bluuebunny/crossref_metadata_2025_split huggingface dataset:
A semiquantitative color Doppler ultrasound scoring system for evaluation of synovitis in joints of patients with blood-induced arthropathy
Authors: Zhang Ningning , Yang Sheng , Zwagemaker Anne-Fleur , Huo Aihua , Li Ying-Jia , Zhou Fang , Hilliard Pamela , Squire Sandra , Bouskill Vanessa , Mohanta Arun , Zhou Alex , Jarrin Jose , Wu Runhui , Sun Jing , Luke Brian , Moineddin Rahim , Blanchette Victor S. , Peng Yun , Doria  Andrea S. 
Published: September 2021

Abstract
Background
Intra-articular bleeds in patients with inherited bleeding disorders lead to active synovitis which may progress to a chronic state over time. We explored the diagnostic value of color Doppler ultrasound in detecting synovitis in boys with bleeding disorders.

Results
Sixty boys with hemophilia and 3 boys with type 3 von Willebrand disease aged 5 to 18 years (median 12.3 years) were imaged by gray-scale and color Doppler ultrasound (US) in three centers (Beijing, China [n = 22], Guangzhou, China [n = 12] and Toronto, Canada [n = 29])) in this observational study. Images were independently reviewed by two radiologists blinded to clinical data using a subjective semi-quantitative scoring system and objective measurements of synovial thickness and vascularity. Inter-reader reliability for using subjective versus objective color Doppler US methods for assessing synovial vascularity was excellent for the subjective method and moderate/lower range of substantial for the objective method. Agreement between degree of vascularity on color Doppler and extent of synovial hypertrophy on gray-scale US was overall poor for Canada data and moderate for China data. Correlations between degree of vascularity on color Doppler and synovial hypertrophy on gray-scale US, and clinical constructs (total and itemized HJHS scores and total Pettersson X-ray scores) for assessment of blood-induced arthropathy were all poor.

Conclusion
Color Doppler US is a valuable scoring method for evaluating reactive synovitis in joints of subjects with inherited bleeding disorders and holds potential for assessing post-bleed reactive synovitis once further information on its association with timing of the joint bleed becomes available in the literature.
Cost-effectiveness of artificial intelligence aided vessel occlusion detection in acute stroke: an early health technology assessment
Authors: van Leeuwen Kicky G. , Meijer Frederick J. A. , Schalekamp Steven , Rutten Matthieu J. C. M. , van Dijk Ewoud J. , van Ginneken Bram , Govers Tim M. , de Rooij Maarten 
Published: September 2021

Abstract
Background
Limited evidence is available on the clinical impact of artificial intelligence (AI) in radiology. Early health technology assessment (HTA) is a methodology to assess the potential value of an innovation at an early stage. We use early HTA to evaluate the potential value of AI software in radiology. As a use-case, we evaluate the cost-effectiveness of AI software aiding the detection of intracranial large vessel occlusions (LVO) in stroke in comparison to standard care. We used a Markov based model from a societal perspective of the United Kingdom predominantly using stroke registry data complemented with pooled outcome data from large, randomized trials. Different scenarios were explored by varying missed diagnoses of LVOs, AI costs and AI performance. Other input parameters were varied to demonstrate model robustness. Results were reported in expected incremental costs (IC) and effects (IE) expressed in quality adjusted life years (QALYs).

Results
Applying the base case assumptions (6% missed diagnoses of LVOs by clinicians, $40 per AI analysis, 50% reduction of missed LVOs by AI), resulted in cost-savings and incremental QALYs over the projected lifetime (IC: − $156, − 0.23%; IE: + 0.01 QALYs, + 0.07%) per suspected ischemic stroke patient. For each yearly cohort of patients in the UK this translates to a total cost saving of $11 million.

