bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of the cardiac proteome in a rat model of myocardial ischemia-reperfusion using a TMT-based quantitative proteomic strategy
Authors: Lim Sun Ha , Lee Jongwon , Han Mee-Jung 
Published: March 2020

Abstract
Background
Traditional studies of the cardiac proteome have mainly investigated in an animal model by two-dimensional gel electrophoresis (2-DE). However, the results have not been of satisfactory quality for an understanding of the underlying mechanism. Recent quantitative proteomic methods have been improved to overcome these limitations. To comprehensively study the cardiac proteome in a rat model of ischemia-reperfusion (IR), we developed a tandem mass tag (TMT)-based quantitative proteomic strategy. Furthermore, using this strategy, we examined the molecular mechanisms underlying the prevention of myocardial infarction by the intake of Triticum aestivum L. extract (TALE), a representative dietary fiber grain.

Methods
Cardiac proteomes were analyzed by 2-DE as a gel-based approach, and TMT labeling coupled with two-dimensional liquid chromatography (2D-LC) and tandem mass spectrometry (MS/MS) as a non-gel-based quantitative approach. Additionally, gene ontology annotation was conducted by PANTHER database. Several proteins of interest were verified by a Western blot analysis.

Results
Total 641 proteins were identified commonly from two independent MS datasets using 2D-LC MS/MS. Among these, we identified 151 IR-related proteins that were differentially expressed between the sham-operation group and IR group, comprising 62 up-regulated proteins and 89 down-regulated proteins. Most of the reduced proteins were involved in metabolic processes. In addition, 57 of the IR-related proteins were affected by TALE intake, representing 25 up-regulated proteins and 32 down-regulated proteins. In particular, TALE intake leads to a switch in metabolism to reduce the loss of high-energy phosphates and the accumulation of harmful catabolites (especially reactive oxygen species (ROS)) and to maintain cytoskeleton balance, leading to a reduction in cardiac IR injury.

Conclusions
Our study provides a comprehensive proteome map of IR-related proteins and potential target proteins and identifies mechanisms implicated in the prevention of myocardial infarction by TALE intake in a rat IR model.
The (pro)renin receptor: a novel biomarker and potential therapeutic target for various cancers
Authors: Wang Juan , Nishiyama Akira , Matsuyama Makoto , Wang Zhiyu , Yuan Ying 
Published: March 2020

Abstract
Background
The (pro) renin receptor ((P)RR) plays important roles in various pathways, such as the Wnt/β-catenin, renin-angiotensin system (RAS), MAPK/ERK and PI3K/AKT/mTOR pathways, that are involved in a wide range of physiological and pathological processes incorporating the tumorigenesis. However, our knowledge about (P) RR was mostly limited to its roles in cardiovascular and renal physiological functions and diseases. In the past 5 years, however, compelling evidence has revealed that (P) RR is aberrantly expressed in and contributes to the development of various cancers by different means. For instance, (P) RR was recently demonstrated to induce the oncogenesis of pancreatic, colorectal and brain cancers via the Wnt signaling, while promote the endometrial cancer and glioblastoma through the RAS.

Methods
Combining with the deep analysis of big data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, this review updates and summarizes the recent studies about the newly recognized roles of (P) RR in the pathophysiological processes of cancer development and its detailed functions through related pathways, as well as the novel research progress of (P) RR in related fields including the development and application of soluble (P) RR detection kit and monoclonal (P) RR antibody.

Results
This review provides an overview of the essential roles of (P) RR in the tumorigenesis and progression of various cancers and offers a translational outlook for the future research and clinical practices.

Conclusion
(P) RR in the tumor tissues and/or body fluids of patients may be a novel and promising biomarker and potential therapeutic target for diagnosis, treatment and prognosis prediction in various cancers.

Graphical abstract
Towards single-cell ionomics: a novel micro-scaled method for multi-element analysis of nanogram-sized biological samples
Authors: Chen Anle , Hansen Thomas H. , Olsen Lene I. , Palmgren Michael , Husted Søren , Schjoerring Jan K. , Persson Daniel Pergament 
Published: March 2020

Abstract
Background
To understand processes regulating nutrient homeostasis at the single-cell level there is a need for new methods that allow multi-element profiling of biological samples ultimately only available as isolated tissues or cells, typically in nanogram-sized samples. Apart from tissue isolation, the main challenges for such analyses are to obtain a complete and homogeneous digestion of each sample, to keep sample dilution at a minimum and to produce accurate and reproducible results. In particular, determining the weight of small samples becomes increasingly challenging when the sample amount decreases.

