bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation
Authors: von Zur-Mühlen Bengt , Lundgren Torbjörn , Bayman Levent , Berne Christian , Bridges Nancy , Eggerman Thomas , Foss Aksel , Goldstein Julia , Jenssen Trond , Jorns Carl , Morrison Yvonne , Rydén Mikael , Schwieger Traci , Tufveson Gunnar , Nilsson Bo , Korsgren Olle 
Published: September 2018

Background.
When transplanted human pancreatic islets are exposed to blood during intraportal infusion, an innate immune response is triggered. This instant blood-mediated inflammatory reaction (IBMIR) activates the coagulation and complement cascades and leads to the destruction of 25% of all transplanted islets within minutes, contributing to the need, in most patients, for islets from more than 1 donor. Low molecular dextran sulfate (LMW-DS) has been shown in experimental settings to inhibit IBMIR.

Methods.
The Clinical Islet Transplantation consortium 01 study was a phase II, multicenter, open label, active control, randomized study. Twenty-four subjects were randomized to peritransplant intraportal and systemic treatment with either LMW-DS or heparin, targeting an activated partial thromboplastin time of 150 ± 10 seconds and 50 ± 5 seconds, respectively. C-peptide response was measured with a mixed meal tolerance test at 75 and 365 days after transplant.

Results.
Low molecular dextran sulfate was safe and well tolerated with similar observed adverse events (mostly attributed to immunosuppression) as in the heparin arm. There was no difference in the primary endpoint (stimulated C-peptide 75 ± 5 days after the first transplant) between the 2 arms (1.33 ± 1.10 versus 1.56 ± 1.36 ng/mL, P = 0.66). Insulin requirement, metabolic parameters, Clarke and HYPO score, quality of life, and safety were similar between the 2 treatments groups.

Conclusions.
Even with low dosing, LMW-DS showed similar efficacy in preventing IBMIR to promote islet engraftment when compared to “state-of-the art” treatment with heparin. Furthermore, no substantial differences in the efficacy and safety endpoints were detected, providing important information for future studies with more optimal dosing of LMW-DS for the prevention of IBMIR in islet transplantation.
Kinetics of Torque Teno Virus-DNA Plasma Load Predict Rejection in Lung Transplant Recipients
Authors: Frye Björn C. , Bierbaum Sibylle , Falcone Valeria , Köhler Thomas C. , Gasplmayr Markus , Hettich Ina , Dürk Thorsten , Idzko Marco , Zissel Gernot , Hengel Hartmut , Müller-Quernheim Joachim 
Published: September 2018

Background.
Lung transplantation is the only therapeutic option in end-stage lung diseases; however, survival after transplantation is limited by acute and chronic rejection or infectious events being results of inappropriate immunosuppression. Torque Teno Viruses (TTVs) are ubiquitous DNA viruses in humans but not found to be causative for any disease. However, some reports suggest that TTV-DNA levels reflect the grade of immunosuppression with higher levels being found in more immunosuppressed individuals.

Methods.
We investigated the TTV-DNA levels in 34 lung transplant recipients within their first year after transplantation by quantitative real-time polymerase chain reaction. Clinical data were extracted from charts.

Results.
In accordance with previous results TTV-DNA levels increase after lung transplantation reaching a steady state after 3 months. The TTV-DNA levels were not correlated with immunosuppressive trough levels and a selective increase was not observed with other DNA viruses. In steady state TTV-DNA levels were significantly higher in patients with infectious complications compared to the group of patients without. Additionally, TTV-DNA levels decreased significantly before biopsy-proven rejection. Sensitivity of a 10-fold decrease in TTV-DNA levels for a subsequent rejection episode was 0.74 with a specificity of 0.99.

Conclusions.
In summary, TTV-DNA might be used as an additional tool to monitor immunosuppression in lung transplant recipients. Higher TTV-DNA levels reflect more intense immunosuppression, whereas the TTV-DNA kinetic (ie, decrease of TTV-DNA levels) indicate rejection.
Liraglutide, a Glucagon-like Peptide-1 Receptor Agonist, Attenuates Development of Cardiac Allograft Vasculopathy in a Murine Heart Transplant Model
Authors: Wang ZhiMin , Wang Mengjun , Hu Xiaofan , Li Yakun , Ma DongXia , Li ShangLin , Zhao GuangYuan , Xie YaNan , Shu Yanwen , Yang Jun 
Published: September 2018

Background.
Advances in immunosuppressive therapy have significantly improved short-term but not long-term survival of cardiac transplant recipients; this is largely due to severe cardiac allograft vasculopathy (CAV). Glucagon-like peptide-1 receptor (GLP-1R)-based therapy exerts physiological effects on the cardiovascular system in addition to its traditional role in controlling glucose. We have investigated the effects of liraglutide, a GLP-1R agonist, on the development of CAV in a murine heart transplant model.

