bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blocked O-GlcNAc cycling disrupts mouse hematopoeitic stem cell maintenance and early T cell development
Authors: Abramowitz Lara K. , Harly Christelle , Das Arundhoti , Bhandoola Avinash , Hanover John A. 
Published: August 2019

AbstractSmall numbers of hematopoietic stem cells (HSCs) balance self-renewal and differentiation to produce the diversity and abundance of cell types that make up the blood system. How nutrients are recruited to support this massive differentiation and proliferation process remains largely unknown. The unique metabolism of adult HSCs, which rely on glycolysis and glutaminolysis, suggests a potential role for the post-translational modification O-GlcNAc as a critical nutrient signal in these cells. Glutamine, glucose, and other metabolites drive the hexosamine biosynthetic pathway (HBP) ultimately leading to the O-GlcNAc modification of critical intracellular targets. Here, we used a conditional targeted genetic deletion of the enzyme that removes O-GlcNAc, O-GlcNAcase (OGA), to determine the consequences of blocked O-GlcNAc cycling on HSCs. Oga deletion in mouse HSCs resulted in greatly diminished progenitor pools, impaired stem cell self-renewal and nearly complete loss of competitive repopulation capacity. Further, early T cell specification was particularly sensitive to Oga deletion. Loss of Oga resulted in a doubling of apoptotic cells within the bone marrow and transcriptional deregulation of key genes involved in adult stem cell maintenance and lineage specification. These findings suggest that O-GlcNAc cycling plays a critical role in supporting HSC homeostasis and early thymocyte development.
Deep Learning to Improve Breast Cancer Detection on Screening Mammography
Authors: Shen Li , Margolies Laurie R. , Rothstein Joseph H. , Fluder Eugene , McBride Russell , Sieh Weiva 
Published: August 2019

AbstractThe rapid development of deep learning, a family of machine learning techniques, has spurred much interest in its application to medical imaging problems. Here, we develop a deep learning algorithm that can accurately detect breast cancer on screening mammograms using an “end-to-end” training approach that efficiently leverages training datasets with either complete clinical annotation or only the cancer status (label) of the whole image. In this approach, lesion annotations are required only in the initial training stage, and subsequent stages require only image-level labels, eliminating the reliance on rarely available lesion annotations. Our all convolutional network method for classifying screening mammograms attained excellent performance in comparison with previous methods. On an independent test set of digitized film mammograms from the Digital Database for Screening Mammography (CBIS-DDSM), the best single model achieved a per-image AUC of 0.88, and four-model averaging improved the AUC to 0.91 (sensitivity: 86.1%, specificity: 80.1%). On an independent test set of full-field digital mammography (FFDM) images from the INbreast database, the best single model achieved a per-image AUC of 0.95, and four-model averaging improved the AUC to 0.98 (sensitivity: 86.7%, specificity: 96.1%). We also demonstrate that a whole image classifier trained using our end-to-end approach on the CBIS-DDSM digitized film mammograms can be transferred to INbreast FFDM images using only a subset of the INbreast data for fine-tuning and without further reliance on the availability of lesion annotations. These findings show that automatic deep learning methods can be readily trained to attain high accuracy on heterogeneous mammography platforms, and hold tremendous promise for improving clinical tools to reduce false positive and false negative screening mammography results. Code and model available at: https://github.com/lishen/end2end-all-conv.
Fine-tuning the expression of target genes using a DDI2 promoter gene switch in budding yeast
Authors: Wang Yong , Zhang Kaining , Li Hanfei , Xu Xin , Xue Huijun , Wang Pingping , Fu Yu V. 
Published: August 2019

