bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parkinson’s disease with early motor complications: predicting EQ-5D- 3L utilities from PDQ-39 data in the EARLYSTIM trial
Authors: Zahra Mehdi , Durand-Zaleski Isabelle , Górecki Michal , Walleser Autiero Silke , Barnett Gillian , Schüpbach W. M. Michael 
Published: March 2020

Abstract
Background
A utility value is a health-related quality of life metric (HRQoL) metric used in a cost-effectiveness analysis. While utilities as outcomes in the treatment of advanced Parkinson’s disease (PD) with deep brain stimulation (DBS) are available, they do not currently exist for PD with early motor complications. The objectives of this study were to predict utilities from observed disease-specific HRQoL data using two mapping algorithms, and investigate their performance in terms of longitudinal changes within and between treatment groups, and distribution by PD severity.

Methods
This is a post hoc analysis of data from the EARLYSTIM trial of DBS compared with best medical therapy (BMT) in PD patients with early motor complications We used two published algorithms comprising ordinal and multinomial regression models to map EQ-5D-3L utilities from observed PD-specific 39 item Questionnaire (PDQ-39) scores in EARLYSTIM. Utilities were calculated using the predicted functioning levels of EQ-5D-3L dimensions and the established EQ-5D-3L UK tariffs. Statistical analyses (analysis of variance, two-tailed Student’s t-test) were used to test the change from baseline within groups and difference in change from baseline between groups in utilities. Boxplots were developed to investigate the distribution of predicted utilities by PD severity, measured using the Hoehn and Yahr scale.

Results
The change from baseline in predicted mean utilities was statistically significant at all visits up to 24 months for the DBS group (p < 0.001) with both algorithms, and statistically significant at 12 months only (p = 0.04) for the BMT group with one algorithm. With both algorithms, the between-groups difference in change from baseline in predicted mean utilities favored DBS at all follow-up visits (p < 0.001). Based on the Hoehn and Yahr scale, predicted utilities deteriorated with increasing disease severity.

Conclusions
Among PD patients with early motor complications, utilities predicted by both mapping algorithms using PDQ-39 data demonstrated a statistically and clinically meaningful improvement with DBS compared with BMT. It was not possible to conclude if one algorithm was more responsive than other. In the absence of utilities collected directly from patients, mapping is an acceptable option permitting economic evaluations to be undertaken.
Multiple trauma including pelvic fracture with multiple arterial embolization: an autopsy case report
Authors: Miyake Takahito , Okada Hideshi , Kanda Norihide , Yamaji Fuminori , Okamoto Haruka , Ushikoshi Hiroaki , Noguchi Kei , Tomita Hiroyuki , Yoshida Shozo , Ogura Shinji 
Published: March 2020

Abstract
Background
Pelvic fracture with high energy trauma has a high mortality rate, especially in men. In addition, severe multiple trauma, major hemorrhage, and administration of red blood cells predict mortality in elderly patients with pelvic fracture. We herein report a rare case in which multiple arterial embolization occurred after pelvic fracture.

Case presentation
An 83-year-old male cyclist was transported to our hospital after being struck by a car. On arrival, he was diagnosed with multiple trauma, including rib fractures with hemothorax, lumbar fractures of the transverse process, and injuries in the right acetabulum, left adrenal gland, and liver. He underwent massive transfusion and transcatheter arterial embolization due to extravasation from the right superior gluteal artery and left adrenal gland. On the second day, owing to right lower leg ischemia, serum creatinine kinase and myoglobin levels were markedly elevated from the reference value; hence, a right above-knee amputation was performed 12 h after the accident. However, both protein levels remained high after amputation, resulting in acute renal injury, which was treated via hemodiafiltration on hospital day 3. In addition, sustained low efficiency hemodialysis and plasma exchange were performed on hospital day 4. Despite these treatments, the patient’s hemodynamics did not improve, and he died on hospital day 8. The autopsy revealed necropsy of the iliopsoas muscles and the digestive tract.

