bluuebunny/crossref_metadata_2025_split huggingface dataset:
High frequency audible calls in northern birch mice Sicista betulina in response to handling: effects of individuality, sex and body mass on the acoustics
Authors: Volodin Ilya A. , Klenova Anna V. , Ilchenko Olga G. , Volodina Elena V. 
Published: October 2019

Abstract

Objectives
This is the first study of the sonic and ultrasonic vocalization in a Dipodidae rodent. For the small-sized quadrupedal northern birch mouse Sicista betulina, phylogenetically related to the bipedal jerboas (Dipodidae), we report null results for ultrasonic vocalization and investigate the acoustic cues to individual identity, sex and body size in the discomfort-related high-frequency tonal sonic calls.

Results
We used a parallel audio recording in the sonic and ultrasonic ranges during weighting adult northern birch mice before the scheduled hibernation in captivity. The sonic (audible) high-frequency tonal calls (ranging from 6.21 to 9.86 kHz) were presented in all individuals (7 males and 4 females). The ultrasonic calls lacked in the recordings. Two-way nested ANOVA revealed the effects of caller individual identity on all 10 measured acoustic variables and the effects of sex on four out of 10 measured acoustic variables. Discriminant function analyses with 10 acoustic variables included in the analysis showed 85.5% correct assignment of calls to individual and 79.7% correct assignment of calls to sex; both values significantly exceeded the random values (23.1% and 54.3%, respectively) calculated with randomization procedure. Body mass did not differ between sexes and did not correlate significantly with the acoustic variables.
Random forest-based modelling to detect biomarkers for prostate cancer progression
Authors: Toth Reka , Schiffmann Heiko , Hube-Magg Claudia , Büscheck Franziska , Höflmayer Doris , Weidemann Sören , Lebok Patrick , Fraune Christoph , Minner Sarah , Schlomm Thorsten , Sauter Guido , Plass Christoph , Assenov Yassen , Simon Ronald , Meiners Jan , Gerhäuser Clarissa 
Published: October 2019

Abstract

Background
The clinical course of prostate cancer (PCa) is highly variable, demanding an individualized approach to therapy. Overtreatment of indolent PCa cases, which likely do not progress to aggressive stages, may be associated with severe side effects and considerable costs. These could be avoided by utilizing robust prognostic markers to guide treatment decisions.

Results
We present a random forest-based classification model to predict aggressive behaviour of prostate cancer. DNA methylation changes between PCa cases with good or poor prognosis (discovery cohort with n = 70) were used as input. DNA was extracted from formalin-fixed tumour tissue, and genome-wide DNA methylation differences between both groups were assessed using Illumina HumanMethylation450 arrays. For the random forest-based modelling, the discovery cohort was randomly split into a training (80%) and a test set (20%). Our methylation-based classifier demonstrated excellent performance in discriminating prognosis subgroups in the test set (Kaplan-Meier survival analyses with log-rank p value < 0.0001). The area under the receiver operating characteristic curve (AUC) for the sensitivity analysis was 95%. Using the ICGC cohort of early- and late-onset prostate cancer (n = 222) and the TCGA PRAD cohort (n = 477) for external validation, AUCs for sensitivity analyses were 77.1% and 68.7%, respectively. Cancer progression-related DNA hypomethylation was frequently located in ‘partially methylated domains’ (PMDs)—large-scale genomic areas with progressive loss of DNA methylation linked to mitotic cell division. We selected several candidate genes with differential methylation in gene promoter regions for additional validation at the protein expression level by immunohistochemistry in > 12,000 tissue micro-arrayed PCa cases. Loss of ZIC2 protein expression was associated with poor prognosis and correlated with significantly shorter time to biochemical recurrence. The prognostic value of ZIC2 proved to be independent from established clinicopathological variables including Gleason grade, tumour stage, nodal stage and prostate-specific-antigen.

Conclusions
Our results highlight the prognostic relevance of methylation loss in PMD regions, as well as of several candidate genes not previously associated with PCa progression. Our robust and externally validated PCa classification model either directly or via protein expression analyses of the identified top-ranked candidate genes will support the clinical management of prostate cancer.
Epigenetic silencing of MEIS2 in prostate cancer recurrence
Authors: Nørgaard Maibritt , Haldrup Christa , Bjerre Marianne Trier , Høyer Søren , Ulhøi Benedicte , Borre Michael , Sørensen Karina D. 
Published: October 2019

Abstract

Background
Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, resulting in overdiagnosis and overtreatment of clinically insignificant tumors. Thus, to improve the management of PC, novel biomarkers are urgently needed.

