bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Advanced MRI in the Development of Treat-to-Target Therapeutic Strategies, Patient Stratification and Phenotyping in Rheumatoid Arthritis
Authors: Mobasheri Ali , Hinton Mark , Kubassova Olga 
Published: June 2019

Abstract
In this commentary we discuss the potential of advanced imaging, particularly Dynamic Contrast Enhanced (DCE) magnetic resonance imaging (MRI) for the objective assessment of disease progression in rheumatoid arthritis (RA). We emphasise the potential DCE-MRI in advancing the field and exploring new areas of research and development in RA. We believe that different grades of bone marrow edema (BME) and synovitis in RA can be examined and monitored in a more sensitive manner with DCE-MRI. Future treatments for RA will be significantly improved by enhanced imaging of BMEs and synovitis. DCE-MRI will also facilitate enhanced stratification and phenotyping of patients enrolled in clinical trials.
Health professionals’ perceptions of colorectal cancer patients’ treatment burden and their supportive work to ameliorate the burden - a qualitative study
Authors: Husebø Anne Marie Lunde , Karlsen Bjørg , Husebø Sissel I. Eikeland 
Published: June 2019

Abstract
Background

Support is pivotal for patients in managing colorectal cancer treatment, as they might be overwhelmed by the burden of treatment. There is scarce knowledge regarding health professionals’ perceptions of colorectal cancer patients’ burden in the treatment trajectory during the hospital stay and their views on supportive factors that may ameliorate the burden.

Aim

The aim of the study was to describe how health professionals perceive aspects of the treatment burden among patients receiving curative surgical treatment for colorectal cancer during the hospital stay and how they support patients to ameliorate the burden.

Methods

This study has an explorative, qualitative design, using semi-structured interviews with nine health professionals recruited from a university hospital. Data were systematised and coded by systematic text condensation.Results: Data analysis identified the themes “capturing patients’ burdens of colorectal cancer treatment” and “health professionals’ support to ameliorate the burden”. Patients with colorectal cancer had to face burdens related to a challenging emotional situation, treatment complications and side effects, and an extensive need for information. A trusting patient-carer relationship was therefore perceived as the essence of health professionals’ support. Health professionals focused their support on safeguarding patients, motivating patients to self-manage, and involving family and peers as supporters. Patients’ journey characteristics and illness severity challenged health professionals’ supportive work.

Conclusion

Support from health professionals includes providing patients emotional support and relevant treatment-related information and motivating patients for early post-surgical mobilisation. Health professionals should thus be aware of identifying colorectal cancer patients’ information needs according to the specific treatment stages, which may ameliorate the burden of colorectal cancer treatment and enable patients to self-manage at home.
Transcriptome analysis provides insights into key gene(s) involved in steroidal alkaloid biosynthesis in the medicinally important herb Fritillaria taipaiensis
Authors: Wang Xiaoyue , Luo Hong-mei , Wei Xue-min , Cao Pei , Gao Zi-tong , Han Jian-ping 
Published: June 2019

Abstract
Background

Fritillariae Cirrhosae Bulbus, which is a traditional antitussive and expectorant medicine in China, is derived from six original plants. Among these six species, all except for Fritillaria taipaiensis and Fritillaria unibracteata var. wabuensis have been recorded in the National Protected Plants III. Their major bioactive compounds, including imperialine and peimisine, are steroidal alkaloids, derived from the steroid synthesis pathway. However, research on the F. taipaiensis genome, transcriptomes and steroid-synthesis-related genes has been lacking for a long time. In this study, the first transcriptome sequencing of F. taipaiensis was performed.

Results

A total of 94,396,694 (~11.4 Gb) high-quality reads obtained using paired-end Illumina sequencing were de novo assembled into 190,350 transcripts. Functional annotation with multiple public databases identified an array of genes involved in steroidal alkaloid biosynthesis and other secondary metabolite pathways, including steroid and terpenoid backbone biosynthesis, and important oxidoreductases. The large number of differentially expressed transcripts together with CYPs suggests the involvement of these candidates in tissue-specific expression. The expression analysis revealed that bulbs may be the main site of the upstream steroidal alkaloid biosynthesis pathway, and we speculated that the downstream reactions, including the oxidation-reduction reaction catalyzed by CYPs, might also occur primarily in bulbs.

