bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the relationship between ACE I/D gene polymorphism and renal allograft survival
Authors: Yang Chun-Hua , Lu Yi , Chen Xue-Xia , Xian Wen-Feng , Tu Wei-Feng , Li Hong-Yan 
Published: March 2015

Background and objective: The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and renal allograft survival after renal transplantation from the published reports are still debatable. This study was performed to evaluate the relationship between the ACE I/D gene polymorphism and renal allograft survival after renal transplantation using meta-analysis. Method: Eligible studies were identified from PubMed and Cochrane Library on 1 November 2014, and eligible studies were recruited and synthesized using a meta-analysis methodology. Results: Twelve investigations were included in this meta-analysis for the assessment of the relationship between the ACE I/D gene polymorphism and renal allograft survival. In this meta-analysis, the ACE I/D gene polymorphism was not associated with renal allograft survival after renal transplantation for overall populations, Caucasians, Brazilians and Africans. Interestingly, the ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. Conclusions: ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. However, more studies should be performed to confirm this association.
Cardiovascular actions of mineralocorticoid receptor antagonists in patients with chronic kidney disease: A systematic review and meta-analysis of randomized trials
Authors: Ng Khai P , Arnold Julia , Sharif Adnan , Gill Paramjit , Townend Jonathan N , Ferro Charles J 
Published: March 2015

Introduction: The safety and actions of mineralocorticoid receptor antagonists on surrogate markers of cardiovascular disease as well as major patient level cardiovascular end-points in patients with chronic kidney disease are unclear. Methods: MEDLINE, EMBASE, Trip Database, Cochrane Central Register of Controlled Trials, Cochrane Renal Group specialized register, Current Controlled Trials and clinicaltrials.gov were searched for relevant trials. Results: Twenty-nine trials (1581 patients) were included. Overall, mineralocorticoid receptor antagonists lowered both systolic and diastolic blood pressure (–5.24, 95% confidence interval (CI) –8.65, −1.82 mmHg; p=0.003 and −1.96, 95% CI −3.22, –0.69 mmHg; p=0.002 respectively). There were insufficient data to perform a meta-analysis of other cardiovascular effects. However, a systematic review of the studies included suggested a consistent improvement in surrogate markers of cardiovascular disease. Overall, the use of mineralocorticoid receptor antagonists was associated with an increased serum potassium (0.23, 95% CI 0.13, 0.33 mmol/l; p<0.0001) and higher risk ratio (1.76, 95% CI 1.20, 2.57; p=0.001) of hyperkalemia. Data on long-term cardiovascular outcomes and mortality were not available in any of the trials. Conclusions: The long-term effects of mineralocorticoid receptor antagonists on cardiovascular events, mortality and safety need to be established.
How I treat refractory thrombotic thrombocytopenic purpura
Authors: Sayani Farzana A. , Abrams Charles S. 
Published: March 2015

AbstractAcquired thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) without an obvious cause, and may include fever, mild renal failure, and neurologic deficits. It is characterized by a deficiency of the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13), resulting in formation of microthrombi in the high sheer environment of the microvasculature. This causes microvascular occlusion, MAHA, and organ ischemia. Diagnosis is based on the presence of clinical symptoms, laboratory aberrations consistent with MAHA, decreased ADAMTS13 activity, and possibly presence of anti-ADAMTS13 autoantibodies. Upfront treatment of acute TTP includes plasma exchange and corticosteroids. A significant number of patients are refractory to this treatment and will require further interventions. There are limited data and consensus on the management of the refractory TTP patient. Management involves simultaneously ruling out other causes of thrombocytopenia and MAHA, while also considering other treatments. In this article, we describe our management of the patient with refractory TTP, and discuss use of rituximab, increased plasma exchange, splenectomy, and immunosuppressive options, including cyclophosphamide, vincristine, and cyclosporine. We also review recent evidence for the potential roles of bortezomib and N-acetylcysteine, and explore new therapeutic approaches, including recombinant ADAMTS13 and anti-VWF therapy.
The national review of asthma deaths: what did we learn and what needs to change?
Authors: Levy Mark L. 
Published: March 2015