Conclusions
AI tools for LVO detection in emergency care have the potential to improve healthcare outcomes and save costs. We demonstrate how early HTA may be applied for the evaluation of clinically applied AI software for radiology.
Meniscal ramp lesions: an illustrated review
Authors: Taneja Atul K. , Miranda Frederico C. , Rosemberg Laercio A. , Santos Durval C. B. 
Published: September 2021

AbstractThe purpose of this review is to describe the anatomy and lesions affecting the peripheral portion of posterior horn of medial menisci (ramp lesions), along with illustrations and MRI cases. We will correlate imaging features with arthroscopic classification of ramp lesions. Also, postoperative and chronic changes related to meniscocapsular tears will be presented, as well as biomechanical consequences and treatment approach.
Computed tomography-based multiple body composition parameters predict outcomes in Crohn’s disease
Authors: Zhou Ziling , Xiong Ziman , Xie Qingguo , Xiao Peng , Zhang Qingpeng , Gu Jian , Li Jing , Hu Daoyu , Hu Xuemei , Shen Yaqi , Li Zhen 
Published: September 2021

Abstract
Background
The efficacy of computed tomography-based multiple body composition parameters in assessing disease behavior and prognosis has not been comprehensively evaluated in Crohn’s disease. This study aimed to assess the association of body composition parameters with disease behavior and outcomes in Crohn’s disease and to compare the efficacies of indexes derived from body and lumbar spinal heights in body composition analysis.

Results
One hundred twenty-two patients with confirmed Crohn’s disease diagnoses and abdominal computed tomography scans were retrospectively included in this study. Skeletal muscle, visceral, and subcutaneous fat indexes were calculated by dividing each type of tissue area by height2 and lumbar spinal height2. Parameters reflecting the distribution of adiposity were also assessed. Principal component analysis was used to deal with parameters with multicollinearity. Patients were grouped according to their disease behavior (inflammatory vs. structuring/penetrating) and outcomes. Adverse outcome included need for intestinal surgery or anti-TNF therapy. Predictors of disease course from multiple parameters were evaluated using multivariate analysis. Indexes derived from body and lumbar spinal heights were strongly correlated (r, 0.934–0.995; p < 0.001). Low skeletal muscle-related parameters were significantly associated with complicated disease behavior in multivariate analysis (p = 0.048). Complicated disease behavior (p < 0.001) and adipose tissue parameters-related first principal component (p = 0.029) were independent biomarkers for predicting adverse outcomes.

Conclusions
Skeletal muscle and adipose tissue principle component were associated with complicated Crohn’s disease behavior and adverse outcome, respectively. Indexes derived from body and lumbar spinal heights have similar efficacies in body composition analysis.
AKT signaling is associated with epigenetic reprogramming via the upregulation of TET and its cofactor, alpha-ketoglutarate during iPSC generation
Authors: Sekita Yoichi , Sugiura Yuki , Matsumoto Akari , Kawasaki Yuki , Akasaka Kazuya , Konno Ryo , Shimizu Momoka , Ito Toshiaki , Sugiyama Eiji , Yamazaki Terushi , Kanai Eriko , Nakamura Toshinobu , Suematsu Makoto , Ishino Fumitoshi , Kodera Yoshio , Kohda Takashi , Kimura Tohru 
Published: September 2021