AbstractTuned gene expression is crucial to the proper growth and response to the environmental changes of an organism. To enable tunable gene expression as designed is desirable in both scientific research and industrial application. Here, we introduce a novel promoter switching method based on the DDI2 promoter (PDDI2) that can fine tune the expression of target genes. We constructed a recyclable cassette (PDDI2-URA3-PDDI2) and integrated it upstream of yeast target genes to replace the native promoters by DDI2 promoter without introducing any junk sequence. We found that the presence or absence of cyanamide as an inducer could turn on or off the expression of target genes. In addition, we showed that PDDI2 could act as a gene switch to linearly regulate the expression levels of target genes in vivo. We switched the original promoters of RAD18, TUP1, and CDC6 with PDDI2 as a proof-of-concept.
Laser-induced fluorescence (LIF) as a smart method for fast environmental virological analyses: validation on Picornaviruses
Authors: Gabbarini Valentina , Rossi Riccardo , Ciparisse Jean-François , Malizia Andrea , Divizia Andrea , De Filippis Patrizia , Anselmi Maurizio , Carestia Mariachiara , Palombi Leonardo , Divizia Maurizio , Gaudio Pasqualino 
Published: August 2019

AbstractVirological analysis is time-consuming and expensive. The aim of this work is to demonstrate the applicability of laser-induced fluorescence (LIF) to the classification of viruses, reducing the time for this analysis and its costs. Experimental tests were performed in which different viruses were irradiated with a UV laser emitting at 266 nm and the emitted spectra were recorded by a spectrometer. The classification techniques show the possibility of discriminating viruses. Although the application of the LIF technique to biological agents has been thoroughly studied by many researchers over the years, this work aims at validating for the first time its applicability to virological analyses. The development of a fast virological analysis may revolutionize this field, allowing fast responses to epidemiologic events, reducing their risks and improving the efficiency of monitoring environments. Moreover, a cost reduction may lead to an increase in the monitoring frequency, with an obvious enhancement of safety and prevention.
Estimating the immunogenicity of measles-rubella vaccination administered during a mass campaign in Lao People’s Democratic Republic using multi-valent seroprevalence data
Authors: Vynnycky Emilia , Miyano Shinsuke , Komase Katsuhiro , Mori Yoshio , Takeda Makoto , Kitamura Tomomi , Xeuatvongsa Anonh , Hachiya Masahiko 
Published: August 2019

AbstractMeasles and rubella are important causes of morbidity and mortality globally. Despite high coverage reported for measles vaccination, outbreaks continue to occur in some countries. The reasons for these outbreaks are poorly understood. We apply Bayesian methods to multi-valent seroprevalence data for measles and rubella, collected 2 years and 3 months after a mass measles-rubella vaccination campaign in Lao PDR to estimate the immunogenicity and vaccination coverage. When the vaccination coverage was constrained to exceed 95% or 90%, consistent with officially-reported values, the immunogenicity of the measles vaccine component was unexpectedly low (75% (95% CR: 63–82%) and 79% (CR: 70–87%) respectively. The estimated immunogenicity increased after relaxing constraints on the vaccination coverage, with best-fitting values of 83% (95% CR: 73–91%) and 97% (95% CR: 90–100%) for the measles and rubella components respectively, with an estimated coverage of 83% (95% CR: 80–88%). The findings suggest that, if the vaccine coverage was as high as that reported, continuing measles outbreaks in Lao PDR, and potentially elsewhere, may be attributable to suboptimal immunogenicity attained in mass campaigns. Vaccine management in countries with high reported levels of coverage and ongoing measles outbreaks needs to be reviewed if measles elimination targets are to be achieved.
Visual short-term memory binding deficit with age-related hearing loss in cognitively normal older adults
Authors: Loughrey David G. , Parra Mario A. , Lawlor Brian A. 
Published: August 2019

AbstractAge-related hearing loss (ARHL) has been posited as a possible modifiable risk factor for neurocognitive impairment and dementia. Measures sensitive to early neurocognitive changes associated with ARHL would help to elucidate the mechanisms underpinning this relationship. We hypothesized that ARHL might be associated with decline in visual short-term memory binding (VSTMB), a potential biomarker for preclinical dementia due to Alzheimer’s disease (AD). We examined differences in accuracy between older adults with hearing loss and a control group on the VSTMB task from a single feature (shapes) condition to a feature binding (shapes-colors) condition. Hearing loss was associated with a weaker capacity to process bound features which appeared to be accounted for by a weaker sensitivity for change detection (A’). Our findings give insight into the neural mechanisms underpinning neurocognitive decline with ARHL and its temporal sequence.
Ensuring access to high-quality resources reduces the impacts of heat stress on bees
Authors: Vanderplanck Maryse , Martinet Baptiste , Carvalheiro Luísa Gigante , Rasmont Pierre , Barraud Alexandre , Renaudeau Coraline , Michez Denis 
Published: August 2019

