bluuebunny/crossref_metadata_2025 huggingface dataset:
A Non-inferiority, Randomized Clinical Trial Comparing Paclitaxel-Coated Balloon Versus New-Generation Drug-Eluting Stents on Angiographic Outcomes for Coronary De Novo Lesions
Authors: Yu Xue , Wang Xinyue , Ji Fusui , Zhang Wenduo , Yang Chenguang , Xu Feng , Wang Fang
Published: March 2021

Background

Drug-coated balloon (DCB) has been proved efficacy for coronary small vessel disease, but data regarding outcomes of DCB in common de novo lesions (including reference vessel diameter more than 3.0mm) compared with new-generation drug-eluting stent (DES) are lacking. We hypothesized that a DCB-only strategy for coronary de novo lesions would be non-inferior to DES treatment on angiographic outcomes.

Methods

In this randomized controlled trial, we compared the effect of DCB with DES on late lumen loss (LLL) at 9-month angiographic follow-up and 12-month major adverse cardiac events (MACEs), including death, non-fatal myocardial infarction, target lesion revascularization (TLR), and target vessel revascularization (TVR).

Results

From July 2017 to July 2018, 288 consecutive patients with reference vessel diameter (RVD) between 2.25 and 4.0mm were screened. After proper pre-dilation, 170 patients were enrolled and randomized to the DCB and the DES groups at 1:1 ratio. Seven patients withdrew the consent forms during hospital stay (1 in DCB group, 6 in DES group). Two patients in DCB group underwent bailout stenting due to severe dissection after DCB release. The primary endpoint of 9-month LLL was −0.19±0.49mm with the DCB versus 0.03±0.64mm with the DES. The one-sided 97.5% upper confidence limit of the difference was −0.04mm, achieving non-inferiority of the DCB compared with the DES (P=0.019). The 12-month cumulative MACE rate was similar in the DCB and DES groups (2.44% vs. 6.33%, P=0.226).

Conclusions

In this prospective study, the DCB only strategy for de novo lesion was non-inferior to the new-generation DES in terms of 9-month late lumen loss.
Phase I first-in-human study of HLX07, a novel and improved recombinant anti-EGFR humanized monoclonal antibody, in patients with advanced solid cancers
Authors: Hou Ming-Mo , Ho Ching-Liang , Lin Hsuan-Yu , Zhu Yunting , Zhang Xiaodi
Published: March 2021

Purpose This study aimed to evaluate the safety and pharmacokinetic (PK) profiles of HLX07, a novel, recombinant, humanized anti-epidermal growth factor receptor (EGFR) antibody, in patients with advanced solid cancers who had failed standard therapy or for whom no standard therapy was available. Methods In this prospective, open-label, Phase I dose escalation study, patients aged ≥18 years (≥20 years for patients in Taiwan) with histologically-confirmed metastatic or recurrent epithelial carcinoma that had no K-RAS or B-RAF mutations were enrolled in a ‘3 + 3’ escalation design. HLX07 was administered weekly by 2-h intravenous infusion at doses ranging from 50 to 800 mg. The primary endpoint was summary listing of participants reporting treatment-emergent adverse events (TEAEs). Secondary endpoints included PK analysis, serum anti-HLX07 antibody assessments and efficacy. Results In total, 19 patients were enrolled between 1 October 2016 and 16 July 2019 to receive HLX07 at doses of 50 (n = 3), 100 (n = 3), 200 (n = 3), 400 (n = 3), 600 (n = 3) and 800 (n = 4) mg per week. All patients experienced at least one TEAE, most commonly fatigue (68.4%), nausea (47.4%), paronychia (31.6%) and vomiting (31.6%). Serious TEAEs were reported in 11 patients but only one serious TEAE (dyspnea in 600 mg cohort) was regarded as possibly related to study treatment. No dose limiting toxicity (DLT) was reported. Systemic exposure to HLX07 increased proportionally with dose. Anti-HLX07 antibodies were not detected in any patients. Conclusion HLX07 was well tolerated (at dose levels up to 800 mg/week) and promising in patients with advanced solid cancers.

Clinical Trial Registration: The study was registered at ClinicalTrials.gov: NCT02648490 (Jan 7, 2016).
Yes Children Need to Learn Their GPCs but There Really Is Little or No Evidence that Systematic or Explicit Phonics Is Effective: a response to Fletcher, Savage, and Sharon (2020)
Authors: Bowers Jeffrey S.
Published: March 2021

Fletcher, Savage, and Sharon (Educational Psychology Review, 2020) have raised a number of conceptual and empirical challenges to my claim that there is little or no evidence for systematic phonics (Bowers, Educational Psychology Review, 32, 681–705, 2020). But there are many mistakes, mischaracterizations, and omissions in the Fletcher et al. response that not only obscure the important similarities and differences in our views but also perpetuate common mischaracterizations of the evidence. In this response, I attempt to clarify a number of conceptual confusions, perhaps most importantly, the conflation of phonics with teaching GPCs. I do agree that children need to learn their GPCs, but that does not entail a commitment to systematic or any other form of phonics. With regard to the evidence, I respond to Fletcher et al.’s analysis of 12 meta-analyses and briefly review the reading outcomes in England following over a decade of legally mandated phonics. I detail why their response does not identify any flaws in my critique nor alter my conclusion that there is little or no support for the claim that phonics by itself or in a richer literacy curriculum is effective. We both agree that future research needs to explore how to combine various forms of instruction most effectively, including an earlier emphasis of morphological instruction, but we disagree that phonics must be part of the mix. I illustrate this by describing an alternative approach that rejects phonics, namely, Structured Word Inquiry.
Compatibility of intravitreally applied epidermal growth factor and amphiregulin
Authors: Bikbov Mukharram M. , Khalimov Timur A. , Cerrada-Gimenez Marc , Ragauskas Symantas , Kalesnykas Giedrius , Jonas Jost B.
Published: March 2021

Introduction

To examine the compatibility of intravitreally injected epidermal growth factor (EGF) and amphiregulin as EGF family member.

