bluuebunny/crossref_metadata_2025 huggingface dataset:
Sucrose promotes caries progression by disrupting the microecological balance in oral biofilms: an in vitro study
Authors: Du Qian , Fu Min , Zhou Yuan , Cao Yangpei , Guo Tingwei , Zhou Zhou , Li Mingyun , Peng Xian , Zheng Xin , Li Yan , Xu Xin , He Jinzhi , Zhou Xuedong
Published: February 2020

Sucrose has long been regarded as the most cariogenic carbohydrate. However, why sucrose causes severer dental caries than other sugars is largely unknown. Considering that caries is a polymicrobial infection resulting from dysbiosis of oral biofilms, we hypothesized that sucrose can introduce a microbiota imbalance favoring caries to a greater degree than other sugars. To test this hypothesis, an in vitro saliva-derived multispecies biofilm model was established, and by comparing caries lesions on enamel blocks cocultured with biofilms treated with sucrose, glucose and lactose, we confirmed that this model can reproduce the in vivo finding that sucrose has the strongest cariogenic potential. In parallel, compared to a control treatment, sucrose treatment led to significant changes within the microbial structure and assembly of oral microflora, while no significant difference was detected between the lactose/glucose treatment group and the control. Specifically, sucrose supplementation disrupted the homeostasis between acid-producing and alkali-producing bacteria. Consistent with microbial dysbiosis, we observed the most significant disequilibrium between acid and alkali metabolism in sucrose-treated biofilms. Taken together, our data indicate that the cariogenicity of sugars is closely related to their ability to regulate the oral microecology. These findings advance our understanding of caries etiology from an ecological perspective.
Dynamic vs static behaviour of a supported nanoparticle with reaction-induced catalytic sites in a lattice model
Authors: Korobov Alexander
Published: February 2020

Modern literature shows a rapidly growing interest to the supported nanocatalysts with dynamic behaviour under reaction conditions. This new frontier of heterogeneous catalysis is recognized as one of the most challenging and worthy of consideration from all possible angles. In this context, a previously suggested lattice model is used to get an insight, by means of kinetic Monte Carlo, into the influence of the mobility of reaction-induced catalytic sites of a two-dimensional supported nanoparticle on the system behaviour. The results speak in favour of feasibility of dynamic nanocatalysts with self-organized structures capable of robust functioning. This approach, from the macroscopic end, is believed to be a useful complement to ever developing experimental and first principle approaches.
Golden Gate assembly with a bi-directional promoter (GBid): A simple, scalable method for phage display Fab library creation
Authors: Chockalingam Karuppiah , Peng Zeyu , Vuong Christine N. , Berghman Luc R. , Chen Zhilei
Published: February 2020

Fabs offer an attractive platform for monoclonal antibody discovery/engineering, but library construction can be cumbersome. We report a simple method – Golden Gate assembly with a bi-directional promoter (GBid) – for constructing phage display Fab libraries. In GBid, the constant domains of the Fabs are located in the backbone of the phagemid vector and the library insert comprises only the variable regions of the antibodies and a central bi-directional promoter. This vector design reduces the process of Fab library construction to “scFv-like” simplicity and the double promoter ensures robust expression of both constituent chains. To maximize the library size, the 3 fragments comprising the insert – two variable chains and one bi-directional promoter – are assembled via a 3-fragment overlap extension PCR and the insert is incorporated into the vector via a high-efficiency one-fragment, one-pot Golden Gate assembly. The reaction setup requires minimal preparatory work and enzyme quantities, making GBid highly scalable. Using GBid, we constructed a chimeric chicken-human Fab phage display library comprising 1010 variants targeting the multi-transmembrane protein human CD20 (hCD20). Selection/counter-selection on transfected whole cells yielded hCD20-specific antibodies in four rounds of panning. The simplicity and scalability of GBid makes it a powerful tool for the discovery/engineering of Fabs and IgGs.
Nanopore sequencing of microbial communities reveals the potential role of sea lice as a reservoir for fish pathogens
Authors: Gonçalves Ana Teresa , Collipal-Matamal Rayen , Valenzuela-Muñoz Valentina , Nuñez-Acuña Gustavo , Valenzuela-Miranda Diego , Gallardo-Escárate Cristian
Published: February 2020

Caligus rogercresseyi is a copepod ectoparasite with a high prevalence in salmon farms in Chile, causing severe welfare and economic concerns to the sector. Information on the parasite’s underpinning mechanisms to support its life strategy is recently being investigated. Due to the critical role of microbiota, this study aimed to characterize the microbiota community associated with C. rogercresseyi from different regions with salmon aquaculture in Chile. Using third-generation sequencing with Nanopore technology (MinION) the full 16S rRNA gene from sea lice obtained from 8 areas distributed over the three main aquaculture regions were sequenced. Microbiota of the parasite is mainly comprised of members of phyla Proteobacteria and Bacteroidetes, and a core microbiota community with 147 taxonomical features was identified, and it was present in sea lice from the three regions. This community accounted for 19% of total identified taxa but more than 70% of the total taxonomical abundance, indicating a strong presence in the parasite. Several taxa with bioactive compound secretory capacity were identified, such as members of genus Pseudoalteromonas and Dokdonia, suggesting a possible role of the lice microbiota during the host infestation processes. Furthermore, the microbiota community was differentially associated with the salmon production, where several potential pathogens such as Vibrio, Tenacibaculum, and Aeromonas in Los Lagos, Aysén, and Magallanes region were identified. Notably, the Chilean salmon industry was initially established in the Los Lagos region but it’s currently moving to the south, where different oceanographic conditions coexist with lice populations. The results originated by this study will serve as foundation to investigate putative role of sea lice as vectors for fish pathogens and also as reservoirs for antibiotic-resistant genes.
Genome-wide association mapping for dominance effects in female fertility using real and simulated data from Danish Holstein cattle
Authors: Mao Xiaowei , Sahana Goutam , Johansson Anna Maria , Liu Aoxing , Ismael Ahmed , Løvendahl Peter , De Koning Dirk-Jan , Guldbrandtsen Bernt
Published: February 2020