Conclusions
The causes of the patient’s death were considered to be persistent rhabdomyolysis and severe hypotension due to iliopsoas necrosis and peritonitis due to digestive tract necrosis. Multiple arterial embolization caused by consumption coagulopathy associated with multiple trauma may account for severe outcomes in this case.
Identification of a robust functional subpathway signature for pancreatic ductal adenocarcinoma by comprehensive and integrated analyses
Authors: Wang Ping , Zhang Chunlong , Li Weidong , Zhai Bo , Jiang Xian , Reddy Shiva , Jiang Hongchi , Sun Xueying 
Published: March 2020

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy and its mortality continues to rise globally. Because of its high heterogeneity and complex molecular landscapes, published gene signatures have demonstrated low specificity and robustness. Functional signatures containing a group of genes involved in similar biological functions may display a more robust performance.

Methods
The present study was designed to excavate potential functional signatures for PDAC by analyzing maximal number of datasets extracted from available databases with a recently developed method of FAIME (Functional Analysis of Individual Microarray Expression) in a comprehensive and integrated way.

Results
Eleven PDAC datasets were extracted from GEO, ICGC and TCGA databases. By systemically analyzing these datasets, we identified a robust functional signature of subpathway (path:00982_1), which belongs to the drug metabolism-cytochrome P450 pathway. The signature has displayed a more powerful and robust capacity in predicting prognosis, drug response and chemotherapeutic efficacy for PDAC, particularly for the classical subtype, in comparison with published gene signatures and clinically used TNM staging system. This signature was verified by meta-analyses and validated in available cell line and clinical datasets with chemotherapeutic efficacy.

Conclusion
The present study has identified a novel functional PDAC signature, which has the potential to improve the current systems for predicting the prognosis and monitoring drug response, and to serve a linkage to therapeutic options for combating PDAC. However, the involvement of path:00982_1 subpathway in the metabolism of anti-PDAC chemotherapeutic drugs, particularly its biological interpretation, requires a further investigation.
Integrative systems and functional analyses reveal a role of dopaminergic signaling in myelin pathogenesis
Authors: Ding Sujun , Gu Yun , Cai Yunyun , Cai Meijuan , Yang Tuo , Bao Shuangxi , Shen Weixing , Ni Xuejun , Chen Gang , Xing Lingyan 
Published: March 2020

Abstract
Background
Myelin sheaths surrounding axons are critical for electrical signal transmission in the central nervous system (CNS). Diseases with myelin defects such as multiple sclerosis (MS) are devastating neurological conditions for which few effective treatments are available. Dysfunction of the dopaminergic system has been observed in multiple neurological disorders. Its role in myelin pathogenesis, however, is unclear.

Methods
This work used a combination of literature curation, bioinformatics, pharmacological and genetic manipulation, as well as confocal imaging techniques. Literature search was used to establish a complete set of genes which is associated with MS in humans. Bioinformatics analyses include pathway enrichment and crosstalk analyses with human genetic association studies as well as gene set enrichment and causal relationship analyses with transcriptome data. Pharmacological and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) genetic manipulation were applied to inhibit the dopaminergic signaling in zebrafish. Imaging techniques were used to visualize myelin formation in vivo.

Results
Systematic analysis of human genetic association studies revealed that the dopaminergic synapse signaling pathway is enriched in candidate gene sets. Transcriptome analysis confirmed that expression of multiple dopaminergic gene sets was significantly altered in patients with MS. Pathway crosstalk analysis and gene set causal relationship analysis reveal that the dopaminergic synapse signaling pathway interacts with or is associated with other critical pathways involved in MS. We also found that disruption of the dopaminergic system leads to myelin deficiency in zebrafish.

Conclusions
Dopaminergic signaling may be involved in myelin pathogenesis. This study may offer a novel molecular mechanism of demyelination in the nervous system.
A high throughput method for quantifying number and size distribution of Arabidopsis seeds using large particle flow cytometry
Authors: Morales Alejandro , Teapal J. , Ammerlaan J. M. H. , Yin X. , Evers J. B. , Anten N. P. R. , Sasidharan R. , van Zanten M. 
Published: March 2020

Abstract
Background
Seed size and number are important plant traits from an ecological and horticultural/agronomic perspective. However, in small-seeded species such as Arabidopsis thaliana, research on seed size and number is limited by the absence of suitable high throughput phenotyping methods.

