bluuebunny/crossref_metadata_2025_split huggingface dataset:
Region-specific astrogliosis: differential vessel formation contributes to different patterns of astrogliosis in the cortex and striatum
Authors: Yang Haijie , An Jiawei , Choi Insup , Lee Kihwang , Park Sang-Myun , Jou Ilo , Joe Eun-Hye 
Published: July 2020

AbstractBrain injury causes astrocytes to become reactive (astrogliosis). In this study, we compared astrogliosis in acutely injured cortex and striatum of adult FVB/N mice induced by stereotaxic injection of ATP, a component of danger-associated molecular patterns (DAMPs). Interestingly, MR analysis showed that same amount of ATP induced smaller damage in the cortex than in the striatum. However, in histological analysis, thick and dense scar-like astrogliosis was found in the injured cortex near meninges within 2 wk., but not in other regions, including the striatum and even the cortex near the corpus callosum for up to 30 d. There was little regional difference in the number of Ki67(+)-proliferating astrocytes or mRNA expression of inflammatory cytokines. The most prominent difference between regions with and without scar-like astrogliosis was blood vessel formation. Blood vessels highly expressing collagen 1A1 formed densely near meninges, and astrocytes converged on them. In other regions, however, both blood vessels and astrocytes were relatively evenly distributed. Consistent with this, inhibition of blood vessel formation with the vascular endothelial growth factor (VEGF)-blocking antibody, Avastin, attenuated scar-like astrogliosis near meninges. These results indicate that region-specific astrogliosis occurs following brain injury, and that blood vessel formation plays a critical role in scar formation.
Molecular detection and genetic characteristics of Babesia gibsoni in dogs in Shaanxi Province, China
Authors: Guo Wen-Ping , Xie Guang-Cheng , Li Dan , Su Meng , Jian Rui , Du Luan-Ying 
Published: July 2020

Abstract
Background
Several members of genus Babesia are important pathogens causing babesiosis in dogs. In China, at least five Babesia species have been described in dogs or ticks. This study sought to determine the prevalence and molecular characteristics of various Babesia spp. in dogs in cities in Shaanxi Province in China, including Xi’an and Hanzhong.

Methods
A total of 371 blood samples were collected from pet dogs presenting to veterinary clinics in the cities of Xi’an and Hanzhong in Shaanxi, China. Babesia spp. DNA was detected via amplification of partial 18S rRNA genes by semi-nested PCR. Almost full-length 18S rRNA, ITS, partial TRAP and complete cytb genes were recovered for analysis of the genetic characteristics and relationships with known isolates.

Results
A single species, Babesia gibsoni, was identified in dogs in Xi’an and Hanzhong. Consistently, B. gibsoni was also detected in 14 ticks collected from positive dogs. Sequence similarities and phylogenetic analysis suggested that the isolates identified herein showed a closer genetic relationship with isolates from East Asian countries rather than India, Bangladesh, or the USA. Sequence analysis based on tandem repeat analysis of the TRAP gene further revealed that specific haplotypes were circulating in both Xi’an and Hanzhong, with no specific regionality. In addition, 10.9% of all isolates with atovaquone (ATV)-resistance were identified because of M121I mutation in the deduced cytb protein.

Conclusions
This study revealed a high prevalence rate of Babesia infection. Babesia gibsoni was the only Babesia species identified in cases of canine babesiosis in the cities of Xi’an and Hanzhong cities in Shaanxi, China. In addition, the TRAP gene presented high genetic diversity across isolates. Such information is useful for elucidating the epidemiological characteristics of canine babesiosis, as well as the overall genetic diversity of Babesia spp. circulating in dog populations in Shaanxi Province.
Differences in serum markers of oxidative stress in well controlled and poorly controlled asthma in Sri Lankan children: a pilot study
Authors: Fernando Yenuli , Wickramasinghe Pujitha , De Silva Udani , Alahakoon Malintha , Anuradha K. W. D. A. , Handunnetti Shiroma 
Published: July 2020