Exploring dominance variance and loci contributing to dominance variation is important to understand the genetic architecture behind quantitative traits. The objectives of this study were i) to estimate dominance variances, ii) to detect quantitative trait loci (QTL) with dominant effects, and iii) to evaluate the power and the precision of identifying loci with dominance effect through post-hoc simulations, with applications for female fertility in Danish Holstein cattle. The female fertility records analyzed were number of inseminations (NINS), days from calving to first insemination (ICF), and days from the first to last insemination (IFL), covering both abilities to recycle and to get pregnant in the female reproductive cycle. There were 3,040 heifers and 4,483 cows with both female fertility records and Illumina BovineSNP50 BeadChip genotypes (35,391 single nucleotide polymorphisms (SNP) after quality control). Genomic best linear unbiased prediction (BLUP) models were used to estimate additive and dominance genetic variances. Linear mixed models were used for association analyses. A post-hoc simulation study was performed using genotyped heifers’ data. In heifers, estimates of dominance genetic variances for female fertility traits were larger than additive genetic variances, but had large standard errors. The variance components for fertility traits in cows could not be estimated due to non-convergence of the statistical model. In total, five QTL located on chromosomes 9, 11 (2 QTL), 19, and 28 were identified and all of them showed both additive and dominance genetic effects. Among them, the SNP rs29018921 on chromosome 9 is close to a previously identified QTL in Nordic Holstein for interval between first and last insemination. This SNP is located in the 3’ untranslated region of gene peptidylprolyl isomerase like 4 (PPIL4), which was shown to be associated with milk production traits in US Holstein cattle but not known for fertility-related functions. Simulations indicated that the current sample size had limited power to detect QTL with dominance effects for female fertility probably due to low QTL variance. More females need to be genotyped to achieve reliable mapping of QTL with dominance effects for female fertility.
Oceanic vortex mergers are not isolated but influenced by the β-effect and surrounding eddies
Authors: de Marez Charly , Carton Xavier , L’Hégaret Pierre , Meunier Thomas , Stegner Alexandre , Le Vu Briac , Morvan Mathieu
Published: February 2020

Oceanic vortices are ubiquitous in the ocean. They dominate the sub-inertial energy spectrum, and their dynamics is key for the evolution of the water column properties. The merger of two like-signed coherent vortices, which ultimately results in the formation of a larger vortex, provides an efficient mechanism for the lateral mixing of water masses in the ocean. Understanding the conditions of such interaction in the ocean is thus essential. Here, we use a merger detection algorithm to draw a global picture of this process in the ocean. We show that vortex mergers are not isolated, contrary to the hypothesis made in most earlier studies. Paradoxically, the merging distance is well reproduced by isolated vortex merger numerical simulations, but it is imperative to consider both the β-effect and the presence of neighbouring eddies to fully understand the physics of oceanic vortex merger.
Analysis of Circulating Waves in Tissue Rings derived from Human Induced Pluripotent Stem Cells
Authors: Zhang Lu , Li Junjun , Liu Li , Tang Chao
Published: February 2020

Developing more mature cardiomyocytes derived from human induced pluripotent stem cells is essential for cell transplantation and drug screening. In a previous study, we described a platform on which cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) formed three-dimensional self-organized tissue rings. Within these rings, traveling waves of action potentials spontaneously originate and propagate for a long time. In order to understand the dynamic behavior of these waves, we developed a mathematical model for the circulation of the electrical signal in such rings. By using the restitution curves of the action potential and the conduction velocity we demonstrated the mechanisms underlying the steady circulation and the features dependent on velocity. The analytic result agreed well with the experimental data in the origination, propagation, and long-term behavior of traveling waves within self-organized tissue rings. The theoretical analysis of traveling waves may also provide a reference to the analysis of reentrant rhythms in hearts.
Semi-quantitative versus quantitative assessments of late gadolinium enhancement extent for predicting spontaneous ventricular tachyarrhythmia events in patients with hypertrophic cardiomyopathy
Authors: Park Young Jun , Park Seung-Jung , Kim Eun-Kyung , Park Kyoung Min , Lee Sang-Cheol , On Young Keun , Kim June Soo
Published: February 2020

Extent of late gadolinium enhancement (LGE) quantified by cardiac magnetic resonance was reportedly helpful for predicting the risk of ventricular tachyarrhythmias (VTA) in hypertrophic cardiomyopathy (HCM) patients. However, only a few data exist on the clinical implication of semi-quantitative assessment LGE extent in this patient population. The extent of left ventricular (LV) LGE was measured in 310 consecutive HCM patients using semi-quantitative (summing the LV segments with LGE, spatial extent) and quantitative (calculating the LGE volume percentage [vol% of LGE] against the total LV myocardial volume) methods, respectively. LV LGE was detected in 255 (82%) patients, most frequently in the mid-LV septum (n = 160, 52%). During the 49 ± 45 month follow-up, spontaneous VTA events were observed in 48 patients (16%) including aborted sudden cardiac death (SCD), appropriate defibrillator shock, and non-sustained VTA. The extent of LGE assessed by the two different methods showed a strong positive correlation (Spearman’s r = 0.63, P < 0.001). Moreover, there was a graded increase in the rates of VTA with the LGE extent evaluated semi-quantitatively and quantitatively. The extent of LGE was identified as an independent predictor of VTA events and more extensive LGE (positive ≥ 4 segments) significantly raised the risk of VTA, irrespective of the presence of conventional risk factors for SCD including family history, unexplained syncope, LV wall thickness ≥30 mm. The extent of LGE, whether assessed by semi-quantitative or quantitative methods, was closely associated with an increased risk of spontaneous VTA events in HCM patients.
Extreme rainfall events pulse substantial nutrients and sediments from terrestrial to nearshore coastal communities: a case study from French Polynesia
Authors: Fong Caitlin R. , Gaynus Camille J. , Carpenter Robert C.
Published: February 2020

