bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical-grade cryopreserved doxorubicin-loaded platelets: role of cancer cells and platelet extracellular vesicles activation loop
Authors: Wu Yu-Wen , Huang Cheng-Chain , Changou Chun Austin , Lu Long-Sheng , Goubran Hadi , Burnouf Thierry 
Published: March 2020

Abstract
Background
Human platelets (PLT) and PLT-extracellular vesicles (PEV) released upon thrombin activation express receptors that interact with tumour cells and, thus, can serve as a delivery platform of anti-cancer agents. Drug-loaded nanoparticles coated with PLT membranes were demonstrated to have improved targeting efficiency to tumours, but remain impractical for clinical translation. PLT and PEV targeted drug delivery vehicles should facilitate clinical developments if clinical-grade procedures can be developed.

Methods
PLT from therapeutic-grade PLT concentrate (PC; N > 50) were loaded with doxorubicin (DOX) and stored at − 80 °C (DOX-loaded PLT) with 6% dimethyl sulfoxide (cryopreserved DOX-loaded PLT). Surface markers and function of cryopreserved DOX-loaded PLT was confirmed by Western blot and thromboelastography, respectively. The morphology of fresh and cryopreserved naïve and DOX-loaded PLT was observed by scanning electron microscopy. The content of tissue factor-expressing cancer-derived extracellular vesicles (TF-EV) present in conditioned medium (CM) of breast cancer cells cultures was measured. The drug release by fresh and cryopreserved DOX-loaded PLT triggered by various pH and CM was determined by high performance liquid chromatography. The thrombin activated PEV was analyzed by nanoparticle tracking analysis. The cellular uptake of DOX from PLT was observed by deconvolution microscopy. The cytotoxicities of DOX-loaded PLT, cryopreserved DOX-loaded PLT, DOX and liposomal DOX on breast, lung and colon cancer cells were analyzed by CCK-8 assay.

Results
15~36 × 106 molecules of DOX could be loaded in each PLT within 3 to 9 days after collection. The characterization and bioreactivity of cryopreserved DOX-loaded PLT were preserved, as evidenced by (a) microscopic observations, (b) preservation of important PLT membrane markers CD41, CD61, protease activated receptor-1, (c) functional activity, (d) reactivity to TF-EV, and (e) efficient generation of PEV upon thrombin activation. The transfer of DOX from cryopreserved PLT to cancer cells was achieved within 90 min, and stimulated by TF-EV and low pH. The cryopreserved DOX-loaded PLT formulation was 7~23-times more toxic to three cancer cells than liposomal DOX.

Conclusions
Cryopreserved DOX-loaded PLT can be prepared under clinically compliant conditions preserving the membrane functionality for anti-cancer therapy. These findings open perspectives for translational applications of PLT-based drug delivery systems.
Long-term LVEF trajectories in patients with type 2 diabetes and heart failure: diabetic cardiomyopathy may underlie functional decline
Authors: Julián María Teresa , Alonso Núria , Lupón Josep , Gavidia-Bovadilla Giovana , Ferrer Elena , de Antonio Marta , López-Ayerbe Jorge , Domingo Mar , Santiago-Vacas Evelyn , Zamora Elisabet , Codina Pau , Moliner Pedro , Núñez Julio , Santesmases Javier , Puig-Domingo Manel , Bayes-Genis Antoni 
Published: March 2020

Abstract
Background
Left ventricular ejection fraction (LVEF) trajectories and functional recovery with current heart failure (HF) management is increasingly recognized. Type 2 diabetes mellitus (T2D) leads to a worse prognosis in HF patients. However, it is unknown whether T2D interferes with LVEF trajectories. The aim of this study was to prospectively assess very long-term (up to 15 years) LVEF trajectories in patients with and without T2D and underlying HF.

Methods
Ambulatory patients admitted to a multidisciplinary HF clinic were prospectively evaluated by scheduled two-dimensional echocardiography at baseline, 1 year, and then every 2 years afterwards, up to 15 years. Statistical analyses of LVEF change with time were performed using the linear mixed effects (LME) models, and locally weighted error sum of squares (Loess) curves were plotted.

