bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNFα/TNFR2 signaling pathway: an active immune checkpoint for mesenchymal stem cell immunoregulatory function
Authors: Beldi Ghada , Khosravi Maryam , Abdelgawad Mohamed Essameldin , Salomon Benoît L. , Uzan Georges , Haouas Houda , Naserian Sina 
Published: July 2020

Abstract
Background
In addition to their multilineage potential, mesenchymal stem cells (MSCs) have a broad range of functions from tissue regeneration to immunomodulation. MSCs have the ability to modulate the immune response and change the progression of different inflammatory and autoimmune disorders. However, there are still many challenges to overcome before their widespread clinical administration including the mechanisms behind their immunoregulatory function. MSCs inhibit effector T cells and other immune cells, while inducing regulatory T cells (T regs), thus, reducing directly and indirectly the production of pro-inflammatory cytokines. TNF/TNFR signaling plays a dual role: while the interaction of TNFα with TNFR1 mediates pro-inflammatory effects and cell death, its interaction with TNFR2 mediates anti-inflammatory effects and cell survival. Many immunosuppressive cells like T regs, regulatory B cells (B regs), endothelial progenitor cells (EPCs), and myeloid-derived suppressor cells (MDSCs) express TNFR2, and this is directly related to their immunosuppression efficiency. In this article, we investigated the role of the TNFα/TNFR2 immune checkpoint signaling pathway in the immunomodulatory capacities of MSCs.

Methods
Co-cultures of MSCs from wild-type (WT) and TNFR2 knocked-out (TNFR2 KO) mice with T cells (WT and TNFα KO) were performed under various experimental conditions.

Results
We demonstrate that TNFR2 is a key regulatory molecule which is strongly involved in the immunomodulatory properties of MSCs. This includes their ability to suppress T cell proliferation, activation, and pro-inflammatory cytokine production, in addition to their capacity to induce active T regs.

Conclusions
Our results reveal for the first time the importance of the TNFα/TNFR2 axis as an active immune checkpoint regulating MSC immunological functions.
A cautionary tale about the use of colony-forming efficiency as a proxy for the survival of mesenchymal stem cells
Authors: O’Connor Kim 
Published: July 2020

AbstractColony-forming efficiency is a time-honored metric of the proliferation potential of mesenchymal stem cells (MSCs). This commentary raises a concern about the practice of using colony-forming efficiency as a proxy for cell survival. A recently published study from my laboratory investigated this issue. A marker of cellular aging, CD264, was employed to separate human bone marrow MSCs into populations of CD264− cells and culture-matched, aging CD264+ cells with high and low colony-forming efficiency, respectively. In vitro cell survival was evaluated with a single-cell assay; in vivo survival by bioluminescence imaging of MSCs attached to scaffolds that were implanted ectopically in immunodeficient mice. In our study, in vitro and in vivo survival of the MSC populations was independent of colony-forming efficiency. This finding indicates that caution should be exercised before using colony-forming efficiency as an indirect metric of cell survival. Direct measurement of survival may be required. Awareness of this issue should foster a robust experimental design and, thereby, facilitate the translation of MSC research into clinical practice.
10-year follow-up results of the prospective, double-blinded, randomized, controlled study on autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of the femoral head
Authors: Li Mengyuan , Ma Yuanchen , Fu Guangtao , Zhang Ruiying , Li Qingtian , Deng Zhantao , Zheng Minghao , Zheng Qiujian 
Published: July 2020

Abstract
Background
Avascular necrosis of the femoral head (ANFH) is a severely disabling disease of the hip. Several clinical trials have shown promising outcomes on the use of mesenchymal stem cells for the treatment of ANFH, but long-term clinical assessments are lacking. Previously, we reported the 2-year follow-up results of a prospective, double-blinded, randomized, controlled study on autologous bone marrow buffy coat grafting combined with core decompression in patients with ANFH. Here, we report the 10-year follow-up results of this study.