Key pointsThe 2014 UK National Review of Asthma Deaths identified potentially preventable factors in two-thirds of the medical records of cases scrutinised45% of people who died from asthma did not call for or receive medical assistance in their final fatal attackOverall asthma management, acute and chronic, in primary and secondary care was judged to be good in less than one-fifth of those who diedThere was a failure by doctors and nurses to identify and act on risk factors for asthma attacks and asthma deathThe rationale for diagnosing asthma was not evident in a considerable number of cases, and there were inaccuracies related to the completion of medical certificates of the cause of death in over half of the cases considered for the UK National Review of Asthma DeathsEducational aimsTo increase awareness of some of the findings of the recent UK National Review of Asthma Deaths and previous similar studiesTo emphasise the need for accurate diagnosis of asthma, and of the requirements for completion of medical certificates of the cause of deathTo consider areas for improving asthma care and prevention of attacks and avoidable deathsSummaryDespite the development and publication of evidence-based asthma guidelines nearly three decades ago, potentially preventable factors are repeatedly identified in studies of the care provided for patients who die from asthma. The UK National Review of Asthma Deaths (NRAD), a confidential enquiry, was no exception: major preventable factors were identified in two-thirds of asthma deaths. Most of these factors, such as inappropriate prescription and failure to provide patients with personal asthma action plans (PAAPs), could possibly have been prevented had asthma guidelines been implemented.NRAD involved in-depth scrutiny by clinicians of the asthma care for 276 people who were classified with asthma as the underlying cause of death in real-life. A striking finding was that a third of these patients did not actually die from asthma, and many had no recorded rationale for an asthma diagnosis.The apparent complacency with respect to asthma care, highlighted in NRAD, serves as a wake-up call for health professionals, patients and their carers to take asthma more seriously. Based on the NRAD evidence, the report made 19 recommendations for change. The author has selected six areas related to the NRAD findings for discussion and provides suggestions for change in the provision of asthma care. The six areas are: systems for provision and optimisation of asthma care, diagnosis, identifying risk, implementation of guidelines, improved patient education and self-management, and improved quality of completion of medical certificates of the cause of death.
Nanostructurization and thermal properties of polyethylenes’ welds
Authors: Galchun Anatoliy , Korab Nikolay , Kondratenko Volodymyr , Demchenko Valeriy , Shadrin Andriy , Anistratenko Vitaliy , Iurzhenko Maksym 
Published: March 2015

Abstract
As it is known, polyethylene (PE) is one of the common materials in the modern world, and PE products take the major share on industrial and trade markets. For example, various types of technical PE like PE-63, PE-80, and PE-100 have wide industrial applications, i.e., in construction, for pipeline systems etc. A rapid development of plastics industry outstrips detailed investigation of welding processes and welds’ formation mechanism, so they remain unexplored. There is still no final answer to the question how weld’s microstructure forms. Such conditions limit our way to the understanding of the problem and, respectively, prevent scientific approaches to the welding of more complicated (from chemical point of view) types of polymers than PE. Taking into account state-of-the-art, the article presents results of complex studies of PE weld, its structure, thermophysical and operational characteristics, analysis of these results, and basing on that some hypotheses of welded joint and weld structure formation. It is shown that welding of dissimilar types of polyethylene, like PE-80 and PE-100, leads to the formation of better-ordered crystallites, restructuring the crystalline phase, and amorphous areas with internal stresses in the welding zone.
Silicon diffusion control in atomic-layer-deposited Al2O3/La2O3/Al2O3 gate stacks using an Al2O3 barrier layer
Authors: Wang Xing , Liu Hong-Xia , Fei Chen-Xi , Yin Shu-Ying , Fan Xiao-Jiao 
Published: March 2015