AbstractBackgroundAsthma is a disease characterised by hyper responsiveness and bronchoconstriction of airways, and is a major health burden globally. A dysfunction of the oxidant-antioxidant balance, termed oxidative stress, has been implicated in the pathophysiology of asthma. The present study aims to assess the changes in oxidative stress markers, namely nitric oxide metabolites and antioxidant capacity, in children with poorly controlled and well controlled asthma, in comparison to healthy controls.MethodsThe present study enrolled 72 children (ages 5-15 years) classified into three groups: (1) poorly controlled asthma (n = 20), (2) well controlled asthma (n = 24) and (3) healthy controls (n = 27). An interviewer-administered questionnaire was used to record socio-demographic data of the participants. The serum concentrations of the oxidant markers (nitrite, nitrate and total nitric oxide metabolites [NOx]) were determined using the Griess test, and the total antioxidant capacity (TAOC) was determined using the ABTS decolorisation method. The concentrations of these markers were compared across the three groups.ResultsThe three study groups were similar in terms of socio-demographic data. The differences across the three groups were statistically significant for serum concentrations of nitrate and NOx(but not nitrite) and serum TAOC. Further analyses showed that the disparity for nitrate and NOx concentrations was greatest between poorly controlled asthma and healthy controls (p = 0.001 and p < 0.001) compared to the well-controlled asthmatics and healthy controls (p = 0.036 and p = 0.049). A significant difference in serum nitrate and NOxconcentrations was not observed between the two asthma groups (p = 0.311 and 0.203). The TAOC were significantly lower in poorly controlled asthmatics as compared to well-controlled asthmatics (p = 0.003) and healthy controls (p < 0.001). However, there was no significant difference in the serum TAOC between healthy controls and well-controlled asthmatics (p = 0.496). These findings may indicate that it is perhaps the higher TAOC that contributes to the well controlled state of asthma.ConclusionsThe present study indicated that an imbalance of oxidants and antioxidants in the serum may have an underlying role in asthma pathophysiology, and how these markers may be effective in asthma management.
Reconstruction of right ventricular outflow tract stenosis and right ventricular failure after Ross procedure – comprehensive assessment of adult congenital heart disease with four-dimensional imaging: a case report
Authors: Takigami Masao , Itatani Keiichi , Nakanishi Naohiko , Morichi Hiroko , Nishino Teruyasu , Miyazaki Shohei , Nakaji Kosuke , Yamano Michiyo , Kajiyama Yo , Maeda Yoshinobu , Matoba Satoaki , Yaku Hitoshi , Yamagishi Masaaki 
Published: July 2020

Abstract
Background
Re-intervention after Ross procedure into the right ventricular outflow tract might be needed in patients in the long term. However, right ventricular outflow tract re-intervention indications are still unclear. Comprehensive assessment of total hemodynamics is needed.

Case summary
A 42-year-old Japanese woman was referred to our hospital for moderately severe pulmonary regurgitation and severe tricuspid regurgitation after a Ross–Konno procedure. Thirteen years after surgery, she developed atrial fibrillation and atrial flutter and complained of dyspnea. Electrophysiological studies showed re-entry circuit around the low voltage area of the lateral wall on the right atrium. Four-dimensional flow magnetic resonance imaging revealed moderate pulmonary regurgitation, severe tricuspid regurgitation, and a dilated right ventricle. Flow energy loss in right ventricle calculated from four-dimensional flow magnetic resonance imaging was five times higher than in normal controls, suggesting an overload of the right-sided heart system. Her left ventricular ejection fraction was almost preserved. Moreover, the total left interventricular pressure difference, which shows diastolic function, revealed that her sucking force in left ventricle was preserved. After the comprehensive assessments, we performed right ventricular outflow tract reconstruction, tricuspid valve annuloplasty, and right-side Maze procedure. A permanent pacemaker with a single atrial lead was implanted 14 days postoperatively. She was discharged 27 days postoperatively. Echocardiography performed 3 months later showed that the size of the dilated right ventricle had significantly reduced.

Discussion
A four-dimensional imaging tool can be useful in the decision of re-operation in patients with complex adult congenital heart disease. The optimal timing of surgery should be considered comprehensively.
Mesenchymal stem cells: current clinical progress in ARDS and COVID-19
Authors: Xiao Kun , Hou Fei , Huang Xiuyu , Li Binbin , Qian Zhi Rong , Xie Lixin 
Published: July 2020

