bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Gasping be Used as a Tool to Determine Whether to Perform Compression-Only CPR versus Conventional CPR?
Authors: Rottenberg Eric M.
Published: February 2018

RottenbergEM. Can gasping be used as a tool to determine whether to perform compression-only CPR versus conventional CPR?Prehosp Disaster Med. 2018;33(2):225–226.
Ultra-processed food product brands on Facebook pages: highly accessed by Brazilians through their marketing techniques
Authors: Horta Paula M , Rodrigues Fernanda T , dos Santos Luana C
Published: February 2018

Objective

To analyse the content and extent of marketing of ultra-processed food products (UPP) and their brand pages on Facebook, which are highly accessed by Brazilians.

Design

Descriptive.

Setting

Sixteen UPP brand pages on Facebook were selected from 250 pages that were the most liked by Brazilians in October 2015.

Subjects

We analysed the frequency of ‘likes’ and members ‘talking about’ each one of the pages, in addition to fifteen marketing techniques used in the previous year (September 2014 to October 2015). The number of posts, likes, ‘shares’ and ‘commentaries’, and the mean number of likes, shares and commentaries per post, were collected for one month, from 23 September to 23 October 2015.

Results

The two most liked pages were: Coke® (93 673 979 likes) and McDonald’s® (59 749 819 likes). Regarding the number of people talking about the pages, McDonald’s led with 555 891 commentaries, followed by Coke (287 274), Burger King® (246 148) and Kibon® (244 523). All pages used marketing techniques, which included photos, user conversations, presence of brand elements and links. Videos were observed on 93·8 % of the pages; promotions on 68·8 %; and celebrities on 62·5 %. In one month, Garoto®, Outback® and Coke were brands that published more than one post per day. Kibon achieved the highest ratio of likes per post (285 845·50) and Burger King had the highest mean shares per post (10 083·93), including commentaries per post (7958·13).

Conclusions

UPP marketing is extensively used on Facebook pages and is highly accessed by Brazilians, with UPP companies employing a diversity of marketing strategies.
Surface mineral crusts: a potential strategy for sampling for evidence of life on Mars
Authors: Brolly Connor , Parnell John , Bowden Stephen
Published: February 2018

Surface mineral crusts on Earth are highly diverse and usually, contain microbial life. Crusts constitute an attractive target to search for life: they require water for their formation, they efficiently entrap organic matter and are relatively easy to sample and process. They hold a record of life in the form of microbial remains, biomolecules and carbon isotope composition. A miniaturized Raman spectrometer is included in the ExoMars 2020 payload as it is sensitive to a range of photosynthetic pigments. Samples from the Haughton Impact Structure, Canadian High Arctic and others, shows the preservation of pigments in a range of crust types, especially supra-permafrost carbonate crusts and cryptogamic crusts. The Raman spectral signatures of these crusts are shown along with biomarker analysis to showcase these techniques prior to the ExoMars 2020 mission. Carotenoids and other photoprotective microbial pigments are identified in the Haughton surface crusts using Raman spectroscopy. Gas chromatography-mass spectrometry analyses show a distribution of fatty acids which are most likely from a cyanobacterial source. The successful demonstration of these analyses in the Haughton Impact structure shows the biosignature of surface mineral crusts can be easily extracted and provides an excellent target for sampling evidence of life on Mars.
RANK TWO TOPOLOGICAL AND INFINITESIMAL EMBEDDED JUMP LOCI OF QUASI-PROJECTIVE MANIFOLDS
Authors: Papadima Stefan , Suciu Alexander I.
Published: February 2018

We study the germs at the origin of $G$-representation varieties and the degree 1 cohomology jump loci of fundamental groups of quasi-projective manifolds. Using the Morgan–Dupont model associated to a convenient compactification of such a manifold, we relate these germs to those of their infinitesimal counterparts, defined in terms of flat connections on those models. When the linear algebraic group $G$ is either $\text{SL}_{2}(\mathbb{C})$ or its standard Borel subgroup and the depth of the jump locus is 1, this dictionary works perfectly, allowing us to describe in this way explicit irreducible decompositions for the germs of these embedded jump loci. On the other hand, if either $G=\text{SL}_{n}(\mathbb{C})$ for some $n\geqslant 3$, or the depth is greater than 1, then certain natural inclusions of germs are strict.
Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation
Authors: Grasselli Chiara , Ferrari Daniela , Zalfa Cristina , Soncini Matias , Mazzoccoli Gianluigi , Facchini Fabio A. , Marongiu Laura , Granucci Francesca , Copetti Massimiliano , Vescovi Angelo Luigi , Peri Francesco , De Filippis Lidia
Published: February 2018

Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation. Activation of TLR4 signaling by lipopolysaccharide (LPS) has a positive effect on proliferation and/or survival while the inverse is observed with TLR4 inhibition by a synthetic antagonist. TLR4 activation promotes neuronal and oligodendrocyte differentiation and/or survival while TLR4 inhibition leads to increased apoptosis. Consistently, endogenous expression of TLR4 is retained by hNSC surviving after transplantation in ALS rats or immunocompromised mice, thus irrespectively of the neuroinflammatory environment. The characterization of downstream signaling of TLR4 in hNSCs has suggested some activation of the inflammasome pathway. This study suggests TLR4 signaling as essential for hNSC self-renewal and as a novel target for the study of neurogenetic mechanisms.
G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner
Authors: Hu Lei , Zang Ming-de , Wang He-xiao , Zhang Bao-gui , Wang Zhen-qiang , Fan Zhi-yuan , Wu Huo , Li Jian-fang , Su Li-ping , Yan Min , Zhu Zhi-qiang , Yang Qiu-meng , Huang Qiang , Liu Bing-ya , Zhu Zheng-gang
Published: February 2018

Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and metastasis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.
Cinacalcet-mediated activation of the CaMKKβ-LKB1-AMPK pathway attenuates diabetic nephropathy in db/db mice by modulation of apoptosis and autophagy
Authors: Lim Ji Hee , Kim Hyung Wook , Kim Min Young , Kim Tae Woo , Kim Eun Nim , Kim Yaeni , Chung Sungjin , Kim Young Soo , Choi Bum Soon , Kim Yong-Soo , Chang Yoon Sik , Kim Hye Won , Park Cheol Whee
Published: February 2018

Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca2+ concentration and the phosphorylation of Ca2+/calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression. Interestingly, intracellular chelator BAPTA-AM reversed cinacalcet-induced CaMKKβ elevation and LKB1 phosphorylation. Cinacalcet reduced albuminuria without influencing either blood glucose or Ca2+ concentration and ameliorated diabetes-induced renal damage, which were related to the increased expression of calcium-sensing receptor and the phosphorylation of CaMKKβ-LKB1. Subsequent activation of AMPK was followed by the activation of peroxisome proliferator-activated receptor γ coactivator-1α and phospho-Ser1177eNOS-nitric oxide, resulting in a decrease in apoptosis and oxidative stress as well as an increase in autophagy.

Our results suggest that cinacalcet increases intracellular Ca2+ followed by an activation of CaMKKβ-LKB1-AMPK signaling in GECs and podocytes in the kidney, which provides a novel therapeutic means for type 2 diabetic nephropathy by modulation of apoptosis and autophagy.
Hemopexin is required for adult neurogenesis in the subventricular zone/olfactory bulb pathway
Authors: Zhu Yanling , Qiu Yang , Chen Mengjia , Zhang Yi , Cao Li , Su Zhida , Yuan Yimin , Huang Aijun , Pu Yinyan , He Cheng
Published: February 2018

The neural stem cells (NSCs) of the subventricular zone (SVZ) reside within a specialized niche critical for neurogenesis. Hemopexin, a plasma glycoprotein, has been extensively studied as a heme scavenger at the systemic level. However, little is known about its function in the central nervous system, especially in neurogenesis. In the present study, we demonstrate that deletion of hemopexin leads to neurogenic abnormalities in the SVZ/olfactory bulb (OB) pathway. The lateral ventricle is enlarged in hemopexin-deficient mice, and more apoptosis was observed in Dcx+ cells. Lineage differentiation of NSCs was also inhibited in the SVZ of hemopexin-deficient mice, with more stem cells stayed in an undifferentiated, GFAP+ radial glia-like cell stage. Moreover, hemopexin deletion resulted in impaired neuroblast migration in the rostral migratory stream. Furthermore, exogenous hemopexin protein inhibited apoptosis and promoted the migration and differentiation of cultured NSCs. Finally, immunohistochemical analysis demonstrated that deletion of hemopexin reduced the number of interneurons in the OB. Together, these results suggest a new molecular mechanism for the NSC niche that regulates adult neurogenesis in the SVZ/OB pathway. Our findings may benefit the understanding for olfactory system development.
Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division
Authors: Shan Zelin , Tu Yuting , Yang Ying , Liu Ziheng , Zeng Menglong , Xu Huisha , Long Jiafu , Zhang Mingjie , Cai Yu , Wen Wenyu
Published: February 2018

Uneven distribution and local concentration of protein complexes on distinct membrane cortices is a fundamental property in numerous biological processes, including Drosophila neuroblast (NB) asymmetric cell divisions and cell polarity in general. In NBs, the cell fate determinant Numb forms a basal crescent together with Pon and is segregated into the basal daughter cell to initiate its differentiation. Here we discover that Numb PTB domain, using two distinct binding surfaces, recognizes repeating motifs within Pon in a previously unrecognized mode. The multivalent Numb-Pon interaction leads to high binding specificity and liquid-liquid phase separation of the complex. Perturbations of the Numb/Pon complex phase transition impair the basal localization of Numb and its subsequent suppression of Notch signaling during NB asymmetric divisions. Such phase-transition-mediated protein condensations on distinct membrane cortices may be a general mechanism for various cell polarity regulatory complexes.
Human Semaphorin-4A drives Th2 responses by binding to receptor ILT-4
Authors: Lu Ning , Li Ying , Zhang Zhiqiang , Xing Junji , Sun Ying , Yao Sheng , Chen Lieping
Published: February 2018

