bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methodology for the identification of alternative manufacturing changes for safety–critical components
Authors: Bergs Thomas , Hermann Lennard , Rey Jan , Barth Sebastian 
Published: April 2020

AbstractA variety of factors are forcing companies to change their products and the components these products are composed of. Examples of current factors are changing customer requirements, product optimizations or ever-shorter product lifecycles. These component changes, particularly in safety–critical components in the medical and aerospace industry, pose great challenges and are limited in scope. The challenges and limitations arise from the high costs and the amount of time involved in component recertification as required by law, as well as revalidations of the manufacturing after a change has been implemented. Some component changes are even mandatory. In this case there are no options for reducing recertification efforts by choosing between different design changes. In contrast, there are alternative manufacturing options with which to implement the prescribed component changes that can reduce the amount of revalidation required on the manufacturing side. Due to the fact that changes to the manufacture of safety–critical components require validation, the existence of alternative manufacturing changes offers the potential to save time and money by selecting the best-suited alternative. In order to be able to select the best-suited alternative, all alternative manufacturing changes must be known, which poses a challenge for technology planners dealing with the complex manufacture of safety–critical components. Therefore, a methodology is introduced to support technology planners in identify alternative manufacturing changes with which to implement scope-restricted changes to safety–critical components. The methodology is validated by applying it to a case study from the medical industry.
Comparative analysis of microsatellite and SNP markers for parentage testing in the golden snub-nosed monkey (Rhinopithecus roxellana)
Authors: Ling Chen , Lixia Wu , Rong Hou , Fujun Shen , Wenping Zhang , Yao Tang , Yaohua Yuan , Bo Zhao , Liang Zhang 
Published: April 2020

AbstractMicrosatellite markers are popular for assigning parentage, but single-nucleotide polymorphisms (SNPs) have only been applied in this area recently. To evaluate these two markers which have been previously studied in golden snub-nosed monkeys, we genotyped 12 individuals using 37 microsatellite loci and 37 SNP markers. The data showed that 32 of 37 microsatellite loci were polymorphic, and most microsatellite loci were high informative (mean PIC = 0.599). Meanwhile, 24 of 37 SNP markers were polymorphic and most were low informative (mean PIC = 0.244). For microsatellites, the combined exclusion probability with one-parent-unknown/known (CE-1P/CE-2P) nearly reached 1, while for the SNP markers, CE-2P only reached 0.9582. Under the condition of one parent known/unknown, the CE-2P and CE-1P could meet the international human parental standard (0.9973) by using five or nine microsatellite loci respectively. For SNP markers, we doubled the loci (n = 48) and simulated parentage testing, and the data showed that the CE-2P was 0.998 while the CE-1P was still low. This result indicated that the SNP loci which we used here had low polymorphism and that more loci need to be developed in the future. In addition, we corrected one case of failed identification by excluding siblings and reducing the range of candidate paternities.
Genome-wide characterization of simple sequence repeats in Palmae genomes
Authors: Manee Manee M. , Al-Shomrani Badr M. , Al-Fageeh Mohamed B. 
Published: April 2020

Abstract
Background
Microsatellites or simple sequence repeats (SSRs) have become the most significant DNA marker technology used in genetic research. The availability of complete draft genomes for a number of Palmae species has made it possible to perform genome-wide analysis of SSRs in these species. Palm trees are tropical and subtropical plants with agricultural and economic importance due to the nutritional value of their fruit cultivars.

Objective
This is the first comprehensive study examining and comparing microsatellites in completely-sequenced draft genomes of Palmae species.

Methods
We identified and compared perfect SSRs with 1–6 bp nucleotide motifs to characterize microsatellites in Palmae species using v0.2.5. We analyzed their relative abundance, relative density, and GC content in five palm species: Phoenix dactylifera, Cocos nucifera, Calamus simplicifolius, Elaeis oleifera, and Elaeis guineensis.

Results
A total of 118241, 328189, 450753, 176608, and 70694 SSRs were identified, respectively. The six repeat types were not evenly distributed across the five genomes. Mono- and dinucleotide SSRs were the most abundant, and GC content was highest in tri- and hexanucleotide SSRs.

