bluuebunny/crossref_metadata_2025 huggingface dataset:
Dichloroacetate attenuates the stemness of colorectal cancer cells via trigerring ferroptosis through sequestering iron in lysosomes
Authors: Sun Jie , Cheng Xiuqin , Pan Shubo , Wang Liangjing , Dou Wenhuan , Liu Jie , Shi Xiaohua
Published: November 2020

Colorectal cancer stem cell (CSC) has been regarded to be the root of colorectal cancer progression. However, there is still no effective therapeutic method targeting colorectal CSC in clinical application. Here, we investigated the effects of dichloroacetate (DCA) on colorectal cancer cell stemness. We showed that DCA could reduce colorectal cancer cell stemness in a dose‐dependent manner, which is evident by the decreased expression of stemness markers, tumor cell sphere‐formation and cell migration ability. In addition, it was found that DCA trigerred the ferroptosis of colorectal CSC, which is characterized as the upregulation of iron concentration, lipid peroxides, and glutathione level, and decreased cell viability. Mechanistic studies demonstrated that DCA could sequester iron in lysosome and thus trigger ferroptosis, which is necessary for DCA‐mediated attenuation on colorectal cancer cell stemness. Taken together, this work suggests that DCA might be a colorectal CSC‐killer.
Geometrically nonlinear models of static deformation of micropolar elastic thin plates and shallow shells
Authors: Sargsyan Armenuhi , Sargsyan Samvel
Published: November 2020

The present paper considers micropolar plates and shallow shells, the elastic deflections of which are comparable with their thickness and are small in comparison with characteristic cross‐section size. At the same time, both rotation angles of the normal to the median surface before deformation and their free rotations are small. Also, in the tensors of deformation and flexures‐torsions, the nonlinear members in the gradients of the displacement are considered. Hypothesis method is developed, on the basis of which general applied models of static deformation of the micropolar elastic flexible plates and shallow shells are constructed. On the basis of these models, specific problems for the micropolar elastic flexible rectangular plates and shallow shells rectangular in cross‐section are solved in case, when bounds are hinge‐supported. On the basis of numerical analysis, certain effective features of the micropolar material are established in comparison with the corresponding classical material.
Introduction: Citizen Organisations, Transnational Solidarity and Collective Learning in Europe
Authors: Lahusen Christian , Zschache Ulrike , Kousis Maria
Published: November 2020

This edited volume is devoted to the analysis of practices of transnational solidarity in response to the various crises affecting Europe, especially the economic and refugee crises. Its aim is to present new insights into existing informal groups, at the grassroots, geared at furthering transnational solidarity in three thematic areas (disability, unemployment and immigration) and builds on extensive fieldwork in eight European countries (Denmark, France, Germany, Greece, Italy, Poland, Switzerland and the UK). The introductory chapter provides an overview of the topic and the related research, discusses conceptual and methodological issues, and presents the structure of the book. It argues that the transnational solidarity work of citizen groups and organisations is strongly shaped by the socio-economic and political context in which they operate, by the action repertoires they promote, the networks of cooperation they are involved in and the experiences and lessons learned by engaged citizens and activists. It argues that in spite of apparent differences tied to contexts, there are a number of similarities in regard to the way transnationally oriented solidarity groups and organisations respond to societal challenges.
Organisational Solidarity in Switzerland Across Fields: Interlinkage Between Immigration and (Un)employment
Authors: Fernández G. G. Eva , Nicole-Berva Ophelia , Nadler Anna-Lena
Published: November 2020

This chapter is devoted to an in-depth analysis of qualitative interviews about practices of solidarity in Switzerland among the fields of (un)employment and immigration. The chapter shows how institutional arrangements (policy frameworks) shape organisational solidarity within and across these two fields. The history of immigration in Switzerland goes hand in hand with the development of labour policies. This entrenchment is reflected in the activities held by the transnational solidarity organisations (TSOs) and the type of beneficiaries they support. The current research assesses TSOs’ solidarity practices while focusing on their networks of cooperation. Findings reveal that although “immigrants” and “workers” are not mutually exclusive groups, there is an implicit boundary between (un)employment and immigration associations. This translates into an organisational gap where people in situations of multiple sources of vulnerability lack full organisational support (e.g., precarious immigrant workers).
Description of the Vascular Anatomy of Livers with Absence of the Portal Bifurcation
Authors: Terasaki Fumihiro , Yamamoto Yusuke , Sugiura Teiichi , Okamura Yukiyasu , Ito Takaaki , Ashida Ryo , Ohgi Katsuhisa , Aramaki Takeshi , Uesaka Katsuhiko
Published: November 2020

Background

The absence of the portal bifurcation (APB) is a rare anatomic variation, in which the horizontal part of the left portal vein (PV) is missing. The aim of this study was to identify the vascular architecture in livers with APB.

Methods

Computed tomography data for 17,651 patients were reviewed; five patients (0.03%) were found to present with APB. The liver volume and anatomy of APB patients were compared with those of 30 patients with normal livers.

Results

All the APB patients exhibited an independent posterior branch of the PV. The intrahepatic left PV (LPV) ran through either the ventral (n = 2, 40%) or dorsal side (n = 3, 60%) of the middle hepatic vein. The frequency of medial branches diverging from the LPV was higher in patients with APB than in normal patients (p < 0.001). The left hepatic duct (LHD) ran through the inside of the left lobe along the left PV in 40% of the patients with APB, whereas in the remaining 60% of the patients with APB, the LHD ran on the outside of the liver separately from the left PV and joined the right hepatic duct. The liver volume of the left lateral section was significantly smaller (p = 0.014), and the posterior section was significantly larger (p = 0.014) in patients with APB than in patients with normal livers.