Results
We report on the development of a high throughput method for counting seeds and measuring individual seed sizes. The method uses a large-particle flow cytometer to count individual seeds and sort them according to size, allowing an average of 12,000 seeds/hour to be processed. To achieve this high throughput, post harvested seeds are first separated from remaining plant material (dust and chaff) using a rapid sedimentation-based method. Then, classification algorithms are used to refine the separation process in silico. Accurate identification of all seeds in the samples was achieved, with relative errors below 2%.

Conclusion
The tests performed reveal that there is no single classification algorithm that performs best for all samples, so the recommended strategy is to train and use multiple algorithms and use the median predictions of seed size and number across all algorithms. To facilitate the use of this method, an R package (SeedSorter) that implements the methodology has been developed and made freely available. The method was validated with seed samples from several natural accessions of Arabidopsis thaliana, but our analysis pipeline is applicable to any species with seed sizes smaller than 1.5 mm.
Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway
Authors: Li Xin-Xing , Zheng Xiaoting , Liu Zhenjie , Xu Qiongming , Tang Hongzhen , Feng Jianfang , Yang Shilin , Vong Chi Teng , Gao Hongwei , Wang Yitao 
Published: March 2020

Abstract
Background
Cryptotanshinone (CPT), as a major component of Salvia miltiorrhiza Bunge (Danshen), displays many pharmacological activities including anti-inflammatory effects. However, the exact cellular and molecular mechanisms of the anti-inflammatory activities of CPT remain to be elucidated. The present study was aimed to clarify its mechanisms on lipopolysaccharide (LPS)-induced inflammatory responses in mouse macrophages, RAW264.7 cells.

Methods
In the current study, the anti-inflammatory properties of CPT were evaluated using LPS-stimulated RAW264.7 cell model. MTT assay was used to determine the viability of RAW264.7 cells. The anti-inflammatory effects of CPT were measured based on the detection of nitric oxide (NO) production (Griess and flow cytometry assay), and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release (ELISA). Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzyme expressions were also determined by western blotting. Besides, by using flow cytometry, we also evaluated the effect of CPT on LPS-induced calcium influx. Finally, the underlying anti-inflammatory mechanisms of CPT were investigated using western blotting to assess the protein levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphatidylinositol 3-kinase (PI3K)/AKT, nuclear factor erythroid 2 related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and nuclear factor-kappa B (NF-κB) pathways.

Results
Our data showed that CPT inhibited LPS-induced pro-inflammatory cytokine release like IL-6, and TNF-α, as well as NO production. It displayed a significant inhibitory effect on the protein expressions such as iNOS, COX-2, NF-κB pathway like inhibitor of kappa B kinase (IKK)α/β, inhibitor of kappa B (IκB)-α and NF-κB/p65, PI3K/AKT pathway like PI3K and AKT, and MAPK pathway like c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, and p38, in LPS-stimulated RAW264.7 macrophages. Moreover, the immunofluorescence results indicated that CPT suppressed NF-κB/p65 translocation from the cytoplasm into the nucleus. Further investigations showed that CPT treatment increased NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1) expressions together with its upstream mediator, Nrf2. In addition, CPT inhibited LPS-induced toll-like receptor 4 (TLR4) and MyD88 expressions in RAW264.7 macrophages.

Conclusions
Collectively, we suggested that CPT exerted significant anti-inflammatory effects via modulating TLR4-MyD88/PI3K/Nrf2 and TLR4-MyD88/NF-κB/MAPK pathways.
Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock
Authors: Stahl Klaus , Schmidt Julius J. , Seeliger Benjamin , Schmidt Bernhard M. W. , Welte Tobias , Haller Hermann , Hoeper Marius M. , Budde Ulrich , Bode Christian , David Sascha 
Published: March 2020

Abstract
Background
A dysbalanced coagulation system is part of the pathological host response to infection in sepsis. Activation of pro-coagulant pathways and attenuation of anti-coagulant activity ultimately lead to microvascular stasis and consequent organ failure. No treatment approaches specifically targeting this axis are available. We explored the effects of therapeutic plasma exchange (TPE) on microvascular coagulation dysbalance in septic shock.

Methods
We conducted a prospective single-center study enrolling 31 patients with early septic shock (onset < 12 h) requiring high doses of norepinephrine (NE > 0.4 μg/kg/min). Clinical and biochemical data, including measurement of protein C; a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13); and von Willebrand factor antigen (vWF:Ag), were obtained before and after TPE against fresh frozen plasma.