Rainfall mobilizes and transports anthropogenic sources of sediments and nutrients from terrestrial to coastal marine ecosystems, and episodic but extreme rainfall may drive high fluxes to marine communities. Between January 13th and January 22nd, 2017, the South Pacific Island of Moorea, French Polynesia experienced an extreme rainfall event. ~57 cm of rain was delivered over a 10-day storm. We quantified pulsed sediments and nutrients transported to nearshore reefs. We determined the spatial and temporal extent of the sediment pulse with estimates of water transparency. We quantified pulsed nutrients at multiple spatial and temporal scales. To determine if terrestrial nutrients were incorporated into the benthic community, we collected macroalgae over 10 days following the storm and measured tissue nutrient concentrations and δN15. Pulsed sediments impacted water clarity for 6 days following the storm, with greatest impacts closest to the river mouth. Nitrite +nitrate concentrations were >100 times the average while phosphate was >25 times average. Macroalgal tissue nutrients were elevated, and δN15 implicates sewage as the source, demonstrating transported nutrients were transferred to producer communities. Future climate change predictions suggest extreme rainfall will become more common in this system, necessitating research on these pulses and their ramifications on marine communities.
Optimal Multi-Stage Arrhythmia Classification Approach
Authors: Zheng Jianwei , Chu Huimin , Struppa Daniele , Zhang Jianming , Yacoub Sir Magdi , El-Askary Hesham , Chang Anthony , Ehwerhemuepha Louis , Abudayyeh Islam , Barrett Alexander , Fu Guohua , Yao Hai , Li Dongbo , Guo Hangyuan , Rakovski Cyril
Published: February 2020

Arrhythmia constitutes a problem with the rate or rhythm of the heartbeat, and an early diagnosis is essential for the timely inception of successful treatment. We have jointly optimized the entire multi-stage arrhythmia classification scheme based on 12-lead surface ECGs that attains the accuracy performance level of professional cardiologists. The new approach is comprised of a three-step noise reduction stage, a novel feature extraction method and an optimal classification model with finely tuned hyperparameters. We carried out an exhaustive study comparing thousands of competing classification algorithms that were trained on our proprietary, large and expertly labeled dataset consisting of 12-lead ECGs from 40,258 patients with four arrhythmia classes: atrial fibrillation, general supraventricular tachycardia, sinus bradycardia and sinus rhythm including sinus irregularity rhythm. Our results show that the optimal approach consisted of Low Band Pass filter, Robust LOESS, Non Local Means smoothing, a proprietary feature extraction method based on percentiles of the empirical distribution of ratios of interval lengths and magnitudes of peaks and valleys, and Extreme Gradient Boosting Tree classifier, achieved an F1-Score of 0.988 on patients without additional cardiac conditions. The same noise reduction and feature extraction methods combined with Gradient Boosting Tree classifier achieved an F1-Score of 0.97 on patients with additional cardiac conditions. Our method achieved the highest classification accuracy (average 10-fold cross-validation F1-Score of 0.992) using an external validation data, MIT-BIH arrhythmia database. The proposed optimal multi-stage arrhythmia classification approach can dramatically benefit automatic ECG data analysis by providing cardiologist level accuracy and robust compatibility with various ECG data sources.
Characteristics and outcomes of bacteremia among ICU-admitted patients with severe sepsis
Authors: Komori Akira , Abe Toshikazu , Kushimoto Shigeki , Ogura Hiroshi , Shiraishi Atsushi , Saitoh Daizoh , Fujishima Seitaro , Mayumi Toshihiko , Naito Toshio , Hifumi Toru , Shiino Yasukazu , Nakada Taka-aki , Tarui Takehiko , Otomo Yasuhiro , Okamoto Kohji , Umemura Yutaka , Kotani Joji , Sakamoto Yuichiro , Sasaki Junichi , Shiraishi Shin-ichiro , Takuma Kiyotsugu , Tsuruta Ryosuke , Hagiwara Akiyoshi , Yamakawa Kazuma , Masuno Tomohiko , Takeyama Naoshi , Yamashita Norio , Ikeda Hiroto , Ueyama Masashi , Fujimi Satoshi , Gando Satoshi ,   JAAM FORECAST group, Tasaki Osamu , Mizobata Yasumitsu , Funakoshi Hiraku , Okuyama Toshiro , Yamashita Iwao , Kanai Toshio , Yamada Yasuo , Aibiki Mayuki , Sato Keiji , Yamashita Susumu , Yoshida Kenichi , Kasaoka Shunji , Kon Akihide , Rinka Hiroshi , Kato Hiroshi , Okudera Hiroshi , Narimatsu Eichi , Fujiwara Toshifumi , Sugita Manabu , Shichinohe Yasuo , Nakae Hajime , Iiduka Ryouji , Nakamura Mitsunobu , Murata Yuji , Sato Yoshitake , Ishikura Hiroyasu , Myojo Yasuhiro , Tsujita Yasuyuki , Kinoshita Kosaku , Yamaguchi Hiroyuki , Sakurai Toshihiro , Miyatake Satoru , Saotome Takao , Yasuda Susumu , Mizushima Yasuaki
Published: February 2020