Conclusion

The unique anatomical characteristics and the positional relation of the vessels should be considered preoperatively in patients with APB.
Stability Analysis of a Periodic Fluid-Conveying Heterogeneous Nanotube System
Authors: Dai Jiayin , Liu Yongshou , Tong Guojun
Published: November 2020

In this paper, the stability of a periodic heterogeneous nanotube conveying fluid is investigated. The governing equations of the nanotube system are derived based on the nonlocal Euler–Bernoulli beam theory. The dynamic stiffness method is employed to analyze the natural frequencies and critical flow velocities of the heteronanotube. The results and discussions are presented from three aspects which reveal the influences of period number, material length ratio and boundary conditions. In particular, we make comparisons between the heterogeneous nanotubes with periodic structure and the homogeneous ones with the same integral values of material properties along the longitudinal direction to isolate the influences of periodic distribution. According to the simulation results, we can conclude that with a proper selection of period number in terms of length ratio, the stability of the constructed nanotube can be improved.
Pension fund management with investment certificates and stochastic dominance
Authors: Vitali Sebastiano , Moriggia Vittorio
Published: November 2020

This paper considers an extension of the common asset universe of a pension fund to investment certificates. Investment certificates are a class of structured products particularly interesting for their special payoff structures and they are acquiring relevancy in the worldwide markets. In fact, some subclasses of certificates offer loss protection and show high liquidity and, thus, they can be very appreciated by pension fund managers. We consider the problem of a pension fund manager who has to implement an Asset and Liability Management model trying to achieve a long-term sustainability. Therefore, we formulate a multi-stage stochastic programming problem adopting a discrete scenario tree and a multi-objective function. We propose a technique to price highly structured products such as investment certificates on a discrete scenario tree. Finally, we solve the investment problem considering some investment certificate types both in term of payoff structure and protection level, and we test whether they are preferred or not to standard hedging contract such as put options. Moreover, we test the inclusion of first-order and second-order stochastic dominance constraints on multiple stages with respect to a benchmark portfolio. Numerical results show that the portfolio composition reacts to the inclusion of the stochastic dominance constraints, and that the optimal portfolio is efficiently able to reach several targets such as liquidity, returns, sponsor’s extraordinary contribution and funding gap.
Mīmāṃsā deontic reasoning using specificity: a proof theoretic approach
Authors: Lellmann Björn , Gulisano Francesca , Ciabattoni Agata
Published: November 2020

Over the course of more than two millennia the philosophical school of Mīmāṃsā has thoroughly analyzed normative statements. In this paper we approach a formalization of the deontic system which is applied but never explicitly discussed in Mīmāṃsā to resolve conflicts between deontic statements by giving preference to the more specific ones. We first extend with prohibitions and recommendations the non-normal deontic logic extracted in Ciabattoni et al. (in: TABLEAUX 2015, volume 9323 of LNCS, Springer, 2015) from Mīmāṃsā texts, obtaining a multimodal dyadic version of the deontic logic$$\mathsf {MD}$$MD. Sequent calculus is then used to close a set of prima-facie injunctions under a restricted form of monotonicity, using specificity to avoid conflicts. We establish decidability and complexity results, and investigate the potential use of the resulting system for Mīmāṃsā philosophy and, more generally, for the formal interpretation of normative statements.
Soil C, N and P cycling enzyme responses to nutrient limitation under elevated CO2
Authors: Keane J. Ben , Hoosbeek Marcel R. , Taylor Christopher R. , Miglietta Franco , Phoenix Gareth K. , Hartley Iain P.
Published: November 2020

Elevated CO2 (eCO2) can stimulate plant productivity and increase carbon (C) input to soils, but nutrient limitation restricts productivity. Despite phosphorus (P)-limited ecosystems increasing globally, it is unknown how nutrient cycling, particularly soil microbial extra cellular enzyme activity (EEA), will respond to eCO2 in such ecosystems. Long-term nutrient manipulation plots from adjacent P-limited acidic and limestone grasslands were exposed to eCO2 (600 ppm) provided by a mini-Free Air CO2 Enrichment system. P-limitation was alleviated (35 kg-P ha−1 y−1 (P35)), exacerbated (35 kg-N ha−1 y−1 (N35), 140 kg-N ha−1 y−1 (N140)), or maintained (control (P0N0)) for > 20 years. We measured EEAs of C-, N- and P-cycling enzymes (1,4-β-glucosidase, cellobiohydrolase, N-acetyl β-D-glucosaminidase, leucine aminopeptidase, and acid phosphatase) and compared C:N:P cycling enzyme ratios using a vector analysis. Potential acid phosphatase activity doubled under N additions relative to P0N0 and P35 treatments. Vector analysis revealed reduced C-cycling investment and increased P-cycling investment under eCO2. Vector angle significantly increased with P-limitation (P35 < P0N0 < N35 < N140) indicating relatively greater investment in P-cycling enzymes. The limestone grassland was more C limited than the acidic grassland, characterised by increased vector length, C:N and C:P enzyme ratios. The absence of interactions between grassland type and eCO2 or nutrient treatment for all enzyme indicators signaled consistent responses to changing P-limitation and eCO2 in both grasslands. Our findings suggest that eCO2 reduces C limitation, allowing increased investment in P- and N-cycle enzymes with implications for rates of nutrient cycling, potentially alleviating nutrient limitation of ecosystem productivity under eCO2.