AbstractAcute respiratory distress syndrome (ARDS) develops rapidly and has a high mortality rate. Survivors usually have low quality of life. Current clinical management strategies are respiratory support and restricted fluid input, and there is no suggested pharmacological treatment. Mesenchymal stromal cells (MSCs) have been reported to be promising treatments for lung diseases. MSCs have been shown to have a number of protective effects in some animal models of ARDS by releasing soluble, biologically active factors. In this review, we will focus on clinical progress in the use of MSCs as a cell therapy for ARDS, which may have clinical implications during the coronavirus disease 2019 (COVID-19) pandemic.
TNFα-TNFR2 signaling pathway in control of the neural stem/progenitor cell immunosuppressive effect: Different experimental approaches to assess this hypothetical mechanism behind their immunological function
Authors: Shamdani Sara , Uzan Georges , Naserian Sina 
Published: July 2020

Abstract
Background
Stem cells have a vast range of functions from tissue regeneration to immunoregulation. They have the ability to modulate immune responses and change the progression of different inflammatory and autoimmune disorders. Tumor cells share many characteristics of stem/progenitor cells too. Both can inhibit effector T cells and other immune cells, while inducing regulatory T cells (T regs), thus, reducing the production of pro-inflammatory cytokines and increasing the production of anti-inflammatory ones. In this context, some cytokines like TNFα are able to control the direction of the immune response. 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.

Main body
We think the expression of TNFR2 confers a level of immunomodulatory properties to its expressing cell and this could be crucially important, particularly, for stem/progenitor and tumor cells. This idea has been already proven in many TNFR2+ cells. Different immunosuppressive cells like T regs, regulatory B cells (B regs), myeloid-derived suppressor cells (MDSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) express TNFR2 and are able to suppress immune cells in presence of TNFα. The other category of rare cells that express TNFR2 is neural cells (NCs). Although little is known about the immunological function of these latter cells, few studies showed their progenitors are able to suppress T cells. Therefore, we hypothesize that the immunosuppressive effect of neural stem cells (NSCs) is potentially TNFα-TNFR2 dependent.

Conclusions
NSCs are among the rare cells that express TNFR2 marker and are able to supress T cells. We believe TNFα-TNFR2 immune checkpoint signaling pathway could be responsible for this immunosuppressive effect.
Formation and optimization of three-dimensional organoids generated from urine-derived stem cells for renal function in vitro
Authors: Sun Guoliang , Ding Beichen , Wan Meimei , Chen Liang , Jackson John , Atala Anthony 
Published: July 2020

Abstract
Background
Organoids play an important role in basic research, drug screening, and regenerative medicine. Here, we aimed to develop a novel kind of three-dimensional (3D) organoids generated from urine-derived stem cells (USCs) and to explore whether kidney-specific extracellular matrix (kECM) could enable such organoids for renal function in vitro.

Methods
USCs were isolated from human urine samples and cultured with kECM extraction to generate 3D organoids in vitro. Eight densities from 1000 to 8000 cells per organoids were prepared, and both ATP assay and Live/Dead staining were used to determine the optimal USC density in forming organoids and kECM additive concentration. The morphology and histology of as-made organoids were evaluated by hematoxylin and eosin (H.E.) staining, immunofluorescence staining and whole mount staining. Additionally, RT-qPCR was implemented to detect renal-related gene expression. Drug toxicity test was conducted to evaluate the potential application for drug screening. The renal organoids generated from whole adult kidney cells were used as a positive control in multiple assessments.

Results
The optimized cell density to generate ideal USC-derived organoids (USC-organoids) was 5000 cells/well, which was set as applying density in the following experiments. Besides, the optimal concentration of kECM was revealed to be 10%. On this condition, Live/Dead staining showed that USC-organoids were well self-organized without significant cell death. Moreover, H.E. staining showed that compact and viable organoids were generated without obvious necrosis inside organoids, which were very close to renal organoids morphologically. Furthermore, specific proximal tubule marker Aquaporin-1 (AQP1), kidney endocrine product erythropoietin (EPO), kidney glomerular markers Podocin and Synaptopodin were detected positively in USC-organoids with kECM. Nephrotoxicity testing showed that aspirin, penicillin G, and cisplatin could exert drug-induced toxicity on USC-organoids with kECM.

