-evaluation of the evolution of influenza H1 viruses using direct PCA
Authors: Konishi Tomokazu 
Published: December 2019

AbstractThe history of influenza H1 virus was re-evaluated by applying a new methodology to sequencing data; this objective method enables comparisons among viral types. The approach led to the segregation of all segments of swine and human viruses into three distinct groups: two of them included the pandemic 1977 and 2009 human viruses, and the remaining group may be new in humans. These three groups might have originated from avian viruses and drifted out independently. Genome shifts occurred occasionally among swine viruses; however, distances between avian and swine/human viruses negated the existence of direct shifts from avian viruses. In humans, only one or two viruses appeared each year, which suggests the presence of competition among viruses that migrated freely. All segments drifted continuously under certain rules and constant velocity. Viruses that had caused an outbreak did not appear again over subsequent decades, which may mean populations had become immune to such viruses. In contrast, the viruses in livestock were rather conserved and maintained unique strains in small, separate areas. Such collections of swine strains included human segments, which could become an epidemic in the future.
Characterization of a live-attenuated HCMV-based vaccine platform
Authors: Caposio Patrizia , van den Worm Sjoerd , Crawford Lindsey , Perez Wilma , Kreklywich Craig , Gilbride Roxanne M. , Hughes Colette M. , Ventura Abigail B. , Ratts Robert , Marshall Emily E. , Malouli Daniel , Axthelm Michael K. , Streblow Daniel , Nelson Jay A. , Picker Louis J. , Hansen Scott G. , Früh Klaus 
Published: December 2019

AbstractVaccines based on cytomegalovirus (CMV) demonstrate protection in animal models of infectious disease and cancer. Vaccine efficacy is associated with the ability of CMV to elicit and indefinitely maintain high frequencies of circulating effector memory T cells (TEM) providing continuous, life-long anti-pathogen immune activity. To allow for the clinical testing of human CMV (HCMV)-based vaccines we constructed and characterized as a vector backbone the recombinant molecular clone TR3 representing a wildtype genome. We demonstrate that TR3 can be stably propagated in vitro and that, despite species incompatibility, recombinant TR3 vectors elicit high frequencies of TEM to inserted antigens in rhesus macaques (RM). Live-attenuated versions of TR3 were generated by deleting viral genes required to counteract intrinsic and innate immune responses. In addition, we eliminated subunits of a viral pentameric glycoprotein complex thus limiting cell tropism. We show in a humanized mouse model that such modified vectors were able to establish persistent infection but lost their ability to reactivate from latency. Nevertheless, attenuated TR3 vectors preserved the ability to elicit and maintain TEM to inserted antigens in RM. We further demonstrate that attenuated TR3 can be grown in approved cell lines upon elimination of an anti-viral host factor using small interfering RNA, thus obviating the need for a complementing cell line. In sum, we have established a versatile platform for the clinical development of live attenuated HCMV-vectored vaccines and immunotherapies.
Hybridization-based capture of pathogen mRNA enables paired host-pathogen transcriptional analysis
Authors: Betin Viktoria , Penaranda Cristina , Bandyopadhyay Nirmalya , Yang Rui , Abitua Angela , Bhattacharyya Roby P. , Fan Amy , Avraham Roi , Livny Jonathan , Shoresh Noam , Hung Deborah T. 
Published: December 2019