AbstractBackgroundPhosphoinositide-3 kinase (PI3K)/AKT signaling participates in cellular proliferation, survival and tumorigenesis. The activation of AKT signaling promotes the cellular reprogramming including generation of induced pluripotent stem cells (iPSCs) and dedifferentiation of primordial germ cells (PGCs). Previous studies suggested that AKT promotes reprogramming by activating proliferation and glycolysis. Here we report a line of evidence that supports the notion that AKT signaling is involved in TET-mediated DNA demethylation during iPSC induction.MethodsAKT signaling was activated in mouse embryonic fibroblasts (MEFs) that were transduced with OCT4, SOX2 and KLF4. Multiomics analyses were conducted in this system to examine the effects of AKT activation on cells undergoing reprogramming.ResultsWe revealed that cells undergoing reprogramming with artificially activated AKT exhibit enhanced anabolic glucose metabolism and accordingly increased level of cytosolic α-ketoglutarate (αKG), which is an essential cofactor for the enzymatic activity of the 5-methylcytosine (5mC) dioxygenase TET. Additionally, the level of TET is upregulated. Consistent with the upregulation of αKG production and TET, we observed a genome-wide increase in 5-hydroxymethylcytosine (5hmC), which is an intermediate in DNA demethylation. Moreover, the DNA methylation level of ES-cell super-enhancers of pluripotency-related genes is significantly decreased, leading to the upregulation of associated genes. Finally, the transduction of TET and the administration of cell-permeable αKG to somatic cells synergistically enhance cell reprogramming by Yamanaka factors.ConclusionThese results suggest the possibility that the activation of AKT during somatic cell reprogramming promotes epigenetic reprogramming through the hyperactivation of TET at the transcriptional and catalytic levels.
Transplantation of mesenchymal stem cells ameliorates systemic lupus erythematosus and upregulates B10 cells through TGF-β1
Authors: Chun Wang , Tian Jilai , Zhang Ying 
Published: September 2021

Abstract
Background
Considerable experimental and clinical evidences have proved that human umbilical cord mesenchymal stem cells (UC-MSCs) transplantation was powerful in systemic lupus erythematosus (SLE) treatment. MSCs could upregulate regulatory B cells (Bregs) in the mice model of the other immune disease. However, the regulation of MSCs on Bregs in SLE environment remains unclear.

Methods
To assess the abilities of UC-MSCs to treat SLE, MSCs were transferred intravenously to 17- to 18-week-old MRL/lpr mice. Four weeks later, mice were sacrificed. Survival rates, anti-dsDNA antibodies and renal histology were evaluated. CD4+ T helper (Th) cell subgroups and interleukin (IL)-10+ Bregs (B10) in the spleen were quantitated by flow cytometry. The changes of transforming growth factor (TGF)-β1, IL-6 and indoleamine 2,3-dioxyenase (IDO) mRNAs expressed by MSCs after co-cultured with B cells were detected using real-time polymerase chain reaction (RT-PCR). MSCs were infected by lentivirus carrying TGF-β1 shRNAs, then MSCs with low expression of TGF-β1 were conducted for co-culture in vitro and transplantation experiments in vivo.

Results
UC-MSCs transplantation could efficiently downregulate 24 h proteinuria and anti-dsDNA antibodies, correct Treg/Th17/Th1 imbalances and increase the frequency of B10 cells. The expression of TGF-β1 in MSCs was significantly increased after co-culture with B cells. Downregulation of TGF-β1 in MSCs could significantly attenuate the upregulation of B10 by MSCs in vitro and in vivo. Downregulation of TGF-β1 also compromised the immunomodulation effects of MSCs on Th17 and Treg cells and the therapeutic effects of MSC transplantation.

Conclusions
UC-MSCs could protect against SLE in mice and upregulate IL-10+ Bregs via TGF-β1.
GenUI: interactive and extensible open source software platform for de novo molecular generation and cheminformatics
Authors: Sicho M. , Liu X. , Svozil D. , van Westen G. J. P. 
Published: September 2021