Semaphorin-4A (Sema4A) has been implicated in the co-stimulation of T cells and drives Th1 immune responses by binding to the receptor T-cell immunoglobulin and mucin domain protein 2 (Tim-2) in mice. Here we show that human, but not murine, Sema4A is preferentially expressed on antigen-presenting cells, and co-stimulates CD4+T-cell proliferation and drives Th2 responses. By employing two independent cloning strategies, we demonstrate that Immunoglobulin-like transcript 4 (ILT-4) is a receptor for human SEMA4A (hSEMA4A) on activated CD4+T cells. We also find hSEMA4A to be highly expressed in human asthmatic lung tissue, implying its potential function in disease pathogenesis. Our study defines a different biological function of hSEMA4A from its murine homolog through its binding to the receptor of ILT-4 to co-stimulate CD4+T cells and regulate Th2 cells differentiation.
Searching for an exotic spin-dependent interaction with a single electron-spin quantum sensor
Authors: Rong Xing , Wang Mengqi , Geng Jianpei , Qin Xi , Guo Maosen , Jiao Man , Xie Yijin , Wang Pengfei , Huang Pu , Shi Fazhan , Cai Yi-Fu , Zou Chongwen , Du Jiangfeng
Published: February 2018

Searching for new particles beyond the standard model is crucial for understanding several fundamental conundrums in physics and astrophysics. Several hypothetical particles can mediate exotic spin-dependent interactions between ordinary fermions, which enable laboratory searches via the detection of the interactions. Most laboratory searches utilize a macroscopic source and detector, thus allowing the detection of interactions with submillimeter force range and above. It remains a challenge to detect the interactions at shorter force ranges. Here we propose and demonstrate that a near-surface nitrogen-vacancy center in diamond can be utilized as a quantum sensor to detect the monopole–dipole interaction between an electron spin and nucleons. Our result sets a constraint for the electron–nucleon coupling, $$g_{{\mathrm{s}}}^{\mathrm{N}}g_{\mathrm{p}}^{\mathrm{e}}$$

g

s

N

g

p

e

, with the force range 0.1–23 μm. The obtained upper bound of the coupling at 20 μm is $$g_{{\mathrm{s}}}^{\mathrm{N}}g_{\mathrm{p}}^{\mathrm{e}}$$

g

s

N

g

p

e

 < 6.24 × 10−15.
Microsecond dark-exciton valley polarization memory in two-dimensional heterostructures
Authors: Jiang Chongyun , Xu Weigao , Rasmita Abdullah , Huang Zumeng , Li Ke , Xiong Qihua , Gao Wei-bo
Published: February 2018

Transition metal dichalcogenides have valley degree of freedom, which features optical selection rule and spin-valley locking, making them promising for valleytronics devices and quantum computation. For either application, a long valley polarization lifetime is crucial. Previous results showed that it is around picosecond in monolayer excitons, nanosecond for local excitons and tens of nanosecond for interlayer excitons. Here we show that the dark excitons in two-dimensional heterostructures provide a microsecond valley polarization memory thanks to the magnetic field induced suppression of valley mixing. The lifetime of the dark excitons shows magnetic field and temperature dependence. The long lifetime and valley polarization lifetime of the dark exciton in two-dimensional heterostructures make them promising for long-distance exciton transport and macroscopic quantum state generations.
Effector CD4+ T cells recognize intravascular antigen presented by patrolling monocytes
Authors: Westhorpe Clare L. V. , Norman M. Ursula , Hall Pam , Snelgrove Sarah L. , Finsterbusch Michaela , Li Anqi , Lo Camden , Tan Zhe Hao , Li Songhui , Nilsson Susan K. , Kitching A. Richard , Hickey Michael J.
Published: February 2018

Although effector CD4+ T cells readily respond to antigen outside the vasculature, how they respond to intravascular antigens is unknown. Here we show the process of intravascular antigen recognition using intravital multiphoton microscopy of glomeruli. CD4+ T cells undergo intravascular migration within uninflamed glomeruli. Similarly, while MHCII is not expressed by intrinsic glomerular cells, intravascular MHCII-expressing immune cells patrol glomerular capillaries, interacting with CD4+ T cells. Following intravascular deposition of antigen in glomeruli, effector CD4+ T-cell responses, including NFAT1 nuclear translocation and decreased migration, are consistent with antigen recognition. Of the MHCII+ immune cells adherent in glomerular capillaries, only monocytes are retained for prolonged durations. These cells can also induce T-cell proliferation in vitro. Moreover, monocyte depletion reduces CD4+ T-cell-dependent glomerular inflammation. These findings indicate that MHCII+ monocytes patrolling the glomerular microvasculature can present intravascular antigen to CD4+ T cells within glomerular capillaries, leading to antigen-dependent inflammation.
Long-distance propagation of short-wavelength spin waves
Authors: Liu Chuanpu , Chen Jilei , Liu Tao , Heimbach Florian , Yu Haiming , Xiao Yang , Hu Junfeng , Liu Mengchao , Chang Houchen , Stueckler Tobias , Tu Sa , Zhang Youguang , Zhang Yan , Gao Peng , Liao Zhimin , Yu Dapeng , Xia Ke , Lei Na , Zhao Weisheng , Wu Mingzhong
Published: February 2018