Results
Of the 1921 patients, 461 diabetic and 699 non-diabetic patients with LVEF < 50% were included in the study. The mean number of echocardiography measurements performed in diabetic patients was 3.3 ± 1.6. Early LVEF recovery was similar in diabetic and non-diabetic patients, but Loess curves showed a more pronounced inverted U shape in diabetics with a more pronounced decline after 9 years. LME analysis showed a statistical interaction between T2D and LVEF trajectory over time (p = 0.009), which was statistically significant in patients with ischemic etiologies (p < 0.001). Other variables that showed an interaction between LVEF trajectories and T2D were male sex (p = 0.04) and HF duration (p = 0.008).

Conclusions
LVEF trajectories in T2D patients with depressed systolic function showed a pronounced inverted U shape with a marked decline after 9 years. Diabetic cardiomyopathy may underlie the functional decline observed.
Simultaneous determination of five essential amino acids in plasma of Hyperlipidemic subjects by UPLC-MS/MS
Authors: Chen Zhibin , Lin Feiyan , Ye Xuemei , Dong Yuqian , Hu Lufeng , Huang Aifang 
Published: March 2020

Abstract
Background
Millions of adults have been reported with hyperlipemia in the world. It is still unclear whether the plasma level of essential amino acids (AAs) will be influenced by the hyperlipemia. This study was aimed to investigate the AAs levels and the underlying metabolic relationship in hyperlipidemic subjects.

Methods
An ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination of phenylalanine (Phe), valine (Val), histidine (His), tryptophan (Trp), and methionine (Met). Plasma samples (100 μL) were precipitated by acetonitrile (300 μL) and analyzed on a BEH C18 (2.1 mm × 100 mm, 1.7 μm) column at 40 °C by gradient elution. The mobile phase composed of 0.1% formic acid and acetonitrile was used with flow rate at 0.2–0.4 ml/0-3 min. Five AAs were determined at positive electrospray ionization (ESI+) at m/z 118.1/72.1 (Val), 150.12/104.02(Met), 156.06/110.05(His), 166.1/120.1(Phe), and 205.2/188.02 (Trp). A total of 75 healthy subjects and 83 hyperlipidemic subjects, who had blood routine test and plasma lipid test were determined by developed UPLC-MS/MS.

Results
It was shown that there was good linearity for Val, Met, His, Phe, and Trp within 1–100 μg/mL. The relative standard deviations of precision and accuracy were all within 15%. The level of Val, Phe, Trp, His, and Met were 35.34 ± 15.64, 22.72 ± 9.13, 17.23 ± 4.94, 16.78 ± 13.64, and 6.24 ± 1.97 μg/mL in healthy subjects, while they were 38.04 ± 16.70, 22.41 ± 8.45, 15.62 ± 5.77, 18.35 ± 14.49, and 6.21 ± 1.97 μg/mL in hyperlipidemic subjects respectively. The Spearman’s correlations analysis showed that there were high correlations between Val, Phe, Trp, His, Met and triglyceride in healthy subjects. While, those correlations decreased in hyperlipemia cases.

Conclusion
A convenient and sensitive method for simultaneous determination of Val, Phe, Trp, His, and Met in human plasma was developed. There was a high correlation between Val, Phe, Trp, His, Met and triglyceride. Hyperlipemia influences the metabolic balance of His, Phe, Trp, Met and Val.
Evaluating networked drug checking services in Toronto, Ontario: study protocol and rationale
Authors:   Drug Checking Services in Toronto Working Group, Maghsoudi N. , McDonald K. , Stefan C. , Beriault D. R. , Mason K. , Barnaby L. , Altenberg J. , MacDonald R. D. , Caldwell J. , Nisenbaum R. , Leece P. , Watson T. M. , Tupper K. W. , Kufner L. , Scheim A. I. , Werb D. 
Published: March 2020

Abstract
Background
The increasing incidence of fatal opioid overdose is a public health crisis in Canada. Given growing consensus that this crisis is related to the presence of highly potent opioid adulterants (e.g., fentanyl) in the unregulated drug supply, drug checking services (DCS) have emerged as part of a comprehensive approach to overdose prevention. In Canada’s largest city, Toronto, a network of DCS launched in 2019 to prevent overdose and overdose-related risk behaviors. This network employs mass spectrometry technologies, with intake sites co-located with supervised consumption services (SCS) at three frontline harm reduction agencies. The protocol and rationale for assessing the impact of this multi-site DCS network in Toronto is described herein. The aims of this study are to (1) evaluate the impact of DCS access on changes in and factors influencing overdose and related risk behaviors, (2) investigate the perceived capacity of DCS to prevent overdose, and (3) identify composition (qualitative and quantitative) trends in Toronto’s unregulated drug supply.