Conclusion
We envisage that this analysis would further substantiate more in-depth computational, biochemical, and molecular studies on the roles SSRs may play in the genome organization of the palm species. The current study contributes a detailed characterization of simple sequence repeats in palm genomes.
The organic formation of a&nbsp;wellness committee: A&nbsp;unique, student-led approach to implementing a&nbsp;wellness program in medical school
Authors: Brunner Michael R. , Peters Daniel , Portera Mary Virginia , Fazili Irtiqa , McBride Mary , Dennis Mallie , Herr Michael J. 
Published: April 2020

Background Medical school wellness programs are rapidly becoming a prevalent feature of medical education. The wellness component of medical education is addressed by a multitude of different approaches, but is often led by administrative faculty rather than students.
Approach The first-year medical student authors collectively established a medical school wellness committee that is entirely student-driven. The goal of the wellness committee was to organize and promote student ideas centered on six aspects of wellness.
Evaluation The formation, initial successes, and hurdles to the inception and continuation of the committee are described in a repeatable way.
Reflection This perspective provides insight into a student-led innovation that was formally accepted by faculty and administration to serve as part of the university’s overall wellness initiatives.
Limited Early Warnings and Public Attention to Coronavirus Disease 2019 in China, January–February, 2020: A Longitudinal Cohort of Randomly Sampled Weibo Users
Authors: Zhu Yuner , Fu King-Wa , Grépin Karen A. , Liang Hai , Fung Isaac Chun-Hai 
Published: April 2020

ABSTRACTObjective:Awareness and attentiveness have implications for the acceptance and adoption of disease prevention and control measures. Social media posts provide a record of the public’s attention to an outbreak. To measure the attention of Chinese netizens to coronavirus disease 2019 (COVID-19), a pre-established nationally representative cohort of Weibo users was searched for COVID-19-related key words in their posts.Methods:COVID-19-related posts (N = 1101) were retrieved from a longitudinal cohort of 52 268 randomly sampled Weibo accounts (December 31, 2019–February 12, 2020).Results:Attention to COVID-19 was limited prior to China openly acknowledging human-to-human transmission on January 20. Following this date, attention quickly increased and has remained high over time. Particularly high levels of social media traffic appeared around when Wuhan was first placed in quarantine (January 23–24, 8–9% of the overall posts), when a scandal associated with the Red Cross Society of China occurred (February 1, 8%), and, following the death of Dr Li Wenliang (February 6–7, 11%), one of the whistleblowers who was reprimanded by the Chinese police in early January for discussing this outbreak online.Conclusion:Limited early warnings represent missed opportunities to engage citizens earlier in the outbreak. Governments should more proactively communicate early warnings to the public in a transparent manner.
NPM1 upregulates the transcription of PD-L1 and suppresses T cell activity in triple-negative breast cancer
Authors: Qin Ge , Wang Xin , Ye Shubiao , Li Yizhuo , Chen Miao , Wang Shusen , Qin Tao , Zhang Changlin , Li Yixin , Long Qian , Hu Huabin , Shi Dingbo , Li Jiaping , Zhang Kai , Zhai Qinglian , Tang Yanlai , Kang Tiebang , Lan Ping , Xie Fangyun , Lu Jianjun , Deng Wuguo 
Published: April 2020

AbstractProgrammed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction plays a crucial role in tumor-associated immune escape. Here, we verify that triple-negative breast cancer (TNBC) has higher PD-L1 expression than other subtypes. We then discover that nucleophosmin (NPM1) binds to PD-L1 promoter specifically in TNBC cells and activates PD-L1 transcription, thus inhibiting T cell activity in vitro and in vivo. Furthermore, we demonstrate that PARP1 suppresses PD-L1 transcription through its interaction with the nucleic acid binding domain of NPM1, which is required for the binding of NPM1 at PD-L1 promoter. Consistently, the PARP1 inhibitor olaparib elevates PD-L1 expression in TNBC and exerts a better effect with anti-PD-L1 therapy. Together, our research has revealed NPM1 as a transcription regulator of PD-L1 in TNBC, which could lead to potential therapeutic strategies to enhance the efficacy of cancer immunotherapy.
Functional brain network reconfiguration during learning in a dynamic environment
Authors: Kao Chang-Hao , Khambhati Ankit N. , Bassett Danielle S. , Nassar Matthew R. , McGuire Joseph T. , Gold Joshua I. , Kable Joseph W. 
Published: April 2020