Recent years have witnessed a rapidly growing interest in exploring the use of spin waves for information transmission and computation toward establishing a spin-wave-based technology that is not only significantly more energy efficient than the CMOS technology, but may also cause a major departure from the von-Neumann architecture by enabling memory-in-logic and logic-in-memory architectures. A major bottleneck of advancing this technology is the excitation of spin waves with short wavelengths, which is a must because the wavelength dictates device scalability. Here, we report the discovery of an approach for the excitation of nm-wavelength spin waves. The demonstration uses ferromagnetic nanowires grown on a 20-nm-thick Y3Fe5O12 film strip. The propagation of spin waves with a wavelength down to 50 nm over a distance of 60,000 nm is measured. The measurements yield a spin-wave group velocity as high as 2600 m s−1, which is faster than both domain wall and skyrmion motions.
Trace metals from historical mining sites and past metallurgical activity remain bioavailable to wildlife today
Authors: Camizuli Estelle , Scheifler Renaud , Garnier Stéphane , Monna Fabrice , Losno Rémi , Gourault Claude , Hamm Gilles , Lachiche Caroline , Delivet Guillaume , Chateau Carmela , Alibert Paul
Published: February 2018

Throughout history, ancient human societies exploited mineral resources all over the world, even in areas that are now protected and considered to be relatively pristine. Here, we show that past mining still has an impact on wildlife in some French protected areas. We measured cadmium, copper, lead, and zinc concentrations in topsoils and wood mouse kidneys from sites located in the Cévennes and the Morvan. The maximum levels of metals in these topsoils are one or two orders of magnitude greater than their commonly reported mean values in European topsoils. The transfer to biota was effective, as the lead concentration (and to a lesser extent, cadmium) in wood mouse kidneys increased with soil concentration, unlike copper and zinc, providing direct evidence that lead emitted in the environment several centuries ago is still bioavailable to free-ranging mammals. The negative correlation between kidney lead concentration and animal body condition suggests that historical mining activity may continue to play a role in the complex relationships between trace metal pollution and body indices. Ancient mining sites could therefore be used to assess the long-term fate of trace metals in soils and the subsequent risks to human health and the environment.
Spatial geometry of stem cell proliferation in the adult hippocampus
Authors: Mineyeva Olga A. , Enikolopov Grigori , Koulakov Alexei A.
Published: February 2018

The modes of stem cell divisions (e.g., symmetric vs. asymmetric) can have a profound impact on the number of progeny and tissue growth, repair, and function. This is particularly relevant for adult neural stem cells, since stem cell-derived neurons affect cognitive and mental states, resistance to stress and disease, and response to therapies. Here we show that although dividing stem cells in the adult hippocampus display a certain bias towards paired distribution (which could imply the prevalence of symmetric divisions), this bias already exists in the distribution of the general population of stem cells and may be responsible for the perceived occurrence of symmetric stem cell divisions. Remarkably, the bias in the distribution of stem cells decreases with age. Our results argue that the preexisting bias in stem cell distribution may affect current assumptions regarding stem cell division and fate as well as conjectures on the prospects of brain repair and rejuvenation.
Distinguishing Human Peripheral Blood NK Cells from CD56dimCD16dimCD69+CD103+ Resident Nasal Mucosal Lavage Fluid Cells
Authors: Rebuli Meghan E. , Pawlak Erica A. , Walsh Dana , Martin Elizabeth M. , Jaspers Ilona
Published: February 2018

Natural killer (NK) cells are members of the innate lymphoid cells group 1 (ILC1s), which play a critical role in innate host defense against viruses and malignancies. While many studies have examined the role of circulating peripheral blood (PB) CD56+NK cells, little is known about the resident CD56+cell population. Therefore, matched CD56+cells from nasal lavage fluid (NLF) and PB of smokers and non-smokers were compared phenotypically, via flow cytometry, and functionally, via NK-cell specific gene expression. NLF and PB CD56+cells had similar expression of CD56, but differentially expressed tissue residency (CD69 and CD103) and cytotoxicity (CD16) markers. In addition, NLF CD56dimcells expressed lower levels of cytotoxicity-associated genes, perforin (PRF1) and granzyme B (GZMB), and increased levels of cytokines and cell signaling molecules,TRAIL,IFNGR2, andIL8, as compared to PB CD56dimcells. In smokers,ITGA2was downregulated in NLF CD56dimcells, while markers of cytotoxic function were primarily downregulated in PB CD56dimNK cells. Overall, NLF CD56dimcells are a unique cell population that likely play a role in orchestrating innate immune responses in the nasal cavity, which is distinct from their role as a non-antigen-restricted cytotoxic CD56dimlymphocytes in the PB.
Tunable Mechanical Metamaterials through Hybrid Kirigami Structures
Authors: Hwang Doh-Gyu , Bartlett Michael D.
Published: February 2018

Inspired by the art of paper cutting, kirigami provides intriguing tools to create materials with unconventional mechanical and morphological responses. This behavior is appealing in multiple applications such as stretchable electronics and soft robotics and presents a tractable platform to study structure-property relationships in material systems. However, mechanical response is typically controlled through a single or fractal cut type patterned across an entire kirigami sheet, limiting deformation modes and tunability. Here we show how hybrid patterns of major and minor cuts creates new opportunities to introduce boundary conditions and non-prismatic beams to enable highly tunable mechanical responses. This hybrid approach reduces stiffness by a factor of ~30 while increasing ultimate strain by a factor of 2 (up to 750% strain) relative to single incision patterns. We present analytical models and generate general design criteria that is in excellent agreement with experimental data from nanoscopic to macroscopic systems. These hybrid kirigami materials create new opportunities for multifunctional materials and structures, which we demonstrate with stretchable kirigami conductors with nearly constant electrical resistance up to >400% strain and magnetoactive actuators with extremely rapid response (>10,000% strain s−1) and high, repeatable elongation (>300% strain).
Culture-free bacterial detection and identification from blood with rapid, phenotypic, antibiotic susceptibility testing
Authors: Shi Xuyang , Kadiyala Usha , VanEpps J. Scott , Yau Siu-Tung
Published: February 2018