The clinical implications of bacteremia among septic patients remain unclear, although a vast amount of data have been accumulated on sepsis. We aimed to compare the clinical characteristics and outcomes of severe sepsis patients with and without bacteremia. This secondary analysis of a multicenter, prospective cohort study included 59 intensive care units (ICUs) in Japan between January 2016 and March 2017. The study cohort comprised 1,184 adults (aged ≥ 16 years) who were admitted to an ICU with severe sepsis and diagnosed according to the Sepsis-2 criteria. Of 1,167 patients included in the analysis, 636 (54.5%) had bacteremia. Those with bacteremia had significantly higher rates of septic shock (66.4% vs. 58.9%, p = 0.01) and higher sepsis severity scores, including the Acute Physiology and Chronic Health Evaluation (APACHE) II and the Sequential Organ Failure Assessment (SOFA). No significant difference in in-hospital mortality was seen between patients with and without bacteremia (25.6% vs. 21.0%, p = 0.08). In conclusion, half of severe sepsis patients in ICUs have bacteremia. Although patients with bacteremia had more severe state, between-group differences in patient-centered outcomes, such as in-hospital mortality, have not been fully elucidated.
Evaluating the significance of contact maps in low-homology protein modeling using contact-assisted threading
Authors: Bhattacharya Sutanu , Bhattacharya Debswapna
Published: February 2020

The development of improved threading algorithms for remote homology modeling is a critical step forward in template-based protein structure prediction. We have recently demonstrated the utility of contact information to boost protein threading by developing a new contact-assisted threading method. However, the nature and extent to which the quality of a predicted contact map impacts the performance of contact-assisted threading remains elusive. Here, we systematically analyze and explore this interdependence by employing our newly-developed contact-assisted threading method over a large-scale benchmark dataset using predicted contact maps from four complementary methods including direct coupling analysis (mfDCA), sparse inverse covariance estimation (PSICOV), classical neural network-based meta approach (MetaPSICOV), and state-of-the-art ultra-deep learning model (RaptorX). Experimental results demonstrate that contact-assisted threading using high-quality contacts having the Matthews Correlation Coefficient (MCC) ≥ 0.5 improves threading performance in nearly 30% cases, while low-quality contacts with MCC <0.35 degrades the performance for 50% cases. This holds true even in CASP13 dataset, where threading using high-quality contacts (MCC ≥ 0.5) significantly improves the performance of 22 instances out of 29. Collectively, our study uncovers the mutual association between the quality of predicted contacts and its possible utility in boosting threading performance for improving low-homology protein modeling.
Nonlinear dynamic stability of piezoelectric thermoelastic electromechanical resonators
Authors: SoltanRezaee Masoud , Bodaghi Mahdi
Published: February 2020

This research work deals with analyzing instability and nonlinear behaviors of piezoelectric thermal nano-bridges. An adjustable thermo-elastic model with the ability to control stability conditions is developed to examine the system behavior at different temperatures. To increase the performance range and improve system characteristics, a piezovoltage is applied and a spring is connected to the sliding end of the deformable beam as design parameters. The partial differential equations (PDEs) are derived using the extended Hamilton’s principle and Galerkin decomposition is implemented to discretize the nonlinear equations, which are solved via a computational method called the step-by-step linearization method (SSLM). To improve the accuracy of the solution, the number of mode shapes and the size of voltage increments are analyzed and sufficient values are employed in the solution. The validity of the formulation and solution method is verified with experimental, analytical, and numerical data for several cases. Finally, the vibration and eigenvalue problem of the actuated nano-manipulator subjected to electrostatic and Casimir attractions are investigated. It is concluded that the fringing-fields correction changes the system frequency, static equilibrium, and pull-in characteristics significantly. The results are expected to be instrumental in the analysis, design, and operation of numerous adjustable advanced nano-systems.
A genetic analysis identifies a haplotype at adiponectin locus: Association with obesity and type 2 diabetes
Authors: Palit Sayantani Pramanik , Patel Roma , Jadeja Shahnawaz D. , Rathwa Nirali , Mahajan Ankit , Ramachandran A. V. , Dhar Manoj K. , Sharma Swarkar , Begum Rasheedunnisa
Published: February 2020

Adiponectin is a prime determinant of the status of insulin resistance. Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (SNPs) and metabolic diseases have been reported earlier. However, results are ambiguous due to apparent contradictions. Hence, we investigated (1) the association between ADIPOQ SNPs: −11377C/G, +10211T/G, +45T/G and +276G/T for the risk towards type 2 diabetes (T2D) and, (2) genotype-phenotype association of these SNPs with various biochemical parameters in two cohorts. Genomic DNA of diabetic patients and controls from Gujarat and, Jammu and Kashmir (J&K) were genotyped using PCR-RFLP, TaqMan assay and MassArray. Transcript levels of ADIPOQ were assessed in visceral adipose tissue samples, and plasma adiponectin levels were estimated by qPCR and ELISA respectively. Results suggest: (i) reduced HMW adiponectin/total adiponectin ratio in Gujarat patients and its association with +10211T/G and +276G/T, and reduced ADIPOQ transcript levels in T2D, (ii) association of the above SNPs with increased FBG, BMI, TG, TC in Gujarat patients and (iii) increased GGTG haplotype in obese patients of Gujarat population and, (iv) association of −11377C/G with T2D in J&K population. Reduced HMW adiponectin, in the backdrop of obesity and ADIPOQ genetic variants might alter metabolic profile posing risk towards T2D.
Quantitative expansion microscopy for the characterization of the spectrin periodic skeleton of axons using fluorescence microscopy
Authors: Martínez Gaby F. , Gazal Nahir G. , Quassollo Gonzalo , Szalai Alan M. , Cid-Pellitero Esther Del , Durcan Thomas M. , Fon Edward A. , Bisbal Mariano , Stefani Fernando D. , Unsain Nicolas
Published: February 2020