Methods.
Heterotopic murine cardiac transplantation was performed with a major histocompatibility complex class II-mismatched model. Recipient mice were subcutaneously administered vehicle (0.9% saline solution) or liraglutide (300 μg·kg−1 every 12 hours) from the day of transplantation. Allografts were harvested at 2 or 8 weeks and histologically analyzed. Inflammatory infiltrates were measured by immunohistochemistry, and immunofluorescence and western blotting analyzes were used to evaluate GLP-1R expression and markers of endothelial-to-mesenchymal transition (EndMT) in cardiac allografts and human coronary artery endothelial cells challenged with transforming growth factor-beta 1.

Results.
Glucagon-like peptide-1 receptor was predominantly localized to vascular endothelial cells and was upregulated in cardiac allografts after liraglutide treatment. Liraglutide ameliorated CAV and cardiac fibrosis with reduced inflammatory cell infiltration and downregulated expression of adhesion molecules. Liraglutide inhibited EndMT in allografts and attenuated EndMT by inhibiting Smad3 activation in transforming growth factor-beta 1–treated human coronary artery endothelial cells.

Conclusions.
Administration of liraglutide from the time of transplantation upregulated GLP-1R in the transplanted heart and reduced cardiac fibrosis, inflammation, and CAV development. Therefore, liraglutide may be a novel therapy for CAV.
Kidney Transplant in the Era of Modern Therapy for Multiple Myeloma
Authors: Huskey Janna L. , Heilman Raymond L. , Khamash Hasan , Fonseca Rafael 
Published: September 2018

Abstract
Chronic kidney disease is common in patients with multiple myeloma. Historically, individuals with end-stage renal disease and multiple myeloma did poorly with renal transplantation due to higher mortality rates from the malignancy itself or associated comorbidities. However, over the past 2 decades, there have been significant advances in the treatment of multiple myeloma with the advent of new therapeutic agents resulting in an improvement of long-term survival. As a result, more individuals with multiple myeloma are being referred for kidney transplantation, especially those with good functional capacity and minimal comorbidities. Recent literature has suggested that certain patients with multiple myeloma can successfully undergo renal transplantation after stem transplantation with consideration for maintenance therapy, although caution should be used with immunomodulating drugs due to the anecdotally reported risk of acute rejection. Therefore, having a multidisciplinary approach with the transplant team and hematology both before and after transplant is crucial in maximizing the chance of success for these individuals. This review summarizes the literature on renal transplantation in patients with multiple myeloma as well as the therapeutic advancements that have occurred which may allow certain patients to undergo successful transplantation.
Potentiating Renal Regeneration Using Mesenchymal Stem Cells
Authors: Brasile Lauren , Henry Nicholas , Orlando Giuseppe , Stubenitsky Bart 
Published: September 2018

Background
The potential of a mesenchymal stem cell (MSC) therapy to accelerate the repair of ischemically damaged human kidneys during 24 hours of warm perfusion was evaluated. The hypothesis was that by administering MSC directly to the renal tissue, there would be an improved opportunity for cellular repair mediated by intrarenal paracrine effects.

Methods
Studies were performed using the exsanguinous metabolic support (EMS) tissue-engineering platform. Five pairs of human kidney allografts from donation after circulatory death donors were studied. One human kidney was EMS perfused for 24 hours (control), whereas its paired kidney was EMS perfused with MSC (1 × 108). The kidneys were evaluated for DNA synthesis, cytokine/chemokine synthesis, cytoskeletal regeneration, and mitosis.

Results
Treatment with MSC resulted in reduced inflammatory cytokines synthesized by the kidneys. Mesenchymal stem cell treatment led to a significant increase in the synthesis of adenosine triphosphate and growth factors resulting in normalization of metabolism and the cytoskeleton. Toluidine Blue staining of MSC-treated kidneys demonstrated a significant increase in the number of renal cells undergoing mitosis (26%) compared with EMS perfusion alone.