The current culture-based approach for the diagnosis of bloodstreams infection is incommensurate with timely treatment and curbing the prevalence of multi-drug resistant organisms (MDROs) due to its long time-to-result. Bloodstream infections typically involve extremely low (e.g., <10 colony-forming unit (CFU)/mL) bacterial concentrations that require a labor-intensive process and as much as 72 hours to yield a diagnosis. Here, we demonstrate a culture-free approach to achieve rapid diagnosis of bloodstream infections. An immuno-detection platform with intrinsic signal current amplification was developed for the ultrasensitive, rapid detection, identification (ID) and antibiotic susceptibility testing (AST) of infections. With its capability of monitoring short-term (1–2 hours) bacterial growth in blood, the platform is able to provide 84-minute simultaneous detection and ID in blood samples below the 10 CFU/mL level and 204-minute AST. The susceptible-intermediate-resistant AST capacity was demonstrated.
The impact of computed high b-value images on the diagnostic accuracy of DWI for prostate cancer: A receiver operating characteristics analysis
Authors: Ning Peigang , Shi Dapeng , Sonn Geoffrey A. , Vasanawala Shreyas S. , Loening Andreas M. , Ghanouni Pejman , Obara Piotr , Shin Lewis K. , Fan Richard E. , Hargreaves Brian A. , Daniel Bruce L.
Published: February 2018

To evaluate the performance of computed high b value diffusion-weighted images (DWI) in prostate cancer detection. 97 consecutive patients who had undergone multiparametric MRI of the prostate followed by biopsy were reviewed. Five radiologists independently scored 138 lesions on native high b-value images (b = 1200 s/mm2), apparent diffusion coefficient (ADC) maps, and computed high b-value images (contrast equivalent to b = 2000 s/mm2) to compare their diagnostic accuracy. Receiver operating characteristic (ROC) analysis and McNemar’s test were performed to assess the relative performance of computed high b value DWI, native high b-value DWI and ADC maps. No significant difference existed in the area under the curve (AUC) for ROCs comparing B1200 (b = 1200 s/mm2) to computed B2000 (c-B2000) in 5 readers. In 4 of 5 readers c-B2000 had significantly increased sensitivity and/or decreased specificity compared to B1200 (McNemar’s p < 0.05), at selected thresholds of interpretation. ADC maps were less accurate than B1200 or c-B2000 for 2 of 5 readers (P < 0.05). This study detected no consistent improvement in overall diagnostic accuracy using c-B2000, compared with B1200 images. Readers detected more cancer with c-B2000 images (increased sensitivity) but also more false positive findings (decreased specificity).
Evaluation of Macaca radiata as a non-human primate model of Dengue virus infection
Authors: Kato Fumihiro , Ishida Yuki , Kawakami Akihiko , Takasaki Tomohiko , Saijo Masayuki , Miura Tomoyuki , Hishiki Takayuki
Published: February 2018

Dengue virus (DENV) causes a wide range of illnesses in humans, including dengue fever and dengue haemorrhagic fever. Current animal models of DENV infection are limited for understanding infectious diseases in humans. Bonnet monkeys (Macaca radiata), a type of Old World monkey, have been used to study experimental and natural infections by flaviviruses, but Old World monkeys have not yet been used as DENV infection models. In this study, the replication levels of several DENV strains were evaluated using peripheral blood mononuclear cells. Our findings indicated that DENV-4 09-48 strain, isolated from a traveller returning from India in 2009, was a highly replicative virus. Three bonnet monkeys were infected with 09-48 strain and antibody responses were assessed. DENV nonstructural protein 1 antigen was detected and high viraemia was observed. These results indicated that bonnet monkeys and 09-48 strain could be used as a reliable primate model for the study of DENV.
Early Detection of Preeclampsia Using Circulating Small non-coding RNA
Authors: Yoffe Liron , Gilam Avital , Yaron Orly , Polsky Avital , Farberov Luba , Syngelaki Argyro , Nicolaides Kypros , Hod Moshe , Shomron Noam
Published: February 2018

Preeclampsia is one of the most dangerous pregnancy complications, and the leading cause of maternal and perinatal mortality and morbidity. Although the clinical symptoms appear late, its origin is early, and hence detection is feasible already at the first trimester. In the current study, we investigated the abundance of circulating small non-coding RNAs in the plasma of pregnant women in their first trimester, seeking transcripts that best separate the preeclampsia samples from those of healthy pregnant women. To this end, we performed small non-coding RNAs sequencing of 75 preeclampsia and control samples, and identified 25 transcripts that were differentially expressed between preeclampsia and the control groups. Furthermore, we utilized those transcripts and created a pipeline for a supervised classification of preeclampsia. Our pipeline generates a logistic regression model using a 5-fold cross validation on numerous random partitions into training and blind test sets. Using this classification procedure, we achieved an average AUC value of 0.86. These findings suggest the predictive value of circulating small non-coding RNA in the first trimester, warranting further examination, and lay the foundation for producing a novel early non-invasive diagnostic tool for preeclampsia, which could reduce the life-threatening risk for both the mother and fetus.
Fabrication of transparent hemispherical 3D nanofibrous scaffolds with radially aligned patterns via a novel electrospinning method
Authors: Kim Jeong In , Kim Ju Yeon , Park Chan Hee
Published: February 2018