Graphic abstract

"Image missing"
Color Representations of Ising Models
Authors: Forsström Malin P.
Published: November 2020

In Steif and Tykesson (J Prob 16:899–955, 2019), the authors introduced the so-called general divide and color models. One of the best-known examples of such a model is the Ising model with external field $$ h = 0 $$

h
=
0

, which has a color representation given by the random cluster model. In this paper, we give necessary and sufficient conditions for this color representation to be unique. We also show that if one considers the Ising model on a complete graph, then for many $$ h > 0 $$

h
>
0

, there is no color representation. This shows, in particular, that any generalization of the random cluster model which provides color representations of Ising models with external fields cannot, in general, be a generalized divide and color model. Furthermore, we show that there can be at most finitely many $$ \beta > 0 $$

β
>
0

at which the random cluster model can be continuously extended to a color representation for $$ h \not = 0 $$

h
≠
0

.
A qualitative study of prescribing errors among multi-professional prescribers within an e-prescribing system
Authors: Alshahrani Fahad , Marriott John F. , Cox Anthony R.
Published: November 2020

Background Computerised Physician Order Entry (CPOE) is considered to enhance the safety of prescribing. However, it can have unintended consequences and new forms of prescribing error have been reported. Objective The aim of this study was to explore the causes and contributing factors associated with prescribing errors reported by multidisciplinary prescribers working within a CPOE system. Main Outcome Measure Multidisciplinary prescribers experience of prescribing errors in an CPOE system. Method This qualitative study was conducted in a hospital with a well-established CPOE system. Semi-structured qualitative interviews were conducted with prescribers from the professions of pharmacy, nursing, and medicine. Interviews analysed using a mixed inductive and deductive approach to develop a framework for the causes of error. Results Twenty-three prescribers were interviewed. Six main themes influencing prescribing were found: the system, the prescriber, the patient, the team, the task of prescribing and the work environment. Prominent issues related to CPOE included, incorrect drug name picking, default auto-population of dosages, alert fatigue and remote prescribing. These interacted within a complex prescribing environment. No substantial differences in the experience of CPOE were found between the professions. Conclusion Medical and non-medical prescribers have similar experiences of prescribing errors when using CPOE, aligned with existing published literature about medical prescribing. Causes of electronic prescribing errors are multifactorial in nature and prescribers describe how factors interact to create the conditions errors. While interventions should focus on direct CPOE issues, such as training and design, socio-technical, and environmental aspects of practice remain important.
The Zariski topology-graph of modules over commutative rings II
Authors: Ansari-Toroghy H. , Habibi S.
Published: November 2020

Let M be a module over a commutative ring R. In this paper, we continue our study about the Zariski topology-graph $$G(\tau _T)$$

G
(

τ
T

)

which was introduced in Ansari-Toroghy et al. (Commun Algebra 42:3283–3296, 2014). For a non-empty subset T of $$\mathrm{Spec}(M)$$

Spec
(
M
)

, we obtain useful characterizations for those modules M for which $$G(\tau _T)$$

G
(

τ
T

)

is a bipartite graph. Also, we prove that if $$G(\tau _T)$$

G
(

τ
T

)

is a tree, then $$G(\tau _T)$$

G
(

τ
T

)

is a star graph. Moreover, we study coloring of Zariski topology-graphs and investigate the interplay between $$\chi (G(\tau _T))$$

χ
(
G

(

τ
T

)

)

and $$\omega (G(\tau _T))$$

ω
(
G

(

τ
T

)

)

.
Tribological behavior and microstructural evolution of lubricating film of silver matrix self-lubricating nanocomposite
Authors: Kang Xiao , Yu Shuang , Yang Hailin , Sun Yang , Zhang Lei
Published: November 2020

The aim of this study is to fabricate the nanocomposite with low friction and high wear resistance using binary solid lubricant particles. The microstructure and tribological performance of the nanocomposite are evaluated, and the composition and film thickness of the lubricating film are observed and analyzed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The nanocomposite exhibited improved tribological properties with a friction coefficient as low as 0.12 and a low wear rate of 2.17 × 10−6mm3/(N·m) in high-purity nitrogen atmosphere. Decreasing sliding speed can increase lubricating film thickness, and the thickest lubricating film is approximately 125 nm. As the film thickness of the lubricating film exceeded 90 nm, the friction coefficient curves became smooth. In compared with WS2, MoS2can be more effective in forming the transfer layer on the worn surfaces at the initial stage of the tribological process.
Variational symmetries and pluri-Lagrangian structures for integrable hierarchies of PDEs
Authors: Petrera Matteo , Vermeeren Mats
Published: November 2020

We investigate the relation between pluri-Lagrangian hierarchies of 2-dimensional partial differential equations and their variational symmetries. The aim is to generalize to the case of partial differential equations the recent findings in Petrera and Suris (Nonlinear Math. Phys. 24(suppl. 1):121–145, 2017) for ordinary differential equations. We consider hierarchies of 2-dimensional Lagrangian PDEs (many of which have a natural $$(1\,{+}\,1)$$

(
1

+

1
)