Methods

Four rabbits (age: 4 months; body weight: 2.5 kg) received three intravitreal injections of EGF (100 ng) uniocularly in monthly intervals and underwent ocular photography, tonometry, biometry, and optical coherence tomography. After sacrificing the rabbits, the globes were histomorphometrically examined. In a second study part, eyes of 22 guinea pigs (age: 2–3 weeks) received two intravitreal administrations of amphiregulin (10 ng) or phosphate buffered solution (PBS) in 10-day interval, or were left untouched. Ten days after the second injection, the guinea pigs were sacrificed, the enucleated eyes underwent histological and immune-histological examinations.

Results

The rabbit eyes with EGF injections versus the contralateral untouched eyes did not show significant differences in intraocular pressure (7.5 ± 2.4 mmHg vs. 6.8 ± 2.2 mmHg; P = 0.66), retinal thickness (158 ± 5 µm vs. 158 ± 3 µm; P = 1.0), cell counts in the retinal ganglion cell layer (3.3 ± 1.7 cells/150 µm vs. 3.0 ± 1.4 cells/150 µm; P = 0.83), inner nuclear layer (46.4 ± 23.2 cells/150 µm vs. 39.6 ± 6.4 cells/150 µm; P = 0.61), and outer nuclear layer (215 ± 108 cells/150 µm vs. 202 ± 47 cells/150 µm; P = 0.83), or any apoptotic retinal cells. The guinea pig eyes injected with amphiregulin versus eyes with PBS injections did not differ (P = 0.72) in the degree of microglial activation, and both groups did not differ from untouched eyes in number of apoptotic retinal cells and retinal gliosis.

Conclusions

Intravitreal applications of EGF (100 ng) in rabbits nor intravitreal applications of amphiregulin (10 ng) in guinea pigs led to intraocular specific inflammation or any observed intraocular destructive effect. The findings support the notion of a compatibility of intraocular applied EGF and amphiregulin.
Adapting the DeepSARM approach for dual-target ligand design
Authors: Yoshimori Atsushi , Hu Huabin , Bajorath Jürgen
Published: March 2021

The structure–activity relationship (SAR) matrix (SARM) methodology and data structure was originally developed to extract structurally related compound series from data sets of any composition, organize these series in matrices reminiscent of R-group tables, and visualize SAR patterns. The SARM approach combines the identification of structural relationships between series of active compounds with analog design, which is facilitated by systematically exploring combinations of core structures and substituents that have not been synthesized. The SARM methodology was extended through the introduction of DeepSARM, which added deep learning and generative modeling to target-based analog design by taking compound information from related targets into account to further increase structural novelty. Herein, we present the foundations of the SARM methodology and discuss how DeepSARM modeling can be adapted for the design of compounds with dual-target activity. Generating dual-target compounds represents an equally attractive and challenging task for polypharmacology-oriented drug discovery. The DeepSARM-based approach is illustrated using a computational proof-of-concept application focusing on the design of candidate inhibitors for two prominent anti-cancer targets.
Trichoderma harzianum Strain T22 Modulates Direct Defense of Tomato Plants in Response to Nezara viridula Feeding Activity
Authors: Alınç Tuğcan , Cusumano Antonino , Peri Ezio , Torta Livio , Colazza Stefano
Published: March 2021

Plant growth-promoting fungi belonging to genus Trichoderma are known to help plants when dealing with biotic stressors by enhancing plant defenses. While beneficial effects of Trichoderma spp. against plant pathogens have long been documented, fewer studies have investigated their effect on insect pests. Here, we studied the impact of Trichoderma root colonization on the plant defense responses against stink bug feeding attack. For this purpose, a model system consisting of tomato plant, Solanum lycopersicum cv Dwarf San Marzano, Trichoderma harzianum strain T22 and the southern green stink bug, Nezara viridula, was used. We firstly determined stink bug performance in terms of relative growth rate and survival on tomato plants inoculated by T. harzianum T22. Then, we evaluated relative expression of plant defense-related genes on inoculated plants induced by stink bug feeding. We found evidence that T. harzianum T22 affects tomato defense responses against N. viridula nymphs leading to reduction of growth rate. Our results also showed that T. harzianum T22 enhances plant direct defenses by an early increase of transcript levels of jasmonic acid marker genes. Yet this effect was time-dependent and only detected 8 h after herbivore induction. Taken together, our findings provide better understanding on the mechanisms underlying tomato induced resistance against herbivorous stink bugs.
Which graphs are rigid in $$\ell _p^d$$?
Authors: Dewar Sean , Kitson Derek , Nixon Anthony
Published: March 2021

We present three results which support the conjecture that a graph is minimally rigid in d-dimensional $$\ell _p$$

ℓ
p

-space, where $$p\in (1,\infty )$$

p
∈
(
1
,
∞
)

and $$p\not =2$$

p
≠
2

, if and only if it is (d, d)-tight. Firstly, we introduce a graph bracing operation which preserves independence in the generic rigidity matroid when passing from $$\ell _p^d$$