Tissue engineering has significantly contributed to the development of optimal treatments for individual injury sites based on their unique functional and histologic properties. Human organs and tissue have three-dimensional (3D) morphologies; for example, the morphology of the eye is a spherical shape. However, most conventional electrospinning equipment is only capable of fabricating a two-dimensional (2D) structured fibrous scaffold and no report is available on a 3D electrospinning method to fabricate a hemispherical scaffold to mimic the native properties of the cornea, including microscopic to macroscopic morphology and transparency. We proposed a novel electrospinning method using a single nonconductive hemispherical device and a metal pin. A designed peg-top shaped collector, a hemispherical nonconductive device with a metal pin in the center and copper wire forming a circle around at the edge was attached to a conventional conductive collector. A 3D hemispherical transparent scaffold with radially aligned nanofibers was successfully fabricated with the designed peg-top collector. In summary, our fabricated 3D electrospun scaffold is expected to be suitable for the treatment of injuries of ocular tissues owing to the hemispherical shape and radially aligned nanofibers which can guide the direction of the main collagen and cellular actin filament in the extracellular matrix.
Spin canting across core/shell Fe3O4/MnxFe3−xO4 nanoparticles
Authors: Oberdick Samuel D. , Abdelgawad Ahmed , Moya Carlos , Mesbahi-Vasey Samaneh , Kepaptsoglou Demie , Lazarov Vlado K. , Evans Richard F. L. , Meilak Daniel , Skoropata Elizabeth , van Lierop Johan , Hunt-Isaak Ian , Pan Hillary , Ijiri Yumi , Krycka Kathryn L. , Borchers Julie A. , Majetich Sara A.
Published: February 2018

Magnetic nanoparticles (MNPs) have become increasingly important in biomedical applications like magnetic imaging and hyperthermia based cancer treatment. Understanding their magnetic spin configurations is important for optimizing these applications. The measured magnetization of MNPs can be significantly lower than bulk counterparts, often due to canted spins. This has previously been presumed to be a surface effect, where reduced exchange allows spins closest to the nanoparticle surface to deviate locally from collinear structures. We demonstrate that intraparticle effects can induce spin canting throughout a MNP via the Dzyaloshinskii-Moriya interaction (DMI). We study ~7.4 nm diameter, core/shell Fe3O4/MnxFe3−xO4 MNPs with a 0.5 nm Mn-ferrite shell. Mössbauer spectroscopy, x-ray absorption spectroscopy and x-ray magnetic circular dichroism are used to determine chemical structure of core and shell. Polarized small angle neutron scattering shows parallel and perpendicular magnetic correlations, suggesting multiparticle coherent spin canting in an applied field. Atomistic simulations reveal the underlying mechanism of the observed spin canting. These show that strong DMI can lead to magnetic frustration within the shell and cause canting of the net particle moment. These results illuminate how core/shell nanoparticle systems can be engineered for spin canting across the whole of the particle, rather than solely at the surface.
Representations of naturalistic stimulus complexity in early and associative visual and auditory cortices
Authors: Güçlütürk Yağmur , Güçlü Umut , van Gerven Marcel , van Lier Rob
Published: February 2018

The complexity of sensory stimuli has an important role in perception and cognition. However, its neural representation is not well understood. Here, we characterize the representations of naturalistic visual and auditory stimulus complexity in early and associative visual and auditory cortices. This is realized by means of encoding and decoding analyses of two fMRI datasets in the visual and auditory modalities. Our results implicate most early and some associative sensory areas in representing the complexity of naturalistic sensory stimuli. For example, parahippocampal place area, which was previously shown to represent scene features, is shown to also represent scene complexity. Similarly, posterior regions of superior temporal gyrus and superior temporal sulcus, which were previously shown to represent syntactic (language) complexity, are shown to also represent music (auditory) complexity. Furthermore, our results suggest the existence of gradients in sensitivity to naturalistic sensory stimulus complexity in these areas.
Tubulation repair mitigates misdirection of regenerating motor axons across a sciatic nerve gap in rats
Authors: Liu Dan , Mi Daguo , Zhang Tuanjie , Zhang Yanping , Yan Junying , Wang Yaxian , Tan Xuefeng , Yuan Ying , Yang Yumin , Gu Xiaosong , Hu Wen
Published: February 2018