AbstractIn this study, the physical and electrical characteristics of Al2O3/La2O3/Al2O3/Si stack structures affected by the thickness of an Al2O3barrier layer between Si substrate and La2O3layer are investigated after a rapid thermal annealing (RTA) treatment. Time of flight secondary ion mass spectrometry (TOF-SIMS) and X-ray photoelectron spectroscopy (XPS) tests indicate that an Al2O3barrier layer (15 atomic layer deposition (ALD) cycles, approximately 1.5 nm) plays an important role in suppressing the diffusion of silicon atoms from Si substrate into the La2O3layer during the annealing process. As a result, some properties of La2O3dielectric degenerated by the diffusion of Si atoms are improved. Electrical measurements (C-V,J-V) show that the thickness of Al2O3barrier layer can affect the shift of flat band voltage (VFB) and the magnitude of gate leakage current density.
Protamine nanoparticles for improving shRNA-mediated anti-cancer effects
Authors: Liu Ming , Feng Bo , Shi Yijie , Su Chang , Song Huijuan , Cheng Wei , Zhao Liang 
Published: March 2015

Abstract
Protamine nanoparticles were designed by encapsulating small hairpin RNA (shRNA)-expressing plasmid DNA targeting the Bcl-2 gene (shBcl-2) to silence apoptosis-related Bcl-2 protein for improving the transfection efficiency and cytotoxicity in cancer therapy. Our findings demonstrated that the obtained protamine nanoparticles possessed excellent characterizations of small particle size, homogenous distribution, positive charge, and high encapsulation efficiency of gene. shBcl-2 loaded in nanoparticles (NPs) was protected effectively from the degradation of DNase I and serum. More importantly, it significantly improved the efficiency of transfection of shRNA in vitro in A549 cells and increased its cytotoxicity and induced more cell apoptosis by silencing Bcl-2.
Results of a proof of concept, double-blind, randomized trial of a second generation antisense oligonucleotide targeting high-sensitivity C-reactive protein (hs-CRP) in rheumatoid arthritis
Authors: Warren Marshelle S , Hughes Steven G , Singleton Walter , Yamashita Mason , Genovese Mark C 
Published: March 2015

Abstract
Introduction
This randomized, double-blind, phase II study evaluated the pharmacodynamics, safety and tolerability of ISIS 329993 (ISIS-CRPRx), an antisense oligonucleotide, in patients with active rheumatoid arthritis (RA).

Methods
Patients with active RA of at least six months duration were randomized into three cohorts to receive ISIS-CRPRx (100 mg, 200 mg or 400 mg) or placebo (3 active:1 placebo within each cohort) via subcutaneous (SC) injection on Days 1, 3, 5 and 8 and then once weekly for the next 11 weeks. The effects of study treatment on high-sensitivity C-reactive protein (hs-CRP) level were evaluated. An exploratory analysis on disease activity was assessed via the American College of Rheumatology 20% improvement criteria (ACR20). Safety was evaluated via adverse events and laboratory measures.

Results
Fifty-one patients received one of the following treatments: ISIS-CRPRx 100 mg, n = 12; 200 mg, n = 13, 400 mg, n = 14; placebo n = 12. In the ISIS-CRPRx treatment groups there were dose-dependent reductions in hs-CRP. At Day 36 the mean percent change from baseline was: placebo: −14.4%; ISIS-CRPRx 100 mg: −19.5%; 200 mg: −56.6% and 400 mg: −76.7%, (P = 0.0015 placebo compared to 400 mg). There were no differences between treatment groups and placebo in the ACR20 at Day 36 or Day 92. There were no serious infections and no elevations in liver function tests, lipids, creatinine or other lab abnormalities related to ISIS-CRPRx.

Conclusions
In this study, ISIS-CRPRx selectively reduced hs-CRP in a dose-dependent manner, and was well-tolerated in patients with RA. Its utility as a therapy in RA remains unclear.

Trial registration
Clinicaltrials.gov NCT01414101. Registered 21 July 2011.
Fate determination in mesenchymal stem cells: a perspective from histone-modifying enzymes
Authors: Huang Biao , Li Gang , Jiang Xiao Hua 
Published: March 2015