AbstractPollinators are experiencing declines globally, negatively affecting the reproduction of wild plants and crop production. Well-known drivers of these declines include climatic and nutritional stresses, such as a change of dietary resources due to the degradation of habitat quality. Understanding potential synergies between these two important drivers is needed to improve predictive models of the future effects of climate change on pollinator declines. Here, bumblebee colony bioassays were used to evaluate the interactive effects of heat stress, a reduction of dietary resource quality, and colony size. Using a total of 117 colonies, we applied a fully crossed experiment to test the effect of three dietary quality levels under three levels of heat stress with two colony sizes. Both nutritional and heat stress reduced colony development resulting in a lower investment in offspring production. Small colonies were much more sensitive to heat and nutritional stresses than large ones, possibly because a higher percentage of workers helps maintain social homeostasis. Strikingly, the effects of heat stress were far less pronounced for small colonies fed with suitable diets. Overall, our study suggests that landscape management actions that ensure access to high-quality resources could reduce the impacts of heat stress on bee decline.
de novo MEPCE nonsense variant associated with a neurodevelopmental disorder causes disintegration of 7SK snRNP and enhanced RNA polymerase II activation
Authors: Schneeberger Pauline E. , Bierhals Tatjana , Neu Axel , Hempel Maja , Kutsche Kerstin 
Published: August 2019

AbstractIn eukaryotes, the elongation phase of transcription by RNA polymerase II (RNAP II) is regulated by the transcription elongation factor b (P-TEFb), composed of Cyclin-T1 and cyclin-dependent kinase 9. The release of RNAP II is mediated by phosphorylation through P-TEFb that in turn is under control by the inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex. The 7SK snRNP consists of the 7SK non-coding RNA and the proteins MEPCE, LARP7, and HEXIM1/2. Biallelic LARP7 loss-of-function variants underlie Alazami syndrome characterized by growth retardation and intellectual disability. We report a boy with global developmental delay and seizures carrying the de novo MEPCE nonsense variant c.1552 C > T/p.(Arg518*). mRNA and protein analyses identified nonsense-mediated mRNA decay to underlie the decreased amount of MEPCE in patient fibroblasts followed by LARP7 and 7SK snRNA downregulation and HEXIM1 upregulation. Reduced binding of HEXIM1 to Cyclin-T1, hyperphosphorylation of the RNAP II C-terminal domain, and upregulated expression of ID2, ID3, MRPL11 and snRNAs U1, U2 and U4 in patient cells are suggestive of enhanced activation of P-TEFb. Flavopiridol treatment and ectopic MEPCE protein expression in patient fibroblasts rescued increased expression of six RNAP II-sensitive genes and suggested a possible repressive effect of MEPCE on P-TEFb-dependent transcription of specific genes.
Hypercalcemia is common during Pneumocystis pneumonia in kidney transplant recipients
Authors: Hamroun Aghilès , Lenain Rémi , Bui Nguyen Linh , Chamley Paul , Loridant Séverine , Neugebauer Yann , Lionet Arnaud , Frimat Marie , Hazzan Marc 
Published: August 2019