Results
In this study, we integrated genome-wide methylome (Illumina 450K DNA methylation array (450K)) and RNA sequencing (RNAseq) data performed in a discovery set of 27 PC and 15 adjacent normal (AN) prostate tissue samples to identify candidate driver genes involved in PC development and/or progression. We found significant enrichment for homeobox genes among the most aberrantly methylated and transcriptionally dysregulated genes in PC. Specifically, homeobox gene MEIS2 (Myeloid Ecotropic viral Insertion Site 2) was significantly hypermethylated (p < 0.0001, Mann-Whitney test) and transcriptionally downregulated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue in our discovery sample set, which was also confirmed in an independent validation set including > 500 PC and AN tissue samples in total (TCGA cohort analyzed by 450K and RNAseq). Furthermore, in three independent radical prostatectomy (RP) cohorts (n > 700 patients in total), low MEIS2 transcriptional expression was significantly associated with poor biochemical recurrence (BCR) free survival (p = 0.0084, 0.0001, and 0.0191, respectively; log-rank test). Next, we analyzed another RP cohort consisting of > 200 PC, AN, and benign prostatic hyperplasia (BPH) samples by quantitative methylation-specific PCR (qMSP) and found that MEIS2 was significantly hypermethylated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue samples (AN and BPH) with an AUC > 0.84. Moreover, in this cohort, aberrant MEIS2 hypermethylation was significantly associated with post-operative BCR (p = 0.0068, log-rank test), which was subsequently confirmed (p = 0.0067; log-rank test) in the independent TCGA validation cohort (497 RP patients; 450K data).

Conclusions
To the best of our knowledge, this is the first study to investigate, demonstrate, and independently validate a prognostic biomarker potential for MEIS2 at the transcriptional expression level and at the DNA methylation level in PC.
A novel real-time intravascular ultrasound double-lumen microcatheter for recanalization of chronic total occlusion: a case report
Authors: Ma Yanzhuo , Peng Yuhong , Wang Gang , Ru Leisheng 
Published: October 2019

Abstract

Background
Chronic total occlusion revascularization remains a challenging problem because of its complexity. We present a case of a patient with chronic total occlusion who was successfully revascularized with the use of a new device called a real-time intravascular ultrasound double-lumen microcatheter.

Case presentation
A 58-year-old East Asians woman presented to our hospital with a complaint of recurrent chest pain of 5 months’ duration. Angiography revealed chronic total occlusion of the right coronary artery from the right coronary artery ostium to the ostia of the posterolateral and posterior descending branches. A guidewire was passed to the distal right coronary artery but went into the false lumens at the posterior descending and posterolateral ostia after use of the antegrade and retrograde approaches. Hence, we used the new device to pass through the subintimal right coronary artery space with reentry into the true lumen before the posterior descending and posterolateral ostia. A stent was successfully deployed at the posterior descending and posterolateral ostia, and the final result was excellent.

Conclusions
This device was useful for finding the entry point and for reentry into the true lumen of a chronic total occlusion. It may be a valuable tool for recanalization of complex chronic total occlusion lesions.
Does co-transplantation of mesenchymal and spermatogonial stem cells improve reproductive efficiency and safety in mice?
Authors: Kadam Prashant , Ntemou Elissavet , Onofre Jaime , Van Saen Dorien , Goossens Ellen 
Published: October 2019