Conclusion

In conclusion, the comprehensive transcriptome dataset created in this study will serve as a resource for the identification of potential candidates for the genetic manipulation of targeted bioactive metabolites and will also contribute to the development of functionally relevant molecular marker resources to expedite molecular breeding and conservation efforts for F. taipaiensis.
One-step dual CRISPR/Cas9 guide RNA cloning protocol
Authors: Beucher Anthony , Cebola Ines 
Published: June 2019

Abstract
Existing protocols for dual guide RNA cloning rely on synthesised DNA oligonucleotides of >100 bp that contain both guide RNA sequences, and are therefore not reusable in alternative experimental designs. Here, we describe a single-step protocol to rapidly and inexpensively generate vectors expressing two guide RNAs (gRNAs) simultaneously, which allows re-usage of gRNAs oligonucleotides from one experimental design to another. This protocol is applicable to cloning gRNAs into virtually any CRISPR/Cas9 backbone that allows cloning by Golden Gate, by adapting the primer design. Here, we provide details for cloning gRNAs into vectors with BbsI and BsmBI sites, two of the most frequently found enzymes in CRISPR/Cas9 gRNA expression cassettes.This protocol has been successfully applied to delete pancreatic islet enhancers that harbour type 2 diabetes variants and to validate enhancer-promoter interactions (Miguel-Escalada et al., Nature Genetics 2019).In the future, we foresee that this simple protocol may also be applied to target coding sequences, as well as to target other important kinds of noncoding regulatory elements, including lncRNAs, miRNAs, and chromatin structural anchor points.
Barriers to epilepsy care in central Uganda, a qualitative interview and focus group study involving PLWE and their caregivers
Authors: Kaddumukasa Mark , Nalubwama Haddy , Kaddumukasa Martin N , Lhatoo Samden , Sewankambo Nelson , Katabira Elly , Sajatovic Martha , Blixen Carol 
Published: June 2019

Abstract
Background

Epilepsy is a common neurological disease with substantial impact on the subject and their caretakers. This exploratory study identified barriers to care for persons living with epilepsy (PLWE) to develop a culturally acceptable nurse led self-management intervention for PLWE previously developed in the United States.

Methods

The study involving 48 participants (31 PLWE and 17 caregivers) with in depth interviews and focus groups was conducted. We obtained insights into barriers to care in PLWE and their caregivers. Using a thematic analytic procedure emphasizing the dominant themes the qualitative responses were analyzed. Median age of PLWE was 24 years (IQR 19–30), and10 (52.6%) were male. The median age of epilepsy onset was 12 years (IQR 6 – 18), range of 1 -37 years. The median age of caregivers was 50 years (IQR 45 – 50.5), with a range of 18 -78 years. Seventy five percent of caregivers (6/8) were females.

Results

Three major areas of perceived barriers involving individual, family or community and provider and healthcare system barriers to epilepsy care emerged. Individual factors like limited epilepsy knowledge and medication non-adherence were reported to be key barriers to epilepsy care. Caregiver burden and lack of family support as well as poor health care access were identified from the family and health care systems.

Conclusions

The main barrier to epilepsy care is limited epilepsy knowledge in PLWE and their caregivers. Improving epilepsy care awareness and knowledge within communities and appropriate health care provider service for epilepsy would help reduce epilepsy barriers and improve care.
A Randomised Controlled Trial on Analgesic Effect of Repeated Quadratus Lumborum Block Versus Continuous Epidural Analgesia Following Laparoscopic Nephrectomy
Authors: Aditianingsih Dita , Pryambodho Pryambodho , Anasy Naufal , Tantri Aida Rosita , Mochtar Chaidir Arif 
Published: June 2019