AbstractMesenchymal stem cells (MSCs) hold great promise for therapeutic use in regenerative medicine and tissue engineering. A detailed understanding of the molecular processes governing MSC fate determination will be instrumental in the application of MSCs. Much progress has been made in recent years in defining the epigenetic events that control the differentiation of MSCs into different lineages. A complex network of transcription factors and histone modifiers, in concert with specific transcriptional co-activators and co-repressors, activates or represses MSC differentiation. In this review, we summarize recent progress in determining the effects of histone-modifying enzymes on the multilineage differentiation of MSCs. In addition, we propose that the manipulation of histone signatures associated with lineage-specific differentiation by small molecules has immense potential for the advancement of MSC-based regenerative medicine.
Transplantation of cryopreserved human umbilical cord blood-derived endothelial progenitor cells induces recovery of carotid artery injury in nude rats
Authors: Yin Yangguang , Liu Huanyun , Wang Fangjuan , Li Lufeng , Deng Mengyang , Huang Lan , Zhao Xiaohui 
Published: March 2015

Abstract
Introduction
Transplantation of endothelial progenitor cells (EPCs) restores endothelial function in patients with endothelial dysfunction and initial denudation. The goal of the present study was to determine the effect of cryopreserved human umbilical cord blood (UCB)-derived EPC infusion on the repair of carotid artery injury in nude rats.

Methods
Mononuclear cells (MNCs) from human cryopreserved UCB and peripheral blood (PB) of patients with cardiovascular diseases and healthy volunteers were cultured in a conditioned medium. The in vitro migration, proliferation, adhesion, and survival capacities, as well as paracrine cytokine release of EPCs were investigated. EPC homing, induced reendothelialization, and the effect on neointima formation were also assessed in vivo.

Results
Patient-derived PB EPCs (PPB-EPCs) displayed decreased migration, proliferation, adhesion, and survival capabilities as compared to PB-EPCs from healthy volunteers (HPB-EPCs) and cryopreserved UCB-EPCs. However, there was no difference in the release of vascular endothelial growth factor (VEGF) and stromal cell derived factor 1 (SDF-1) between the three groups. Two weeks after transplantation, more labeled UCB-EPCs and HPB-EPCs than PPB-EPCs were found by cell tracking in the injury zone. Administration of PPB-EPCs, HPB-EPCs, and UCB-EPCs enhanced reendothelialization and inhibited neointima formation compared to the saline control. However, UCB-EPC and HPB-EPC infusion showed a greater improvement than PPB-EPCs.

Conclusions
Cryopreserved UCB-MNCs derived EPCs and HPB-EPCs show better responses to cytokines and vascular injury than PPB-EPCs. Thus, cryopreservation and delivery of cryopreserved autogenous UCB-EPCs or HPB-EPCs may be a promising vasculoprotective approach for patients with multiple cardiovascular risk factors.
CCR5 facilitates endothelial progenitor cell recruitment and promotes the stabilization of atherosclerotic plaques in ApoE−/− mice
Authors: Zhang Zhongwen , Dong Jianjun , Lobe Corrinne G , Gong Peiyun , Liu Ju , Liao Lin 
Published: March 2015

Abstract
Introduction
Unstable atherosclerotic plaques are prone to rupture, which leads to atherothrombosis. Endothelial progenitor cells (EPCs) are bone marrow-derived precursor cells that may repair vascular injury in atherosclerosis. Chemokine (C-C motif) receptor 5 (CCR5) promotes mobilization of EPCs. In this study, we investigated the therapeutic potential of CCR5-overexpressing EPCs on plaque stabilization in an apolipoprotein E (ApoE)−/− mouse model.

Methods
The expression of CCR5 and its cognate ligand chemokine (C-C motif) ligand 5 (CCL5) was examined in atherosclerotic aortas of humans and mice by immunohistochemistry. Splenectomized ApoE−/− C57BL/6 J mice fed a high-fat diet for 24 weeks were intravenously injected with EPCs transfected with CCR5 overexpression lentivirus. The recruitment of EPCs over the atherosclerotic plaques was evaluated by immunofluorescence. The content of lipid, smooth muscle cells, monocytes/macrophages, and endothelial cells in atherosclerotic plaques was assayed by specific immunostaining. The serum levels of atherosclerosis-related inflammatory factors in ApoE−/− mice were measured by mouse atherosclerosis antibody array I.