Conclusions
USC-organoids could be developed from USCs via an optimal procedure. Combining culture with kECM, USC-organoid properties including morphology, histology, and specific gene expression were identified to be similar with real renal organoids. Additionally, USC-organoids posed kECM in vitro showed the potential to be a drug screening tool which might take the place of renal organoids to some extent in the future.
RETRACTED ARTICLE: Overexpression of TGFβ1 in murine mesenchymal stem cells improves lung inflammation by impacting the Th17/Treg balance in LPS-induced ARDS mice
Authors: Chen Jianxiao , Zhang Xiwen , Xie Jianfeng , Xue Ming , Liu Ling , Yang Yi , Qiu Haibo 
Published: July 2020

Abstract
Background
T helper 17 cells (Th17)/regulatory T cells (Treg), as subtypes of CD4+ T cells, play an important role in the inflammatory response of acute respiratory distress syndrome (ARDS). However, there is still a lack of effective methods to regulate the differentiation balance of Th17/Treg. It was proven that mesenchymal stem cells (MSCs) could regulate the differentiation of CD4+ T cells, but the mechanism is still unclear. TGFβ1, a paracrine cytokine of MSCs, could also regulate the differentiation of Th17/Treg but is lowly expressed in MSCs. Therefore, mouse MSCs (mMSCs) overexpressing TGFβ1 were constructed by lentivirus transduction and intratracheally transplanted into LPS-induced ARDS mice in our study. The aim of this study was to evaluate the therapeutic effects of mMSCs overexpressing TGFβ1 on inflammation and immunoregulation by impacting the Th17/Treg balance in LPS-induced ARDS mice.

Methods
mMSCs overexpressing TGFβ1 were constructed using lentiviral vectors. Then, mouse bone-marrow-derived MSCs (mBM-MSC) and mBM-MSC-TGFβ1 (mBM-MSC overexpressing TGFβ1) were transplanted intratracheally into ARDS mice induced by lipopolysaccharide. At 3 and 7 days after transplantation, the mice were sacrificed, and the homing of the mMSCs was assayed by ex vivo optical imaging. The relative numbers of Th17 and Treg in the lungs and spleens of mice were detected by FCM. IL-17A and IL-10 levels in the lungs of mice were analysed by western blot. Permeability and inflammatory cytokines were evaluated by analysing the protein concentration of BALF using ELISA. Histopathology of the lungs was assessed by haematoxylin and eosin staining and lung injury scoring. Alveolar lung fibrosis was assessed by Masson’s trichrome staining and Ashcroft scoring. The mortality of ARDS mice was followed until 7 days after transplantation.

Results
The transduction efficiencies mediated by the lentiviral vectors ranged from 82.3 to 88.6%. Overexpressing TGFβ1 inhibited the proliferation of mMSCs during days 5–7 (p < 0.05) but had no effect on mMSC differentiation or migration (p > 0.05). Compared to that in the LPS + mBM-MSC-NC group mice, engraftment of mMSCs overexpressing TGFβ1 led to much more differentiation of T cells into Th17 or Treg (p < 0.05), improved permeability of injured lungs (p < 0.05) and ameliorative histopathology of lung tissue in ARDS mice (p < 0.05). Moreover, IL-17A content was also decreased while IL-10 content was increased in the LPS + mBM-MSC-TGFβ1 group compared with those in the LPS + mBM-MSC-NC group (p < 0.05). Finally, mMSCs overexpressing TGFβ1 did not aggravate lung fibrosis in ARDS mice (p > 0.05).

Conclusion
MSCs overexpressing TGFβ1 could regulate lung inflammation and attenuate lung injuries by modulating the imbalance of Th17/Treg in the lungs of ARDS mice.
Management and prevention of anemia (acute bleeding excluded) in adult critical care patients
Authors: Lasocki Sigismond , Pène Frédéric , Ait-Oufella Hafid , Aubron Cécile , Ausset Sylvain , Buffet Pierre , Huet Olivier , Launey Yoann , Legrand Matthieu , Lescot Thomas , Mekontso Dessap Armand , Piagnerelli Michael , Quintard Hervé , Velly Lionel , Kimmoun Antoine , Chanques Gérald 
Published: July 2020

Abstract
Objective
Anemia is very common in critical care patients, on admission (affecting about two-thirds of patients), but also during and after their stay, due to repeated blood loss, the effects of inflammation on erythropoiesis, a decreased red blood cell life span, and haemodilution. Anemia is associated with severity of illness and length of stay.

Methods
A committee composed of 16 experts from four scientific societies, SFAR, SRLF, SFTS and SFVTT, evaluated three fields: (1) anemia prevention, (2) transfusion strategies and (3) non-transfusion treatment of anemia. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE® methodology.