Fluorescent nanoscopy approaches have been used to characterize the periodic organization of actin, spectrin and associated proteins in neuronal axons and dendrites. This membrane-associated periodic skeleton (MPS) is conserved across animals, suggesting it is a fundamental component of neuronal extensions. The nanoscale architecture of the arrangement (190 nm) is below the resolution limit of conventional fluorescent microscopy. Fluorescent nanoscopy, on the other hand, requires costly equipment and special analysis routines, which remain inaccessible to most research groups. This report aims to resolve this issue by using protein-retention expansion microscopy (pro-ExM) to reveal the MPS of axons. ExM uses reagents and equipment that are readily accessible in most neurobiology laboratories. We first explore means to accurately estimate the expansion factors of protein structures within cells. We then describe the protocol that produces an expanded specimen that can be examined with any fluorescent microscopy allowing quantitative nanoscale characterization of the MPS. We validate ExM results by direct comparison to stimulated emission depletion (STED) nanoscopy. We conclude that ExM facilitates three-dimensional, multicolor and quantitative characterization of the MPS using accessible reagents and conventional fluorescent microscopes.
Associations between brain inflammatory profiles and human neuropathology are altered based on apolipoprotein E ε4 genotype
Authors: Friedberg Jacob S. , Aytan Nurgul , Cherry Jonathan D. , Xia Weiming , Standring Oliver J. , Alvarez Victor E. , Nicks Raymond , Svirsky Sarah , Meng Gaoyuan , Jun Gyungah , Ryu Hoon , Au Rhoda , Stein Thor D.
Published: February 2020

Alzheimer disease (AD) is a chronic neurodegenerative disease with a multitude of contributing genetic factors, many of which are related to inflammation. The apolipoprotein E (APOE) ε4 allele is the most common genetic risk factor for AD and is related to a pro-inflammatory state. To test the hypothesis that microglia and AD-implicated cytokines were differentially associated with AD pathology based on the presence of APOE ε4, we examined the dorsolateral frontal cortex from deceased participants within a community-based aging cohort (n = 154). Cellular density of Iba1, a marker of microglia, was positively associated with tau pathology only in APOE ε4 positive participants (p = 0.001). The cytokines IL-10, IL-13, IL-4, and IL-1α were negatively associated with tau pathology, independent of Aβ1–42 levels, only in APOE ε4 negative participants. Overall, the association of mostly anti-inflammatory cytokines with less tau pathology suggests a protective effect in APOE ε4 negative participants. These associations are largely absent in the presence of APOE ε4 where tau pathology was significantly associated with increased microglial cell density. Taken together, these results suggest that APOE ε4 mediates an altered inflammatory response and increased tau pathology independent of Aβ1–42 pathology.
A comparison of bee communities between primary and mature secondary forests in the longleaf pine ecosystem
Authors: Ulyshen Michael D. , Pokswinski Scott , Hiers J. Kevin
Published: February 2020

Much of the once-dominant longleaf pine (Pinus palustris Mill.) ecosystem has been lost from the Coastal Plain of the southeastern United States and only a few scattered remnants of primary forest remain. Despite much interest in understanding and restoring this ecosystem, relatively few studies have attempted to characterize or assess the conservation status of the longleaf bee fauna. The objective of this study was to compare the diversity and composition of bee communities between primary and mature secondary (>100 years old) fire-maintained forests in Georgia and Florida. We used colored pan traps to sample bees at three primary and four secondary locations divided between two regions characterized by sandy (Eglin Air Force Base) or clayey (Red Hills) soils. There were no overall differences between primary and secondary forests in bee richness, diversity, evenness or abundance. Community composition differed among locations but we found no evidence that primary remnants provide critical habitat to sensitive bee species.
Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity
Authors: Rodius Sophie , de Klein Niek , Jeanty Céline , Sánchez-Iranzo Héctor , Crespo Isaac , Ibberson Mark , Xenarios Ioannis , Dittmar Gunnar , Mercader Nadia , Niclou Simone P. , Azuaje Francisco
Published: February 2020

Myocardial infarction (MI) is a leading cause of death worldwide. Reperfusion is considered as an optimal therapy following cardiac ischemia. However, the promotion of a rapid elevation of O2 levels in ischemic cells produces high amounts of reactive oxygen species (ROS) leading to myocardial tissue injury. This phenomenon is called ischemia reperfusion injury (IRI). We aimed at identifying new and effective compounds to treat MI and minimize IRI. We previously studied heart regeneration following myocardial injury in zebrafish and described each step of the regeneration process, from the day of injury until complete recovery, in terms of transcriptional responses. Here, we mined the data and performed a deep in silico analysis to identify drugs highly likely to induce cardiac regeneration. Fisetin was identified as the top candidate. We validated its effects in an in vitro model of MI/IRI in mammalian cardiac cells. Fisetin enhances viability of rat cardiomyocytes following hypoxia/starvation – reoxygenation. It inhibits apoptosis, decreases ROS generation and caspase activation and protects from DNA damage. Interestingly, fisetin also activates genes involved in cell proliferation. Fisetin is thus a highly promising candidate drug with clinical potential to protect from ischemic damage following MI and to overcome IRI.
A simple and effective method to discern the true commercial Chinese cordyceps from counterfeits
Authors: Zhang Fu-Li , Yang Xiao-Feng , Wang Dong , Lei Shao-Rong , Guo Ling-An , Liu Wen-Juan , Song Jun
Published: February 2020