AbstractMany contemporary cheminformatics methods, including computer-aided de novo drug design, hold promise to significantly accelerate and reduce the cost of drug discovery. Thanks to this attractive outlook, the field has thrived and in the past few years has seen an especially significant growth, mainly due to the emergence of novel methods based on deep neural networks. This growth is also apparent in the development of novel de novo drug design methods with many new generative algorithms now available. However, widespread adoption of new generative techniques in the fields like medicinal chemistry or chemical biology is still lagging behind the most recent developments. Upon taking a closer look, this fact is not surprising since in order to successfully integrate the most recent de novo drug design methods in existing processes and pipelines, a close collaboration between diverse groups of experimental and theoretical scientists needs to be established. Therefore, to accelerate the adoption of both modern and traditional de novo molecular generators, we developed Generator User Interface (GenUI), a software platform that makes it possible to integrate molecular generators within a feature-rich graphical user interface that is easy to use by experts of diverse backgrounds. GenUI is implemented as a web service and its interfaces offer access to cheminformatics tools for data preprocessing, model building, molecule generation, and interactive chemical space visualization. Moreover, the platform is easy to extend with customizable frontend React.js components and backend Python extensions. GenUI is open source and a recently developed de novo molecular generator, DrugEx, was integrated as a proof of principle. In this work, we present the architecture and implementation details of GenUI and discuss how it can facilitate collaboration in the disparate communities interested in de novo molecular generation and computer-aided drug discovery.
Lipocalin 2 regulates expression of MHC class I molecules in Mycobacterium tuberculosis-infected dendritic cells via ROS production
Authors: Choi Ji-Ae , Cho Soo-Na , Lee Junghwan , Son Sang-Hun , Nguyen Doan Tam , Lee Seong-Ahn , Song Chang-Hwa 
Published: September 2021

AbstractBackgroundIron has important roles as an essential nutrient for all life forms and as an effector of the host defense mechanism against pathogenic infection. Lipocalin 2 (LCN2), an innate immune protein, plays a crucial role in iron transport and inflammation. In the present study, we examined the role of LCN2 in immune cells duringMycobacterium tuberculosis(Mtb) infection.ResultsWe found that infection with Mtb H37Ra induced LCN2 production in bone marrow-derived dendritic cells (BMDCs). Notably, expression of MHC class I molecules was significantly reduced in LCN2−/−BMDCs during Mtb infection. The reduced expression of MHC class I molecules was associated with the formation of a peptide loading complex through LCN2-mediated reactive oxygen species production. The reduced expression of MHC class I molecules affected CD8+T-cell proliferation in LCN2−/−mice infected with Mtb. The difference in the population of CD8+effector T cells might affect the survival of intracellular Mtb. We also found a reduction of the inflammation response, including serum inflammatory cytokines and lung inflammation in LCN2−/−mice, compared with wild-type mice, during Mtb infection.ConclusionsThese data suggest that LCN2-mediated reactive oxygen species affects expression of MHC class I molecules in BMDCs, leading to lower levels of CD8+effector T-cell proliferation during mycobacterial infection.
On some geometric properties for the combination of generalized Lommel–Wright function
Authors: Zayed Hanaa M. , Bulboacă Teodor 
Published: September 2021

AbstractThe scope of our investigation is to study the geometric properties of the normalized form of the combination of generalized Lommel–Wright function $J_{\nu ,\lambda }^{\mu ,m}$

J

ν
,
λ

μ
,
m

defined by $\mathfrak{J}_{\nu ,\lambda }^{\mu ,m}(z):=\Gamma ^{m}(\lambda +1) \Gamma (\lambda +\nu +1)2^{2\lambda +\nu } z^{1-(\nu /2)-\lambda } \mathcal{I}_{\nu ,\lambda }^{\mu ,m}(\sqrt{z})$

J

ν
,
λ

μ
,
m

(
z
)
:
=

Γ
m

(
λ
+
1
)
Γ
(
λ
+
ν
+
1
)

2

2
λ
+
ν

z

1
−
(
ν
/
2
)
−
λ

I

ν
,
λ

μ
,
m

(

z

)
, where $\mathcal{I}_{\nu ,\lambda }^{\mu ,m}(z):=(1-2\lambda -\nu )J_{\nu , \lambda }^{\mu ,m}(z)+z (J_{\nu ,\lambda }^{\mu ,m}(z) )^{ \prime }$

I

ν
,
λ

μ
,
m

(
z
)
:
=
(
1
−
2
λ
−
ν
)