-dimensional space-time interpretation) and show that if the flow of each PDE is a variational symmetry of all others, then there exists a pluri-Lagrangian 2-form for the hierarchy. The corresponding multi-time Euler–Lagrange equations coincide with the original system supplied with commuting evolutionary flows induced by the variational symmetries.
COVID-19 and the Human Rights of Nationals Abroad
Authors: Liu Guofu
Published: November 2020

The COVID-19 pandemic is having serious and disproportionate effects on nationals abroad and their families globally. Many states have adopted positive measures including temporarily suspending forced returns as well providing visa and work permit extensions, temporary residence, or other forms of regular status to ensure that migrants are accounted for in national responses to the pandemic. Nevertheless, the human rights of nationals abroad and nationals with foreign family members have faced significant challenges. Some states have fully or partially closed entry to all of their own nationals and their foreign family members, in violation of nationals’ right to return and their right of family unification. Other states’ nationals abroad have been unable to enjoy the right to an adequate standard of living and the right to health. Many have also encountered the burdens of hate speech in both their home states and the states in which they live, the effect of which has been to undermine freedom of opinion and expression and the right to equality and non-discrimination. This essay identifies and explains these threats to human rights in the era of COVID-19. The essay encourages states to recommit to rights protection.
SOME HOMOLOGICAL PROPERTIES OF FOURIER ALGEBRAS ON HOMOGENEOUS SPACES
Authors: ESMAILVANDI REZA , NEMATI MEHDI
Published: November 2020

Let

$ H $
be a compact subgroup of a locally compact group

$ G $
. We first investigate some (operator) (co)homological properties of the Fourier algebra

$A(G/H)$
of the homogeneous space

$G/H$
such as (operator) approximate biprojectivity and pseudo-contractibility. In particular, we show that

$ A(G/H) $
is operator approximately biprojective if and only if

$ G/H $
is discrete. We also show that

$A(G/H)^{**}$
is boundedly approximately amenable if and only if G is compact and H is open. Finally, we consider the question of existence of weakly compact multipliers on

$A(G/H)$
.
Cross-linguistic syntactic priming in Korean learners of English
Authors: Son Myeongeun
Published: November 2020

This study investigates whether L2 learners develop and share an abstract syntactic representation between an L1 and L2 with different word orders and, if so, whether one language’s unique syntactic features affect the shared representation. Korean (SOV) and English (SVO) have equivalent dative alternations; however, because Korean allows word-order scrambling, several dative structures are available in Korean that do not have English counterparts. In this study’s cross-linguistic syntactic priming experiment, intermediate and advanced Korean learners of English described pictures in English after reading various types of Korean dative sentences. The study found evidence of cross-linguistic syntactic priming between Korean and English, regardless of L2 proficiency, but only when prime and target structures shared identical functional assignments, information structures, and order of thematic roles. These results suggest that, within limits created by language-specific features, L2 learners can develop and share abstract representations between two languages with different word orders.
Counteracting CAR T cell dysfunction
Authors: Poorebrahim Mansour , Melief Jeroen , Pico de Coaña Yago , L. Wickström Stina , Cid-Arregui Angel , Kiessling Rolf
Published: November 2020

In spite of high rates of complete remission following chimeric antigen receptor (CAR) T cell therapy, the efficacy of this approach is limited by generation of dysfunctional CAR T cells in vivo, conceivably induced by immunosuppressive tumor microenvironment (TME) and excessive antigen exposure. Exhaustion and senescence are two critical dysfunctional states that impose a pivotal hurdle for successful CAR T cell therapies. Recently, modified CAR T cells with an “exhaustion-resistant” phenotype have shown superior antitumor functions and prolonged lifespan. In addition, several studies have indicated the feasibility of senescence delay in CAR T cells. Here, we review the latest reports regarding blockade of CAR T cell exhaustion and senescence with a particular focus on the exhaustion-inducing pathways. Subsequently, we describe what potential these latest insights offer for boosting the potency of adoptive cell transfer (ACT) therapies involving CAR T cells. Furthermore, we discuss how induction of costimulation, cytokine exposure, and TME modulation can impact on CAR T cell efficacy and persistence, while potential safety issues associated with reinvigorated CAR T cells will also be addressed.
Toxicity evaluation of an essential oil mixture from the Cretan herbs thyme, Greek sage and Cretan dittany
Authors: Kalyvianaki Konstantina , Malamos Panagiotis , Mastrodimou Niki , Manoura-Zonou Ioanna , Vamvoukaki Rodanthi , Notas George , Malliaraki Niki , Moustou Eleni , Tzardi Maria , Pirintsos Stergios , Lionis Christos , Sourvinos George , Castanas Elias , Kampa Marilena
Published: November 2020

The importance of herbal extracts on health, which was initially based on ethnopharmacological and traditional knowledge, becomes increasingly well documented by numerous experimental and intervention studies. The daily use of beverages from different aromatic plants which becomes more popular nowadays, has been a tradition in Crete, and a habit that has been linked to the longevity seen in the island. Additionally, a certain combination of aromatic plants has been used against common cold and influenza. Interestingly, when such a mixture of essential oils from Cretan herbs (Cretan Aromatic Plants essential oil, CAPeo, from thyme, Greek sage, and Cretan dittany) was formulated, significant antiviral properties were observed in vitro and a significant reduction in the duration and severity of symptoms of patients with upper respiratory tract infections was found in a clinical study. However, since many plants extracts can exert toxic effects, toxicity issues should be properly addressed. In the present work we present an acute and sub-chronic toxicity evaluation for this mixture of aromatic plants’ essential oils in rats. In fact, it is the only toxicity study for Cretan dittany. We report absence of toxicity, rendering the use of the mixture of essential oils from Cretan dittany, Greek sage and thyme as safe.
Paired rRNA-depleted and polyA-selected RNA sequencing data and supporting multi-omics data from human T cells
Authors: Chen Li , Yang Ruirui , Kwan Tony , Tang Chao , Watt Stephen , Zhang Yiming , Bourque Guillaume , Ge Bing , Downes Kate , Frontini Mattia , Ouwehand Willem H. , Lin Jing-wen , Soranzo Nicole , Pastinen Tomi , Chen Lu
Published: November 2020