Abstract
Background Epidural analgesia as the pain management for abdominal surgery has side effects such as paraesthesia, hypotension, haematomas, and impaired motoric of lower limbs. The quadratus lumborum block (QLB) has potential as an abdominal truncal block, however, the analgesic efficacy of QLB compared to epidural analgesia is unknown. This prospective randomised controlled study compared the effectiveness of QLB on postoperative opioid requirement and pain intensity with the epidural analgesia technique in transperitoneal laparoscopic nephrectomy. Methods Sixty-two patients underwent laparoscopic donor nephrectomy were randomised to receive QLB (n=31) or continuous epidural (n=31). The QLB group received bilateral QLB with 0.3–0.4 ml/kg bupivacaine 0.25% and the epidural group received bupivacaine 0.25% 6 ml/h for intraoperative analgesia. As postoperative analgesia, the QLB group received repeated bilateral QLB and the epidural group received the decreased dosage of bupivacaine 0.125% 6 ml/h for 24 hours after surgery completion. The primary outcome was cumulative morphine requirement 24 hours postoperatively. Secondary outcomes included haemodynamic changes, postoperative pain scores, sensory block coverage, Bromage score, postoperative nausea and vomiting (PONV), and duration of urinary catheterisation. Result Postoperative cumulative morphine requirement, pain scores, PONV and Bromage score were not significantly different between the QLB and epidural group. The QLB affected T9–L2, continuous epidural block affected T8–L3 dermatomes. Duration of urinary catheterisation was shorter (p < 0.001) in the QLB group. The mean arterial pressure (MAP) measured at 24 hours after surgery was lower in the epidural group (p = 0.001). Conclusion The repeated QLB had similar cumulative 24-h morphine requirement, higher MAP, similar postoperative pain scores, similar PONV and degree of motor and sensory blockade, and shorter urinary catheterisation duration, compared with continuous epidural analgesia after transperitoneal laparoscopic nephrectomy. Trial Registration ClinicalTrial.gov NCT03520205 retrospectively registered on May 9th 2018.
Electrocoagulation of azo dye containing synthetic wastewater using monopolar iron electrodes and the characterization of the sludge
Authors: Suresh A. , Sathish S. , Narendrakumar G. 
Published: June 2019

Abstract
In this study, the decolourisation of Congo red dye is studied using the natural coagulant Maize Seed Powder (MSP); a suitable alternative for chemical coagulants in electro coagulation (EC) using iron electrodes. The effects of various parameters such as initial dye concentration, pH, applied voltage and time on the decolourisation of dye were studied. The cost of water treatment is increasing due to suspended and colloidal particle load. The coagulation process can be used as a primary step for water and wastewater treatment processes. Among plant materials that have been tested, the seeds of maize have been shown to be one of the most effective primary coagulants in water and wastewater treatment. The removal efficiency of the dye with and without the presence of MSP as a coagulant aid was determined. In the EC process maximum Congo red removal was achieved by using the natural coagulant MSP. Congo red (CR) decolourisation efficiency is 95.23% at a coagulant dosage of 50 mg/lit, pH of 5, operating time of 15 minutes, and a power of 40 volts with iron electrodes. In the absence of coagulant MSP, Congo red decolourisation efficiency was found to be 80.31% at pH of 5, operating time of 15 minutes, and a power of 40 volts with iron electrodes.
Protein Post-Translational Modification Crosstalk in Acute Myeloid Leukemia Calls for Action
Authors: Hernandez-Valladares Maria , Wangen Rebecca , Berven Frode S. , Guldbrandsen Astrid 
Published: June 2019

Background:
Post-translational modification (PTM) crosstalk is a young research field.
However, there is now evidence of the extraordinary characterization of the different proteoforms
and their interactions in a biological environment that PTM crosstalk studies can describe. Besides
gene expression and phosphorylation profiling of acute myeloid leukemia (AML) samples, the
functional combination of several PTMs that might contribute to a better understanding of the
complexity of the AML proteome remains to be discovered.