AbstractBackgroundSpermatogonial stem cell transplantation (SSCT) is a promising therapy in restoring the fertility of childhood cancer survivors. However, the low efficiency of SSCT is a significant concern. SSCT could be improved by co-transplanting transforming growth factor beta 1 (TGFβ1)-induced mesenchymal stem cells (MSCs). In this study, we investigated the reproductive efficiency and safety of co-transplanting spermatogonial stem cells (SSCs) and TGFβ1-induced MSCs.MethodsA mouse model for long-term infertility was used to transplant SSCs (SSCT,n = 10) and a combination of SSCs and TGFβ1-treated MSCs (MSi-SSCT,n = 10). Both transplanted groups and a fertile control group (n = 7) were allowed to mate naturally to check the reproductive efficiency after transplantation. Furthermore, the testes from transplanted males and donor-derived male offspring were analyzed for the epigenetic markers DNA methyltransferase 3A (DNMT3A) and histone 4 lysine 5 acetylation (H4K5ac).ResultsThe overall tubular fertility index (TFI) after SSCT (76 ± 12) was similar to that after MSi-SSCT (73 ± 14). However, the donor-derived TFI after MSi-SSCT (26 ± 14) was higher compared to the one after SSCT (9 ± 5;P = 0.002), even after injecting half of the number of SSCs in MSi-SSCT. The litter sizes after SSCT (3.7 ± 3.7) and MSi-SSCT (3.7 ± 3.6) were similar but differed significantly with the control group (7.6 ± 1.0;P < 0.001). The number of GFP+offspring per litter obtained after SSCT (1.6 ± 0.5) and MSi-SSCT (2.0 ± 1.0) was also similar. The expression of DNMT3A and H4K5ac in germ cells of transplanted males was found to be significantly reduced compared to the control group. However, in donor-derived offspring, DNMT3A and H4K5ac followed the normal pattern.ConclusionCo-transplanting SSCs and TGFβ1-treated MSCs results in reproductive efficiency as good as SSCT, even after transplanting half the number of SSCs. Although transplanted males showed lower expression of DNMT3A and H4K5ac in donor-derived germ cells, the expression was restored to normal levels in germ cells of donor-derived offspring. This procedure could become an efficient method to restore fertility in a clinical setup, but more studies are needed to ensure safety in the long term.
Multi-layer intrusion detection system with ExtraTrees feature selection, extreme learning machine ensemble, and softmax aggregation
Authors: Sharma Jivitesh , Giri Charul , Granmo Ole-Christoffer , Goodwin Morten 
Published: October 2019

Abstract
Recent advances in intrusion detection systems based on machine learning have indeed outperformed other techniques, but struggle with detecting multiple classes of attacks with high accuracy. We propose a method that works in three stages. First, the ExtraTrees classifier is used to select relevant features for each type of attack individually for each (ELM). Then, an ensemble of ELMs is used to detect each type of attack separately. Finally, the results of all ELMs are combined using a softmax layer to refine the results and increase the accuracy further. The intuition behind our system is that multi-class classification is quite difficult compared to binary classification. So, we divide the multi-class problem into multiple binary classifications. We test our method on the UNSW and KDDcup99 datasets. The results clearly show that our proposed method is able to outperform all the other methods, with a high margin. Our system is able to achieve 98.24% and 99.76% accuracy for multi-class classification on the UNSW and KDDcup99 datasets, respectively. Additionally, we use the weighted extreme learning machine to alleviate the problem of imbalance in classification of attacks, which further boosts performance. Lastly, we implement the ensemble of ELMs in parallel using GPUs to perform intrusion detection in real time.
Phylogeny of certain members of Hyrcanus group (Diptera: Culicidae) in China based on mitochondrial genome fragments
Authors: Zhu Hui-Min , Luo Shu-Han , Gao Man , Tao Feng , Gao Jing-Peng , Chen Han-Ming , Li Xiang-Yu , Peng Heng , Ma Ya-Jun 
Published: October 2019