ℓ
p
d

to $$\ell _p^{d+1}$$

ℓ
p

d
+
1

. We then prove that every (d, d)-sparse graph with minimum degree at most $$d+1$$

d
+
1

and maximum degree at most $$d+2$$

d
+
2

is independent in $$\ell _p^d$$

ℓ
p
d

. Finally, we prove that every triangulation of the projective plane is minimally rigid in $$\ell _p^3$$

ℓ
p
3

. A catalogue of rigidity preserving graph moves is also provided for the more general class of strictly convex and smooth normed spaces and we show that every triangulation of the sphere is independent for 3-dimensional spaces in this class.
A novel kind of room temperature self-healing poly(urethane-urea) with robust mechanical strength based on aromatic disulfide
Authors: He Jin , Song Fangfang , Li Xiong , Chen Liyi , Gong Xingyu , Tu Weiping
Published: March 2021

An innovative poly(urethane-urea) elastomer, which exhibited excellent stretchability, thermal stability and autonomous self-healing abilities, was synthesized from the commercially available poly(propylene glycol) (PPG), isophorone diisocyanate (IPDI), 2,4 / 2,6-toluene diisocyanate (80: 20, w / w) (TDI-80) and bis (2-aminophenyl) disulfide (DSDA). This aromatic disulfide containing poly(urethane-urea) (ss-PUs) achieved both rapid room temperature self-healing abilities and robust mechanical strength (the ultimate tensile strength was up to 4.20 ± 0.10 MPa and elongation at break was up to 954 ± 35.6%), through facile metathesis of the aromatic disulfides which embedded in hard segments. After the ss-PUs was cut into two-halves and reconnected, the mechanical properties could recover to ~ 90% of those of the original samples within 12 h at room temperature without extra self-healing agents or any change of environmental conditions.
Towards a pragmatist dealing with algorithmic bias in medical machine learning
Authors: Starke Georg , De Clercq Eva , Elger Bernice S.
Published: March 2021

Machine Learning (ML) is on the rise in medicine, promising improved diagnostic, therapeutic and prognostic clinical tools. While these technological innovations are bound to transform health care, they also bring new ethical concerns to the forefront. One particularly elusive challenge regards discriminatory algorithmic judgements based on biases inherent in the training data. A common line of reasoning distinguishes between justified differential treatments that mirror true disparities between socially salient groups, and unjustified biases which do not, leading to misdiagnosis and erroneous treatment. In the curation of training data this strategy runs into severe problems though, since distinguishing between the two can be next to impossible. We thus plead for a pragmatist dealing with algorithmic bias in healthcare environments. By recurring to a recent reformulation of William James’s pragmatist understanding of truth, we recommend that, instead of aiming at a supposedly objective truth, outcome-based therapeutic usefulness should serve as the guiding principle for assessing ML applications in medicine.
Efficient iterative solutions to complex-valued nonlinear least-squares problems with mixed linear and antilinear operators
Authors: Kim Tae Hyung , Haldar Justin P.
Published: March 2021

We consider a setting in which it is desired to find an optimal complex vector $${\mathbf {x}}\in {\mathbb {C}}^N$$

x
∈

C

N

that satisfies $${\mathcal {A}}({\mathbf {x}}) \approx {\mathbf {b}}$$

A
(
x
)
≈
b

in a least-squares sense, where $${\mathbf {b}} \in {\mathbb {C}}^M$$

b
∈

C

M

is a data vector (possibly noise-corrupted), and $${\mathcal {A}}(\cdot ): {\mathbb {C}}^N \rightarrow {\mathbb {C}}^M$$

A

(
·
)

:

C

N

→

C

M

is a measurement operator. If $${\mathcal {A}}(\cdot )$$

A
(
·
)

were linear, this reduces to the classical linear least-squares problem, which has a well-known analytic solution as well as powerful iterative solution algorithms. However, instead of linear least-squares, this work considers the more complicated scenario where $${\mathcal {A}}(\cdot )$$

A
(
·
)

is nonlinear, but can be represented as the summation and/or composition of some operators that are linear and some operators that are antilinear. Some common nonlinear operations that have this structure include complex conjugation or taking the real-part or imaginary-part of a complex vector. Previous literature has shown that this kind of mixed linear/antilinear least-squares problem can be mapped into a linear least-squares problem by considering $${\mathbf {x}}$$
x
as a vector in $${\mathbb {R}}^{2N}$$

R

2
N

instead of $${\mathbb {C}}^N$$

C

N

. While this approach is valid, the replacement of the original complex-valued optimization problem with a real-valued optimization problem can be complicated to implement, and can also be associated with increased computational complexity. In this work, we describe theory and computational methods that enable mixed linear/antilinear least-squares problems to be solved iteratively using standard linear least-squares tools, while retaining all of the complex-valued structure of the original inverse problem. An illustration is provided to demonstrate that this approach can simplify the implementation and reduce the computational complexity of iterative solution algorithms.
Network design for line-based autonomous bus services
Authors: Hatzenbühler Jonas , Cats Oded , Jenelius Erik
Published: March 2021