AbstractA few cases of hypercalcemia related to Pneumocystis jirovecii pneumonia (PJP) have previously been described, supposedly associated with an 1α-hydroxylase enzyme-dependent mechanism. The prevalence and significance of hypercalcemia in PJP remain unclear, especially in kidney transplant recipients (KTR) who frequently display hypercalcemia via persisting hyperparathyroidism. We here retrospectively identified all microbiologically-proven PJP in adult KTR from 2005 to 2017 in the Lille University Hospital, and studied the mineral and bone metabolism parameters during the peri-infectious period. Clinical features of PJP-patients were analyzed according to their serum calcium level. Hypercalcemia (12.6 ± 1.6 mg/dl) was observed in 37% (18/49) of PJP-patients and regressed concomitantly to specific anti-infectious treatment in all cases. No other cause of hypercalcemia was identified. In hypercalcemic patients, serum levels of 1,25-dihydroxyvitamin D were high at the time of PJP-diagnosis and decreased after anti-infectious treatment (124 ± 62 versus 28 ± 23 pg/mL, p = 0.006) while PTH serum levels followed an inverse curve (35 ± 34 versus 137 ± 99 pg/mL, p = 0.009), suggesting together a granuloma-mediated mechanism. Febrile dyspnea was less frequent in hypercalcemic PJP-patients compared to non-hypercalcemic (29 versus 67%). In summary, hypercalcemia seems common during PJP in KTR. Unexplained hypercalcemia could thus lead to specific investigations in this particular population, even in the absence of infectious or respiratory symptoms.
Association between long-term orthokeratology responses and corneal biomechanics
Authors: Lam Andrew K. C. , Hon Ying , Leung Stanley Y. Y. , Shu-Ho Lu , Chong Jones , Lam David C. C. 
Published: August 2019

AbstractMyopia is very prevalent worldwide, especially among Asian populations. Orthokeratology is a proven intervention to reduce myopia progression. The current study investigated association between baseline corneal biomechanics and orthokeratology responses, and changes of corneal biomechanics from long-term orthokeratology. We fitted 59 adult subjects having myopia between −4.00D to −5.00D with overnight orthokeratology. Corneal biomechanics was measured through dynamic bidirectional corneal applanation (in terms of corneal hysteresis, CH and corneal resistance factor, CRF) and corneal indentation (in terms of corneal stiffness, S and tangent modulus, E). Subjects with poor orthokeratology responses had lower E (mean 0.474 MPa) than subjects with good orthokeratology responses (mean 0.536 MPa). Successful orthokeratology for 6 months resulted in reducing CH (reduced by 5.8%) and CRF (reduced by 8.7%). Corneal stiffness was stable, but E showed an increasing trend. Among subjects with successful orthokeratology, a higher baseline S resulted in greater myopia reduction (Pearson correlation coefficient, r = 0.381, p = 0.02).
Genome-wide single nucleotide polymorphism array analysis unveils the origin of heterozygous androgenetic complete moles
Authors: Usui Hirokazu , Nakabayashi Kazuhiko , Maehara Kayoko , Hata Kenichiro , Shozu Makio 
Published: August 2019

AbstractHydatidiform moles are abnormal pregnancies, which show trophoblastic hyperplasia. Most often, the nuclear genome in complete hydatidiform moles (CHMs) is composed of only paternal chromosomes. Diploid androgenetic conceptuses can be divided into homozygous and heterozygous CHMs. Heterozygous CHMs originate from two sperms or a diploid sperm, the distinction of which has not been established. Here, we assessed the origin of heterozygous CHMs using single nucleotide polymorphism (SNP) array. Thirteen heterozygous CHMs were analysed using B allele frequency (BAF) plotting to determine the centromeric zygosity status of all chromosomes. One case was from the duplication of a single sperm with an XY chromosome. In the other twelve cases, centromeric zygosity was random, i.e. mixed status. Thus, the twelve heterozygous CHMs were considered to be of dispermic origin but not diploid sperm origin. BAF plotting of SNP array can be a powerful tool to estimate the type of hydatidiform moles.
Retrieval of negative autobiographical memories is associated with hostile attributions in ambiguous situations amongst people with schizophrenia
Authors: Barry Tom J. , Hernández-Viadel José V. , Fernández Dolores , Ros Laura , Ricarte Jorge J. , Berna Fabrice 
Published: August 2019