Results
Antithrombotic acting proteins such as antithrombin-III (ATIII) and protein C were markedly reduced in septic patients, but their activity increased after TPE (ATIII, 51% (41–61) vs. 63% (48–70), p = 0.029; protein C, 47% (38–60) vs. 62% (54–69), p = 0.029). Median ADAMTS13 activity was increased by TPE from 27 (21–42) % before to 47 (38–62) % after TPE (p < 0.001). In contrast, vWF:Ag was elevated and could be reduced by TPE (353 (206–492) IU/dL vs. 170 (117–232) IU/dL, p < 0.001). Regression analysis yielded a correlation between ADAMTS13 activity and platelet count (p = 0.001, R2 = 0.316).

Conclusions
Septic shock was associated with activation of pro-coagulant pathways and simultaneous depletion of anti-coagulant factors. TPE partially attenuated this dysbalance by removing pro- and by replacing anti-coagulant factors.

Trial registration
ClinicalTrials.gov, NCT03065751. Retrospectively registered on 28 February 2017.
High-resolution MRI of flexor tendon pulleys using a 16-channel hand coil: disease detection and differentiation of psoriatic and rheumatoid arthritis
Authors: Abrar Daniel B. , Schleich Christoph , Nebelung Sven , Frenken Miriam , Radke Karl Ludger , Vordenbäumen Stefan , Brinks Ralph , Schneider Matthias , Ostendorf Benedikt , McGonagle Dennis , Sewerin Philipp 
Published: March 2020

Abstract
Background
To evaluate the value of 3 Tesla (T) magnetic resonance imaging (MRI) changes of flexor tendon pulleys for the differentiation of psoriatic (PsA) and rheumatoid arthritis (RA), using a novel 16-channel high-resolution hand coil.

Methods
Seventeen patients with active PsA, 20 patients with active RA, and 16 healthy controls (HC) underwent high-resolution 3 T MRI using the dedicated 16-channel hand coil. Images were analyzed by three independent readers for the degree of inflammatory changes, thickness of flexor tendon pulleys, and comparison to the outcome measures for RA clinical trials (OMERACT) PsA MRI score (PsAMRIS) and to its sub-scores. For correlation analyses, Spearman rho correlation was calculated.

Results
Flexor tendon pulleys were thicker in PsA than in RA patients (mean difference 0.16 mm, p < 0.001) and HC (mean difference 0.2 mm, p < 0.001) and showed a higher degree of associated inflammatory changes (mean difference from RA 4.7, p = 0.048; mean difference from HC 14.65, p < 0.001). Additionally, there was a strong correlation of accessory pulley inflammation and PsAMRIS and its acute-inflammatory sub-scores, flexor tenosynovitis, synovitis, and periarticular inflammation (for the second digit synovitis ρ = 0.72, flexor tenosynovitis ρ = 0.7, overall PsAMRIS ρ = 0.72, p < 0.01). Similar robust correlations were evident in digits 3–5. Weaker correlations were evident in RA (synovitis ρ = 0.49, flexor tenosynovitis ρ = 0.49, periarticular inflammation ρ = 0.4).

Conclusion
The assessment of MRI changes of flexor tendon pulleys is potentially beneficial for disease detection in PsA, as well as for its distinction from RA and HC.

Trial registration
2014123117, December 2014.
Kinesiotaping for postoperative oedema – what is the evidence? A systematic review
Authors: Hörmann Julie , Vach Werner , Jakob Marcel , Seghers Saskia , Saxer Franziska 
Published: March 2020