The maturing of autonomous driving technology in recent years has led to several pilot projects and the initial integration of autonomous pods and buses into the public transport (PT) system. An emerging field of interest is the design of public transport networks operating autonomous buses and the potential to attract higher levels of travel demand. In this work a multi-objective optimization and multi-agent simulation framework is developed to study potential changes in the network design and frequency settings compared to conventional PT systems when autonomous vehicles (AV) systems are deployed on fixed-route networks. During the optimization process multiple deployment scenarios (network configurations and service frequency) are evaluated and optimized considering the operator cost, user cost and infrastructure preparation costs of the system. User-focused network design and operator-focused network design are studied for a real-world urban area in Sweden. The results provide insights into the network design and level of service implications brought about by the deployment of autonomous bus (AB) when those are integrated in route-based PT systems. We show that the deployment of autonomous buses result with a network design that increases service ridership. In the context of our case study this increase is likely to primarily substitute walking.
A multiplicative version of the Lindley recursion
Authors: Boxma Onno , Löpker Andreas , Mandjes Michel , Palmowski Zbigniew
Published: March 2021

This paper presents an analysis of the stochastic recursion $$W_{i+1} = [V_iW_i+Y_i]^+$$

W

i
+
1

=

[

V
i

W
i

+

Y
i

]

+

that can be interpreted as an autoregressive process of order 1, reflected at 0. We start our exposition by a discussion of the model’s stability condition. Writing $$Y_i=B_i-A_i$$

Y
i

=

B
i

-

A
i

, for independent sequences of nonnegative i.i.d. random variables $$\{A_i\}_{i\in {\mathbb N}_0}$$

{

A
i

}

i
∈

N
0

and $$\{B_i\}_{i\in {\mathbb N}_0}$$

{

B
i

}

i
∈

N
0

, and assuming $$\{V_i\}_{i\in {\mathbb N}_0}$$

{

V
i

}

i
∈

N
0

is an i.i.d. sequence as well (independent of $$\{A_i\}_{i\in {\mathbb N}_0}$$

{

A
i

}

i
∈

N
0

and $$\{B_i\}_{i\in {\mathbb N}_0}$$

{

B
i

}

i
∈

N
0

), we then consider three special cases (i) $$V_i$$

V
i

equals a positive value a with certain probability $$p\in (0,1)$$

p
∈
(
0
,
1
)

and is negative otherwise, and both $$A_i$$

A
i

and $$B_i$$

B
i

have a rational LST, (ii) $$V_i$$

V
i

attains negative values only and $$B_i$$

B
i

has a rational LST, (iii) $$V_i$$

V
i

is uniformly distributed on [0, 1], and $$A_i$$

A
i

is exponentially distributed. In all three cases, we derive transient and stationary results, where the transient results are in terms of the transform at a geometrically distributed epoch.
Health-related quality of life in refugee youth and the mediating role of mental distress and post-migration stressors
Authors: Dangmann Cecilie , Solberg Øivind , Andersen Per Normann
Published: March 2021

Purpose

The aim of this study is to explore how potentially traumatic events (PTEs) from war and flight influence health-related quality of life (HRQoL) in young refugees after recent resettlement. In a model based on earlier theory, we tested if post-migration stressors and mental distress mediated the effect of PTEs on HRQoL, individually and in serial. We also explored how different types of post-migration stressors influenced different dimensions of HRQoL.

Methods

This study used a cross-sectional design where 160 Syrian youth recently resettled in Norway completed questionnaires at school between May and December 2018. Correlations between types of post-migration stressors and dimensions of HRQoL were explored and a serial multiple mediator model was tested. Models were adjusted for age and gender, using two types of mental distress; post-traumatic stress disorder (PTSD) and general mental distress.

Results

Higher levels of PTEs reduced experienced HRQoL, but this direct effect was mediated by post-migration stressors alone and in serial with mental distress. Despite high levels of mental distress, this did not affect HRQoL independently, only in serial mediation with increased post-migration stressors. Economic concerns and discrimination were types of post-migration stressors affecting several dimensions of HRQoL.

Conclusion

Quality of life in refugee is affected by past events from war, stressors in current resettlement and elevated mental distress through complex interrelations. The study reiterates the importance of considering structural and everyday post-migration stressors in policy and intervention to improve the health and wellbeing of refugee youth.
Correction to: A Multi-Perspective Reflection on How Indigenous Knowledge and Related Ideas Can Improve Science Education for Sustainability
Authors: Zidny Robby , Sjöström Jesper , Eilks Ingo
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1007/s11191-021-00194-2
A Community-Structure-Based Method for Estimating the Fractal Dimension, and its Application to Water Networks for the Assessment of Vulnerability to Disasters
Authors: Giudicianni C. , Di Nardo A. , Greco R. , Scala A.
Published: March 2021

Most real-world networks, from the World-Wide-Web to biological systems, are known to have common structural properties. A remarkable point is fractality, which suggests the self-similarity across scales of the network structure of these complex systems. Managing the computational complexity for detecting the self-similarity of big-sized systems represents a crucial problem. In this paper, a novel algorithm for revealing the fractality, that exploits the community structure principle, is proposed and then applied to several water distribution systems (WDSs) of different size, unveiling a self-similar feature of their layouts. A scaling-law relationship, linking the number of clusters necessary for covering the network and their average size is defined, the exponent of which represents the fractal dimension. The self-similarity is then investigated as a proxy of recurrent and specific response to multiple random pipe failures – like during natural disasters – pointing out a specific global vulnerability for each WDS. A novel vulnerability index, called Cut-Vulnerability is introduced as the ratio between the fractal dimension and the average node degree, and its relationships with the number of randomly removed pipes necessary to disconnect the network and with some topological metrics are investigated. The analysis shows the effectiveness of the novel index in describing the global vulnerability of WDSs.
XChange: A Universal Mechanism for Asset Exchange between Permissioned Blockchains
Authors: de Vos Martijn , Ileri Can Umut , Pouwelse Johan
Published: March 2021