Both poly(A) enrichment and ribosomal RNA depletion are commonly used for RNA sequencing. Either has its advantages and disadvantages that may lead to biases in the downstream analyses. To better access these effects, we carried out both ribosomal RNA-depleted and poly(A)-selected RNA-seq for CD4+ T naive cells isolated from 40 healthy individuals from the Blueprint Project. For these 40 individuals, the genomic and epigenetic data were also available. This dataset offers a unique opportunity to understand how library construction influences differential gene expression, alternative splicing and molecular QTL (quantitative loci) analyses for human primary cells.
MFRED, 10 second interval real and reactive power for groups of 390 US apartments of varying size and vintage
Authors: Meinrenken Christoph J. , Rauschkolb Noah , Abrol Sanjmeet , Chakrabarty Tuhin , Decalf Victor C. , Hidey Christopher , McKeown Kathleen , Mehmani Ali , Modi Vijay , Culligan Patricia J.
Published: November 2020

Building electricity is a major component of global energy use and its environmental impacts. Detailed data on residential electricity use have many interrelated research applications, from energy conservation to non-intrusive load monitoring, energy storage, integration of renewables, and electric vs. fossil-based heating. The dataset presented here, Multifamily Residential Electricity Dataset (MFRED), contains the electricity use of 390 apartments, ranging from studios to four-bedroom units. All apartments are located in the Northeastern United States (IECC-climate-zone 4 A), but differ in their heating/cooling system and construction year (early to late 20th century). To adhere to privacy guidelines, data were averaged across 15 apartments each, based on annual electricity use. MFRED includes real and reactive power, at 10-second resolution, for January to December 2019 (246 million data points). The annual average real power per apartment is 343 W (3.27 W/m2 of floor area), with strong variation between seasons and apartment size. Considering its large number of apartments, high time resolution, real and reactive power, and 12-month duration, MFRED is currently unique for the multifamily-sector.
Evaluating the value of day 0 of an ICSI cycle on indicating laboratory outcome
Authors: Maziotis E. , Sfakianoudis K. , Giannelou P. , Grigoriadis S. , Rapani A. , Tsioulou P. , Nikolettos K. , Pantou A. , Tiptiri-Kourpeti A. , Koutsilieris M. , Asimakopoulos B. , Nikolettos N. , Pantos K. , Simopoulou Mara
Published: November 2020

A number of oocyte characteristics have been associated with fertilization, implantation and live-birth rates, albeit without reaching a consensus. This study aims to delineate possible associations between oocyte characteristics, oocyte behavior during intracytoplasmic sperm injection (ICSI), fertilization potential, and laboratory outcomes. Four-hundred and seventy-seven patients, yielding 3452 oocytes, were enrolled in this prospective observational study from 2015 to 2018. Οoplasm granularity was associated with poor embryo quality and higher probabilities of post-ICSI oocytes and embryos discarded in any developmental stage and never selected for embryo transfer or cryopreservation (p < 0.001). Both sudden or difficult ooplasm aspiration, and high or lack of resistance during ICSI were associated with either a poor Zygote-Score or fertilization failure (p < 0.001). Sudden or difficult ooplasm aspiration and high resistance during ICSI penetration were positively associated with resulting to a post-ICSI oocyte or embryo that would be selected for discard. Evaluation of oocyte characteristics and oocyte behavior during ICSI may provide early information regarding laboratory and cycle outcomes. Particularly, ooplasm granularity, and fragmentation of polar body, along with sudden or difficult ooplasm aspiration and high or lack of resistance during ICSI penetration may hinder the outcome of an ICSI cycle. The associations presented herein may contribute towards development of a grading system or a prediction model. Taking into account information on oocytes and ICSI behavior may effectively assist in enhancing IVF outcome rates.
Magnetic susceptibility imaging of human habenula at 3 T
Authors: Yoo Seulki , Kim Joo-won , Schenck John F. , Lee Seung-Kyun
Published: November 2020

The habenula plays an important role in brain reward circuitry and psychiatric conditions. While much work has been done on the function and structure of the habenula in animal models, in vivo imaging studies of the human habenula have been relatively scarce due to its small size, deep brain location, and lack of clear biomarkers for its heterogeneous substructure. In this paper, we report high-resolution (0.5 × 0.5 × 0.8 mm3) MRI of the human habenula with quantitative susceptibility mapping (QSM) at 3 T. By analyzing 48 scan datasets collected from 21 healthy subjects, we found that magnetic susceptibility contrast is highly non-uniform within the habenula and across the subjects. In particular, we observed high prevalence of elevated susceptibility in the posterior subregion of the habenula. Correlation analysis between the susceptibility and the effective transverse relaxation rate (R2*) indicated that localized susceptibility enhancement in the habenula is more associated with increased paramagnetic (such as iron) rather than decreased diamagnetic (such as myelin) sources. Our results suggest that high-resolution QSM could make a potentially useful tool for substructure-resolved in vivo habenula imaging, and provide a groundwork for the future development of magnetic susceptibility as a quantitative biomarker for human habenula studies.
Genetic analyses in mouse fibroblast and melanoma cells demonstrate novel roles for PDGF-AB ligand and PDGF receptor alpha
Authors: Kadrmas Julie L. , Beckerle Mary C. , Yoshigi Masaaki
Published: November 2020