The Chinese cordyceps, a complex of the fungus Ophiocordyceps sinensis and its species-specific host insects, is also called “DongChongXiaCao” in Chinese. Habitat degradation in recent decades and excessive harvesting by humans has intensified its scarcity and increased the prices of natural populations. Some counterfeits are traded as natural Chinese cordyceps for profit, causing confusion in the marketplace. To promote the safe use of Chinese cordyceps and related products, a duplex PCR method for specifically identifying raw Chinese cordyceps and its primary products was successfully established. Chinese cordyceps could be precisely identified by detecting an internal transcribed spacer amplicon from O. sinensis and a cytochrome oxidase c subunit 1 amplicon from the host species, at a limit of detection as low as 32 pg. Eleven commercial samples were purchased and successfully tested to further verify that the developed duplex PCR method could be reliably used to identify Chinese cordyceps. It provides a new simple way to discern true commercial Chinese cordyceps from counterfeits in the marketplace. This is an important step toward achieving an authentication method for this Chinese medicine. The methodology and the developmental strategy can be used to authenticate other traditional Chinese medicinal materials.
Egocentric Temporal Order Bias Robust Across Manipulations of Cue Predictability and Sensory Modality
Authors: Tang Ty Y. , McBeath Michael K.
Published: February 2020

The Egocentric Temporal Order (ETO) bias is the finding that self-initiated action-events are perceived as having occurred prior to simultaneous externally triggered events. Here, we test if the ETO bias is affected by predictability of the stimulus cue used to initiate a self-action or by the sensory modality of that cue. Without separating out the potential influence of the stimulus cue on the ETO bias, further investigations into the mechanisms underlying the bias are difficult to interpret. Our findings robustly confirm and replicate the ETO bias, providing evidence that the bias is not an artifact of the experimental design, but rather indicates a true temporal bias in the perception of self-initiated action-events.
Association between Lower Extremity Skeletal Muscle Mass and Impaired Cognitive Function in Type 2 Diabetes
Authors: Low Serena , Ng Tze Pin , Lim Chin Leong , Moh Angela , Ang Su Fen , Wang Jiexun , Goh Kiat Sern , Ang Keven , Tang Wern Ee , Kwan Pek Yee , Subramaniam Tavintharan , Sum Chee Fang , Lim Su Chi
Published: February 2020

Lower extremity skeletal muscle mass (LESM) in Type 2 Diabetes (T2D) has been linked to adverse clinical events, but it is not known whether it is associated with cognitive difficulties. We conducted a cross-sectional study on 1,235 people (mean age 61.4 ± 8.0 years) with T2D under primary and secondary care in Singapore. Bioelectrical impedance analyses (BIA) measures of upper extremity skeletal muscle mass (UESM), LESM and appendicular skeletal muscle index (SMI) were related to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measures of cognition, in multiple linear regression. In multivariable models, tertile 1 LESM (b = −2.62 (−3.92 to −1.32)) and tertile 2 LESM (b = −1.73 (−2.73 to −0.73)), referenced to tertile 3) were significantly associated with decreased RBANS total score. Significant associations of LESM with cognitive domain performances were observed for tertile 1 (b = −3.75 (−5.98 to −1.52)) and tertile 2 (b = −1.98 (−3.69 to −0.27)) with immediate memory, and for tertile 1 (b = −3.05 (−4.86 to −1.24)) and tertile 2 (b = −1.87 (−3.25 to −0.48)) with delayed memory, and for tertile 1 (b = −2.99 (−5.30 to −0.68)) with visuospatial/constructional ability. Tertile 1 SMI (b = −1.94 (−3.79 to −0.08) and tertile 2 SMI (b = −1.75 (−3.14 to −0.37)) were also associated with delayed memory. There were no associations between UESM with cognitive performance. Lower LESM may be a useful marker of possible co-occuring cognitive dysfunction.
Three-dimensional radiomics of triple-negative breast cancer: Prediction of systemic recurrence
Authors: Koh Jieun , Lee Eunjung , Han Kyunghwa , Kim Sujeong , Kim Dong-kyu , Kwak Jin Young , Yoon Jung Hyun , Moon Hee Jung
Published: February 2020

This paper evaluated 3-dimensional radiomics features of breast magnetic resonance imaging (MRI) as prognostic factors for predicting systemic recurrence in triple-negative breast cancer (TNBC) and validated the results with a different MRI scanner. The Rad score was generated from 3-dimensional radiomic features of MRI for 231 TNBCs (training set (GE scanner), n = 182; validation set (Philips scanner), n = 49). The Clinical and Rad models to predict systemic recurrence were built up and the models were externally validated. In the training set, the Rad score was significantly higher in the group with systemic recurrence (median, −8.430) than the group without (median, −9.873, P < 0.001). The C-index of the Rad model to predict systemic recurrence in the training set was 0.97, which was significantly higher than in the Clinical model (0.879; P = 0.009). When the models were externally validated, the C-index of the Rad model was 0.848, lower than the 0.939 of the Clinical model, although the difference was not statistically significant (P = 0.100). The Rad model for predicting systemic recurrence in TNBC showed a significantly higher C-index than the Clinical model. However, external validation with a different MRI scanner did not show the Rad model to be superior over the Clinical model.
Some Gammaproteobacteria are enriched within CD14+ macrophages from intestinal lamina propria of Crohn’s disease patients versus mucus
Authors: Sekido Yuki , Nishimura Junichi , Nakano Kazuhiro , Osu Takeaki , Chow Cheryl-Emiliane T. , Matsuno Hiroshi , Ogino Takayuki , Fujino Shiki , Miyoshi Norikatsu , Takahashi Hidekazu , Uemura Mamoru , Matsuda Chu , Kayama Hisako , Mori Masaki , Doki Yuichiro , Takeda Kiyoshi , Uchino Motoi , Ikeuchi Hiroki , Mizushima Tsunekazu
Published: February 2020