Methods
We recruited 43 (53 hips) patients from 2009 to 2010. The hips were randomly allocated to code decompression (CD) with or without bone marrow buffy coat (BBC) grafting. Participants underwent follow-up at 24, 60, and 120 months postoperatively. The visual analogue scale (VAS), Lequesne algofunctional index, and Western Ontario and McMaster Universities Arthritis Index (WOMAC) osteoarthritis scores were recorded. Survival rate analysis and prognostic factor analysis were performed. The endpoint was defined as progression to Ficat stage IV or conversion to hip arthroplasty.

Results
A total of 31 patients (41 hips) were included in the final analysis. The CD + BBC group had better subjective assessment scores than the CD group. The average survival times were 102.3 months and 78.1 months in the CD + BBC group and CD group, respectively (log-rank test, P = 0.029). In the univariate Cox proportional hazards regression model, age [hazard ratio (HR) = 1.079, P = 0.047] and preoperative Ficat stage (HR = 3.283, P = 0.028) indicated a high risk for progression, while the use of BBC (HR = 0.332, P = 0.042) indicated a low risk. Preoperative Ficat stage III was isolated as an independent risk factor for clinical failure in the multivariate model (HR = 3.743, P = 0.018).

Conclusion
The 10-year follow-up results of this prospective, double-blinded, randomized, controlled study showed that the use of autologous BBC in combination with core decompression was more effective than the use of core decompression alone.

Trial registration
ClinicalTrials.gov, NCT01613612. Registered on 13 December 2011—retrospectively registered
Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study
Authors: Diehl J.-L. , Peron N. , Chocron R. , Debuc B. , Guerot E. , Hauw-Berlemont C. , Hermann B. , Augy J. L. , Younan R. , Novara A. , Langlais J. , Khider L. , Gendron N. , Goudot G. , Fagon J.-F. , Mirault T. , Smadja D. M. 
Published: July 2020

Abstract
Rationale
COVID-19 ARDS could differ from typical forms of the syndrome.

Objective
Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics.

Methods
Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1–4] day after intubation (median [IQR]).

Measurements and main results
Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1–44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721–2434] mL. Gas exchanges were characterized by hypercapnia 55 [44–62] mmHg, high physiological dead-space (VD/VT): 75 [69–85.5] % and ventilatory ratio (VR): 2.9 [2.2–3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12–46] cells per mL and 1483 [999–2217] ng/mL, respectively.

Conclusions
We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.
New lower bounds for the minimum M-eigenvalue of elasticity M-tensors and applications
Authors: Che Haitao , Chen Haibin , Xu Na , Zhu Qingni 
Published: July 2020

AbstractM-eigenvalues of elasticity M-tensors play an important role in nonlinear elasticity and materials. In this paper, we present several new lower bounds for the minimum M-eigenvalue of elasticity M-tensors and propose numerical examples to illustrate the efficiency of the obtained results. As applications, we provide several checkable sufficient conditions for the strong ellipticity and positive definiteness of irreducible elasticity M-tensors.
Finite volume element method with the WSGD formula for nonlinear fractional mobile/immobile transport equations
Authors: Zhao Jie , Fang Zhichao , Li Hong , Liu Yang 
Published: July 2020

AbstractIn this article, a finite volume element method with the second-order weighted and shifted Grünwald difference (WSGD) formula is proposed and studied for nonlinear time fractional mobile/immobile transport equations on triangular grids. By using the WSGD formula of approximating the Riemann–Liouville fractional derivative and an interpolation operator$I_{h}^{*}$Ih∗, a second-order fully discrete finite volume element (FVE) scheme is formulated. The existence, uniqueness, and unconditional stability for the fully discrete FVE scheme are derived, the optimala priorierror estimates in$L^{\infty }(L^{2}(\varOmega))$L∞(L2(Ω))and$L^{2}(H^{1}(\varOmega))$L2(H1(Ω))norms are obtained, in which the convergence orders are independent of the fractional parameters. At the end of this article, two numerical examples with different nonlinear terms are given to verify the feasibility and effectiveness.
The surviving sepsis campaign: basic/translational science research priorities
Authors: Deutschman Clifford S. , Hellman Judith , Roca Ricard Ferrer , De Backer Daniel , Coopersmith Craig M. ,   for the Research Committee of the Surviving Sepsis Campaign, Coopersmith Craig M. , De Backer Daniel , Antonelli Massimo , Deutschman Clifford S. , Evans Laura , Ferrer-Roca Ricard , Hellman Judith , Jog Sameer , Kesecioglu Jozef , Lat Ishaq , Levy Mitchell M. , Machado Flavia , Martin Greg , Martin-Loeches Ignacio , Nunnally Mark E. , Rhodes Andrew 
Published: July 2020

