bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin regulates expression of small RNAs to help maintain transposon methylome homeostasis in Arabidopsis
Authors: Papareddy Ranjith K. , Páldi Katalin , Paulraj Subramanian , Kao Ping , Lutzmayer Stefan , Nodine Michael D. 
Published: September 2020

AbstractBackgroundEukaryotic genomes are partitioned into euchromatic and heterochromatic domains to regulate gene expression and other fundamental cellular processes. However, chromatin is dynamic during growth and development and must be properly re-established after its decondensation. Small interfering RNAs (siRNAs) promote heterochromatin formation, but little is known about how chromatin regulates siRNA expression.ResultsWe demonstrate that thousands of transposable elements (TEs) produce exceptionally high levels of siRNAs inArabidopsis thalianaembryos. TEs generate siRNAs throughout embryogenesis according to two distinct patterns depending on whether they are located in euchromatic or heterochromatic regions of the genome. siRNA precursors are transcribed in embryos, and siRNAs are required to direct the re-establishment of DNA methylation on TEs from which they are derived in the new generation. Decondensed chromatin also permits the production of 24-nt siRNAs from heterochromatic TEs during post-embryogenesis, and siRNA production from bipartite-classified TEs is controlled by their chromatin states.ConclusionsDecondensation of heterochromatin in response to developmental, and perhaps environmental, cues promotes the transcription and function of siRNAs in plants. Our results indicate that chromatin-mediated siRNA transcription provides a cell-autonomous homeostatic control mechanism to help reconstitute pre-existing chromatin states during growth and development including those that ensure silencing of TEs in the future germ line.
Does immediate smart feedback on therapy adherence and inhalation technique improve asthma control in children with uncontrolled asthma? A study protocol of the IMAGINE I study
Authors: Sportel Esther T. , Oude Wolcherink Martijn J. , van der Palen Job , Lenferink Anke , Thio Boony J. , Movig Kris L. L. , Brusse-Keizer Marjolein G. J. 
Published: September 2020

Abstract
Background
Many asthmatic children suffer from uncontrolled asthma with frequent exacerbations, despite an optimal treatment plan using inhalation medication. Studies have shown that therapy adherence and inhalation technique are often suboptimal in asthmatic children, but these have traditionally been hard to measure. A novel device functioning as an add-on to the inhaler has been developed to measure both aspects by recording vibration patterns during inhalation. This data can be converted to smart feedback and provided to patients immediately via a mobile application. The aim of this study is to improve asthma control in children between 6 and 18 years old by providing immediate smart feedback on the intake of inhalation medication. Asthma control will be measured by forced expiratory volume in 1 s, (Childhood) Asthma Control Test ((c-)ACT) score, and lung function variability and reversibility.

Methods
The study will be performed in Medisch Spectrum Twente (Enschede, The Netherlands). The goal is to include 68 uncontrolled moderate to severe asthmatic children between 6 and 18 years old who receive controller inhalation medication through the Nexthaler®, Ellipta®, or Spiromax®. The study consists of three phases. Phase 1 is observational and will last 4 weeks to observe the baseline adherence and inhalation technique as monitored by the add-on device. A randomised controlled trial lasting 6 weeks will be performed in phase 2. Patients in the intervention group will receive immediate smart feedback about the performed inhalations via a mobile application. In the control group, adherence and inhalation technique will be monitored, but patients will not receive feedback. In phase 3, also lasting 6 weeks, the feedback will be ceased for all children and revision of current therapy may occur, depending on the findings in phase 2. Asthma control can be assessed by means of spirometry (both at home and in the hospital) and (c-)ACT questionnaires.

Discussion
Immediate smart feedback may improve therapy adherence and inhalation technique, and thus asthma control in children and prevent unnecessary switches to targeted biologics. Performing this study in children is desired, since they are known to react differently to feedback and medication than adults.