Methods
We will use a parallel-mixed-methods design with complementary data sources (including data from chemical analysis of drug samples, quantitative intake and post-test surveys, SCS, coroners, paramedic services, and qualitative interviews), followed by a meta-inference process wherein results from analyses are synthesized.

Results
Whereas most DCS globally target “recreational drug users,” in Toronto, this networked DCS will primarily target marginalized people who use drugs accessing frontline services, many of whom use drugs regularly and by injection. This evolution in the application of DCS poses important questions that have not yet been explored, including optimal service delivery models and technologies, as well as unique barriers for this population. Increasing information on the unregulated drug supply may modify the risk environment for this population of people who use drugs.

Conclusions
This study addresses evidence gaps on the emerging continuum of overdose prevention responses and will generate critical evidence on a novel approach to reducing the ongoing high incidence of drug-related morbidity and mortality in Canada and elsewhere.
Importance of pediatric rheumatologists and transitional care for juvenile idiopathic arthritis-associated uveitis: a retrospective series of 9 cases
Authors: Yamazaki Susumu , Shimbo Asami , Akutsu Yuko , Takase Hiroshi , Morio Tomohiro , Mori Masaaki 
Published: March 2020

Abstract
Background
Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a serious condition associated with the risk of blindness. However, pediatric rheumatologists rarely encounter cases of blindness, because most patients reach adulthood during the course of follow-up before blindness occurs. Here, we report the progress of 9 patients with JIA-U, including 2 patients who became blind after the transition period. We aimed to highlight the importance of the role of pediatric rheumatologists and transitional care in preventing blindness associated with JIA-U.

Case presentation
We conducted a retrospective analysis of the case records of 9 JIA-U patients (1 male, 8 female; median age 16.8 years, range 5.5–19.8 years). All patients presented with oligo-juvenile idiopathic arthritis (oligo-JIA) (one presented with extended oligo-JIA); the median age of uveitis onset was 5.0 years (range 3.0–13.0 years), and the onset of uveitis preceded the onset of arthritis in 2 patients. The median disease duration was 12.5 years (range 3.5–24.7 years); 4 patients had anti-nuclear antibody (ANA) positivity (≧1:160) (all with a homogeneous and speckled-pattern subtype). All patients were negative for rheumatoid factor. Eight patients received methotrexate, 7 patients received one or more biologic drugs (etanercept, infliximab, adalimumab, and golimumab), and 6 patients required ophthalmic surgery at an early age (≦ 18 years).
Two patients developed blindness after the transition period. Medical examination by pediatric rheumatologists and use of biologics had been delayed in both patients. One patient developed depression after transition and interrupted her own treatment.

Conclusions
The reason for blindness in the 2 patients was thought to be the delay in the commencement of treatment and failure to provide transitional care. Inflammation is difficult to control in JIA-U even with appropriate treatment. Pediatric rheumatologists must be informed about the risk of JIA-U blindness, especially after transition. To ensure a good prognosis, the specialized treatment with the involvement of pediatric rheumatologists is necessary early on, and consideration for transitional medicine is essential. Therefore, this report reaffirms the importance of planned transitional care that has been advocated for globally.
Work related cardiovascular load in professional dance teachers – a pilot study
Authors: Wanke Eileen M. , Schmidt Mike , Oremek Gerhard , Groneberg David A. 
Published: March 2020

AbstractObjectiveThere have been only a limited number of studies available on the physical requirements in dance teachers (DT), who are responsible for the training of recreational and/or professional dancers and/or dance students. First results provide indications that a consideration of physical work load (teaching load) of this occupational group is necessary.MethodsHR measurements were done on a total of 21 DT (f:n = 18, m:n = 3) aged 48.2 ± 9.3 years during their lessons in three dance styles: ballet (B), jazz/modern dance (J/MD) and pre-school dance (CD). The HR data were objectified using the spiroergometrically measured maximum HR (HRmax). In addition, the rating of perceived exertion (RPE) was asked directly after the lesson using the Borg scale together with an additional questionnaire.ResultsDepending on the dance style, the average HR load during the lessons ranged between 56.7% ± 7.4%) (B) and 63.6% ± 9.8% (CD) of the individual HRmax. No significant differences could be found between the dance styles for the minimum, medium and maximum teaching loads. The DTs rated the average RPE of the teaching units according to BORG (11.4 ± 2.1). Correlations between the RPE and the mean and maximum cardiovascular loads (r = 0.376,p = 0.037 and r = 0.441,p = 0.013) could be shown for all dance units and for the mean loads in J/MD (r = 0.558,p = 0.044).ConclusionMost dance units do not represent a load in the sense of a endurance training unit. An increase in aerobic fitness and possible positive effects in the context of injury prevention is not to be expected. In J/MD, the use of RPEs for the rough estimation of cardiovascular stress is conceivable. The assessment of cardiovascular load in dance lessons requires further investigations for more precise assessments.
Potential mechanisms for lumbar spinal stiffness change following spinal manipulative therapy: a scoping review
Authors: Jun Peter , Pagé Isabelle , Vette Albert , Kawchuk Greg 
Published: March 2020