J

ν
,
λ

μ
,
m

(
z
)
+
z

(

J

ν
,
λ

μ
,
m

(
z
)
)

′

and $$ J_{\nu ,\lambda }^{\mu ,m}(z)= \biggl(\frac{z}{2} \biggr)^{2\lambda + \nu } \sum_{n=0}^{\infty } \frac{(-1)^{n}}{\Gamma ^{m} (n+\lambda +1 )\Gamma (n\mu +\nu +\lambda +1 )} \biggl(\frac{z}{2} \biggr)^{2n}, $$

J

ν
,
λ

μ
,
m

(
z
)
=

(

z
2

)

2
λ
+
ν

∑

n
=
0

∞

(
−
1
)

n

Γ
m

(
n
+
λ
+
1
)
Γ
(
n
μ
+
ν
+
λ
+
1
)

(

z
2

)

2
n

,
with $m\in \mathbb{N}$
m
∈
N
, $\mu >0$
μ
>
0
and $\lambda ,\nu \in \mathbb{C}$
λ
,
ν
∈
C
, including starlikeness and convexity of order α ($0\leq \alpha <1$
0
≤
α
<
1
) in the open unit disc using the two-sided inequality for the Fox–Wright functions that has been proved by Pogány and Srivastava in (Comput. Math. Appl. 57(1):127–140, 2009). Further, the orders of starlikeness and convexity are also evaluated using some classical tools. We then compare the orders of starlikeness and convexity given by both techniques to illustrate the efficacy of the approach. In addition, we proved that for some values of α, if $\lambda >-1$
λ
>
−
1
then $\operatorname{Re} (\mathfrak{J}_{\nu ,\lambda }^{\mu ,m}(z)/z )>\alpha $
Re
(

J

ν
,
λ

μ
,
m

(
z
)
/
z
)
>
α
, $z\in \mathbb{U}$
z
∈
U
, and if $\lambda \ge (\sqrt{10}-6 )/4$
λ
≥
(

10

−
6
)
/
4
then the function $(\mathfrak{J}_{\nu ,\lambda }^{\mu ,m}(z^{2})/z )\ast \sin z$
(

J

ν
,
λ

μ
,
m

(

z
2

)
/
z
)
∗
sin
z
is close-to-convex with respect to $1/2\log ((1+z)/(1-z) )$
1
/
2
log
(
(
1
+
z
)
/
(
1
−
z
)
)
where ∗ stands for the Hadamard product (or convolution) of two power series.
A rational delegating computation protocol based on reputation and smart contract
Authors: Ma Juan , Chen Yuling , Wang Ziping , Liu Guoxu , Zhu Hongliang 
Published: September 2021

AbstractThe delegating computation has become an irreversible trend, together comes the pressing need for fairness and efficiency issues. To solve this problem, we leverage game theory to propose a smart contract-based solution. First, according to the behavioral preferences of the participants, we design an incentive contract to describe the motivation of the participants. Next, to satisfy the fairness of the rational delegating computation, we propose a rational delegating computation protocol based on reputation and smart contract. More specifically, rational participants are to gain the maximum utility and reach the Nash equilibrium in the protocol. Besides, we design a reputation mechanism with a reputation certificate, which measures the reputation from multiple dimensions. The reputation is used to assure the client’s trust in the computing party to improve the efficiency of the protocol. Then, we conduct a comprehensive experiment to evaluate the proposed protocol. The simulation and analysis results show that the proposed protocol solves the complex traditional verification problem. We also conduct a feasibility study that involves implementing the contracts in Solidity and running them on the official Ethereum network. Meanwhile, we prove the fairness and correctness of the protocol.
Oncolytic viruses for triple negative breast cancer and beyond
Authors: Jin Shengye , Wang Qin , Wu Hao , Pang Da , Xu Shouping 
Published: September 2021