Trial registration
Dutch Trial Register NL7705. Registered on 29 April 2019
Tocilizumab in treatment-naïve patients with Takayasu arteritis: TOCITAKA French prospective multicenter open-labeled trial
Authors: Mekinian Arsene , Saadoun David , Vicaut Eric , Thietart Sara , Lioger Bertrand , Jego Patrick , Bleibtreu Alexandre , Limal Nicolas , Connault Jerome , Gottenberg Jacques-Eric , Lhorte Pauline , Bertola Jean Pierre , Delforge Juliette , Ferreira-Maldent Nicole , Perlat Antoinette , Talib Zohra , Vautier Matthieu , Savey Léa , Quiere Isabelle , Cacoub Patrice , Fain Olivier ,   for the French Takayasu network
Published: September 2020

AbstractObjectivesTo assess long-term efficacy of tocilizumab in treatment-naive patients with Takayasu arteritis (TAK).MethodsProspective open-labeled trial in naïve patients with TAK who received steroids at the dose of 0.7 mg/kg/day and 7 infusions of 8 mg/kg/month of tocilizumab. The primary endpoint was the number of patients who discontinued steroids after 7 infusions of tocilizumab. Secondary endpoints included disease activity and the number of relapses during 18-month follow-up.ResultsThirteen patients with TAK were included, with a median age of 32 years [19–45] and 12 (92%) females. Six (54%) patients met the primary end-point. A significant decrease of disease activity was observed after 6 months of tocilizumab therapy: decrease of median NIH scale (3 [3, 4] at baseline, versus 1 [0–2] after 6 months;p < 0.001), ITAS-2010 score (5 [2–7] versus 3 [0–8];p = 0.002), and ITAS-A score (7 [4–10] versus 4 [1–15];p = 0.0001)]. During the 12-month follow-up after tocilizumab discontinuation, a relapse occurred among 5 patients (45%) out of 11 in which achieved remission after 6 months of tocilizumab.ConclusionTocilizumab seems an effective steroid sparing therapy in TAK, but maintenance therapy is necessary.Trial registrationClinicalTrials.govNCT02101333. Registered on 02 April 2014.
Laparoscopic sleeve gastrectomy in obese patients with ventricular assist devices: a data note
Authors: daSilva-deAbreu Adrian , Garikapati Kiran , Alhafez Bader Aldeen , Desai Sapna , Eiswirth Clement , Krim Selim , Patel Hamang , Lavie Carl J. , Ventura Hector O. , Loro-Ferrer Juan Francisco , Mandras Stacy A. 
Published: September 2020

Abstract
Objectives
Patients with end-stage heart failure (ESHF) treated with ventricular assist devices (VADs) tend to gain weight after implantation, which is associated with higher complication rates and is a contraindication for heart transplantation (HT). The objective was to analyze the outcomes of obese patients with ESHF and VADs who underwent laparoscopic sleeve gastrectomy (LSG) at Ochsner Medical Center in New Orleans, which is the only program performing VADs and HT in the State of Louisiana, and also one of the largest VAD centers in the USA.

Data description
This dataset contains detailed baseline, perioperative, and long-term data of patients with VADs undergoing LSG. These variables were collected retrospectively from electronic medical records. Patients who achieved ≥ 50% excess BMI loss, BMI ≤ 35 kg/m2, listing for HT, HT, or myocardial recovery were identified and the timing to each of these milestones was documented. These data can be used alone or in combination with other datasets to achieve a larger sample size with more power for further analysis of these variables, which include the most important, standard, and objective bariatric and ESHF outcomes of patients with VADs undergoing LSG. Elaboration of composite outcomes is feasible.
FOXQ1 promotes the osteogenic differentiation of bone mesenchymal stem cells via Wnt/β-catenin signaling by binding with ANXA2
Authors: Xiang Lusai , Zheng Junming , Zhang Mengdan , Ai Tingting , Cai Bin 
Published: September 2020

Abstract
Background
This study investigated the role of Forkhead box Q1 (FOXQ1) in the osteogenic differentiation of bone mesenchymal stem cells.