Platelet Derived Growth Factor Receptor (PDGFR) signaling is a central mitogenic pathway in development, as well as tissue repair and homeostasis. The rules governing the binding of PDGF ligand to the receptor to produce activation and downstream signaling have been well defined over the last several decades. In cultured cells after a period of serum deprivation, treatment with PDGF leads to the rapid formation of dramatic, actin-rich Circular Dorsal Ruffles (CDRs). Using CDRs as a robust visual readout of early PDGFR signaling, we have identified several contradictory elements in the widely accepted model of PDGF activity. Employing CRISPR/Cas9 gene editing to disrupt the Pdgfra gene in two different murine cell lines, we show that in addition to the widely accepted function for PDGFR-beta in CDR formation, PDGFR-alpha is also clearly capable of eliciting CDRs. Moreover, we demonstrate activity for heterodimeric PDGF-AB ligand in the vigorous activation of PDGFR-beta homodimers to produce CDRs. These findings are key to a more complete understanding of PDGF ligand-receptor interactions and their downstream signaling consequences. This knowledge will allow for more rigorous experimental design in future studies of PDGFR signaling and its contributions to development and disease.
X-ray diffraction and second harmonic imaging reveal new insights into structural alterations caused by pressure-overload in murine hearts
Authors: Nicolas Jan-David , Khan Amara , Markus Andrea , Mohamed Belal A. , Toischer Karl , Alves Frauke , Salditt Tim
Published: November 2020

We demonstrate a label-free imaging approach to study cardiac remodeling of fibrotic and hypertrophic hearts, bridging scales from the whole organ down to the molecular level. To this end, we have used mice subjected to transverse aortic constriction and imaged adjacent cardiac tissue sections by microfocus X-ray diffraction and second harmonic generation (SHG) imaging. In this way, the acto-myosin structure was probed in a spatially resolved manner for entire heart sections. From the recorded diffraction data, spatial maps of diffraction intensity, anisotropy and orientation were obtained, and fully automated analysis depicted the acto-myosin filament spacing and direction. X-ray diffraction presented an overview of entire heart sections and revealed that in regions of severe cardiac remodeling the muscle mass is partly replaced by connective tissue and the acto-myosin lattice spacing is increased at these regions. SHG imaging revealed sub-cellular structure of cardiac tissue and complemented the findings from X-ray diffraction by revealing micro-level distortion of myofibrils, immune cell infiltration at regions of cardiac remodeling and the development of fibrosis down to the scale of a single collagen fibril. Overall, our results show that both X-ray diffraction and SHG imaging can be used for label-free and high-resolution visualization of cardiac remodeling and fibrosis progression at different stages in a cardiac pressure-overload mouse model that cannot be achieved by conventional histology.
Genotypic antimicrobial resistance characterization of E. coli from dairy calves at high risk of respiratory disease administered enrofloxacin or tulathromycin
Authors: Pereira R. V. , Foditsch C. , Siler J. D. , Dulièpre S. C. , Altier C. , Garzon A. , Warnick L. D.
Published: November 2020

The objective of this study was to evaluate the longitudinal effect of enrofloxacin or tulathromycin use in calves at high risk of bovine respiratory disease (BRD) on antimicrobial resistance genes and mutation in quinolone resistance-determining regions (QRDR) in fecal E. coli. Calves at high risk of developing BRD were randomly enrolled in one of three groups receiving: (1) enrofloxacin (ENR; n = 22); (2) tulathromycin (TUL; n = 24); or (3) no treatment (CTL; n = 21). Fecal samples were collected at enrollment and at 7, 28, and 56 days after beginning treatment, cultured for Escherichiacoli (EC) and DNA extracted. Isolates were screened for cephalosporin, quinolone and tetracycline resistance genes using PCR. QRDR screening was conducted using Sanger sequencing. The only resistance genes detected were aac(6′)Ib-cr (n = 13), bla-CTX-M (n = 51), bla-TEM (n = 117), tetA (n = 142) and tetB (n = 101). A significantly higher detection of gyrA mutated at position 248 at time points 7 (OR = 11.5; P value = 0.03) and 28 (OR = 9.0; P value = 0.05) was observed in the ENR group when compared to calves in the control group. Our findings support a better understanding of the potential impacts from the use of enrofloxacin in calves on the selection and persistence of resistance.
Lateral diffusion of CD14 and TLR2 in macrophage plasma membrane assessed by raster image correlation spectroscopy and single particle tracking
Authors: Makaremi Sara , Rose Markus , Ranjit Suman , Digman Michelle A. , Bowdish Dawn M. E. , Moran-Mirabal Jose M.
Published: November 2020