Results
We developed a novel method for sampling, digestion and multi-element analysis of nanogram-sized plant tissue, along with strategies to quantify element concentrations in samples too small to be weighed. The method is based on tissue isolation by laser capture microdissection (LCM), followed by pressurized micro-digestion and ICP-MS analysis, the latter utilizing a stable µL min−1 sample aspiration system. The method allowed for isolation, digestion and analysis of micro-dissected tissues from barley roots with an estimated sample weight of only ~ 400 ng. In the collection and analysis steps, a number of contamination sources were identified. Following elimination of these sources, several elements, including magnesium (Mg), phosphorus (P), potassium (K) and manganese (Mn), could be quantified. By measuring the exact area and thickness of each of the micro-dissected tissues, their volume was calculated. Combined with an estimated sample density, the sample weights could subsequently be calculated and the fact that these samples were too small to be weighed could thereby be circumvented. The method was further documented by analysis of Arabidopsis seeds (~ 20 µg) as well as tissue fractions of such seeds (~ 10 µg).

Conclusions
The presented method enables collection and multi-element analysis of small-sized biological samples, ranging down to the nanogram level. As such, the method paves the road for single cell and tissue-specific quantitative ionomics, which allow for future transcriptional, proteomic and metabolomic data to be correlated with ionomic profiles. Such analyses will deepen our understanding of how the elemental composition of plants is regulated, e.g. by transporter proteins and physical barriers (i.e. the Casparian strip and suberin lamellae in the root endodermis).
Comparison of different bridging anticoagulation therapies used after mechanical heart valve replacement in Chinese patients - a prospective cohort study
Authors: Li Bo-Xia , Liu Shi-Dong , Qi Liang , Sun Shusen , Sun Wei , Li Yuan-Min , Song Bing , Wu Xin-An 
Published: March 2020

Abstract
Objective
To assess different bridging anticoagulation therapies early after mechanical heart valve replacement (MHVR) in Chinese patients.

Methods
We performed a prospective, single-center, observational cohort study of 305 patients who underwent elective MHVR with different bridging anticoagulation regimens. Patients enrolled in the study were divided into three bridging therapy groups: the unfractionated heparin (UFH) group (n = 109), the low-molecular-weight heparin (LMWH) group (n = 97), and the UFH with sequential LMWH (UFH-LMWH) group (n = 99). All patients were followed for 4 weeks.

Results
Two patients experienced thromboembolic stroke events in the UFH group. The LMWH group was associated with an increase in the incidence of bleeding events compared with the UFH group (10.3% VS 2.8%; P = 0.03). With a comparison of LMWH and UFH group in secondary endpoints, the statistical test for significance indicated a trend of reduced ICU length of stay (P = 0.08), postoperative length of stay (P = 0.08) and time of achieving target INR (P = 0.06). The creatinine level (odds ratio = 1.03; 95% confidence interval = 1.01 to 1.05; P = 0.02) and hypertension (odds ratio = 3.72; 95% confidence interval = 1.35 to 10.28; P = 0.01) were risk factors for bleeding events.

Conclusion
For Chinese patients, the LMWH bridging anticoagulation presents the increased the incidence of bleeding events, but enables patients to benefit from achieving an early anticoagulation effect. Close follow-up and personalized management are required in patients with thromboembolic and bleeding risk factors.

Trial registration
Chinese Clinical Trial Registry ChiCTR1800019841. Registered 2 December 2018 retrospectively.
The volume-outcome relationship among severely injured patients admitted to English major trauma centres: a registry study
Authors: Sewalt Charlie A. , Wiegers Eveline J. A. , Lecky Fiona E. , den Hartog Dennis , Schuit Stephanie C. E. , Venema Esmee , Lingsma Hester F. 
Published: March 2020

Abstract
Background
Many countries have centralized and dedicated trauma centres with high volumes of trauma patients. However, the volume-outcome relationship in severely injured patients (Injury Severity Score (ISS) > 15) remains unclear. The aim of this study was to determine the association between hospital volume and outcomes in Major Trauma Centres (MTCs).