AbstractBackgroundSpecies of theAnopheles hyrcanusgroup are widely distributed in Palearctic and Oriental regions and some of them are important malaria vectors. The cryptic species ofAn. hyrcanusgroup was almost impossible to identify based only on their morphology. The phylogenetic relationship ofAn. hyrcanusgroup was also not clear.MethodsFive members ofAn. hyrcanusgroup were identified by rDNA ITS2 sequencing asAn. yatsushiroensis, An. belenrae, An. kleini, An. lesteriandAn. sineroides.The mitochondrial genome fragments were sequenced and annotated using the mitochondrial genome ofAn. sinensisas reference. Based on the four segments and Joint Data sequences of these species, and other four anopheline species downloaded from GenBank, intraspecific as well as interspecific genetic distances were calculated and the phylogenetic trees were reconstructed by the methods of neighbor joining, maximum parsimony, minimum evolution and maximum likelihood.FindingsFour parts of mitochondrial genomes, which were partial fragmentsCOI + tRNA + COII(F5),ATP6 + COIII(F7 + F8),ND1(F19) andlrRNA(F21), were obtained. All fragments were connected as one sequence (referred as Joint Data), which had a total length of 3393 bp. All fragment sequences were highly conservative within species, with the maximumpdistance (0.026) calculated by F19 ofAn. belenrae. The pairwise interspecificpdistance calculated by each fragment showed minor or even no difference amongAn. sinensis,An. kleiniandAn. belenrae. However, interspecificpdistances calculated by the Joint Data sequence ranged from 0.004 (An. belenraevsAn. kleini) to 0.089 (An. sineroidesvsAn. minimus), and thepdistances of the six members ofAn. hyrcanusgroup were all less than 0.029. The phylogenetic tree showed two major clades: all subgenusAnophelesspecies (including six members ofAn. hyrcanusgroup,An. atroparvusandAn. quadrimaculatusA) and subgenusCellia(includingAn. dirusandAn. minimus). TheAn. hyrcanusgroup was divided into two clusters as ((An. lesteri, An. sineroides)An. yatsushiroensis) and ((An. belenrae, An. sinensis)An. kleini)).ConclusionsTheAn. hyrcanusgroup in this study could be divided into two clusters, in one of whichAn. belenrae, An. sinensisandAn. kleiniwere most closely related. More molecular markers would make greater contribution to phylogenetic analysis.
Isocitrate dehydrogenase inhibitors in acute myeloid leukemia
Authors: Liu Xiaoyan , Gong Yuping 
Published: October 2019

AbstractIsocitrate dehydrogenase (IDH) is a key enzyme involved in the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA) cycle. IDH mutation produces a neomorphic enzyme, which can lead to the abnormal accumulation of R-2-HG and promotes leukemogenesis. IDH mutation occurs in 20% of acute myeloid leukemia (AML) patients, mainly including IDH1 R132, IDH2 R140, and IDH2 R172. Different mutant isoforms have different prognostic values. In recent years, IDH inhibitors have shown good clinical response in AML patients. Hence, enasidenib and ivosidenib, the IDH2 and IDH1 inhibitors developed by Agios Pharmaceuticals, have been approved by the Food and Drug Administration on 1 August 2017 and 20 July 2018 for the treatment of adult relapsed or refractory (R/R) AML with IDH2 and IDH1 mutations, respectively. IDH inhibitor monotherapy for R/R AML is efficacious and safe; however, there are problems, such as primary or acquired resistance. Clinical trials of IDH inhibitors combined with hypomethylating agents or standard chemotherapy for the treatment of R/R AML or newly diagnosed AML, as well as in post hematopoietic stem cell transplantation as maintenance therapy, are ongoing. This article summarizes the use of IDH inhibitors in AML with IDH mutations.
Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants
Authors: Lin Li-Chun , Nana Alissa L. , Hepker Mackenzie , Hwang Ji-Hye Lee , Gaus Stephanie E. , Spina Salvatore , Cosme Celica G. , Gan Li , Grinberg Lea T. , Geschwind Daniel H. , Coppola Giovanni , Rosen Howard J. , Miller Bruce L. , Seeley William W. 
Published: October 2019

Abstract
Tau aggregation is a hallmark feature in a subset of patients with frontotemporal dementia (FTD). Early and selective loss of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices (ACC) is observed in patients with sporadic behavioral variant FTD (bvFTD) due to frontotemporal lobar degeneration (FTLD), including FTLD with tau inclusions (FTLD-tau). Recently, we further showed that these specialized neurons show preferential aggregation of TDP-43 in FTLD-TDP. Whether VENs and fork cells are prone to tau accumulation in FTLD-tau remains unclear, and no previous studies of these neurons have focused on patients with pathogenic variants in the gene encoding microtubule-associated protein tau (FTLD-tau/MAPT). Here, we examined regional profiles of tau aggregation and neurodegeneration in 40 brain regions in 8 patients with FTLD-tau/MAPT and 7 with Pick’s disease (PiD), a sporadic form of FTLD-tau that often presents with bvFTD. We further qualitatively assessed the cellular patterns of frontoinsular tau aggregation in FTLD-tau/MAPT using antibodies specific for tau hyperphosphorylation, acetylation, or conformational change. ACC and mid-insula were among the regions most affected by neurodegeneration and tau aggregation in FTLD-tau/MAPT and PiD. In these two forms of FTLD-tau, severity of regional neurodegeneration and tau protein aggregation were highly correlated across regions. In FTLD-tau/MAPT, VENs and fork cells showed disproportionate tau protein aggregation in patients with V337 M, A152T, and IVS10 + 16 variants, but not in patients with the P301L variant. As seen in FTLD-TDP, our data suggest that VENs and fork cells represent preferentially vulnerable neuron types in most, but not all of the MAPT variants we studied.
Highly sensitive and selective visual detection of Cr(VI) ions based on etching of silver-coated gold nanorods
Authors: Kim Dasom , Choi Eunjin , Lee Chaedong , Choi Yejung , Kim Hoonsub , Yu Taekyung , Piao Yuanzhe 
Published: October 2019