Permissioned blockchains are increasingly being used as a solution to record transactions between companies. Several use cases that leverage permissioned blockchains focus on the representation and management of real-world assets. Since the number of incompatible blockchains is quickly growing, there is an increasing need for a universal mechanism to exchange, or trade, digital assets between these isolated platforms. There currently is no universal mechanism for inter-blockchain asset exchange without a requirement for trusted authorities that coordinate the trade. We address this shortcoming and present XChange, a universal mechanism for asset exchange between permissioned blockchains. To achieve universality and to avoid trusted authorities that coordinate a trade, XChange does not provide atomic guarantees but leverages risk mitigation strategies to reduce value at stake. Our mechanism records the specifications and progression of each trade within records on a distributed log. XChange reduces the economic gains of adversaries by bounding the total amount of fraud they can commit at any time. After having committed fraud, an adversary is forced to finish its ongoing trades before it can engage in new trades. We first present a four-phased protocol that coordinates an asset exchange between two traders. We then outline how trade records can be stored on TrustChain, which is a lightweight distributed ledger specifically built for the tamper-proof storage of data elements. We implement XChange and conduct experiments. Our experiments demonstrate that XChange is capable of reducing the economic gains of adversaries by more than 99.9% when replaying a real-world trading dataset. A deployment on low-resource devices reveals that the latency added to a trade by XChange is only 493 milliseconds. Finally, our scalability evaluation shows that XChange achieves over 1’000 trades per second and that its throughput, in terms of trades per second, scales linearly with the system load.
Does cattle and sheep grazing under best management significantly elevate sediment losses? Evidence from the North Wyke Farm Platform, UK
Authors: Pulley S. , Cardenas L. M. , Grau P. , Mullan S. , Rivero M. J. , Collins A. L.
Published: March 2021

Purpose

Intensive livestock grazing has been associated with an increased risk of soil erosion and concomitant negative impacts on the ecological status of watercourses. Whilst various mitigation options are promoted for reducing livestock impacts, there is a paucity of data on the relationship between stocking rates and quantified sediment losses. This evidence gap means there is uncertainty regarding the cost–benefit of policy preferred best management.

Methods

Sediment yields from 15 hydrologically isolated field scale catchments on a heavily instrumented ruminant livestock farm in the south west UK were investigated over ~ 26 months spread across 6 years. Sediment yields were compared to cattle and sheep stocking rates on long-term, winter (November–April), and monthly timescales. The impacts of livestock on soil vegetation cover and bulk density were also examined. Cattle were tracked using GPS collars to determine how grazing related to soil damage.

Results

No observable impact of livestock stocking rates of 0.15–1.00 UK livestock units (LU) ha−1 for sheep, and 0–0.77 LU ha−1 for cattle on sediment yields was observed at any of the three timescales. Cattle preferentially spent time close to specific fences where soils were visually damaged. However, there was no indication that livestock have a significant effect on soil bulk density on a field scale. Livestock were housed indoors during winters when most rainfall occurs, and best management practices were used which when combined with low erodibility clayey soils likely limited sediment losses.

Conclusion

A combination of clayey soils and soil trampling in only a small proportion of the field areas lead to little impact from grazing livestock. Within similar landscapes with best practice livestock grazing management, additional targeted measures to reduce erosion are unlikely to yield a significant cost-benefit.
Curcumin suppresses LGR5(+) colorectal cancer stem cells by inducing autophagy and via repressing TFAP2A-mediated ECM pathway
Authors: Mao Xiaohong , Zhang Xin , Zheng Xiaowei , Chen Yongwu , Xuan Zixue , Huang Ping
Published: March 2021

Colorectal cancer stem cells (CSCs) have the potential for self-renewal, proliferation, and differentiation. And LGR5 is a stem cell marker gene of colorectal cancer. Curcumin can suppress oncogenicity of many cancer cells, yet the effect and mechanism of curcumin in LGR5(+) colorectal cancer stem cells (CSCs) have not been studied. In this study, we studied the effect of curcumin on LGR5(+) colorectal CSCs using the experiments of tumorsphere formation, cell viability and cell apoptosis. Then autophagy analysis, RNA-Seq, and real-time PCR were used to identify the mechanism responsible for the inhibition of LGR5(+) colorectal CSCs. Our results showed that curcumin inhibited tumorsphere formation, decreased cell viability in a dose-dependent manner, and also promoted apoptosis of LGR5(+) colorectal CSCs. Next, we found curcumin induced autophagy of LGR5(+) colorectal CSCs. When LGR5(+) colorectal CSCs were co-treated with curcumin and the autophagy inhibitor (hydroxychloroquine), curcumin-induced cell proliferation inhibition decreased. In addition, we also found that curcumin inhibited the extracellular matrix (ECM)-receptor interaction pathway via the downregulation of the following genes: GP1BB, COL9A3, COMP, AGRN, ITGB4, LAMA5, COL2A1, ITGB6, ITGA1, and TNC. Further, these genes were transcriptionally regulated by TFAP2A, and the high expression of TFAP2A was associated with poor prognosis in colorectal cancer. In conclusion, curcumin suppressed LGR5(+) colorectal CSCs, potentially by inducing autophagy and repressing the oncogenic TFAP2A-mediated ECM pathway.