Methods
A retrospective observational cohort study was conducted using the Trauma Audit and Research Network (TARN) consisting of all English Major Trauma Centres (MTCs). Severely injured patients (ISS > 15) admitted to a MTC between 2013 and 2016 were included. The effect of hospital volume on outcome was analysed with random effects logistic regression models with a random intercept for centre and was tested for nonlinearity. Primary outcome was in-hospital mortality.

Results
A total of 47,157 severely injured patients from 28 MTCs were included in this study. Hospital volume varied from 69 to 781 severely injured patients per year. There were small between-centre differences in mortality after adjusting for important demographic and injury severity characteristics (adjusted 95% odds ratio range: 0.99–1.01). Hospital volume was found to be linear and not associated with in-hospital mortality (adjusted odds ratio (aOR) 1.02 per 10 patients, 95% confidence interval (CI) 0.68–1.54, p = 0.92).

Conclusions
Despite the large variation in volume of the included MTCs, no relationship between hospital volume and outcome of severely injured patients was found. These results suggest that centres with similar structure and processes of care can achieve comparable outcomes in severely injured patients despite the number of severely injured patients they treat.
Influence of physical strain at high altitude on the quality of cardiopulmonary resuscitation
Authors: Egger Alexander , Niederer Maximilian , Tscherny Katharina , Burger Josef , Fuhrmann Verena , Kienbacher Calvin , Roth Dominik , Schreiber Wolfgang , Herkner Harald 
Published: March 2020

Abstract
Background
High quality cardiopulmonary resuscitation is a key factor in survival with good overall quality of life after out-of-hospital cardiac arrest. Current evidence is predominantly based on studies conducted at low altitude, and do not take into account the special circumstances of alpine rescue missions. We therefore aimed to investigate the influence of physical strain at high altitude on the quality of cardiopulmonary resuscitation.

Methods
Alpine field study. Twenty experienced mountaineers of the Austrian Mountain Rescue Service trained in Basic Life Support (BLS) performed BLS on a manikin in groups of two for 16 min. The scenario was executed at baseline altitude and immediately after a quick ascent over an altitude difference of 1200 m at 3454 m above sea level. The sequence of scenarios was randomised for a cross over analysis.
Quality of CPR and exhaustion of participants (vital signs, Borg-Scale, Nine hole peg test) were measured and compared between high altitude and baseline using random-effects linear regression models.

Results
The primary outcome of chest compression depth significantly decreased at high altitude compared to baseline by 1 cm (95% CI 0.5 to 1.3 cm, p < 0.01). There was a significant reduction in the proportion of chest compressions in the target depth (at least 5 cm pressure depth) by 55% (95% CI 29 to 82%, p < 0.01) and in the duration of the release phase by 75 ms (95% CI 48 to 101 ms, p < 0.01). No significant difference was found regarding hands-off times, compression frequency or exhaustion.

Conclusion
Physical strain during a realistic alpine rescue mission scenario at high altitude led to a significant reduction in quality of resuscitation. Resuscitation guidelines developed at sea level are not directly applicable in the mountain terrain.
The protocol for a multisite, double blind, randomized, placebo-controlled trial of axillary nerve stimulation for chronic shoulder pain
Authors: Cleland Travis , Jain Nitin B. , Chae John , Hansen Kristine M. , Hisel Terri Z. , Gunzler Douglas D. , Whitehair Victoria C. , Kim Chong H. , Wilson Richard D. 
Published: March 2020