AbstractBackgroundPostoperative oedema is a common condition affecting wound healing and function. Traditionally, manual lymphatic drainage is employed to reduce swelling. Kinesiotaping might be an alternative resource-sparing approach. This article explores current evidence for the effectiveness of kinesiotaping for the reduction of oedema in the postoperative setting.MethodsA systematic literature search was performed on the basis of five databases (Pubmed, CINAHL, Embase, Cochrane Library, andClinicaltrials.gov) for studies published between January 2000 and October 2019.Only prospective controlled trials were included. Case studies, uncontrolled case series, studies on oedema caused by other etiologies than by surgery, as well as studies on malignant disease related oedema (especially breast cancer related oedema) were excluded.Articles were screened by title, abstract, and full text and the references were searched for further publications on the topic. A narrative and quantitative (using STATA) analysis was performed.ResultsOne thousand two hundred sixty-three articles were screened, twelve were included in the analysis. All studies evaluated either oedema after extremity surgery or maxillofacial interventions, and showed relevant methodological flaws. Only three studies employed an active comparator. Of the twelve included studies ten found positive evidence for kinesiotape application for the reduction of swelling and beneficial effects on secondary outcome parameters such as pain and patient satisfaction. The available trials were heterogenic in pathology and all were compromised by a high risk of bias.ConclusionThere is some evidence for the efficacy of kinesiotaping for the treatment of postoperative oedema. This evidence is, however, not yet convincing given the limitations of the published trials. Methodologically sound comparison to standard of care or an active comparator is indispensable for an evaluation of effectiveness. In addition, assessments of patient comfort and cost-benefit analyses are necessary to evaluate the potential relevance of this novel technique in daily practice.Systematic review registration numberInternational prospective register of systematic reviews (PROSPERO) ID114129).
Kerosene tolerance in Achromobacter and Pseudomonas species
Authors: Stancu Mihaela Marilena 
Published: March 2020

Abstract
Purpose
The aim of the present study was to investigate the tolerance of five new Achromobacter and Pseudomonas strains to kerosene and to establish if the production of several secondary metabolites increases or not when these bacteria were grown in the presence of kerosene. The biodegradation of kerosene by isolated bacteria was also investigated in this study.

Methods
Five Proteobacteria were isolated from different samples polluted with petroleum and petroleum products. Based on their morphological, biochemical, and molecular characteristics, isolated bacteria were identified as Achromobacter spanius IBBPo18 and IBBPo21, Pseudomonas putida IBBPo19, and Pseudomonas aeruginosa IBBPo20 and IBBPo22.

Results
All these bacteria were able to tolerate and degrade kerosene. Higher tolerance to kerosene and degradation rates were observed for P. aeruginosa IBBPo20 and IBBPo22, compared with that observed for A. spanius IBBPo18 and IBBPo21, and P. putida IBBPo19. All these bacteria were able to produce several secondary metabolites, such as surfactants and pigments. Glycolipid surfactants produced by P. aeruginosa IBBPo20 and IBBPo22, A. spanius IBBPo18 and IBBPo21, and P. putida IBBPo19 have a very good emulsification activity, and their activity increased when they were grown in the presence of kerosene. The production of rhamnolipid surfactants by P. aeruginosa IBBPo20 and IBBPo22 was confirmed by detection of rhlAB gene involved in their biosynthesis. Pyocyanin and pyoverdin pigments were produced only by P. aeruginosa IBBPo20 and IBBPo22, while carotenoid pigments were produced by all the isolated bacteria. Significant changes in pigments production were observed when P. aeruginosa IBBPo20 and IBBPo22, A. spanius IBBPo18 and IBBPo21, and P. putida IBBPo19 were grown in the presence of kerosene.

Conclusion
Due to their ability to tolerate and degrade kerosene, and also to produce several secondary metabolites, the isolated bacteria could be used in the bioremediation of kerosene-polluted environments.
Application of ultrasound multimodal score in the assessment of endometrial receptivity in patients with artificial abortion
Authors: Jiao Yan , Xue Nianyu , Shui Xujuan , Yu Caicha , Hu Chunhong 
Published: March 2020

Abstract
Background
This study aimed to evaluate the value and feasibility of ultrasound multimodal score in the evaluation of endometrial receptivity in patients with artificial abortion (AA).

Methods
Sixty-eight patients with AA (AA group) and 70 women of the childbearing age without any history of abortion (control group) were recruited between January 2018 and December 2018. All subjects received the examination of endometrium in the middle luteum phase (7–9 days after ovulation) with two-dimensional gray-scale ultrasound, two-dimensional color Doppler ultrasound, and three-dimensional ultrasound, and the quantitative scores were obtained and compared between two groups.

Results
The quantitative score of endometrial receptivity was 10.46 ± 2.99 in the AA group and 13.49 ± 2.21 in the control group showing significant difference (p < 0.05).

Conclusions
Ultrasound multimodal quantitative scores can be used to evaluate the endometrial receptivity of patients with AA.