Results
The SFAR–SRLF guideline panel provided ten statements concerning the management of anemia in adult critical care patients. Acute haemorrhage and chronic anemia were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for ten recommendations. Three of these recommendations had a high level of evidence (GRADE 1±) and four had a low level of evidence (GRADE 2±). No GRADE recommendation could be provided for two questions in the absence of strong consensus.

Conclusions
The experts reached a substantial consensus for several strong recommendations for optimal patient management. The experts recommended phlebotomy reduction strategies, restrictive red blood cell transfusion and a single-unit transfusion policy, the use of red blood cells regardless of storage time, treatment of anaemic patients with erythropoietin, especially after trauma, in the absence of contraindications and avoidance of iron therapy (except in the context of erythropoietin therapy).
Clinical characteristics and time trends of hospitalized methadone exposures in the United States based on the Toxicology Investigators Consortium (ToxIC) case registry: 2010–2017
Authors: Mehrpour Omid , Hoyte Christopher , Amirabadizadeh Alireza , Brent Jeffrey ,   On behalf of the Toxicology Investigators Consortium (ToxIC)
Published: July 2020

Abstract
Background
Methadone is well known for its long duration of action and propensity for mortality after an overdose. The present research was aimed at evaluating the clinical manifestations and time trends of methadone exposure in patients in US hospitals.

Methods
We queried the American College of Medical Toxicology’s Toxicology Investigators Consortium case registry for all cases of methadone exposure between January 1, 2010, and December 31, 2017. The collected information included demographic features, clinical presentations, therapeutic interventions, poisoning type (acute, chronic, or acute on chronic), and the reason(s) for exposure. Descriptive data and relative frequencies were used to investigate the participants’ characteristics.
Our data analysis was performed using SPSS version 19 and Prism software. The trends and clinical manifestations of methadone poisoning over the time period of the study were specifically investigated.

Results
Nine hundred and seventy-three patients who met our inclusion criteria, with a mean age of 41.9 ± 16.6 years (range: 11 months-78 years) were analyzed. Five hundred eighty-two (60.2%) were male. The highest rate of methadone poisoning was observed in 2013. There was an increasing rate of methadone exposures in 2010–2013, followed by a decline in 2014–2017. The most common clinical manifestations in methadone-poisoned patients were coma (48.6%) and respiratory depression (33.6%). The in-hospital mortality rate of methadone poisoning was 1.4%.

Conclusion
ToxIC Registry data showed that inpatient methadone exposures enhanced from 2010 to 2013, after which a reduction occurred in the years 2014 to 2017.
Impact of frailty on inpatient outcomes in thyroid cancer surgery: 10-year results from the U.S. national inpatient sample
Authors: Xu Dong , Fei Mengjia , Lai Yi , Shen Yuling , Zhou Jiaqing 
Published: July 2020

Background Frailty is linked to perioperative morbidity and mortality. We evaluated the impact of preoperative frailty on inpatient outcomes of patients undergoing surgery for thyroid malignancy. Methods This population-based, retrospective observational study extracted data of hospitalized patients who were 18 years and older with a primary diagnosis of thyroid cancer undergoing thyroidectomy from the US Nationwide Inpatient Sample (NIS) database (2005–2014). Participants were stratified into frail and non-frail using the Johns Hopkins (ACG) frailty-defining diagnosis indicator. Study endpoints were in-hospital mortality, incidence of surgical and medical complications and prolonged length of stay. Univariate and multivariate analysis were performed to determine associations between the endpoints and frailty. Results Data of 38,202 patients were included. After adjusting for possible confounders, frailty remained significantly associated with higher odds of in-hospital mortality (OR: 3.839, 95% CI: 1.738–8.480), prolonged length of stay (OR: 5.420, 95% CI: 3.799–7.733), surgical complications (OR: 3.144, 95% CI: 2.443–4.045) and medical complications (OR: 6.734, 95% CI: 5.099–8.893) compared with non-frailty. In patients > age 65 years, adjusted odds ratio for frailty was 4.099 (95% CI: 1.736–9.679) for in-hospital mortality, 6.164 (95% CI: 3.514–10.812) for prolonged length of stay, 3.736 (95% CI: 2.620–5.328) for surgical complications, and 5.970, 95% CI: 4.088–8.720 for medical complications, all with significance. Conclusion Frailty is associated with increased risk for adverse inpatient outcomes, including prolonged hospital stay, surgical and medical complications and mortality independent of age and comorbidities in thyroid cancer patients undergoing surgery. Study findings may provide valuable information for preoperative risk stratification.