Graphic abstract
Citizen Science Fiction: The Potential of Situated Speculative Prototyping for Public Engagement on Emerging Technologies
Authors: Schuijer Jantien W. , Broerse Jacqueline E. W. , Kupper Frank
Published: March 2021

In response to calls for a research and innovation system that is more open to public scrutiny, we have seen a growth of formal and informal public engagement activities in the past decades. Nevertheless, critiques of several persistent routines in public engagement continue to resurface, in particular the focus on expert knowledge, cognitive exchange, risk discourse, and understandings of public opinion as being static. In an attempt to break out of these routines, we experimented with an innovative engagement format that employs situated speculative prototyping to support citizens in contextualizing and discussing developments regarding—in this case—nanotechnology. This format invites participants to imagine and critically reflect on technological futures through collaborative prototyping and story-writing. In this paper, we outline five reconstructed contextualization patterns in which participants engaged during the format’s exercises and use these to assess the value of the format in the current engagement landscape. We show that situated speculative prototyping has potential in the realm of informal public engagement initiatives, taking an explorative approach, but also warn of ‘the designer fallacy’ as a prominent pitfall of prototyping that could reproduce techno-scientific framings and obstruct critical reflection on technological directions and implications if not treated with caution.
Is It Possible to Predict Weight Loss After Bariatric Surgery?—External Validation of Predictive Models
Authors: Karpińska Izabela A. , Kulawik Jan , Pisarska-Adamczyk Magdalena , Wysocki Michał , Pędziwiatr Michał , Major Piotr
Published: March 2021

Background

Bariatric surgery is the most effective obesity treatment. Weight loss varies among patients, and not everyone achieves desired outcome. Identification of predictive factors for weight loss after bariatric surgery resulted in several prediction tools proposed. We aimed to validate the performance of available prediction models for weight reduction 1 year after surgical treatment.

Materials and Methods

The retrospective analysis included patients after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) who completed 1-year follow-up. Postoperative body mass index (BMI) predicted by 12 models was calculated for each patient. The correlation between predicted and observed BMI was assessed using linear regression. Accuracy was evaluated by squared Pearson’s correlation coefficient (R2). Goodness-of-fit was assessed by standard error of estimate (SE) and paired sample t test between estimated and observed BMI.

Results

Out of 760 patients enrolled, 509 (67.00%) were women with median age 42 years. Of patients, 65.92% underwent SG and 34.08% had RYGB. Median BMI decreased from 45.19 to 32.53kg/m2 after 1 year. EWL amounted to 62.97%. All models presented significant relationship between predicted and observed BMI in linear regression (correlation coefficient between 0.29 and 1.22). The best predictive model explained 24% variation of weight reduction (adjusted R2=0.24). Majority of models overestimated outcome with SE 5.03 to 5.13kg/m2.

Conclusion

Although predicted BMI had reasonable correlation with observed values, none of evaluated models presented acceptable accuracy. All models tend to overestimate the outcome. Accurate tool for weight loss prediction should be developed to enhance patient’s assessment.

Graphical abstract
Non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and cardiovascular events in atrial fibrillation. A prospective multicenter cohort study
Authors: Pastori Daniele , Sciacqua Angela , Marcucci Rossella , Del Ben Maria , Baratta Francesco , Violi Francesco , Pignatelli Pasquale ,   the ATHERO-AF study group, Saliola Mirella , Menichelli Danilo , Casciaro Marco Antonio , Angelico Francesco , Cammisotto Vittoria , Nocella Cristina , Bartimoccia Simona , Carnevale Roberto , Novelli Laura
Published: March 2021

Whether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular events (CVEs) independently from metabolic syndrome (MetS) is still matter of debate. Aim of the study was to investigate the risk of CVEs in a high-risk population of patients with non-valvular atrial fibrillation (AF) according to the presence of MetS and NAFLD. Prospective observational multicenter study including 1,735 patients with non-valvular AF treated with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). NAFLD was defined by a fatty liver index ≥ 60. We categorized patients in 4 groups: 0 = neither MetS or NAFLD (38.6%), 1 = NAFLD alone (12.4%), 2 = MetS alone (19.3%), 3 = both MetS and NAFLD (29.7%). Primary endpoint was a composite of CVEs. Mean age was 75.4 ± 9.4 years, and 41.4% of patients were women. During a mean follow-up of 34.1 ± 22.8 months (4,926.8 patient-years), 155 CVEs were recorded (incidence rate of 3.1%/year): 55 occurred in Group 0 (2.92%/year), 12 in Group 1 (2.17%/year), 45 in Group 2 (4.58%/year) and 43 in Group 3 (2.85%/year). Multivariable Cox regression analysis showed that use of DOACs, and female sex were inversely associated with CVEs, whilst age, heart failure, previous cardiac and cerebrovascular events, and group 2 (Group 2, Hazard Ratio 1.517, 95% Confidence Interval, 1.010–2.280) were directly associated with CVEs. In patients with AF, MetS increases the risk of CVEs. Patients with NAFLD alone have lower cardiovascular risk but may experience higher liver-related complications.
Diagnosis and management of leukocytoclastic vasculitis
Authors: Fraticelli Paolo , Benfaremo Devis , Gabrielli Armando
Published: March 2021