AbstractWhen learning about dynamic and uncertain environments, people should update their beliefs most strongly when new evidence is most informative, such as when the environment undergoes a surprising change or existing beliefs are highly uncertain. Here we show that modulations of surprise and uncertainty are encoded in a particular, temporally dynamic pattern of whole-brain functional connectivity, and this encoding is enhanced in individuals that adapt their learning dynamics more appropriately in response to these factors. The key feature of this whole-brain pattern of functional connectivity is stronger connectivity, or functional integration, between the fronto-parietal and other functional systems. Our results provide new insights regarding the association between dynamic adjustments in learning and dynamic, large-scale changes in functional connectivity across the brain.
Pyrazinamide triggers degradation of its target aspartate decarboxylase
Authors: Gopal Pooja , Sarathy Jickky Palmae , Yee Michelle , Ragunathan Priya , Shin Joon , Bhushan Shashi , Zhu Junhao , Akopian Tatos , Kandror Olga , Lim Teck Kwang , Gengenbacher Martin , Lin Qingsong , Rubin Eric J. , Grüber Gerhard , Dick Thomas 
Published: April 2020

AbstractPyrazinamide is a sterilizing first-line tuberculosis drug. Genetic, metabolomic and biophysical analyses previously demonstrated that pyrazinoic acid, the bioactive form of the prodrug pyrazinamide (PZA), interrupts biosynthesis of coenzyme A in Mycobacterium tuberculosis by binding to aspartate decarboxylase PanD. While most drugs act by inhibiting protein function upon target binding, we find here that pyrazinoic acid is only a weak enzyme inhibitor. We show that binding of pyrazinoic acid to PanD triggers degradation of the protein by the caseinolytic protease ClpC1-ClpP. Thus, the old tuberculosis drug pyrazinamide exerts antibacterial activity by acting as a target degrader, a mechanism of action that has recently emerged as a successful strategy in drug discovery across disease indications. Our findings provide the basis for the rational discovery of next generation PZA.
A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer
Authors:   Variant Interpretation for Cancer Consortium, Wagner Alex H. , Walsh Brian , Mayfield Georgia , Tamborero David , Sonkin Dmitriy , Krysiak Kilannin , Deu-Pons Jordi , Duren Ryan P. , Gao Jianjiong , McMurry Julie , Patterson Sara , del Vecchio Fitz Catherine , Pitel Beth A. , Sezerman Ozman U. , Ellrott Kyle , Warner Jeremy L. , Rieke Damian T. , Aittokallio Tero , Cerami Ethan , Ritter Deborah I. , Schriml Lynn M. , Freimuth Robert R. , Haendel Melissa , Raca Gordana , Madhavan Subha , Baudis Michael , Beckmann Jacques S. , Dienstmann Rodrigo , Chakravarty Debyani , Li Xuan Shirley , Mockus Susan , Elemento Olivier , Schultz Nikolaus , Lopez-Bigas Nuria , Lawler Mark , Goecks Jeremy , Griffith Malachi , Griffith Obi L. , Margolin Adam A. 
Published: April 2020

AbstractPrecision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations. We demonstrated large gains in overlap between resources across variants, diseases and drugs as a result of this harmonization. We subsequently demonstrated improved matching between a patient cohort and harmonized interpretations of potential clinical significance, observing an increase from an average of 33% per individual knowledgebase to 57% in aggregate. Our analyses illuminate the need for open, interoperable sharing of variant interpretation data. We also provide a freely available web interface (search.cancervariants.org) for exploring the harmonized interpretations from these six knowledgebases.
Combined chemo-magnetic field-photothermal breast cancer therapy based on porous magnetite nanospheres
Authors: Sharifi Majid , Hasan Anwarul , Nanakali Nadir Mustafa Qadir , Salihi Abbas , Qadir Fikry Ali , Muhammad Hawzheen A. , Shekha Mudhir Sabir , Aziz Falah Mohammad , Amen Karwan M. , Najafi Farrokh , Yousefi-Manesh Hasan , Falahati Mojtaba 
Published: April 2020