Abstract
Introduction
In individuals having low back pain, the application of spinal manipulative therapy (SMT) has been shown to reduce spinal stiffness in those who report improvements in post-SMT disability. The underlying mechanism for this rapid change in stiffness is not understood presently. As clinicians and patients may benefit from a better understanding of this mechanism in terms of optimizing care delivery, the objective of this scoping review of current literature was to identify if potential mechanisms that explain this clinical response have been previously described or could be elucidated from existing data.

Methods
Three literature databases were systematically searched (MEDLINE, CINAHL, and PubMed). Our search terms included subject headings and keywords relevant to SMT, spinal stiffness, lumbar spine, and mechanism. Inclusion criteria for candidate studies were publication in English, quantification of lumbar spinal stiffness before and after SMT, and publication between January 2000 and June 2019.

Results
The search identified 1931 articles. Of these studies, 10 were included following the application of the inclusion criteria. From these articles, 7 themes were identified with respect to potential mechanisms described or derived from data: 1) change in muscle activity; 2) increase in mobility; 3) decrease in pain; 4) increase in pressure pain threshold; 5) change in spinal tissue behavior; 6) change in the central nervous system or reflex pathways; and 7) correction of a vertebral dysfunction.

Conclusions
This scoping review identified 7 themes put forward by authors to explain changes in spinal stiffness following SMT. Unfortunately, none of the studies provided data which would support the promotion of one theme over another. As a result, this review suggests a need to develop a theoretical framework to explain rapid biomechanical changes following SMT to guide and prioritize future investigations in this important clinical area.
Minimally invasive surgical treatment of minimally displaced acetabular fractures does not improve pain, mobility or quality of life compared to conservative treatment: a matched-pair analysis of 50 patients
Authors: Swartman Benedict , Pelzer Johanna , Vetter Sven Yves , Beisemann Nils , Schnetzke Marc , Keil Holger , Gruetzner Paul Alfred , Franke Jochen 
Published: March 2020

AbstractBackgroundCurrently available procedures for the treatment of minimally displaced acetabular fractures include conservative treatment and minimally invasive percutaneous screw fixation. Screw fixation of acetabular fractures allows patients’ early full-weight bearing due to improved biomechanic stability. Can the range of motion, pain and mobility and quality of life in patients with acetabular fractures be improved by minimally invasive screw fixation, compared to conservative treatment in the long term?MethodsPatients treated for a minimally displaced acetabular fracture, either conservatively or by closed reduction percutaneous screw fixation, in the period from 2001 to 2013 were included in this retrospective study. Minimal displacement was considered to be less than 5 mm. As well as the collection and analysis of baseline data, Harris Hip Score, Merle d’Aubigné score and Short Form 12 (SF-12) questionnaire data were recorded in the context of a clinical study. To better account for confounding factors, patients of each group were matched. The matched-pair criteria included age, BMI, Letournel fracture classification and the presence of associated injuries.ResultsTwenty-five patients from each group were matched. On the Harris Hip Score, conservatively treated patients obtained 96 points (52–100, SD 17) vs. 89 points (45–100, SD 17,p= 0.624). On the Merle d’Aubigné score, conservatively treated patients obtained 17 points (10–18, SD 2) vs. 17 points (11–18, SD 2,p= 0.342).Patients with acetabular fractures treated by minimally invasive screw fixation did not result in improved quality of life, measured by SF-12 questionnaire, compared to conservatively treated patients (PCS 47, SD 9 vs. 44, SD 10;p= 0.294 and MCS 51, SD 7 vs. 53, SD 7;p= 0.795).ConclusionsThe clinical results of the two groups revealed no statistically significant differences. From the data, it cannot be deduced that minimally invasive surgical therapy is superior to conservative treatment of minimally displaced acetabular fractures. Prospective randomised studies are recommended to allow reliable evaluation of both treatment options.Trial registrationRetrospectively registered
Prognostic value of clinical and morphologic findings in patients with type B aortic intramural hematoma
Authors: Li Zilun , Liu Chenshu , Wu Ridong , Zhang Jian , Pan Hong , Tan Jinghong , Guo Zhuang , Guo Yingying , Yu Nan , Yao Chen , Chang Guangqi 
Published: March 2020