Leukocytoclastic vasculitis (LCV) is a histopathologic description of a common form of small vessel vasculitis (SVV), that can be found in various types of vasculitis affecting the skin and internal organs. The leading clinical presentation of LCV is palpable purpura and the diagnosis relies on histopathological examination, in which the inflammatory infiltrate is composed of neutrophils with fibrinoid necrosis and disintegration of nuclei into fragments (“leukocytoclasia”). Several medications can cause LCV, as well as infections, or malignancy. Among systemic diseases, the most frequently associated with LCV are ANCA-associated vasculitides, connective tissue diseases, cryoglobulinemic vasculitis, IgA vasculitis (formerly known as Henoch–Schonlein purpura) and hypocomplementemic urticarial vasculitis (HUV). When LCV is suspected, an extensive workout is usually necessary to determine whether the process is skin-limited, or expression of a systemic vasculitis or disease. A comprehensive history and detailed physical examination must be performed; platelet count, renal function and urinalysis, serological tests for hepatitis B and C viruses, autoantibodies (anti-nuclear antibodies and anti-neutrophil cytoplasmic antibodies), complement fractions and IgA staining in biopsy specimens are part of the usual workout of LCV. The treatment is mainly focused on symptom management, based on rest (avoiding standing or walking), low dose corticosteroids, colchicine or different unproven therapies, if skin-limited. When a medication is the cause, the prognosis is favorable and the discontinuation of the culprit drug is usually resolutive. Conversely, when a systemic vasculitis is the cause of LCV, higher doses of corticosteroids or immunosuppressive agents are required, according to the severity of organ involvement and the underlying associated disease.
Multiple small tumor formation on both surfaces of the aortic valve cusps in Epstein–Barr virus-associated T/NK-cell lymphoproliferative disease: a case report
Authors: Tai Ryuta , Irie Hiroyuki , Kinugasa Yusuke , Teshima Hideki , Ikebuchi Masahiko , Kaneko Keiko , Miyazaki Nobuhiro , Enzan Hideaki , Yoshino Tadashi
Published: March 2021

A 41-year-old woman presented acute cerebral infarction. Transesophageal echocardiography revealed multiple masses only on both surfaces of the aortic valve cusps. There was no primary lesion outside the heart according to various examinations. After treatment for cerebral infarction, we replaced the aortic valve instead of preservation because the intraoperative histological examination reported that malignancy was highly suspected. Contrary to the rapid frozen section diagnosis, histological and immunohistochemical examinations failed to exhibit malignancy. The tumors were composed of atypical large lymphoid cells and they were assessed to be related to T-/natural killer-cells. Furthermore, Epstein–Barr virus related markers were also positive. Her three-year postoperative course was uneventful without chemotherapy. We report an extremely rare case of Epstein–Barr virus-associated T-/natural killer-cell lymphoproliferative disease which formed multiple small tumors on both surfaces of the aortic valve.
Archaeology, Participatory Democracy and Social Justice in Newfoundland and Labrador, Canada
Authors: Rankin Lisa , Gaulton Barry
Published: March 2021

Memorial University, located in St. John’s, Newfoundland and Labrador, was created in 1925 to help build a better future for the people of Canada’s easternmost province, whose largely rural fishing communities were rapidly transforming through industrialization and urbanization. Mandated by a “special obligation to the people of the province,” university archaeologists embraced applied, community-based projects which encouraged local solutions to the social and economic issues arising from the transformation to modernity. Today, community archaeology remains integral to our research program and the majority of our research is undertaken in partnership with rural and Indigenous populations who continue to be marginalized both geographically and economically. Two case studies describe how archaeological resources are being used to promote economic and social justice, as well as reconciliation, and how archaeology has the potential to make valuable local contributions that change lives in the present.
From Exploration to Re-Enactment: Instructional Uses of a Desktop Virtual Environment for Training Nuclear Plant Field Operators
Authors: Drakos Artémis , Flandin Simon , Filippi Geneviève , Palaci François , Veyrunes Philippe , Poizat Germain
Published: March 2021

Despite the growing use of virtual environments for training in complex industrial settings, we have little understanding of how these innovative settings transform training and trainers everyday work. This study investigates the instructional use of an industrial building’s virtual environment by expert trainers during a training session for nuclear power plant field operators. Drawing from the course-of-action theoretical and methodological framework, field notes, continuous video-recording of the training sessions and verbalisations during post-training self-confrontation interviews with the trainers were collected and analysed. The results point out four typical instructional uses of the virtual environment in authentic settings: (a) showing the material elements and spatial layout of certain areas of the reactor building, (b) displaying safe and typical paths through the building, (c) explaining functional aspects to help trainees develop an operating model of the nuclear building, and (d) sharing salient experience through real-life anecdotes. These typical uses and their related learning dimensions are anchored in the re-enactments of expert trainer’s embodied past events. The discussion develops the counterintuitive idea that from an instructional point of view, the intensified immersion of trainers afforded by the virtual environment seems less influential than emerging practice-based learning experiences. We conclude with new possibilities for improving learning through and for work thanks to re-enactment of expert trainers’ past work practices.
Assimilation of D-InSAR snow depth data by an ensemble Kalman filter
Authors: Yang Jinming , Li Chengzhi
Published: March 2021