Methods
Mouse bone mesenchymal stem cells (mBMSCs) were transfected with lentivirus to generate Foxq1-overexpressing mBMSCs, Foxq1-suppressed mBMSCs, and mBMSC controls. The activity of osteogenic differentiation was evaluated with alizarin red staining, alkaline phosphatase activity assay, and RT-qPCR. Wnt/β-catenin signaling activities were compared among groups by TOPFlash/FOPFlash assay, immunofluorescence staining, and western blot assay of beta-catenin (CTNNB1). Coimmunoprecipitation mass spectrometry was also carried out to identify proteins binding with FOXQ1.

Results
Our data showed that FOXQ1 expression was positively correlated with the osteogenic differentiation of the mBMSCs. FOXQ1 also promoted the nuclear translocation of CTNNB1 in the mBMSCs, enhancing Wnt/β-catenin signaling, which was also shown to be essential for the osteogenic differentiation-promoting effect of FOXQ1 in the mBMSCs. Annexin A2 (ANXA2) was bound with FOXQ1, and its depletion reversed the promoting effect of FOXQ1 on Wnt/β-catenin signaling.

Conclusion
These results showed that FOXQ1 binds with ANXA2, promoting Wnt/β-catenin signaling in bone mesenchymal stem cells, which subsequently promotes osteogenic differentiation.
Molecular representations in AI-driven drug discovery: a review and practical guide
Authors: David Laurianne , Thakkar Amol , Mercado Rocío , Engkvist Ola 
Published: September 2020

AbstractThe technological advances of the past century, marked by the computer revolution and the advent of high-throughput screening technologies in drug discovery, opened the path to the computational analysis and visualization of bioactive molecules. For this purpose, it became necessary to represent molecules in a syntax that would be readable by computers and understandable by scientists of various fields. A large number of chemical representations have been developed over the years, their numerosity being due to the fast development of computers and the complexity of producing a representation that encompasses all structural and chemical characteristics. We present here some of the most popular electronic molecular and macromolecular representations used in drug discovery, many of which are based on graph representations. Furthermore, we describe applications of these representations in AI-driven drug discovery. Our aim is to provide a brief guide on structural representations that are essential to the practice of AI in drug discovery. This review serves as a guide for researchers who have little experience with the handling of chemical representations and plan to work on applications at the interface of these fields.
Effects of health insurance on patient demand for physician services
Authors: Dugan Jerome 
Published: September 2020

Abstract
Background
In recent years, policymakers have sought to reduce health disparities between the insured and uninsured through a federal health insurance expansion policy; however, disparities continue to persist among the insured population. One potential explanation is that the use of healthcare services varies by the type of health insurance coverage due to differences in the design of coverage. The aim of this study is to examine whether health insurance coverage type is associated with the structure and use of healthcare services.

Methods
The nationally representative Medical Expenditure Panel Survey and multinomial logistic regression are used to estimate the effects of different types of health coverage on the combinations of routine and emergency care sought and received.

Results
The multinomial logistic regression analysis for the overall sample revealed privately insured respondents reported higher use of routine care only p < 0.01 and lower use of emergency room care only (− 2.13%; p < 0.01) than the uninsured. The publicly insured reported similar trends for use of routine care only (17.93%; p < 0.01) as the privately insured, as compared to the uninsured. Both the privately and publicly insured reported higher use of a mixture of care; however, publicly insured were more likely to use a mixture of care (8.57%, p < 0.01).