Crohn’s disease causes chronic inflammation in the gastrointestinal tract and its pathogenesis remains unclear. In the intestine of Crohn’s disease patients, CD14+CD11+CD163low macrophages contribute to inflammation through the induction of Th17 cells and production of inflammatory cytokines; the CD14+CD11c+163high fraction is anti-inflammatory through the production of IL-10 in normal cases. In this report, the 16S rRNA gene amplicon sequencing method was used to identify bacteria that are specifically present in intestinal CD14+CD11c+ macrophages of Crohn’s disease patients. Bacteria present in intestinal CD14+CD11c+ macrophages and mucus of Crohn’s disease patients were separated into different clusters in principal coordinates analysis. There was a statistically significant increase in the relative composition of CD14+CD11c+ macrophages from mucus in two phyla (Proteobacteria [p = 0.01] and Actinobacteria [p = 0.02]) and two families (Moraxellaceae [p < 0.001] and Pseudomonadaceae [p = 0.01]). In addition, OTU-1: Acinetobacter and OTU-8: Pseudomonadaceae tended to concentrate in the CD14+CD11c+CD163low subset, whereas OTU-10: Proteus, OTU-15: Collinsella tended to concentrate more in the CD14+CD11c+CD163high subset than the other subset and mucus.
Abundance of mobile genetic elements in an Acinetobacter lwoffii strain isolated from Transylvanian honey sample
Authors: Veress Alexandra , Nagy Tibor , Wilk Tímea , Kömüves János , Olasz Ferenc , Kiss János
Published: February 2020

Based on phylogenetic analyses, strain M2a isolated from honey, an unexpected source of acinetobacters, was classified as Acinetobacter lwoffii. The genome of this strain is strikingly crowded with mobile genetic elements. It harbours more than 250 IS elements of 15 IS-families, several unit and compound transposons and 15 different plasmids. These IS elements, including 30 newly identified ones, could be classified into at least 53 IS species. Regarding the plasmids, 13 of the 15 belong to the Rep-3 superfamily and only one plasmid, belonging to the “Low-GC” family, possesses a seemingly complete conjugative system. The other plasmids, with one exception, have a mobilization region of common pattern, consisting of the divergent mobA/mobL-family and mobS-, mobC- or traD-like genes separated by an oriT-like sequence. Although two plasmids of M2a are almost identical to those of A. lwoffi strains isolated from gold mine or Pleistocene sediments, most of them have no close relatives. The presence of numerous plasmid-borne and chromosomal metal resistance determinants suggests that M2a previously has also evolved in a metal-polluted environment. The numerous, possibly transferable, plasmids and the outstanding number of transposable elements may reflect the high potential of M2a for rapid evolution.
Regional Comparison of Goblet Cell Number and Area in Exposed and Covered Dry Eyes and Their Correlation with Tear MUC5AC
Authors: Khimani Karima S. , Go Jonathan A. , De Souza Rodrigo Guimaraes , Mitchell Travis , Yu Zhiyuan , de Paiva Cintia S. , Saumur Meghan , Pflugfelder Stephen C.
Published: February 2020

To compare goblet cell (GC) number and area in the covered superior (SB) versus exposed temporal (TB) bulbar conjunctiva in control versus aqueous tear deficient eyes (ATD) and evaluate correlation with tear MUC5AC protein. SB and TB impression cytology performed on control eyes, Sjögren syndrome (SS) ATD, and non-SS ATD was stained with period acid Schiff. GC number and area were measured with image analysis software. Protein-normalized MUC5AC level was measured in Schirmer strip-collected tears. Compared to control conjunctiva, GC number and area were significantly lower in SS, non-SS, and combined ATD groups in exposed TB, and were also significantly lower in SS and combined ATD groups in covered SB. In all ATD, GC number and area were significantly correlated, but differences between SB and TB were non-significant. Normalized tear MUC5AC protein was lower in all ATD groups versus control eyes, and correlated only with GC area. GCs are significantly decreased in the covered and exposed conjunctiva in SS. GC area may be a better disease measure than number for ATD. Correlation between tear MUC5AC concentration and GC area suggests tear MUC5AC mucin can be used as a disease-relevant biomarker for conjunctiva GC health.
Investigation and Feasibility of Combined 3D Printed Thermoplastic Filament and Polymeric Foam to Simulate the Cortiocancellous Interface of Human Vertebrae
Authors: Clifton William , Pichelmann Mark , Vlasak Alexander , Damon Aaron , ReFaey Karim , Nottmeier Eric
Published: February 2020