AbstractSchizophrenia is characterised by difficulty understanding the thoughts and intentions of other people. Misunderstandings could lead people to attribute hostility to others’ actions. Theories suggest that we use our autobiographical memories to inform our understanding of other people but no study has examined the relation between memory and hostile attributions in schizophrenia. People with (n = 42) and without (n = 34) schizophrenia diagnoses completed The Ambiguous Intentions and Hostility Questionnaire (AIHQ) to assess their tendency to attribute hostility to other people’s actions and the Autobiographical Memory Test (AMT) to assess their ability to recall specific positive and negative autobiographical memories. In linear regressions the interaction between diagnostic group and the proportion of specific negative memories participants retrieved explained significant variance in each AIHQ index. Follow-up correlation analyses showed that participants with schizophrenia who retrieved more negative memories also attributed greater hostility to other people’s actions (r = 0.47) and reported that they would respond with greater aggression (r = 0.59). These correlations were in the opposite direction for controls. People with schizophrenia may use their memories for negative past events to understand the actions and intentions of other people, leading to attributions of hostility for otherwise benign actions.
A graphene-assisted all-pass filter for a tunable terahertz transmissive modulator with near-perfect absorption
Authors: Tran Thang Q. , Lee Sangjun , Kim Sangin 
Published: August 2019

AbstractWe proposed an all-pass filter based perfect absorber scheme which also can function as a highly efficient transmissive modulator. We theoretically analyzed the proposed scheme using the temporal coupled mode theory and showed that near-perfect absorption could be achieved with practically modest deviation from the critical coupling condition. We also demonstrated the feasibility of the proposed scheme in a grating-based all-pass filter device with a variable loss implemented by two separate graphene layers, achieving an absorption of ~99.8% and a transmission modulation depth of ~70 dB in a terahertz frequency range. We also numerically investigated the tunability of the designed device.
Detection of Permethrin pesticide using silver nano-dendrites SERS on optical fibre fabricated by laser-assisted photochemical method
Authors: Pham Thanh Binh , Hoang Thi Hong Cam , Pham Van Hai , Nguyen Van Chuc , Nguyen Thuy Van , Vu Duc Chinh , Pham Van Hoi , Bui Huy 
Published: August 2019

AbstractPermethrin, 3-Phenoxybenzyl (1 RS)-cis,trans-3-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropanecarboxylate, has a wide range of applications like insecticide, insect repellent and prevents mosquito-borne diseases, such as dengue fever and malaria in tropical areas. In this work, we develop a prominent monitoring method for the detection of permethrin pesticide using surface-enhanced Raman scattering (SERS) optical fibre substrates. The novel SERS-active optical fibre substrates were grown and deposited silver (Ag) nano-dendrites on the end of multi-mode fibre core by laser-assisted photochemical method. The characteristic of the Ag-nanostructures could be controlled by the experimental conditions, namely, laser illumination time. Ag nanoparticles optical fibre substrates and Ag nano-dendrites optical fibre substrates were prepared with laser illumination time of 3 min and 8 min, respectively. The achieved SERS-activity optical fibre substrates were tested with Rhodamine 6G aqueous solutions. We demonstrate that the SERS activity coupled with Ag nano-dendrites optical fibre substrate has higher Raman enhancement factor due to the creation of many of hot-spots for amplifying Raman signals. Besides, the stability and reproducibility of the Ag nano-dendrites optical fibre substrate were also evaluated with stored time of 1000 hours and relative standard deviation of less than 3%. The Ag nano-dendrite optical fibre substrate was selected for detection of permethrin pesticide in the concentration range of 0.1 ppm–20 ppm with limit of quantification (LOQ) of 0.1 ppm and calculated limit of detection (LOD) of 0.0035 ppm, proving its great potential for direct, rapid detection and monitoring of permethrin.
Generalized Mohr-Coulomb strain criterion for bulk metallic glasses under complex compressive loading
Authors: Yu Li , Wang Tzu-Chiang 
Published: August 2019

AbstractThe Mohr-Coulomb (M-C) stress criterion is widely applied to describe the pressure sensitivity of bulk metallic glasses (BMGs). However, this criterion is incapable of predicting the variation in fracture angles under different loading modes. Moreover, the M-C criterion cannot describe the plastic fracture of BMGs under compressive loading because the nominal stress of most BMGs remains unchanged after the materials yield. Based on these limitations, we propose a new generalized M-C strain criterion and apply it to analyze the fracture behaviors of two typical Zr-based BMG round bar specimens under complex compressive loading. In this case, the predicted initial yielding stress is in good agreement with the experimental results. The theoretical results can also describe the critical shear strain and fracture angle of BMGs that are associated with the deformation mode.