The diffusion of membrane receptors is central to many biological processes, such as signal transduction, molecule translocation, and ion transport, among others; consequently, several advanced fluorescence microscopy techniques have been developed to measure membrane receptor mobility within live cells. The membrane-anchored receptor cluster of differentiation 14 (CD14) and the transmembrane toll-like receptor 2 (TLR2) are important receptors in the plasma membrane of macrophages that activate the intracellular signaling cascade in response to pathogenic stimuli. The aim of the present work was to compare the diffusion coefficients of CD14 and TLR2 on the apical and basal membranes of macrophages using two fluorescence-based methods: raster image correlation spectroscopy (RICS) and single particle tracking (SPT). In the basal membrane, the diffusion coefficients obtained from SPT and RICS were found to be comparable and revealed significantly faster diffusion of CD14 compared with TLR2. In addition, RICS showed that the diffusion of both receptors was significantly faster in the apical membrane than in the basal membrane, suggesting diffusion hindrance by the adhesion of the cells to the substrate. This finding highlights the importance of selecting the appropriate membrane (i.e., basal or apical) and corresponding method when measuring receptor diffusion in live cells. Accurately knowing the diffusion coefficient of two macrophage receptors involved in the response to pathogen insults will facilitate the study of changes that occur in signaling in these cells as a result of aging and disease.
Renal developmental genes are differentially regulated after unilateral ureteral obstruction in neonatal and adult mice
Authors: Kubik Melanie J. , Wyczanska Maja , Gasparitsch Mojca , Keller Ursula , Weber Stefanie , Schaefer Franz , Lange-Sperandio Bärbel
Published: November 2020

Congenital obstructive nephropathy hinders normal kidney development. The severity and the duration of obstruction determine the compensatory growth of the contralateral, intact opposite kidney. We investigated the regulation of renal developmental genes, that are relevant in congenital anomalies of the kidney and urinary tract (CAKUT) in obstructed and contralateral (intact opposite) kidneys after unilateral ureteral obstruction (UUO) in neonatal and adult mice. Newborn and adult mice were subjected to complete UUO or sham-operation, and were sacrificed 1, 5, 12 and 19 days later. Quantitative RT-PCR was performed in obstructed, intact opposite kidneys and sham controls for Gdnf, Pax2, Six4, Six2, Dach1, Eya1, Bmp4, and Hnf-1β. Neonatal UUO induced an early and strong upregulation of all genes. In contrast, adult UUO kidneys showed a delayed and less pronounced upregulation. Intact opposite kidneys of neonatal mice revealed a strong upregulation of all developmental genes, whereas intact opposite kidneys of adult mice demonstrated only a weak response. Only neonatal mice exhibited an increase in BMP4 protein expression whereas adult kidneys strongly upregulated phosphatidylinositol 3 kinase class III, essential for compensatory hypertrophy. In conclusion, gene regulation differs in neonatal and adult mice with UUO. Repair and compensatory hypertrophy involve different genetic programs in developing and adult obstructed kidneys.
Amylase quantification in the terminal Ileum following formation of an Ileostomy
Authors: Clark D. A. , Cuda T. , Pretorius C. , Edmundson A. , Solomon M. , Riddell A. D.
Published: November 2020

Amylase is elevated in the foregut and has been used to confirm anastomotic integrity after pancreatic surgery. The physiological activity of pancreatic enzymes in the ileum has been studied in healthy volunteers but not quantitated with the simple and readily available amylase measurements employed with serum tests. We aim to quantitate the levels of amylase in the terminal ileum. This was a prospective, non-randomised, non-blinded, consecutive cohort study conducted at the Royal Brisbane and Women’s Hospital. Consecutive patients undergoing routine surgery with an ileostomy were invited to participate in the study. Ileostomy effluent was collected and analysed daily for the first 5 post-operative days. This validation cohort included 8 males and 3 females, with a mean age of 49 years. Median daily amylase levels ranged from 4470 U/L to 23,000 U/L, with no specimens falling within the laboratory serum reference range of 40 to 130 U/L. Two specimens were not available on day one post-operative due to complete ileus. The sample size of 11 patients is small but was considered sufficient given that 55 effluent specimens were anticipated for analysis. Amylase levels remain highly elevated as the enzyme transits through the length of the small intestine and measured in the terminal ileum, and can be readily quantitated by the existing testing methodology routinely available.
Diagnostic accuracy of deep-learning with anomaly detection for a small amount of imbalanced data: discriminating malignant parotid tumors in MRI
Authors: Matsuo Hidetoshi , Nishio Mizuho , Kanda Tomonori , Kojita Yasuyuki , Kono Atsushi K. , Hori Masatoshi , Teshima Masanori , Otsuki Naoki , Nibu Ken-ichi , Murakami Takamichi
Published: November 2020

We hypothesized that, in discrimination between benign and malignant parotid gland tumors, high diagnostic accuracy could be obtained with a small amount of imbalanced data when anomaly detection (AD) was combined with deep leaning (DL) model and the L2-constrained softmax loss. The purpose of this study was to evaluate whether the proposed method was more accurate than other commonly used DL or AD methods. Magnetic resonance (MR) images of 245 parotid tumors (22.5% malignant) were retrospectively collected. We evaluated the diagnostic accuracy of the proposed method (VGG16-based DL and AD) and that of classification models using conventional DL and AD methods. A radiologist also evaluated the MR images. ROC and precision-recall (PR) analyses were performed, and the area under the curve (AUC) was calculated. In terms of diagnostic performance, the VGG16-based model with the L2-constrained softmax loss and AD (local outlier factor) outperformed conventional DL and AD methods and a radiologist (ROC-AUC = 0.86 and PR-ROC = 0.77). The proposed method could discriminate between benign and malignant parotid tumors in MR images even when only a small amount of data with imbalanced distribution is available.
Common occurrence of Belerina virus, a novel paramyxovirus found in Belgian hedgehogs
Authors: Vanmechelen Bert , Vergote Valentijn , Merino Michelle , Verbeken Erik , Maes Piet
Published: November 2020