The repair of peripheral nerve laceration injury to obtain optimal function recovery remains a big challenge in the clinic. Misdirection of regenerating axons to inappropriate target, as a result of forced mismatch of endoneurial sheaths in the case of end-to-end nerve anastomosis or nerve autografting, represents one major drawback that limits nerve function recovery. Here we tested whether tubulation repair of a nerve defect could be beneficial in terms of nerve regeneration accuracy and nerve function. We employed sequential retrograde neuronal tracing to assess the accuracy of motor axon regeneration into the tibial nerve after sciatic nerve laceration and entubulation in adult Sprague-Dawley rats. In a separate cohort of rats with the same sciatic nerve injury/repair protocols, we evaluated nerve function recovery behaviorally and electrophysiologically. The results showed that tubulation repair of the lacerated sciatic nerve using a 3-6-mm-long bioabsorbable guidance conduit significantly reduced the misdirection of motor axons into the tibial nerve as compared to nerve autografting. In addition, tubulation repair ameliorated chronic flexion contracture. This study suggests that tubulation repair of a nerve laceration injury by utilizing a bioresorbable nerve guidance conduit represents a potential substitute for end-to-end epineurial suturing and nerve autografting.
Synthetic dimensions in ultracold polar molecules
Authors: Sundar Bhuvanesh , Gadway Bryce , Hazzard Kaden R. A.
Published: February 2018

Synthetic dimensions alter one of the most fundamental properties in nature, the dimension of space. They allow, for example, a real three-dimensional system to act as effectively four-dimensional. Driven by such possibilities, synthetic dimensions have been engineered in ongoing experiments with ultracold matter. We show that rotational states of ultracold molecules can be used as synthetic dimensions extending to many – potentially hundreds of – synthetic lattice sites. Microwaves coupling rotational states drive fully controllable synthetic inter-site tunnelings, enabling, for example, topological band structures. Interactions leads to even richer behavior: when molecules are frozen in a real space lattice with uniform synthetic tunnelings, dipole interactions cause the molecules to aggregate to a narrow strip in the synthetic direction beyond a critical interaction strength, resulting in a quantum string or a membrane, with an emergent condensate that lives on this string or membrane. All these phases can be detected using local measurements of rotational state populations.
Development of a model predicting non-satisfaction 1 year after primary total knee replacement in the UK and transportation to Switzerland
Authors: Garriga Cesar , Sanchez-Santos Maria T. , Judge Andrew , Perneger Thomas , Hannouche Didier , Lübbeke Anne , Arden Nigel K.
Published: February 2018

We aimed to develop a predictive model for non-satisfaction following primary total knee replacement (TKR) and to assess its transportability to another health care system. Data for model development were obtained from two UK tertiary hospitals. Model transportation data were collected from Geneva University Hospitals in Switzerland. Participants were individuals undergoing primary TKR with non-satisfaction with surgery after one year the outcome of interest. Multiple imputation and logistic regression modelling with bootstrap backward selection were used to identify predictors of outcome. Model performance was assessed by discrimination and calibration. 64 (14.2%) patients in the UK and 157 (19.9%) in Geneva were non-satisfied with their TKR. Predictors in the UK cohort were worse pre-operative pain and function, current smoking, treatment for anxiety and not having been treated with injected corticosteroids (corrected AUC = 0.65). Transportation to the Geneva cohort showed an AUC of 0.55. Importantly, two UK predictors (treated for anxiety, injected corticosteroids) were not predictive in Geneva. A better model fit was obtained when coefficients were re-estimated in the Geneva sample (AUC = 0.64). The model did not perform well when transported to a different country, but improved when it was re-estimated. This emphasises the need to re-validate the model for each setting/country.
Development and validation of a clinical prediction model for patient-reported pain and function after primary total knee replacement surgery
Authors: Sanchez-Santos M. T. , Garriga C. , Judge A. , Batra R. N. , Price A. J. , Liddle A. D. , Javaid M. K. , Cooper C. , Murray D. W. , Arden N. K.
Published: February 2018

To develop and validate a clinical prediction model of patient-reported pain and function after undergoing total knee replacement (TKR). We used data of 1,649 patients from the Knee Arthroplasty Trial who received primary TKR across 34 centres in the UK. The external validation included 595 patients from Southampton University Hospital, and Nuffield Orthopaedic Centre (Oxford). The outcome was the Oxford Knee Score (OKS) 12-month after TKR. Pre-operative predictors including patient characteristics and clinical factors were considered. Bootstrap backward linear regression analysis was used. Low pre-operative OKS, living in poor areas, high body mass index, and patient-reported anxiety or depression were associated with worse outcome. The clinical factors associated with worse outcome were worse pre-operative physical status, presence of other conditions affecting mobility and previous knee arthroscopy. Presence of fixed flexion deformity and an absent or damaged pre-operative anterior cruciate ligament (compared with intact) were associated with better outcome. Discrimination and calibration statistics were satisfactory. External validation predicted 21.1% of the variance of outcome. This is the first clinical prediction model for predicting self-reported pain and function 12 months after TKR to be externally validated. It will help to inform to patients regarding expectations of the outcome after knee replacement surgery.
Neuronal avalanche dynamics indicates different universality classes in neuronal cultures
Authors: Yaghoubi Mohammad , de Graaf Ty , Orlandi Javier G. , Girotto Fernando , Colicos Michael A. , Davidsen Jörn
Published: February 2018