Abstract
We report a visual detection of Cr(VI) ions using silver-coated gold nanorods (AuNR@Ag) as sensing probes. Au NRs were prepared by a seed-mediated growth process and AuNR@Ag nanostructures were synthesized by growing Ag nanoshells on Au NRs. Successful coating of Ag nanoshells on the surface of Au NRs was demonstrated with TEM, EDS, and UV–vis spectrometer. By increasing the overall amount of the deposited Ag on Au NRs, the localized surface plasmon resonance (LSPR) band was significantly blue-shifted, which allowed tuning across the visible spectrum. The sensing mechanism relies on the redox reaction between Cr(VI) ions and Ag nanoshells on Au NRs. As the concentration of Cr(VI) ions increased, more significant red-shift of the longitudinal peak and intensity decrease of the transverse peak could be observed using UV–vis spectrometer. Several parameters such as concentration of CTAB, thickness of the Ag nanoshells and pH of the sample were carefully optimized to determine Cr(VI) ions. Under optimized condition, this method showed a low detection limit of 0.4 μM and high selectivity towards Cr(VI) over other metal ions, and the detection range of Cr(VI) was tuned by controlling thickness of the Ag nanoshells. From multiple evaluations in real sample, it is clear that this method is a promising Cr(VI) ion colorimetric sensor with rapid, sensitive, and selective sensing ability.
Hydrus microstent implantation for surgical management of glaucoma: a review of design, efficacy and safety
Authors: Samet Saba , Ong Jeb A. , Ahmed Iqbal Ike K. 
Published: October 2019

Abstract
With the advent of microinvasive glaucoma surgery (MIGS), the spectrum of modalities available to manage patients with this chronic and heterogeneous condition has broadened. Despite its novelty however, there has been a rapid evolution in the development of a multitude of devices, each targeting a structure along the aqueous drainage pathway. A growing body of evidence has demonstrated IOP and medication burden reduction, and a more favorable safety profile with MIGS procedures in contrast to traditional incisional surgeries. Among the array of MIGS, the Hydrus® Microstent (Ivantis, Inc., Irvine, CA) is a recent FDA approved device, designed to bypass the trabecular meshwork and provide a scaffold for Schlemm’s canal. The objective of this article is to review the Hydrus from conception to clinical use, and present data on its efficacy and safety to date. The available literature has shown promise, however inherent to all novel devices, only long-term monitoring will ensure sustained IOP control and an acceptable safety profile. Surgical advancements in glaucoma have revolutionized the field, and continued research and development will establish these approaches in clinical treatment algorithms.
Using Cultural Historical Activity Theory to understand how emerging technologies can mediate teaching and learning in a mathematics classroom: a review of literature
Authors: Batiibwe Marjorie Sarah Kabuye 
Published: October 2019

Abstract
The purpose of this paper was to review literature on the Cultural Historical Activity Theory (CHAT) and how it has been used to understand the mediation between emerging technologies and teaching and learning in a mathematics classroom. Specifically, it aimed at understanding the genesis of CHAT and further analyzing the studies that have employed CHAT as an analytical framework for teaching and learning in a mathematics classroom context. Two major concerns arise out of this review. Firstly, CHAT has been synonymously used with Activity Theory, leaving one wondering what actually the difference between the two in terms of researchers’ conceptualization is. Secondly, although CHAT has been widely utilized in education research, scholarly articles that have employed it as their theoretical or analytical frameworks in a mathematics classroom context are still too few and yet still, the few that have utilized it have not exploited its maximum potential. The implications for this review for teachers in Uganda are active student engagement and creation of collaboration spaces for dialogue and interaction in the teaching and learning process.