Snow depth mirrors regional climate change and is a vital parameter for medium- and long-term numerical climate prediction, numerical simulation of land-surface hydrological process, and water resource assessment. However, the quality of the available snow depth products retrieved from remote sensing is inevitably affected by cloud and mountain shadow, and the spatiotemporal resolution of the snow depth data cannot meet the need of hydrological research and decision-making assistance. Therefore, a method to enhance the accuracy of snow depth data is urgently required. In the present study, three kinds of snow depth data which included the D-InSAR data retrieved from the remote sensing images of Sentinel-1 synthetic aperture radar, the automatically measured data using ultrasonic snow depth detectors, and the manually measured data were assimilated based on ensemble Kalman filter. The assimilated snow depth data were spatiotemporally consecutive and integrated. Under the constraint of the measured data, the accuracy of the assimilated snow depth data was higher and met the need of subsequent research. The development of ultrasonic snow depth detector and the application of D-InSAR technology in snow depth inversion had greatly alleviated the insufficiency of snow depth data in types and quantity. At the same time, the assimilation of multi-source snow depth data by ensemble Kalman filter also provides high-precision data to support remote sensing hydrological research, water resource assessment, and snow disaster prevention and control program.
Two-season agriculture and irrigated rice during the Dian: radiocarbon dates and archaeobotanical remains from Dayingzhuang, Yunnan, Southwest China
Authors: Dal Martello Rita , Li Xiaorui , Fuller Dorian Q.
Published: March 2021

Historical sources describe irrigation and intensive agriculture being practiced in lowland Yunnan from at least the first century AD, but so far archaeobotanical remains allowing investigation of this issue have been scarce. Here, we present new archaeobotanical evidence, including macro-botanical and phytoliths results, from the Dian settlement site of Dayingzhuang, with direct AMS radiocarbon dates on two wheat grains falling between 750 and 390 BC. We compare these results with contemporary Dian sites and analyse the agricultural systems in Central Yunnan between the eight and fourth centuries BC. We propose that agriculture was intensified toward the end of the Dian through both multiple cropping seasons and increased evidence for irrigated rice fields.
Optimizing the innovation and development process of medical devices - a study based on angiographic equipment
Authors: Busch Erik , Strobel Norbert , Nobach Kai , Bulitta Clemens , Hirshfeld John W. , Wu Lin , de Abreu Marcel Gama
Published: March 2021

Cardiovascular diseases are the leading cause of death. The gold standard for their diagnosis and treatment are angiographic procedures, which require specialized equipment. The speed of their continued development is important as better technology enables progress in clinical outcomes. This article proposes a new process model for the innovation and development and shows how to optimize it such that it takes minimal time. The conducted literature research identifies this closed loop process model as being unique in comparison to the well-established models proposed by Brockhoff, Cooper, Crawford, Durfee, Ebert, Eppinger, Hughes, Pleschak, Thom, Ulrich, Vahs and Witt. During a long-term observation of the innovation and development process of angiographic systems 672 data sets on 302 topics were collected over 47 months to validate this process model. The data collected is equivalent to efforts worth 30 man-years. This input was used to calculate key process parameters, analyse key process roles, evaluate the use of problem-solving methods and identify key technologies. We recommend to apply a continuous loop process in the context of innovation and development of medical devices. In the analysed datasets a potential of an up to 20% shorter process time was identified. Our results can be used for an Activity Based Costing Approach or be applied to bring new or upgraded angiography systems faster to market benefitting patient outcome due to improved diagnosis and treatment. According to the best knowledge of the authors no comparable data collection relating to angiography systems has been performed and presented anywhere else yet.
Probiotic Properties of Alcaligenes faecalis Isolated from Argyrosomus regius in Experimental Peritonitis (Rat Model)
Authors: Gutiérrez-Falcón A. I. , Ramos-Nuez A. M. , de los Monteros y Zayas A. Espinosa , Castillo D. F. Padilla , García-Laorden M. Isabel , Chamizo-López F. J. , Real Valcárcel F. , Campelo F. Artilles , Benítez A. Bordes , Salgueiro P. Nogueira , Cabrera C. Domínguez , Rivero-Vera J. C. , González-Martín J. M. , Caballero J. Martín , Frías-Beneyto R. , Villar Jesús , Martín-Barrasa J. L.
Published: March 2021

A strain ofAlcaligenes faecalisA12C (A. faecalisA12C) isolated fromArgyrosomus regiusis a probiotic in fish. Previous experiments showed thatA. faecalisA12C had inhibitory effects on the growth of multidrug-resistant bacteria. We aimed to confirm whetherA. faecalisA12C is safe and has adequate intestinal colonization in experimental rats, and evaluate its efficacy in an animal model of peritonitis.We used 30 male rats, randomly divided into 6 groups (n = 5): three groups (HA7, HA15, HA30) receivedA. faecalisA12C in drinking water (6 × 108 CFU/mL) for 7 days, and three control groups received drinking water only. All groups were evaluated at 7, 15, and 30 days. Survival afterA. faecalisA12C administration was 100% in all groups. Mild eosinophilia (1.5%,p < 0.01) and increased aspartate aminotransferase (86 IU/L,p < 0.05) were observed in HA7, followed by progressive normalization. No histological signs of organ injury were found. We observed significantE. colidecline in faeces, parallel to an increase inA. faecalisA12C at 7 days.E. colihad a tendency to recover initial values, whileA. faecalisA12C disappeared from the intestinal microbiota at 30 days. To evaluate its efficacy against peritonitis, we studied two additional groups of animals: IA group pretreated withA. faecalisA12C beforeE. coliintra-abdominal inoculation, and IC group inoculated with noA. faecalisA12C. We found an increase in C-reactive protein, alanine aminotransferase, urea, and eosinophils in IC animals when compared with IA. Peritonitis was more evident in IC than in IA animals. Our findings suggest thatA. faecalisA12C altered clinically relevant parameters in sepsis and was associated with a lesser spread of infection.