Objective:
By reviewing current workflows for the simultaneous enrichment of several PTMs and
bioinformatics tools to analyze mass spectrometry (MS)-based data, our major objective is to introduce
the PTM crosstalk field to the AML research community.

Results:
After an introduction to PTMs and PTM crosstalk, this review introduces several protocols
for the simultaneous enrichment of PTMs. Two of them allow a simultaneous enrichment of at
least three PTMs when using 0.5-2 mg of cell lysate. We have reviewed many of the bioinformatics
tools used for PTM crosstalk discovery as its complex data analysis, mainly generated from
MS, becomes challenging for most AML researchers. We have presented several non-AML PTM
crosstalk studies throughout the review in order to show how important the characterization of
PTM crosstalk becomes for the selection of disease biomarkers and therapeutic targets.

Conclusion:
Herein, we have reviewed the advances and pitfalls of the emerging PTM crosstalk
field and its potential contribution to unravel the heterogeneity of AML. The complexity of sample
preparation and bioinformatics workflows demands a good interaction between experts of several
areas.
iMTBGO: An Algorithm for Integrating Metabolic Networks with Transcriptomes Based on Gene Ontology Analysis
Authors: Mao Zhitao , Ma Hongwu 
Published: June 2019

Background:Constraint-based metabolic network models have been widely used in phenotypic prediction and metabolic engineering design. In recent years, researchers have attempted to improve prediction accuracy by integrating regulatory information and multiple types of “omics” data into this constraint-based model. The transcriptome is the most commonly used data type in integration, and a large number of FBA (flux balance analysis)-based integrated algorithms have been developed.Methods and Results:We mapped the Kcat values to the tree structure of GO terms and found that the Kcat values under the same GO term have a higher similarity. Based on this observation, we developed a new method, called iMTBGO, to predict metabolic flux distributions by constraining reaction boundaries based on gene expression ratios normalized by marker genes under the same GO term. We applied this method to previously published data and compared the prediction results with other metabolic flux analysis methods which also utilize gene expression data. The prediction errors of iMTBGO for both growth rates and fluxes in the central metabolic pathways were smaller than those of earlier published methods.Conclusion:Considering the fact that reaction rates are not only determined by genes/expression levels, but also by the specific activities of enzymes, the iMTBGO method allows us to make more precise predictions of metabolic fluxes by using expression values normalized based on GO.
Monocytes as Carriers of Magnetic Nanoparticles for Tracking Inflammation in the Epileptic Rat Brain
Authors: Han Hadas , Eyal Sara , Portnoy Emma , Mann Aniv , Shmuel Miriam , Benifla Mony , Ekstein Dana , Polyak Boris 
Published: June 2019

Background:
Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have
shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite-
laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a
compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain.

Objective:
In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the
epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded
monocytes.

Methods:
The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical
imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the
rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated
using immunohistochemistry.

Results:
89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling
overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes
into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and
380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater
nanoparticle accumulation within the liver and the spleen (p<0.05).

Conclusion:
Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used
for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds.
The effect of seizures on monocyte biodistribution should be further explored to better
understand the systemic effects of epilepsy.
Inhibitors of Cyclin-Dependent Kinase 1/2 for Anticancer Treatment
Authors: Mou Jiajia , Chen Danghui , Deng Yanru 
Published: June 2019

Background:
The cell cycle is regulated by cyclin-dependent kinases (CDKs) and their
cognate cyclins, along with their endogenous inhibitors (CDKIs). CDKs act as central regulators in
this process. Different CDKs play relevant roles in different phases. Among all CDKs, CDK1 is
indispensible, which can drive all events that are required in the cell cycle in the absence of interphase
CDKs (CDK2, CDK3, CDK4 and CDK6). So, CDK1 is an attractive target for anticancer
drug development.

Methods:
CDK1 and CDK2 have 89.19% similar residues and 74.32% identical residues, their
structures especially the ATP-binding sites are of great similarity. So, it is difficult to inhibit
CDK1 and CDK2 individually. In this review, recent advances about CDK1/2 inhibitors were
summarized. The chemical structures of different classes of CDK1/2 inhibitors and their structure
activity are presented.