Neuronal avalanches have become an ubiquitous tool to describe the activity of large neuronal assemblies. The emergence of scale-free statistics with well-defined exponents has led to the belief that the brain might operate near a critical point. Yet not much is known in terms of how the different exponents arise or how robust they are. Using calcium imaging recordings of dissociated neuronal cultures we show that the exponents are not universal, and that significantly different exponents arise with different culture preparations, leading to the existence of different universality classes. Naturally developing cultures show avalanche statistics consistent with those of a mean-field branching process, however, cultures grown in the presence of folic acid metabolites appear to be in a distinct universality class with significantly different critical exponents. Given the increased synaptic density and number of feedback loops in folate reared cultures, our results suggest that network topology plays a leading role in shaping the avalanche dynamics. We also show that for both types of cultures pronounced correlations exist in the sizes of neuronal avalanches indicating size clustering, being much stronger in folate reared cultures.
A Simple 3-Parameter Model for Cancer Incidences
Authors: Zhang Xiaoxiao , Fröhlich Holger , Grigoriev Dima , Vakulenko Sergey , Zimmermann Jörg , Weber Andreas Günter
Published: February 2018

We propose a simple 3-parameter model that provides very good fits for incidence curves of 18 common solid cancers even when variations due to different locations, races, or periods are taken into account. From a data perspective, we use model selection (Akaike information criterion) to show that this model, which is based on the Weibull distribution, outperforms other simple models like the Gamma distribution. From a modeling perspective, the Weibull distribution can be justified as modeling the accumulation of driver events, which establishes a link to stem cell division based cancer development models and a connection to a recursion formula for intrinsic cancer risk published by Wu et al. For the recursion formula a closed form solution is given, which will help to simplify future analyses. Additionally, we perform a sensitivity analysis for the parameters, showing that two of the three parameters can vary over several orders of magnitude. However, the shape parameter of the Weibull distribution, which corresponds to the number of driver mutations required for cancer onset, can be robustly estimated from epidemiological data.
Changes in functional brain network topology after successful and unsuccessful corpus callosotomy for Lennox-Gastaut Syndrome
Authors: Liang Jun-Ge , Kim Nam-Young , Ko Ara , Kim Heung Dong , Lee Dongpyo
Published: February 2018

Corpus callosotomy (CC) is an effective palliative surgical treatment for patients with Lennox-Gastaut Syndrome (LGS). However, research on the long-term functional effects of CC is sparse. We aimed to investigate these effects and their associated clinical conditions over the two years after CC. Long-term clinical EEG recordings of 30 patients with LGS who had good and bad seizure outcome after CC were collected and retrospectively studied. It was found that CC caused brain network ‘hubs’ to shift from paramedian to lateral regions in the good-recovery group, which reorganized the brain network into a more homogeneous state. We also found increased local clustering coefficients in patients with bad outcomes and decreases, implying enhanced network integration, in patients with good outcomes. The small worldness of brain networks in patients with good outcomes increased in the two years after CC, whereas it decreased in patients with bad outcomes. The covariation of small-worldness with the rate of reduction in seizure frequency suggests that this can be used as an indicator of CC outcome. Local and global network changes during the long-term state might be associated with the postoperative recovery process and could serve as indicators for CC outcome and long-term LGS recovery.
Optimized Bone Regeneration in Calvarial Bone Defect Based on Biodegradation-Tailoring Dual-shell Biphasic Bioactive Ceramic Microspheres
Authors: Xu Antian , Zhuang Chen , Xu Shuxin , He Fuming , Xie Lijun , Yang Xianyan , Gou Zhongru
Published: February 2018

Bioceramic particulates capable of filling bone defects have gained considerable interest over the last decade. Herein, dual-shell bioceramic microspheres (CaP@CaSi@CaP, CaSi@CaP@CaSi) with adjustable beta-tricalcium phosphate (CaP) and beta-calcium silicate (CaSi) distribution were fabricated using a co-concentric capillary system enabling bone repair via a tailorable biodegradation process. The in vitro results showed the optimal concentration (1/16 of 200 mg/ml) of extracts of dual-shell microspheres could promote bone marrow mesenchymal cell (BMSC) proliferation and enhance the level of ALP activity and Alizarin Red staining. The in vivo bone repair and microsphere biodegradation in calvarial bone defects were compared using micro-computed tomography and histological evaluations. The results indicated the pure CaP microspheres were minimally resorbed at 18 weeks post-operatively and new bone tissue was limited; however, the dual-shell microspheres were appreciably biodegraded with time in accordance with the priority from CaSi to CaP in specific layers. The CaSi@CaP@CaSi group showed a significantly higher ability to promote bone regeneration than the CaP@CaSi@CaP group. This study indicates that the biphasic microspheres with adjustable composition distribution are promising for tailoring material degradation and bone regeneration rate, and such versatile design strategy is thought to fabricate various advanced biomaterials with tailorable biological performances for bone reconstruction.
Visualisation of DCP, a nerve agent mimic, in Catfish brain by a simple chemosensor
Authors: Sarkar Himadri Sekhar , Ghosh Ayndrila , Das Sujoy , Maiti Pulak Kumar , Maitra Sudipta , Mandal Sukhendu , Sahoo Prithidipa
Published: February 2018

A chemosensor, 3-aminophenol-based rhodamine conjugate (ARC) has been developed for visualisation of diethylchlorophosphate (DCP), mimic of a chemical warfare agent, in Catfish brain. The simple detection of DCP by “turn-on” fluorescence property of the chemosensor makes it unique for easy and rapid in vivo and in vitro detection of DCP with the detection limit of 5.6 nM.