AbstractBiological therapy is considered an alternative treatment capable of eliciting the same effects on tumors as surgery, radiotherapy, and chemotherapy. As a major player in biological therapy, oncolytic viruses (OVs) have attracted great attention and achieved good results. Specifically, the successful application of OVs in head and neck cancer, as well as melanoma, promoted its research in triple negative breast cancer (TNBC). TNBC is a high-risk molecular type of breast cancer, characterized by strong invasion, easy recurrence, and metastasis. Due to the absence of estrogen and progesterone receptors, as well as the absence of overexpression or gene amplification of human epidermal growth factor receptor 2 (HER2), endocrine therapy and anti HER-2 targeted therapy have proven ineffective. Although chemotherapy has shown substantial efficacy in some TNBC patients, the occurrence of drug resistance and poor prognosis have prompted the exploration of new and effective treatment methods. The emerging concept of OVs provides a new platform to treat TNBC. Indeed, several studies have confirmed the therapeutic effects of OVs in TNBC. Numerous studies have also investigated the efficacy of OVs in other malignances, including solid tumor clinical trials, thus further demonstrating the promising application of oncolytic virotherapy for TNBC. The primary focus of the current review is the examination of OV mechanisms underlying their antitumor properties, while also summarizing the ongoing progress in OV research regarding TNBC treatment, as well as the various combinatorial strategies comprising OVs and other therapies. We also briefly introduce specific relevant clinical trials and discuss some of the progress in the research of novel OVs for the treatment of other malignancies, thereby affirming the significant therapeutic potential of OVs for the treatment of TNBC, as well as other cancers.
The association of Lewy bodies with limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes and their role in cognition and Alzheimer’s dementia in older persons
Authors: Agrawal Sonal , Yu Lei , Nag Sukriti , Arfanakis Konstantinos , Barnes Lisa L. , Bennett David A. , Schneider Julie A. 
Published: September 2021

AbstractLewy bodies (LBs) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) are common in older persons and associated with cognitive impairment. However, little is known about the relationship between LBs and LATE-NC and their combined roles in cognitive impairment and Alzheimer’s dementia in community-dwelling participants. The study included 1670 community-based participants (mean age-at-death, 89.5 years (SD = 6.65); 69% females) who underwent annual assessments of cognition to create summary measures of global cognition and cognitive domains and evaluation for Alzheimer’s dementia. Systematic neuropathologic evaluations were performed to assess LBs, LATE-NC, and Alzheimer’s disease (AD) pathology. We excluded cases with pathologically confirmed frontotemporal lobar degeneration in this study. Logistic and linear regression analyses were used, adjusted for demographics and AD pathology. LBs were present in 428 (25.6%) decedents (29 nigra-predominant, 165 limbic-type, and 234 neocortical-type) while 865 (51.7%) decedents exhibited LATE-NC (307 stage 1, 167 stage 2, and 391 stage 3). LBs combined with LATE-NC were common (15% of all participants) and in those with Alzheimer’s dementia (25%). Neocortical-type, but not nigral-predominant or limbic-type LBs increased the odds of stage 2/3 LATE-NC (odds ratio = 1.70; 95% confidence interval = 1.26–2.30). The association between neocortical-type LBs and stage 2/3 LATE-NC was stronger in those under 90 years of age and in women. In analyses of cognition and Alzheimer’s dementia, LATE-NC and neocortical-type LBs, separately, were related to lower global cognition, five specific cognitive domains, and an increased odds of Alzheimer’s dementia, above and beyond the AD pathology. Limbic-type LBs were related to lower global cognition, and the domains of episodic, working, and semantic memory, and increased odds of Alzheimer’s dementia. Furthermore, there was no interaction between limbic/neocortical-type LBs and LATE-NC on cognitive function, cognitive domains, or Alzheimer’s dementia. These findings suggest that neocortical-type LBs are associated with LATE-NC, specifically in the younger old and in women. Limbic/neocortical-type LBs and LATE-NC have separate and additive effects on cognitive function and odds of Alzheimer’s dementia.