AbstractThe efficacy of different modalities of treating breast cancer is inhibited by several limitations such as off-targeted drug distribution, rapid drug clearance, and drug resistance. To overcome these limitations, we developed Lf-Doxo-PMNSs for combined chemo-MF-PTT. The PMNSs were synthesized by hydrothermal method and their physicochemical properties were examined by FE-SEM, TEM, DLS, TGA, XRD investigations. The cytotoxicity of as-synthesized NPs against 4T1 cells was carried out by MTT and flow cytometry assays. Afterwards, the anti-cancer activities of as-synthesized Lf-Doxo-PMNSs on the tumor status, drug distribution and apoptosis mechanism were evaluated. The anti-cancer assays showed that Lf-Doxo-PMNSs significantly suppressed the cancer cell proliferation and tumor weight by prolonging drug availability and potential drug loading in tumor cells; whereas they showed a minimum cytotoxicity against non-cancerous cells. Likewise, combined chemo-MF-PTT using Lf-Doxo-PMNSs displayed the highest anti-cancer activity followed by combined chemo-PTT and combined chemo-MF therapy based on altering the apoptosis mechanism. Therefore, these results showed that combined chemo-MF-PTT based on Lf-Doxo-PMNSs can be used as a promising therapeutic platform with potential targeted drug delivery and high loading capacity features as well as reducing cancer drug resistance.
Gradual wiring of olfactory input to amygdala feedback circuits
Authors: Oboti Livio , Sokolowski Katie 
Published: April 2020

AbstractThe amygdala facilitates odor driven behavioral responses by enhancing the saliency of olfactory signals. Before this processing, olfactory input is refined through the feedback provided by amygdala corticofugal projection (ACPs). Although the saliency of odor signals is subject to developmental changes, the stage at which this cortical feedback first occurs is not known. Using optogenetically-assisted intracellular recordings of the mouse cortical amygdala, we identified changes in the electrophysiological properties of ACPs at different developmental stages. These were consistent with a decrease in neuronal excitability and an increase in the amount of incoming accessory olfactory bulb (AOB) inputs, as confirmed by estimates of release probability, quantal size and contact number at the AOB-to-ACP synapse. Moreover, the proportion of ACPs activated in response to odors was dependent on the stage of development as revealed by c-Fos expression analysis. These results update standard accounts of how the amygdala processes social signals by emphasizing the occurrence of critical periods in the development of its sensory gating functions.
Vascular Supply of the Human Spiral Ganglion: Novel Three-Dimensional Analysis Using Synchrotron Phase-Contrast Imaging and Histology
Authors: Mei Xueshuang , Glueckert Rudolf , Schrott-Fischer Annelies , Li Hao , Ladak Hanif M. , Agrawal Sumit K. , Rask-Andersen Helge 
Published: April 2020

AbstractHuman spiral ganglion (HSG) cell bodies located in the bony cochlea depend on a rich vascular supply to maintain excitability. These neurons are targeted by cochlear implantation (CI) to treat deafness, and their viability is critical to ensure successful clinical outcomes. The blood supply of the HSG is difficult to study due to its helical structure and encasement in hard bone. The objective of this study was to present the first three-dimensional (3D) reconstruction and analysis of the HSG blood supply using synchrotron radiation phase-contrast imaging (SR-PCI) in combination with histological analyses of archival human cochlear sections. Twenty-six human temporal bones underwent SR-PCI. Data were processed using volume-rendering software, and a representative three-dimensional (3D) model was created to allow visualization of the vascular anatomy. Histologic analysis was used to verify the segmentations. Results revealed that the HSG is supplied by radial vascular twigs which are separate from the rest of the inner ear and encased in bone. Unlike with most organs, the arteries and veins in the human cochlea do not follow the same conduits. There is a dual venous outflow and a modiolar arterial supply. This organization may explain why the HSG may endure even in cases of advanced cochlear pathology.
Modelling the transmission and persistence of African swine fever in wild boar in contrasting European scenarios
Authors: O’Neill Xander , White Andy , Ruiz-Fons Francisco , Gortázar Christian 
Published: April 2020