Disorders of the spine are among the most common indications for neurosurgical and orthopedic surgical interventions. Spinal fixation in the form of pedicle screw placement is a common form of instrumentation method in the lower cervical, thoracic, and lumbar spine. A vital principle to understand for the safe and accurate placement of pedicle screws is the palpable difference between the cortical and cancellous bone, both of which have different material properties and compositions. Probing and palpation of the hard cortical bone, also known as the “ventral lamina”, covering the neural elements of the spinal canal during screw placement provides manual feedback to the surgeon, indicating an impending breach if continued directional force is applied. Generally, this practice is learned at the expense of patients in live operating room scenarios. Currently, there is a paucity of human vertebra simulation designs that have been validated based on the in vivo ultrastructure and physical properties of human cortical and cancellous bone. In this study, we examined the feasibility of combining three-dimensionally printed thermoplastic polymers with polymeric foam to replicate both the vertebral corticocancellous interface and surface anatomy for procedural education.
Effective removal of anionic textile dyes using adsorbent synthesized from coffee waste
Authors: Wong Syieluing , Ghafar Nawal Abd , Ngadi Norzita , Razmi Fatin Amirah , Inuwa Ibrahim Mohammed , Mat Ramli , Amin Nor Aishah Saidina
Published: February 2020

Adsorption of Reactive Black 5 and Congo Red from aqueous solution by coffee waste modified with polyethylenimine was investigated. The removal percentages of both dyes increased with amount of polyethyleneimine in the modified adsorbent. Characterization revealed that polyethyleneimine modification improved the adsorbent surface chemistry, while slight improvement of adsorbent textural properties was also observed. The adsorbent’s excellent performance was demonstrated by high removal percentages towards the anionic dyes in most experimental runs. The modelling result showed that anionic dyes adsorption occurred via monolayer adsorption, and chemisorption was the rate-controlling step. The adsorbent possesses higher maximum adsorption capacity towards Reactive Black 5 (77.52 mg/g) than Congo Red (34.36 mg/g), due to the higher number of functional groups in Reactive Black 5 that interact with the adsorbent. This study reveals the potential of adsorbent derived from coffee waste in textile wastewater treatment. Furthermore, surface chemistry modification is proven as an effective strategy to enhance the performance of biowaste-derived adsorbents.
The orbitofrontal cortex functionally links obesity and white matter hyperintensities
Authors: Park Bo-yong , Byeon Kyoungseob , Lee Mi Ji , Kim Se-Hong , Park Hyunjin
Published: February 2020

Many studies have linked dysfunction in cognitive control-related brain regions with obesity and the burden of white matter hyperintensities (WMHs). This study aimed to explore how functional connectivity differences in the brain are associated with WMH burden and degree of obesity using resting-state functional magnetic resonance imaging (fMRI) in 182 participants. Functional connectivity measures were compared among four different groups: (1) low WMH burden, non-obese; (2) low WMH burden, obese; (3) high WMH burden, non-obese; and (4) high WMH burden, obese. At a large-scale network-level, no networks showed significant interaction effects, but the frontoparietal network showed a main effect of degree of obesity. At a finer node level, the orbitofrontal cortex showed interaction effects between periventricular WMH burden and degree of obesity. Higher functional connectivity was observed when the periventricular WMH burden and degree of obesity were both high. These results indicate that the functional connectivity of the orbitofrontal cortex is affected by the mutual interaction between the periventricular WMHs and degree of obesity. Our results suggest that this region links obesity with WMHs in terms of functional connectivity.
Author Correction: Thermally and field-driven mobility of emergent magnetic charges in square artificial spin ice
Authors: Morley Sophie A. , Porro Jose Maria , Hrabec Aleš , Rosamond Mark C. , Venero Diego Alba , Linfield Edmund H. , Burnell Gavin , Im Mi-Young , Fischer Peter , Langridge Sean , Marrows Christopher H.
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Visualization and quantification of the degenerative pattern of the talus in unilateral varus ankle osteoarthritis
Authors: Seki Hiroyuki , Ogihara Naomichi , Kokubo Tetsuro , Suda Yasunori , Ishii Ken , Nagura Takeo
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A biodegradable CO2-based polymeric antitumor nanodrugviaa one-pot surfactant- and solvent-free miniemulsion preparation
Authors: Luo Qiaojie , Li Xiaojun , Wang Ying , He Jianfang , Zhang Qiao , Ge Pengfei , Cai Xia , Sun Qiang , Zhu Weipu , Shen Zhiquan , Li Xiaodong
Published: February 2020

A biodegradable CO2-based polymeric nanodrug is obtainedviaa surfactant- and solvent-free miniemulsion preparation, which can be concentrated at tumor site by EPR and releases the encapsulated drug through pH responsiveness.
Alkali metal reduction of 1,3,2-diazaborol and 1,3,2-diazagermol derivatives based on 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene
Authors: Lukina Daria A. , Skatova Alexandra A. , Lukoyanov Anton N. , Kozlova Ekaterina A. , Fedushkin Igor L.
Published: February 2020

The reduction of borol (5) and germol (7) derivatives with sodium in thf proceeds with a transfer of two electrons and one proton to dpp-bian ligand and results in the formation of the products 6 and 8, which consist of the diamagnetic mono-anionic ligand.
Synthesis, characterization, catalytic and biological application of half-sandwich ruthenium complexes bearing hemilabile (κ2-C,S)-thioether-functionalised NHC ligands
Authors: Chen Weiguang , Egly Julien , Poblador-Bahamonde Amalia I. , Maisse-Francois Aline , Bellemin-Laponnaz Stéphane , Achard Thierry
Published: February 2020

A series of cationic Ru(ii)(η6-p-cymene) complexes with thioether-functionalised N-heterocyclic carbene ligands have been prepared and fully characterized.