Results
CCR5 and CCL5 are highly expressed in atherosclerotic plaques in both humans and mice. The ApoE−/− mice with CCR5-overexpressing EPC treatment demonstrated a more stable plaque formation with enhanced recruitment of EPC, reduced lipid, and macrophage content in the atherosclerotic plaques. CCR5-overexpressing EPC treatment also increased the content of endothelial cells and nitric oxide production in the plaques. In addition, the serum levels of interleukin-3 (IL-3), IL-5, IL-6, IL-13, CD40, and tumor necrosis factor-alpha and the plaque contents of IL-6 and matrix metalloproteinase-9 were reduced in mice with CCR5-overexpressing EPC treatment.

Conclusions
These findings suggest that CCR5 is a novel therapeutic target in EPC treatment for stabilization of atherosclerotic plaques.
Large-scale expansion of Wharton’s jelly-derived mesenchymal stem cells on gelatin microbeads, with retention of self-renewal and multipotency characteristics and the capacity for enhancing skin wound healing
Authors: Zhao Guifang , Liu Feilin , Lan Shaowei , Li Pengdong , Wang Li , Kou Junna , Qi Xiaojuan , Fan Ruirui , Hao Deshun , Wu Chunling , Bai Tingting , Li Yulin , Liu Jin Yu 
Published: March 2015

Abstract
Introduction
Successful stem cell therapy relies on large-scale generation of stem cells and their maintenance in a proliferative multipotent state. This study aimed to establish a three-dimension culture system for large-scale generation of hWJ-MSC and investigated the self-renewal activity, genomic stability and multi-lineage differentiation potential of such hWJ-MSC in enhancing skin wound healing.

Methods
hWJ-MSC were seeded on gelatin microbeads and cultured in spinning bottles (3D). Cell proliferation, karyotype analysis, surface marker expression, multipotent differentiation (adipogenic, chondrogenic, and osteogenic potentials), and expression of core transcription factors (OCT4, SOX2, NANOG, and C-MYC), as well as their efficacy in accelerating skin wound healing, were investigated and compared with those of hWJ-MSC derived from plate cultres (2D), using in vivo and in vitro experiments.

Results
hWJ-MSC attached to and proliferated on gelatin microbeads in 3D cultures reaching a maximum of 1.1–1.30 × 107cells on 0.5 g of microbeads by days 8–14; in contrast, hWJ-MSC derived from 2D cultures reached a maximum of 6.5 -11.5 × 105 cells per well in a 24-well plate by days 6–10. hWJ-MSC derived by 3D culture incorporated significantly more EdU (P < 0.05) and had a significantly higher proliferation index (P < 0.05) than those derived from 2D culture. Immunofluorescence staining, real-time PCR, flow cytometry analysis, and multipotency assays showed that hWJ-MSC derived from 3D culture retained MSC surface markers and multipotency potential similar to 2D culture-derived cells. 3D culture-derived hWJ-MSC also retained the expression of core transcription factors at levels comparable to their 2D culture counterparts. Direct injection of hWJ-MSC derived from 3D or 2D cultures into animals exhibited similar efficacy in enhancing skin wound healing.

Conclusions
Thus, hWJ-MSC can be expanded markedly in gelatin microbeads, while retaining MSC surface marker expression, multipotent differential potential, and expression of core transcription factors. These cells also efficiently enhanced skin wound healing in vivo, in a manner comparable to that of hWJ-MSC obtained from 2D culture.
Recurrent hypoglycaemia in type 2 diabetic patient due to hypothyroidism
Authors: Kumar Alok 
Published: March 2015

AbstractObjectiveTo present a case report of recurrent hypoglycaemia in type 2 diabetic patient due to hypothyroidism.MethodsWe describe a case with type 2 diabetes who complained of episodes of recurrent hypoglycaemia in last few weeks. We also discuss the results of the diagnostic workup done to find out the cause of recurrent hypoglycaemia.ResultAfter ruling out common causes like overdosing of oral hypoglycaemic agents or insulin, renal or hepatic impairment we found overt hypothyroidism as a cause of recurrent hypoglycaemia. Levothyroxine therapy was started in this patient. Upon normalization of thyroid function, patient did not further experience any episodes of hypoglycaemia. We did not find any report on hypothyroidism as a cause of recurrent hypoglycaemia in type 2 diabetic patients.ConclusionWe conclude that during workup, clinicians should take hypothyroidism into consideration as a potential cause of hypoglycaemia in type 2 diabetic patients.