Abstract
Objectives
Expound upon priorities for basic/translational science identified in a recent paper by a group of experts assigned by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.

Data sources
Original paper, search of the literature.

Study selection
This study is selected by several members of the original task force with specific expertise in basic/translational science. Data extraction and data synthesis are not available.

Conclusions
In the first of a series of follow-up reports to the original paper, several members of the original task force with specific expertise provided a more in-depth analysis of the five identified priorities directly related to basic/translational science. This analysis expounds on what is known about the question and what was identified as priorities for ongoing research. It is hoped that this analysis will aid the development of future research initiatives.
Evaluating the impact of jatropha oil extract against the Varroa mite, Varroa destructor Anderson & Trueman (Arachnida: Acari: Varroidae), infesting honeybee colonies (Apis mellifera L.)
Authors: Masry Saad H. D. , Abd El-Wahab Tarek E. , Rashad Mohamed 
Published: July 2020

AbstractThe Varroa mite, Varroa destructor Anderson & Trueman (Arachnida: Acari: Varroidae), is a severe external parasitic mite of honeybees that causes great losses of colonies globally. Four concentrations (1, 2%, 5, and 10%) of Jatropha curcas oil were tested for controlling the Varroa mite. Significant effects of reducing percentage of the mite infestation (P = 0.05) after second treatment for sealed brood and after third treatment for adult workers in all tested concentrations of J. curcas were recorded. The low concentrations 1 and 2% of J. curcas were more effective than the higher ones 5 and 10% on reduction of percentage of Varroa mite infestation. Moreover, the colonies treated with the lowest concentrations of jatropha oil had the highest amount of brood area (75.75 and 77.50 inch2) and the highest number of combs covered with bees compared with the colonies treated with the concentrations 5 and 10%. Treated colonies with the concentrations 1, 10, and 5% had a high amount of stored honey and pollen grains, 126.50, 111, and 96 inch2 and 11.25, 9.75, and 9.75 inch2, respectively. Obtained results encourage researchers to study deeply the ability of using jatropha oil in the widely field of Apicultural.
Migraine and tension headache comorbidity with hypothyroidism in Egypt
Authors: Abou Elmaaty Ali A. , Flifel Mohamed E. , Belal Tamer , Zarad Carmen A. 
Published: July 2020

Abstract
Background
Migraine, tension type headache (TTH), and hypothyroidism are clinical problems that affect patient daily activities and quality of life.

Objectives
The purpose of this study was to investigate the potential association between hypothyroidism in patients with migraine and TTH.

Patients and methods
Two hundred and twelve patients with migraine and TTH and one hundred control subjects underwent clinical evaluation, assessment of thyroid hormones, and thyroid ultrasound.

Results
Subclinical and overt hypothyroidism were significantly higher in patients with migraine and TTH (P = 0.001) than control subjects. Patients with migraine and TTH showed significantly more abnormal thyroid gland morphology than healthy control (P = 0.027). Hypothyroidism is significantly expressed in chronic TTH more than TTH with infrequent or frequent TTH (P = 0.009).

Conclusions
Patients having migraine and TTH more prone to develop hypothyroidism when compared with control group. Also patients with chronic TTH are susceptible to develop hypothyroidism (either subclinical or overt) when compared with patients having frequent or infrequent TTH.
The Attributable Mortality of Postoperative Bleeding Exceeds the Attributable Mortality of Postoperative Venous Thromboembolism
Authors: Bellomy Melissa L. , Engoren Milo C. , Martin Barbara J. , Shi Yaping , Shotwell Matthew S. , Hughes Christopher G. , Freundlich Robert E. 
Published: July 2020

Background:
Bleeding and venous thromboembolic disease are considered important sources of postoperative morbidity and mortality. Clinically, treatment of these 2 disorders is often competing. We sought to better understand the relative contributions of bleeding and venous thromboembolic disease to postoperative attributable mortality in a national cohort.