Conclusions
To our knowledge, our work is the first to have demonstrated actual renal regeneration while ischemically damaged human kidneys are perfused ex vivo for 24 hours. The observed regeneration entails: increased synthesis of adenosine triphosphate, a reduced inflammatory response, increased synthesis of growth factors, normalization of the cytoskeleton and mitosis. The ability to regenerate renal tissue ex vivo sufficiently to result in immediate function could revolutionize transplantation by solving the chronic organ shortage.
VCA Deceased Donors in the United States
Authors: Wainright Jennifer L. , Wholley Christopher L. , Rosendale John , Cherikh Wida S. , Di Battista Darren , Klassen David K. 
Published: September 2018

Background.
Vascularized composite allograft (VCA) transplants include diverse organ types and are made possible primarily by deceased donors.

Methods.
We used Organ Procurement and Transplantation Network data to characterize VCA deceased donors (n = 66 of 70) in the United States from 1998 to 2017 and compare their characteristics with those of kidney donors in 2017.

Results.
Through December 31, 2017, 20 transplant programs performed 72 deceased-donor VCA transplants, with organs donated by 70 donors, including 30 upper limb (17 unilateral and 13 bilateral) and 11 face donors. Other donors donated both upper limbs and face (n = 2), uterus (n = 4), abdominal wall (n = 19), larynx (n = 2), penis (n = 1), and scalp (n = 1). About a third of VCA donors were female, and the majority (86.4%) were white. Almost half (45.5%) were between the ages 18 and 34 years. Smaller proportions were younger than 18 years (19.7%), 35 to 44 years (15.2%), 45 to 54 years (13.6%), and older than 55 years (6.1%). Median body mass index for all VCA donors was 24.9 and varied widely, especially for upper limb and face donors. There was considerable variation in Kidney Donor Profile Index among VCA donors (median, 27.5; interquartile range, 11–59). Donor causes of death included head trauma (39.4%), cerebrovascular/stroke (25.8%), and anoxia (31.8%). VCA donors also donated solid organs that were transplanted, including 87.1% of kidneys, 93.9% of livers, 40.2% of lungs, and 56.1% of hearts.

Conclusions.
donors are a demographically and clinically diverse group. Understanding this diversity and future trends in VCA donor characteristics is critical in supporting this life-changing field of transplantation.
Equivalent Outcomes With Retransplantation and Primary Liver Transplantation in the Direct-acting Antiviral Era
Authors: Croome Kristopher P. , Mathur Amit K. , Pungpapong Surakit , Lee David D. , Moss Adyr A. , Rosen Charles B. , Heimbach Julie K. , Taner C. Burcin 
Published: September 2018

Background.
The present multicenter study investigated whether equivalent outcomes to primary liver transplant (LT) could be achieved with liver retransplant (reLT) and whether improvements in outcomes have taken place over time, particularly in the direct-acting antiviral era.

Methods.
All reLT performed at Mayo Clinic Florida, Mayo Clinic Rochester, and Mayo Clinic Arizona were divided into era 1 (2002–2007), era 2 (2008–2012), and era 3 (2013–2017) based on the date of reLT.

Results.
Improvement in graft survival (GS) after reLT was seen over the 3 eras (P < 0.001). In era 1, GS after reLT was inferior to primary LT (P < 0.001), whereas no difference was seen between reLT and primary LT in era 2 (P = 0.68) or era 3 (P = 0.36). A significantly higher proportion of patients achieved sustained viral response (SVR) within the first year after reLT in each subsequent era (era 1: 10.3%, era 2: 22.5%, and era 3: 100%) (P < 0.001). Graft survival was superior in patients undergoing reLT for recurrent hepatitis C virus who achieved SVR after reLT compared with those who did not (P = 0.03).

Conclusions.
Results similar to primary LT were achieved in era 3. These improvements coincide with the availability of direct-acting antivirals, which resulted in a 100% SVR rate in era 3 and a decrease in the number of patients undergoing reLT for recurrent hepatitis C virus. The historic dogma that reLT results in inferior outcomes should be revisited.
Kaposi Sarcoma in HIV-positive Solid-Organ Transplant Recipients: A French Multicentric National Study and Literature Review
Authors: Charpentier Chloé , Delyon Julie , Glotz Denis , Peraldi Marie-Noelle , Rerolle Jean-Philippe , Barrou Benoît , Ducroux Emilie , Coilly Audrey , Legeai Camille , Barete Stéphane , Lebbé Céleste 
Published: September 2018

Background
Kaposi sarcoma is a vascular tumor related to herpesvirus-8 and is promoted by immunosuppression. For the last 15 years, human immunodeficiency virus (HIV) patients have had access to organ transplantation. The dual immunosuppression of HIV and immunosuppressive treatments might increase the risk and severity of Kaposi sarcoma.