AbstractBackgroundShoulder impingement syndrome is one of the most common causes of shoulder pain, accounting for approximately 30% of all shoulder pain. Approximately 35% of patients with shoulder impingement syndrome are refractory to conservative treatment. For patients who fail conservative treatment, there is no established treatment to successfully treat their chronic pain. Prior randomized control trials have demonstrated efficacy for the use of a single lead intramuscular peripheral nerve stimulation of the axillary nerve at the motor points of the deltoid muscle for treatment of hemiplegic shoulder pain. This is the first controlled trial to utilize the same novel technology to treat shoulder impingement syndrome outside of the stroke population.MethodsThis is a dual-site, placebo-controlled, double-blinded, randomized control trial. Participants will be randomized to two treatment groups. The intervention group will be treated with active peripheral nerve stimulation of the axillary nerve of the affected shoulder and the control group will be treated with sham peripheral nerve stimulation of the axillary nerve of the affected shoulder. Both groups will receive a standardized exercise therapy program directed by a licensed therapist.DiscussionThis study protocol will allow the investigators to determine if this novel, non-pharmacologic treatment of shoulder pain can demonstrate the same benefit in musculoskeletal patients which has been previously demonstrated in the stroke population.Trial registrationClinicaltrials.gov,NCT03752619. Registered on 26 November 2018.
Molecular typing of Cyclospora cayetanensis in produce and clinical samples using targeted enrichment of complete mitochondrial genomes and next-generation sequencing
Authors: Cinar Hediye Nese , Gopinath Gopal , Murphy Helen R. , Almeria Sonia , Durigan Mauricio , Choi Dajung , Jang AhYoung , Kim Eunje , Kim RaeYoung , Choi Seonju , Lee Jeongu , Shin Yurim , Lee Jieon , Qvarnstrom Yvonne , Benedict Theresa K. , Bishop Henry S. , da Silva Alexandre 
Published: March 2020

Abstract
Background
Outbreaks of cyclosporiasis, a diarrheal illness caused by Cyclospora cayetanensis, have been a public health issue in the USA since the mid 1990’s. In 2018, 2299 domestically acquired cases of cyclosporiasis were reported in the USA as a result of multiple large outbreaks linked to different fresh produce commodities. Outbreak investigations are hindered by the absence of standardized molecular epidemiological tools for C. cayetanensis. For other apicomplexan coccidian parasites, multicopy organellar DNA such as mitochondrial genomes have been used for detection and molecular typing.

Methods
We developed a workflow to obtain complete mitochondrial genome sequences from cilantro samples and clinical samples for typing of C. cayetanensis isolates. The 6.3 kb long C. cayetanensis mitochondrial genome was amplified by PCR in four overlapping amplicons from genomic DNA extracted from cilantro, seeded with oocysts, and from stool samples positive for C. cayetanensis by diagnostic methods. DNA sequence libraries of pooled amplicons were prepared and sequenced via next-generation sequencing (NGS). Sequence reads were assembled using a custom bioinformatics pipeline.

Results
This approach allowed us to sequence complete mitochondrial genomes from the samples studied. Sequence alterations, such as single nucleotide polymorphism (SNP) profiles and insertion and deletions (InDels), in mitochondrial genomes of 24 stool samples from patients with cyclosporiasis diagnosed in 2014, exhibited discriminatory power. The cluster dendrogram that was created based on distance matrices of the complete mitochondrial genome sequences, indicated distinct strain-level diversity among the 2014 C. cayetanensis outbreak isolates analyzed in this study.

Conclusions
Our results suggest that genomic analyses of mitochondrial genome sequences may help to link outbreak cases to the source.
TGFβ-mediated expression of TGFβ-activating integrins in SSc monocytes: disturbed activation of latent TGFβ?
Authors: van Caam A. , Aarts J. , van Ee T. , Vitters E. , Koenders M. , van de Loo F. , van Lent P. , van den Hoogen F. , Thurlings R. , Vonk M. C. , van der Kraan P. M. 
Published: March 2020

Abstract
Introduction
The pathophysiology of systemic sclerosis (SSc) is closely linked to overactive TGFβ signaling. TGFβ is produced and circulates in latent form, making its activation crucial for signaling. This activation can be mediated via integrins. We investigated the balance between active and latent TGFβ in serum of SSc patients and investigated if this correlates with integrin expression on monocytes.

Methods
A TGFβ/SMAD3- or BMP/SMAD1/5-luciferase reporter construct was expressed in primary human skin fibroblasts. Both acidified and non-acidified sera of ten SSc patients and ten healthy controls were tested on these cells to determine total and active TGFβ and BMP levels respectively. A pan-specific TGFβ1/2/3 neutralizing antibody was used to confirm TGFβ signaling. Monocytes of 20 SSc patients were isolated using CD14+ positive selection, and integrin gene expression was measured using qPCR. Integrin expression was modulated using rhTGFβ1 or a small molecule inhibitor of TGFBR1: SB-505124.