AbstractDual transcriptional profiling of host and bacteria during infection is challenging due to the low abundance of bacterial mRNA. We report Pathogen Hybrid Capture (PatH-Cap), a method to enrich for bacterial mRNA and deplete bacterial rRNA simultaneously from dual RNA-seq libraries using transcriptome-specific probes. By addressing both the differential RNA content of the host relative to the infecting bacterium and the overwhelming abundance of uninformative structural RNAs (rRNA, tRNA) of both species in a single step, this approach enables analysis of very low-input RNA samples. By sequencing libraries before (pre-PatH-Cap) and after (post-PatH-Cap) enrichment, we achieve dual transcriptional profiling of host and bacteria, respectively, from the same sample. Importantly, enrichment preserves relative transcript abundance and increases the number of unique bacterial transcripts per gene in post-PatH-Cap libraries compared to pre-PatH-Cap libraries at the same sequencing depth, thereby decreasing the sequencing depth required to fully capture the transcriptional profile of the infecting bacteria. We demonstrate that PatH-Cap enables the study of low-input samples including single eukaryotic cells infected by 1–3 Pseudomonas aeruginosa bacteria and paired host-pathogen temporal gene expression analysis of Mycobacterium tuberculosis infecting macrophages. PatH-Cap can be applied to the study of a range of pathogens and microbial species, and more generally, to lowly-abundant species in mixed populations.
GIRK1 triggers multiple cancer-related pathways in the benign mammary epithelial cell line MCF10A
Authors: Schratter Gebhard , Scheruebel Susanne , Langthaler Sonja , Ester Katja , Pelzmann Brigitte , Ghaffari-Tabrizi-Wizsy Nassim , Rezania Simin , Gorischek Astrid , Platzer Dieter , Zorn-Pauly Klaus , Ahammer Helmut , Prokesch Andreas , Stanzer Stefanie , Devaney Trevor T. J. , Schmidt Kurt , Jahn Stephan W. , Prassl Ruth , Bauernhofer Thomas , Schreibmayer Wolfgang 
Published: December 2019

AbstractExcessive expression of subunit 1 of GIRK1 in ER+ breast tumors is associated with reduced survival times and increased lymph node metastasis in patients. To investigate possible tumor-initiating properties, benign MCF10A and malign MCF7 mammary epithelial cells were engineered to overexpress GIRK1 neoplasia associated vital parameters and resting potentials were measured and compared to controls. The presence of GIRK1 resulted in resting potentials negative to the controls. Upon GIRK1 overexpression, several cellular pathways were regulated towards pro-tumorigenic action as revealed by comparison of transcriptomes of MCF10AGIRK1 with the control (MCF10AeGFP). According to transcriptome analysis, cellular migration was promoted while wound healing and extracellular matrix interactions were impaired. Vital parameters in MCF7 cells were affected akin the benign MCF10A lines, but to a lesser extent. Thus, GIRK1 regulated cellular pathways in mammary epithelial cells are likely to contribute to the development and progression of breast cancer.
Molecular events in MSC exosome mediated cytoprotection in cardiomyocytes
Authors: Kore Rajshekhar A. , Henson Jeffrey C. , Hamzah Rabab N. , Griffin Robert J. , Tackett Alan J. , Ding Zufeng , Mehta Jawahar L. 
Published: December 2019

AbstractA host of hormonal-metabolic alterations take place following exposure of cardiomyocytes to hypoxia and other noxious stimuli. Here, we demonstrate that exposure of cultured rat cardiomyocytes to lipopolysaccharide (LPS) resulted in upregulation (~1.5 fold) of oxidized low-density lipoprotein receptor-1 (LOX-1). There was also a marked increase in apoptosis 12 hrs after LPS treatment with caspase-3 levels being significantly elevated (~1.3 fold) and a significant increase in LDH release at 24 hrs. Interestingly, there was a ~1.4-fold upregulation of LC-3 expression post-LPS treatment indicating development of autophagy, which probably is a compensatory response to combat cellular injury induced by LPS. Treatment with LPS also reduced the size and morphology of cardiomyocyte spheroids. In an attempt to limit LPS-induced injury, cardiomyocytes were treated with exosomes derived from mesenchymal stromal cells (MSCs). We noted a significant suppression of LOX-1 expression that in turn suppressed apoptosis as well as autophagic response and restored spheroid morphology. Mass spectrophotometric analysis of MSC exosomes revealed a cargo rich in proteins which are involved in pathways negatively modulating cell death and apoptosis while promoting cell survival. This is first report to our knowledge on the initial molecular events in MSC exosome mediated cytoprotection of stressed cardiomyocytes.
Ambulatory blood pressure monitoring-based analysis of long-term outcomes for kidney disease progression
Authors: Ida Tomoharu , Kusaba Tetsuro , Kado Hiroshi , Taniguchi Takuya , Hatta Tsuguru , Matoba Satoaki , Tamagaki Keiichi 
Published: December 2019