Results:
19 kinds of CDK1/2 or CDK1 inhibitors with different scaffolds, including CDK2 allosteric
inhibitors, were summarized. Some inhibitors are nature derived, for example, phenanthrene
derivatives, nortopsentin derivatives, variolin B derivatives and meridians.

Conclusion:
Nature products, especially marine ones are potential resources for CDK1 inhibitors
development. The findings of CDK2 allosteric inhibitors open an avenue to the discovery of novel
selective CDK1 or other CDKs allosteric inhibitors.
Design, Synthesis, and Evaluation of Isoquinoline Ureas as TRPV1 Antagonists
Authors: Gujarati Nehaben A. , Undem Bradley J. , Korlipara Vijaya L. 
Published: June 2019

Background:
The inhibition of transient receptor potential vanilloid receptor 1
(TRPV1) has emerged as a novel approach for the treatment of various pain states. Pyrrolidinyl
urea, SB 705498 with pKb = 7.3 in guinea pig TRPV1 receptor has been investigated in Phase II
clinical trials for pain and chronic cough. Another heteroaryl urea derivative, A-425619 1, has
been reported to be a potent and selective TRPV1 antagonist of capsaicin-evoked receptor activation
with an IC50 value of 4 nM in hTRPV1.

Objective:
A series of thirteen A-425619 1 analogues with modifications centered around the Cregion
were synthesized to understand the binding site characteristics of TRPV1 receptors.

Method:
We synthesized a series of isoquinoline ureas and evaluated their antagonist potency using
smooth muscle assay using guinea pig trachea along with the evaluation of the molecular properties
and molecular modeling using CoMFA studies.

Results:
p-Chloro 4, p-bromo 5, m-isothiocyanate 15, and p-isothiocyanate 16 derivatives were
found to be the most potent members of the series with pKb values in the range of 7.3-7.4 in the
functional assay using guinea pig trachea. The lead compound A-425619 1 exhibited a pKb value
of 8.1 in this assay.

Conclusion:
The para-substituted analogues were found to be more potent than the ortho- and
meta- analogues in the biological assay. This observation was further supported by molecular
modeling studies using CoMFA.
Overcoming Cancer Cell Drug Resistance by a Folic Acid Targeted Polymeric Conjugate of Buthionine Sulfoximine
Authors: Cilurzo Felisa , Cristiano Maria C. , Da Pian Marta , Cianflone Eleonora , Quintieri Luigi , Paolino Donatella , Pasut Gianfranco 
Published: June 2019

Background:Glutathione (GSH), which is the predominant low molecular weight intracellular thiol in mammals, has multiple functions, such as those of protecting against oxidative stress and detoxifying endogenous and exogenous electrophiles. High GSH levels, which have been observed in various types of tumors, have been thought to contribute to the resistance of neoplastic cells to apoptotic stimuli triggered by pro-oxidant therapy. Although L-(S,R)-Buthionine Sulfoximine (BSO), a selective irreversible inhibitor of glutamate cysteine ligase, depletes GSH in vitro and in in vivo and sensitizes tumor cells to radiation and some cancer chemotherapeutics, its toxicity and short in vivo half-life have limited its application to combination anticancer therapies.Objective:To demonstrate that a folate-targeted PEGylated BSO conjugate can sensitize cancer cells to a Reactive Oxygen Species (ROS)-generating anticancer agent by depleting GSH.Methods:A novel folate-targeted PEGylated-BSO conjugate was synthesized and tested in combination with gemcitabine in human cell lines that over-express (HeLa) or do not express (A549) the folate receptor.Results:The prepared folate-PEG-GFLG-BSO conjugate proved to be efficacious in reducing GSH levels and, when used in combination with the pro-oxidant drug gemcitabine, it enhanced drug activity in the cell line overexpressing the folate receptor.Conclusion:The folate-PEG-GFLG-BSO conjugate studied was found to be effective in sensitizing folatereceptor positive cancer cells to the ROS-generating drug gemcitabine.