Abstract
Background
Aortic intramural hematoma (IMH) is a subset of acute aortic syndrome, and its prognosis may differ between races. This study aimed to study the prognosis of Chinese type B IMH patients and to find out risk factors.

Methods
A total of 71 type B IMH patients with or without penetrating atherosclerosis ulcer (PAU) administrated in our center between September 2013 and October 2017 were retrospectively studied. Both clinical and imaging data were collected and analyzed. The primary end point was aorta-related death, and the secondary end point was progression, which was defined as enlargement of aorta, increased aortic wall thickness, and aortic dissection or aneurysm formation. Kaplan-Meier survival analysis and Cox regression analysis were used for prognostic analysis.

Results
Among these 71 patients, 21 had simple type B IMH, when 50 had type B IMH in association with PAU. Twenty-five patients received optimal medical therapy (OMT) alone, while 46 patients received surgery and OMT. The mean follow-up time was 27.5 ± 13.5 months. For type B IMH patients, association with PAU indicated poor prognosis and required more intensive management (HR = 16.68, 1.96~141.87), while maximum aortic diameter (MAD) was an independent risk factor (HR = 1.096, 1.016~1.182). For patients with PAU-IMH, MAD was an independent risk factor (HR = 1.04, 1.021~1.194), while surgical treatment was independent protective factor (HR = 0.172, 0.042~0.696).

Conclusion
Association with PAU and MAD were independent risk factors for type B IMH patients. Surgery may improve the outcomes for type B IMH in association with PAU.
Mapping deep peat carbon stock from a LiDAR based DTM and field measurements, with application to eastern Sumatra
Authors: Vernimmen Ronald , Hooijer Aljosja , Akmalia Rizka , Fitranatanegara Natan , Mulyadi Dedi , Yuherdha Angga , Andreas Heri , Page Susan 
Published: March 2020

Abstract
Background
Reduction of carbon emissions from peatlands is recognized as an important factor in global climate change mitigation. Within the SE Asia region, areas of deeper peat present the greatest carbon stocks, and therefore the greatest potential for future carbon emissions from degradation and fire. They also support most of the remaining lowland swamp forest and its associated biodiversity. Accurate maps of deep peat are central to providing correct estimates of peat carbon stocks and to facilitating appropriate management interventions. We present a rapid and cost-effective approach to peat thickness mapping in raised peat bogs that applies a model of peat bottom elevation based on field measurements subtracted from a surface elevation model created from airborne LiDAR data.

Results
In two raised peat bog test areas in Indonesia, we find that field peat thickness measurements correlate well with surface elevation derived from airborne LiDAR based DTMs (R2 0.83–0.88), confirming that the peat bottom is often relatively flat. On this basis, we created a map of extent and depth of deep peat (> 3 m) from a new DTM that covers two-thirds of Sumatran peatlands, applying a flat peat bottom of 0.61 m +MSL determined from the average of 2446 field measurements. A deep peat area coverage of 2.6 Mha or 60.1% of the total peat area in eastern Sumatra is mapped, suggesting that deep peat in this region is more common than shallow peat and its extent was underestimated in earlier maps. The associated deep peat carbon stock range is 9.0–11.5 Pg C in eastern Sumatra alone.

Conclusion
We discuss how the deep peat map may be used to identify priority areas for peat and forest conservation and thereby help prevent major potential future carbon emissions and support the safeguarding of the remaining forest and biodiversity. We propose rapid application of this method to other coastal raised bog peatland areas in SE Asia in support of improved peatland zoning and management. We demonstrate that the upcoming global ICESat-2 and GEDI satellite LiDAR coverage will likely result in a global DTM that, within a few years, will be sufficiently accurate for this application.