AbstractNon-dipping nocturnal blood pressure (BP) pattern is a predictor of the future decline of renal function; however, it is unclear whether it is still a risk for chronic kidney disease (CKD) patients with normal BP. To solve this question, a retrospective cohort study was conducted, and 1107 CKD patients who underwent ambulatory blood pressure monitoring (ABPM) were enrolled. We divided patients into 4 groups based on their nocturnal BP dipping pattern (dipper or non-dipper) and average 24-hour BP (hypertension or normotension). The cumulative incidence of composite renal outcomes, including a 40% reduction in eGFR, the induction of renal-replacement therapy, or death from renal causes, was analyzed. Overall, 86.1% of participants were non-dippers and 48.2% of them were normotensive. During the median follow-up period of 4.72 years, the incidence of renal composite outcomes was highest in hypertensive non-dipper patients, and was similar between normotensive dipper and non-dipper patients. Multivariate regression analysis revealed that the 24-hour systolic BP, amount of urinary protein, and hemoglobin values were associated with the incidence of renal outcomes. In conclusion, our ABPM-based analysis revealed that a non-dipping BP pattern with normotension does not predict the future incidence of composite renal outcomes in CKD patients.
Determination of 5-nitro-2-furaldehyde as marker residue for nitrofurazone treatment in farmed shrimps and with addressing the use of a novel internal standard
Authors: Wang Qiang , Wang Xu-Feng , Jiang Yong-Yuan , Li Zhi-Guang , Cai Nan , Guan Wan-Qi , Huang Ke , Zhao Dong-Hao 
Published: December 2019

AbstractWe developed a significantly improved ultra-high performance liquid chromatography-tandem mass spectrometry method for determination of 5-nitro-2-furaldehyde (NF) as a surrogate using a novel internal standard for the detection of nitrofurazone. We used 2,4-dinitrophenylhydrazine derivatization and furfural as the internal standard. Derivatization was easily performed in HCl using ultrasonic manipulation for 5 min followed by liquid extraction using ethyl acetate. The samples were concentrated and purified using reverse phase and alumina cartridges in tandem. The derivatives were separated using a linear gradient elution on a C18 column with methanol and water as the mobile phase in negative ionization mode and multiple reaction monitoring. Under the optimized conditions, the calibration curves were linear from 0.2 to 20 μg/L with correlation coefficients >0.999. Mean recoveries were 80.8 to 104.4% with the intra- and inter-day relative standard deviations <15% at spiking levels of 0.1 to 10 μg/kg. The limits of detection and quantification were 0.05 and 0.1 μg/kg, respectively. This method is a robust tool for the identification and quantitative determination of NF in shrimp samples.
Sperm quality and quantity evolve through different selective processes in the Phasianidae
Authors: Liao Wen Bo , Zhong Mao Jun , Lüpold Stefan 
Published: December 2019

AbstractSperm competition is often considered the primary selective force underlying the rapid and diversifying evolution of ejaculate traits. Yet, several recent studies have drawn attention to other forms of selection with the potential of exceeding the effects of sperm competition. Since ejaculates are complex, multivariate traits, it seems plausible that different ejaculate components vary in their responses to different selective pressures. Such information, however, is generally lacking as individual ejaculate traits tend to be studied in isolation. Here, we studied the macroevolutionary patterns of ejaculate volume, sperm number, sperm length and the proportion of viable normal sperm in response to varying levels of sperm competition, body size and the duration of female sperm storage in pheasants and allies (Phasianidae). Ejaculate volume, sperm number and sperm viability were all relatively higher in polygamous than in monogamous mating systems. However, whereas ejaculate volume additionally covaried with body size, sperm number instead increased with the female sperm-storage duration, in conjunction with a decrease in sperm length. Overall, our results revealed important details on how different forms of selection can jointly shape ejaculates as complex, composite traits.
Nutritional profiling of hilsa (Tenualosa ilisha) of different size groups and sensory evaluation of their adults from different riverine systems
Authors: De D. , Mukherjee S. , Anand P. S. Shyne , Kumar P. , Suresh V. R. , Vijayan K. K. 
Published: December 2019