AbstractAfrican swine fever (ASF) is a severe viral disease that is currently spreading among domestic pigs and wild boar (Sus scrofa) in large areas of Eurasia. Wild boar play a key role in the spread of ASF, yet despite their significance, little is known about the key mechanisms that drive infection transmission and disease persistence. A mathematical model of the wild boar ASF system is developed that captures the observed drop in population density, the peak in infected density and the persistence of the virus observed in ASF outbreaks. The model results provide insight into the key processes that drive the ASF dynamics and show that environmental transmission is a key mechanism determining the severity of an infectious outbreak and that direct frequency dependent transmission and transmission from individuals that survive initial ASF infection but eventually succumb to the disease are key for the long-term persistence of the virus. By considering scenarios representative of Estonia and Spain we show that faster degradation of carcasses in Spain, due to elevated temperature and abundant obligate scavengers, may reduce the severity of the infectious outbreak. Our results also suggest that the higher underlying host density and longer breeding season associated with supplementary feeding leads to a more pronounced epidemic outbreak and persistence of the disease in the long-term. The model is used to assess disease control measures and suggests that a combination of culling and infected carcass removal is the most effective method to eradicate the virus without also eradicating the host population, and that early implementation of these control measures will reduce infection levels whilst maintaining a higher host population density and in some situations prevent ASF from establishing in a population.
Associations of C-reactive Protein with 25-hydroxyvitamin D in 24 Specific Diseases: A Cross-sectional Study from NHANES
Authors: Yang Fang , Sun Mengzi , Sun Chong , Li Jiagen , Yang Xiuning , Bi Chunli , Wang Min , Pu Liyuan , Wang Jianmeng , Wang Chunxiao , Xie Meizhen , Yao Yan , Jin Lina 
Published: April 2020

AbstractMost diseases might be associated with acute or chronic inflammation, and the role of vitamin D in diseases has been extensively explored in recent years. Thus, we examined the associations of one of the best markers for inflammation ― C-reactive protein (CRP) with 25-hydroxyvitamin D [25(OH)D] in 24 specific diseases. We performed cross-sectional analyses among 9,809 subjects aged ≥18 years who participated in the U.S. National Health and Nutrition Examination Survey (NHANES) in 2007~2010. The generalized additive model (GAM) was used to explore the associations of CRP with 25(OH)D in different diseases, adjusted for the age, gender, examination period and race. Distributions of CRP were significantly different (P < 0.05) in gender, examination period and race, and distributions of 25(OH)D were different (P < 0.05) in the examination period and race. Generally, CRP was negatively associated with 25(OH)D for majority diseases. 25(OH)D was negatively associated with CRP generally, and the associations were disease-specific and disease category-specific. In respiratory, gastrointestinal and mental diseases, the associations tended to be approximately linear. While in metabolic diseases, the associations were nonlinear, and the slope of the nonlinear curve decreased with 25(OH)D, especially when 25(OH)D < 30 μg/L.
Attractor Concepts to Evaluate the Transcriptome-wide Dynamics Guiding Anaerobic to Aerobic State Transition in Escherichia coli
Authors: Bui Thuy Tien , Selvarajoo Kumar 
Published: April 2020

AbstractFor any dynamical system, like living organisms, an attractor state is a set of variables or mechanisms that converge towards a stable system behavior despite a wide variety of initial conditions. Here, using multi-dimensional statistics, we investigate the global gene expression attractor mechanisms shaping anaerobic to aerobic state transition (AAT) ofEscherichia coliin a bioreactor at early times. Out of 3,389 RNA-Seq expression changes over time, we identified 100 sharply changing genes that are key for guiding 1700 genes into the AAT attractor basin. Collectively, these genes were named asattractorgenes constituting of 6 dynamic clusters. Apart from the expected anaerobic (glycolysis), aerobic (TCA cycle) and fermentation (succinate pathways) processes, sulphur metabolism, ribosome assembly and amino acid transport mechanisms together with 332 uncharacterised genes are also key for AAT. Overall, our work highlights the importance of multi-dimensional statistical analyses for revealing novel processes shaping AAT.