Common or European hedgehogs can be found throughout Western Europe. They are known carriers of a variety of parasitic and bacterial pathogens, and have also been shown to carry several viruses, including morbilli-like paramyxoviruses, although the pathogenic and zoonotic potential of some of these viruses has yet to be determined. We report here the discovery of a novel paramyxovirus in Belgian hedgehogs, named Belerina virus. The virus was detected by nanopore sequencing of RNA isolated from hedgehog tissue. Out of 147 animals screened in this study, 57 tested positive for Belerina virus (39%), indicating a high prevalence of this virus in the Belgian hedgehog population. Based on its divergence from other known paramyxovirus species, Belerina virus is thought to represent a new species in the family Paramyxoviridae. Phylogenetic analysis groups Belerina virus together with the bat-borne Shaan virus within the genus Jeilongvirus, although expanding the tree with partial genomes shows Belerina virus forming a separate subclade within this genus, alongside a yet-unnamed paramyxovirus isolated from a greater tube-nosed bat. In summary, we discuss the complete genome sequence of Belerina virus, a putative new paramyxovirus species commonly found in Belgian hedgehogs.
The approximately universal shapes of epidemic curves in the Susceptible-Exposed-Infectious-Recovered (SEIR) model
Authors: Heng Kevin , Althaus Christian L.
Published: November 2020

Compartmental transmission models have become an invaluable tool to study the dynamics of infectious diseases. The Susceptible-Infectious-Recovered (SIR) model is known to have an exact semi-analytical solution. In the current study, the approach of Harko et al. (Appl. Math. Comput. 236:184–194, 2014) is generalised to obtain an approximate semi-analytical solution of the Susceptible-Exposed-Infectious-Recovered (SEIR) model. The SEIR model curves have nearly the same shapes as the SIR ones, but with a stretch factor applied to them across time that is related to the ratio of the incubation to infectious periods. This finding implies an approximate characteristic timescale, scaled by this stretch factor, that is universal to all SEIR models, which only depends on the basic reproduction number and initial fraction of the population that is infectious.
Author Correction: Mast cells increase adult neural precursor proliferation and differentiation but this potential is not realized in vivo under physiological conditions
Authors: Wasielewska Joanna M. , Grönnert Lisa , Rund Nicole , Donix Lukas , Rust Ruslan , Sykes Alexander M. , Hoppe Anja , Roers Axel , Kempermann Gerd , Walker Tara L.
Published: November 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Genomic and transcriptomic variation defines the chromosome-scale assembly of Haemonchus contortus, a model gastrointestinal worm
Authors: Doyle Stephen R. , Tracey Alan , Laing Roz , Holroyd Nancy , Bartley David , Bazant Wojtek , Beasley Helen , Beech Robin , Britton Collette , Brooks Karen , Chaudhry Umer , Maitland Kirsty , Martinelli Axel , Noonan Jennifer D. , Paulini Michael , Quail Michael A. , Redman Elizabeth , Rodgers Faye H. , Sallé Guillaume , Shabbir Muhammad Zubair , Sankaranarayanan Geetha , Wit Janneke , Howe Kevin L. , Sargison Neil , Devaney Eileen , Berriman Matthew , Gilleard John S. , Cotton James A.
Published: November 2020

Haemonchus contortus is a globally distributed and economically important gastrointestinal pathogen of small ruminants and has become a key nematode model for studying anthelmintic resistance and other parasite-specific traits among a wider group of parasites including major human pathogens. Here, we report using PacBio long-read and OpGen and 10X Genomics long-molecule methods to generate a highly contiguous 283.4 Mbp chromosome-scale genome assembly including a resolved sex chromosome for the MHco3(ISE).N1 isolate. We show a remarkable pattern of conservation of chromosome content with Caenorhabditis elegans, but almost no conservation of gene order. Short and long-read transcriptome sequencing allowed us to define coordinated transcriptional regulation throughout the parasite’s life cycle and refine our understanding of cis- and trans-splicing. Finally, we provide a comprehensive picture of chromosome-wide genetic diversity both within a single isolate and globally. These data provide a high-quality comparison for understanding the evolution and genomics of Caenorhabditis and other nematodes and extend the experimental tractability of this model parasitic nematode in understanding helminth biology, drug discovery and vaccine development, as well as important adaptive traits such as drug resistance.
Microfluidic filter device coupled mass spectrometry for rapid bacterial antimicrobial resistance analysis
Authors: Zhang Dongxue , Zhang Yijie , Yin Fan , Qin Qin , Bi Hongyan , Liu Baohong , Qiao Liang
Published: November 2020

Microfluidic chip and electrospray ionization mass spectrometry based bacterial antimicrobial resistance analysis has been implemented rapidly and accurately.
A quantum cascade laser setup for studying irreversible photoreactions in H2O with nanosecond resolution and microlitre consumption
Authors: Klocke Jessica L. , Kottke Tilman
Published: November 2020

Flavin photoreduction in H2O is elucidated by developing a quantum cascade laser setup for time-resolved infrared spectroscopy on irreversible reactions.