METHODS:
A retrospective analysis of the 2006–2017 American College of Surgeons’ National Surgical Quality Improvement Program (ACS-NSQIP) database was performed to assess the adjusted odds ratio and attributable mortality for postoperative bleeding and venous thromboembolism, adjusted by year.

RESULTS:
After adjustment for confounding variables, bleeding exhibited a high postoperative attributable mortality in every year studied. Venous thromboembolism appeared to contribute minimal attributable mortality.

CONCLUSIONS:
Bleeding complications are a consistent source of attributable mortality in surgical patients, while the contribution of venous thromboembolic disease appears to be minimal in this analysis. Further studies are warranted to better understand the etiology of this disparity.
Ablations over transformer models for biomedical relationship extraction
Authors: Jackson Richard G , Jansson Erik , Lagerberg Aron , Ford Elliot , Poroshin Vladimir , Scrivener Timothy , Axelsson Mats , Johansson Martin , Franco Lesly Arun , Papa Eliseo 
Published: July 2020

Background: Masked language modelling approaches have enjoyed success in improving benchmark performance across many general and biomedical domain natural language processing tasks, including biomedical relationship extraction (RE). However, the recent surge in both the number of novel architectures and the volume of training data they utilise may lead us to question whether domain specific pretrained models are necessary. Additionally, recent work has proposed novel classification heads for RE tasks, further improving performance. Here, we perform ablations over several pretrained models and classification heads to try to untangle the perceived benefits of each. Methods: We use a range of string preprocessing strategies, combined with Bidirectional Encoder Representations from Transformers (BERT), BioBERT and RoBERTa architectures to perform ablations over three RE datasets pertaining to drug-drug and chemical protein interactions, and general domain relationship extraction. We explore the use of the RBERT classification head, compared to a simple linear classification layer across all architectures and datasets. Results: We observe a moderate performance benefit in using the BioBERT pretrained model over the BERT base cased model, although there appears to be little difference when comparing BioBERT to RoBERTa large. In addition, we observe a substantial benefit of using the RBERT head on the general domain RE dataset, but this is not consistently reflected in the biomedical RE datasets. Finally, we discover that randomising the token order of training data does not result in catastrophic performance degradation in our selected tasks. Conclusions: We find a recent general domain pretrained model performs approximately the same as a biomedical specific one, suggesting that domain specific models may be of limited use given the tendency of recent model pretraining regimes to incorporate ever broader sets of data. In addition, we suggest that care must be taken in RE model training, to prevent fitting to non-syntactic features of datasets.
Case Report: Sustained mitochondrial damage in cardiomyocytes in patients with severe propofol infusion syndrome
Authors: Karasawa Satoshi , Nakada Taka-aki , Mori Naoto , Daimon Michiko , Miyauchi Hideyuki , Kanai Tetsuya , Takano Hiroyuki , Kobayashi Yoshio , Oda Shigeto 
Published: July 2020