Conclusion
The results show that health insurance is associated with higher use of the physician services, but does not promote the use of cost-effective schedules of care among the publicly insured.
On high-order compact schemes for the multidimensional time-fractional Schrödinger equation
Authors: Eskar Rena , Feng Xinlong , Kasim Ehmet 
Published: September 2020

AbstractIn this article, some high-order compact finite difference schemes are presented and analyzed to numerically solve one- and two-dimensional time fractional Schrödinger equations. The time Caputo fractional derivative is evaluated by the L1 and L1-2 approximation. The space discretization is based on the fourth-order compact finite difference method. For the one-dimensional problem, the rates of the presented schemes are of order $O(\tau ^{2-\alpha }+h^{4})$
O
(

τ

2
−
α

+

h
4

)
and $O(\tau ^{3-\alpha }+h^{4})$
O
(

τ

3
−
α

+

h
4

)
, respectively, with the temporal step size τ and the spatial step size h, and $\alpha \in (0,1)$
α
∈
(
0
,
1
)
. For the two-dimensional problem, the high-order compact alternating direction implicit method is used. Moreover, unconditional stability of the proposed schemes is discussed by using the Fourier analysis method. Numerical tests are performed to support the theoretical results, and these show the accuracy and efficiency of the proposed schemes.
A radiomics-based model on non-contrast CT for predicting cirrhosis: make the most of image data
Authors: Wang Jin-Cheng , Fu Rao , Tao Xue-Wen , Mao Ying-Fan , Wang Fei , Zhang Ze-Chuan , Yu Wei-Wei , Chen Jun , He Jian , Sun Bei-Cheng 
Published: September 2020

Abstract
Background
To establish and validate a radiomics-based model for predicting liver cirrhosis in patients with hepatitis B virus (HBV) by using non-contrast computed tomography (CT).

Methods
This retrospective study developed a radiomics-based model in a training cohort of 144 HBV-infected patients. Radiomic features were extracted from abdominal non-contrast CT scans. Features selection was performed with the least absolute shrinkage and operator (LASSO) method based on highly reproducible features. Support vector machine (SVM) was adopted to build a radiomics signature. Multivariate logistic regression analysis was used to establish a radiomics-based nomogram that integrated radiomics signature and other independent clinical predictors. Performance of models was evaluated through discrimination ability, calibration and clinical benefits. An internal validation was conducted in 150 consecutive patients.

Results
The radiomics signature comprised 25 cirrhosis-related features and showed significant differences between cirrhosis and non-cirrhosis cohorts (P < 0.001). A radiomics-based nomogram that integrates radiomics signature, alanine transaminase, aspartate aminotransferase, globulin and international normalized ratio showed great calibration and discrimination ability in the training cohort (area under the curve [AUC]: 0.915) and the validation cohort (AUC: 0.872). Decision curve analysis confirmed the most clinical benefits can be provided by the nomogram compared with other methods.

Conclusions
Our developed radiomics-based nomogram can successfully diagnose the status of cirrhosis in HBV-infected patients, that may help clinical decision-making.
Baicalin alleviates lipopolysaccharide-induced neuroglial activation and inflammatory factors activation in hippocampus of adult mice
Authors: Shah Murad-Ali , Park Dong-Ju , Kang Ju-Bin , Kim Myeong-Ok , Koh Phil-Ok 
Published: September 2020

AbstractBaicalin is a natural flavonoid that exerts a variety of pharmaceutical effects such as anti-inflammatory and antioxidant. Lipopolysaccharide (LPS) is an endotoxin that releases inflammatory cytokines and induces inflammatory response. This study was investigated the anti-inflammatory mechanism of baicalin against LPS-induced inflammatory response in the hippocampus. Adult mice were randomly grouped into control, LPS-treated, and LPS and baicalin co-treated animals. LPS (250 μg/kg/day) and baicalin (10 mg/kg/day) were administered intraperitoneally for 7 consecutive days. We measured neuroglia cells activation and inflammatory factors activation using Western blot analysis and immunofluorescence staining techniques. Ionized calcium binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) are widely used as microglia and astrocyte markers, respectively. LPS treatment increased Iba-1 and GFAP expression, while baicalin co-treatment attenuated this overexpression. Nuclear factor-kappa B (NF-κB) is a key mediator of inflammation. Baicalin co-treatment alleviated LPS-induced increase of NF-κB in the hippocampus. In addition, LPS treatment upregulated pro-inflammatory cytokines including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). However, baicalin co-treatment prevented LPS-induced increases of IL-1β and TNF-α in the hippocampus. Results from the present study showed that baicalin suppresses LPS-induced neuroinflammation by regulating microglia and astrocyte activation and modulating inflammatory factors in the hippocampus. Thus, these results demonstrate that baicalin has neuroprotective effect by alleviates microglia and astrocyte activation and modulates inflammatory response by suppressing NF-κB expression in hippocampus with neuroinflammation caused by LPS.
Cryopreservation of mouse resources
Authors: Takeo Toru , Nakao Satohiro , Nakagawa Yoshiko , Sztein Jorge M. , Nakagata Naomi 
Published: September 2020