Results
SSc sera induced 50% less SMAD3-reporter activity than control sera. Serum acidification increased reporter activity, but a difference between healthy control and SSc serum was no longer observed, indicating that total TGFβ levels were not different. Addition of a pan-specific TGFβ1/2/3 neutralizing antibody fully inhibited SMAD3-reporter activity of both acidified and not-acidified control and SSc sera. Both HC and SSc sera induced similar SMAD1/5-reporter activity, and acidification increased this, but not differently between groups. Interestingly, expression of two integrin alpha subunits ITGA5 and ITGAV was significantly reduced in monocytes obtained from SSc patients. Furthermore, ITGB3, ITGB5, and ITGB8 expression was also reduced in SSc monocytes. Stimulation of monocytes with TGFβ1 induced ITGA5 and ITGAV but lowered ITGB8 expression, whereas the use of the TGFβ receptor inhibitor SB-505124 had the opposite effect.

Conclusion
Total TGFβ serum levels are not different between SSc patients and controls, but TGFβ activity is. This coincides with a reduced expression of TGFβ-activating integrins in monocytes of SSc patients. Because TGFβ regulates expression of these integrins in monocytes, a negative feedback mechanism possibly underlies these observations.
68Ga-PSMA PET/CT in radioactive iodine-refractory differentiated thyroid cancer and first treatment results with 177Lu-PSMA-617
Authors: de Vries Lisa H. , Lodewijk Lutske , Braat Arthur J. A. T. , Krijger Gerard C. , Valk Gerlof D. , Lam Marnix G. E. H. , Borel Rinkes Inne H. M. , Vriens Menno R. , de Keizer Bart 
Published: March 2020

Abstract
Background
Differentiated thyroid carcinoma (DTC) is the most common type of thyroid cancer. Treatment with surgery, radioactive iodine (RAI), and TSH suppression is effective in most patients. Five to 15% of patients become RAI refractory and need alternative therapy; however, treatment options are limited. 68Ga-PSMA PET/CT, originally developed for prostate cancer, is also applicable to other malignancies, including thyroid carcinoma. The uptake of PSMA in thyroid carcinoma gives opportunities for imaging and therapy of RAI-refractory DTC. The aim of this study was to analyze imaging on 68Ga-PSMA PET/CT and evaluate the response to 177Lu-PSMA-617 therapy in patients with RAI-refractory DTC.

Materials and methods
Five patients with RAI-refractory DTC underwent 68Ga-PSMA PET/CT to determine their eligibility for 177Lu-PSMA-617 therapy. 68Ga-PSMA PET/CTs were analyzed visually and quantitatively. Response to 177Lu-PSMA-617 therapy was evaluated using imaging and thyroglobulin (Tg) values.

Results
Tracer uptake suspicious for distant metastases was depicted in all 68Ga-PSMA PET/CTs. Based on tracer uptake, three patients were eligible for 177Lu-PSMA-617 therapy, of whom two were treated. One patient showed disease progression on imaging 1 month later, while her Tg values gradually increased from 18 to 63 μg/L in the months after treatment. Another patient showed partial, temporary response of lung and liver metastases. Her Tg levels initially decreased from 17 to 9 μg/L. However, 7 months after treatment, there was disease progression on imaging and Tg levels had increased to 14 μg/L.
Imaging with 68Ga-PSMA PET/CT could be compared to 18FDG PET/CT in three patients. Two patients showed additional lesions on 68Ga-PSMA PET/CT, and one patient showed concordant imaging.

Conclusion
68Ga-PSMA PET/CT appears to have added value in patients with RAI-refractory DTC, as it is able to detect various types of lesions, some of which were not picked up by 18FDG PET/CT. Furthermore, 68Ga-PSMA PET/CT might be used to identify patients eligible for treatment with 177Lu-PSMA-617. One of the two patients who underwent 177Lu-PSMA-617 therapy showed a modest, temporary response. To draw conclusions about the effectiveness of this therapy, more research is needed.