Introduction: Propofol infusion syndrome (PRIS) is rare but a potentially lethal adverse event. The pathophysiologic mechanism is still unknown. Patient concerns: A 22-year-old man was admitted for the treatment of Guillain-Barré syndrome. On day six, he required mechanical ventilation due to progressive muscle weakness; propofol (3.5 mg/kg/hour) was administered for five days for sedation. On day 13, he had hypotension with abnormal electrocardiogram findings, acute kidney injury, hyperkalemia and severe rhabdomyolysis. Diagnosis and interventions: The patient was transferred to our intensive care unit (ICU) on suspicion of PRIS. Administration of noradrenaline and renal replacement therapy and fasciotomy for compartment syndrome of lower legs due to PRIS-rhabdomyolysis were performed. Outcomes: The patient gradually recovered and was discharged from the ICU on day 30. On day 37, he had repeated sinus bradycardia with pericardial effusion in echocardiography. Cardiac 18F-FDG PET on day 67 demonstrated heterogeneous 18F-FDG uptake in the left ventricle. Electron microscopic investigation of endomyocardial biopsy on day 75 revealed mitochondrial myelinization of the cristae, which indicated mitochondrial damage of cardiomyocytes. He was discharged without cardiac abnormality on day 192. Conclusions: Mitochondrial damage in both morphological and functional aspects was observed in the present case. Sustained mitochondrial damage may be a therapeutic target beyond the initial therapy of discontinuing propofol administration.
Health inequities in unscheduled healthcare for children with intellectual disabilities in Ireland: a study protocol
Authors: Nicholson Emma , Doherty Edel , Somanadhan Suja , Guerin Suzanne , Schreiber James , Bury Gerard , Kroll Thilo , Raley Meredith , McAuliffe Eilish 
Published: July 2020

Background: Health inequities for children with intellectual disabilities are prevalent within different health systems, and children with intellectual disabilites have shorter life expectancies than the general population, higher mortality rates before the age of 17 and have a greater risk of potentially preventable hospitalisations. A health systems approach to research in this area provides a useful means through which research can inform policy and practice to ensure people with intellectual disabilities receive equitable healthcare; however, there is a paucity of evidence regarding how to address differences that have been described in the literature to date. The overall aim of this research is to establish the extent of health inequities for children with intellectual disabilities in Ireland compared to children without intellectual disabilities with respect to their utilisation of primary care and rates of hospitalisation, and to gain a better understanding of what influences utilisation of primary care and emergency department services in this population. Methods and analysis: The design of this research adopts a multi-methods approach: statistical analysis of health data to determine the extent of health inequities in relation to healthcare utilisation; discrete choice experiments to explore General Practitioners’ decision making and parental preferences for optimal care; and concept mapping to develop consensus between stakeholders on how to address current healthcare inequities. Discussion: By applying a systems lens to the issue of health inequities for children with intellectual disabilities, the research hopes to gain a thorough understanding of the varying components that can contribute to the maintenance of such healthcare inequities. A key output from the research will be a set of feasible solutions and interventions that can address health inequities for this population.
The impact of liver disease on mortality in cystic fibrosis - a systematic review protocol
Authors: Sasame Ao , Connolly Lucy , Fitzpatrick Emer , Stokes Diarmuid , Bourke Billy , Rowland Marion 
Published: July 2020

Background Cystic fibrosis (CF) is a multiorgan disease affecting the lungs pancreas and gastrointestinal tract. Pulmonary complications are the most common clinical manifestation of the disease. Recent advances in the treatment of pulmonary complications have resulted in substantial improvement in life expectancy. Less than 10% of persons with CF (PWCF) develop liver disease (CFLD). There is conflicting evidence as to the impact of liver disease on mortality in CF, with evidence suggesting that CFLD contributes to increased mortality in CF, while other studies suggest that the impact on mortality is limited. Understanding the contribution of liver disease to mortality in CF is essential if further improvements in life expectancy are to be achieved. Objective: To document the impact of liver disease on life expectancy for PWCF. Methods: This systematic review will be conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P 2015). PubMed, Medline and Embase will be searched for English language publications between 1949 and 2020 reporting liver related and all-cause mortality in CF. Observational studies that use an unambiguous definition of liver disease in well-defined CF populations will be included. Studies with and without a comparator will be evaluated. Clinical trials of ursodeoxycholic acid will be excluded as well as organ transplantation outcome studies. The ROBINS-1 risk of bias tool for non-randomised studies will be used to evaluate the quality of the studies. We will provide a narrative synthesis of our findings using tabular formats to highlight any impact of liver disease on mortality in CF. Conclusion: It is anticipated that this review will bring clarity to the question of whether CFLD shortens life expectancy in PWCF and stimulate new approaches to the management of CFLD. Registration: This protocol has been submitted for registration on PROSPERO and is awaiting review.