AbstractNutritional composition of hilsa, Tenualosa ilisha, of different size groups was analyzed to study variations in their composition with the progression of growth, and to correlate it with the flavor of adult hilsa (>800 g size) collected from different riverine systems (Hooghly and Padma). The amino acid analysis revealed significantly higher arginine (P < 0.01), methionine (P < 0.01) and glycine (P < 0.05) contents in samples below 5 g, whereas samples above 800 g had higher (P < 0.01) leucine and isoleucine contents. Total saturated and monounsaturated fatty acids were lower (P < 0.01) in fish below 5 g as compared to larger size groups (>5 g), whereas docosahexaenoic acid was higher (P < 0.01) in fish below 5 g size. Nutritional composition of adult hilsa (>800 g) from Hooghly and Padma river revealed higher (P < 0.01) aspartic acid, glutamic acid, alanine, palmitoleic and oleic acid in samples from the Padma, whereas leucine and isoleucine contents were higher (P < 0.01) in hilsa from Hooghly. Sensory evaluation test revealed superior (P < 0.05) taste, aroma, and muscle texture of hilsa from the Padma as compared to those from Hooghly. Higher alanine, aspartic acid, glutamic acid, oleic acid, and palmitoleic acid along with higher n3:n6 fatty acid are attributed to the superior taste of hilsa from the Padma.
Dietary fatty acid quality affects systemic parameters and promotes prostatitis and pre-neoplastic lesions
Authors: Ferrucci Danilo , Silva Silas Pinto , Rocha Andr , Nascimento Lucas , Vieira André Schwambach , Taboga Sebastião Roberto , Mori Marcelo , Lenz-Cesar Carlos , Carvalho Hernandes F. 
Published: December 2019

AbstractEnvironmental and nutritional factors, including fatty acids (FA), are associated with prostatitis, benign prostate hyperplasia and prostate cancer. We hypothesized that different FA in normolipidic diets (7%) affect prostate physiology, increasing the susceptibility to prostate disorders. Thus, we fed male C57/BL6 mice with normolipidic diets based on linseed oil, soybean oil or lard (varying saturated and unsaturated FA contents and ω-3/ω-6 ratios) for 12 or 32 weeks after weaning and examined structural and functional parameters of the ventral prostate (VP) in the systemic metabolic context. Mongolian gerbils were included because they present a metabolic detour for low water consumption (i.e., oxidize FA to produce metabolic water). A linseed oil-based diet (LO, 67.4% PUFAs, ω-3/ω-6 = 3.70) resulted in a thermogenic profile, while a soybean oil-based diet (SO, 52.7% PUFAs, ω-3/ω-6 = 0.11) increased body growth and adiposity. Mice fed lard (PF, 13.1% PUFA, ω-3/ω-6 = 0.07) depicted a biphasic growth, resulting in decreased adiposity in adulthood. SO and PF resulted in hepatic steatosis and steatohepatitis, respectively. PF and SO increased prostate epithelial volume, and lard resulted in epithelial hyperplasia. Animals in the LO group had smaller prostates with predominant atrophic epithelia and inflammatory loci. Inflammatory cells were frequent in the VP of PF mice (predominantly stromal) and LO mice (predominantly luminal). RNAseq after 12 weeks revealed good predictors of a later-onset inflammation. The transcriptome unveiled ontologies related to ER stress after 32 weeks on PF diets. In conclusion, different FA qualities result in different metabolic phenotypes and differentially impact prostate size, epithelial volume, inflammation and gene expression.