AbstractThe cryopreservation of sperm and embryos is useful to efficiently archive valuable resources of genetically engineered mice. Till date, more than 60,000 strains of genetically engineered mice have been archived in mouse banks worldwide. Researchers can request for the archived mouse strains for their research projects. The research infrastructure of mouse banks improves the availability of mouse resources, the productivity of research projects, and the reproducibility of animal experiments. Our research team manages the mouse bank at the Center for Animal Resources and Development in Kumamoto University and continuously develops new techniques in mouse reproductive technology to efficiently improve the system of mouse banking. In this review, we introduce the activities of mouse banks and the latest techniques used in mouse reproductive technology.
Prevalence of treatment resistance and clozapine use in early intervention services
Authors: Stokes Imogen , Griffiths Siân Lowri , Jones Rowena , Everard Linda , Jones Peter B. , Fowler David , Hodgekins Joanne , Amos Tim , Freemantle Nick , Sharma Vimal , Marshall Max , Singh Swaran P. , Birchwood Max , Upthegrove Rachel 
Published: September 2020

Background
Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.

Aims
This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.

Method
Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.

Results
A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.

Conclusions
Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.
Gut Dysbiosis Contributes to the Imbalance of Treg and Th17 Cells in Graves’ Disease Patients by Propionic Acid
Authors: Su Xinhuan , Yin Xianlun , Liu Yue , Yan Xuefang , Zhang Shucui , Wang Xiaowei , Lin Zongwei , Zhou Xiaoming , Gao Jing , Wang Zhe , Zhang Qunye 
Published: September 2020

Abstract

Background
Graves’ disease (GD) is a typical organ-specific autoimmune disease. Intestinal flora plays a pivotal role in immune homeostasis and autoimmune disease development. However, the association and mechanism between intestinal flora and GD remain elusive.

Objective
To investigate the association and mechanism between intestinal flora and GD.

Methods
We recruited 58 initially untreated GD patients and 63 healthy individuals in the study. The composition and metabolic characteristics of the intestinal flora in GD patients and the causal relationship between intestinal flora and GD pathogenesis were assessed using 16S rRNA gene sequencing, targeted/untargeted metabolomics, and fecal microbiota transplantation.

Results
The composition, metabolism, and inter-relationships of the intestinal flora were also changed, particularly the significantly reduced short-chain fatty acid (SCFA)-producing bacteria and SCFAs. The YCH46 strain of Bacteroides fragilis could produce propionic acid and increase Treg cell numbers while decreasing Th17 cell numbers. Transplanting the intestinal flora of GD patients significantly increased GD incidence in the GD mouse model. Additionally, there were 3 intestinal bacteria genera (Bacteroides, Alistipes, Prevotella) could distinguish GD patients from healthy individuals with 85% accuracy.

Conclusions
Gut dysbiosis contributes to a Treg/Th17 imbalance through the pathway regulated by propionic acid and promotes the occurrence of GD, together with other pathogenic factors. Bacteroides, Alistipes, and Prevotella have great potential to serve as adjunct markers for GD diagnosis. This study provided valuable clues for improving immune dysfunction of GD patients using B. fragilis and illuminated the prospects of microecological therapy for GD as an adjunct treatment.