Methods
We conducted a multicentric retrospective study by collecting cases from French databases and society members of transplanted patients, among which 7 HIV-infected patients who subsequently developed Kaposi sarcoma were included.

Results
In the CRISTAL database (114 511 patients) and the DIVAT (Données Informatisées et VAlidées en Transplantation) database (19 077 patients), the prevalence of Kaposi sarcoma was 0.18% and 0.46%, respectively, in transplanted patients; these values compare with 0.66% and 0.50%, respectively, in transplanted patients with HIV. The median time from HIV infection to Kaposi sarcoma was 20 years. Kaposi sarcoma occurred during the first year after transplantation in most cases, whereas HIV viral load was undetectable. Only 2 patients had visceral involvement. Five patients were treated with conversion of calcineurin inhibitor to mammalian target of rapamycin inhibitor, and 5 patients were managed by decreasing immunosuppressive therapies. At 1 year, 4 patients had a complete response, and 3 had a partial response.

Conclusions
In our study, Kaposi sarcoma in transplanted patients with HIV did not show any aggressive features and was treated with the usual posttransplant Kaposi sarcoma management protocol.
Urinary Retention Associated With Cariprazine: A Case Report
Authors: Kapulsky Leonid , Brody Benjamin D. 
Published: September 2018

Abstract
Urinary retention is a well-documented adverse effect of antipsychotic medications and is thought to be mediated by anticholinergic, adrenergic, and other neurotransmitter effects. Whereas urinary retention has been reported with typical and some atypical antipsychotics, there have been no reports of urinary retention with the novel antipsychotic cariprazine. We report on a case of urinary retention associated with cariprazine. Possible mechanisms for this adverse effect are discussed.
Natalizumab Treatment for Relapsing-Remitting Multiple Sclerosis: The Experience From Saudi Arabia
Authors: Algahtani Hussein , Shirah Bader , Abobaker Hind , Alghanaim Nebras , Kamel Fatemah 
Published: September 2018

Background
Natalizumab is the first targeted humanized monoclonal antibody to be approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Natalizumab appears to be more effective than current first-line disease-modifying therapies. In our study, we aimed to evaluate the outcome of Saudi patients with active RRMS treated with natalizumab and compare the results with other outcomes in the Gulf and international trials.

Methods
We conducted a retrospective single-center observational study involving 32 patients with RRMS at King Abdulaziz Medical City in Jeddah, Saudi Arabia. The inclusion criteria included all patients diagnosed with RRMS according to the revised McDonald criteria who are currently receiving or received natalizumab treatment in the past for a minimum of 6 months.

Results
The mean baseline Expanded Disability Status Scale score was 4.50 ± 1.80 (range, 1.5–6; median, 5), whereas the mean Expanded Disability Status Scale at the follow-up was 4.02 ± 2.08 (range, 1–6; median, 4.25) (P = 0.3274). The mean annualized relapse rate was significantly reduced from 2.41 ± 2.48 at baseline to 0.16 ± 0.37 at the last follow-up (P < 0.0001). Twenty-seven patients (84.4%) had no relapses since the treatment with natalizumab was started, whereas 5 patients (15.6%) had only 1 relapse. In addition to clinically measurable improvement, radiological improvement was observed through magnetic resonance imaging. Magnetic resonance imaging activity was significantly improved at follow-up magnetic resonance imaging studies when compared with baseline.

Conclusions
Our single-center study in Saudi Arabia provides further support for the efficacy of natalizumab in the clinical practice setting. The sharp decrease in relapse rate and progression of disability following the initiation of natalizumab treatment was similar to other observational studies conducted in different countries across the globe. Natalizumab was a satisfactory therapy for the management of our MS population, both from the patients' and the physicians' perspectives.
Fludarabine-Induced Posterior Reversible Encephalopathy Syndrome in a Pediatric Patient With β-Thalassemia: Case Report and Literature Review
Authors: Navarro Cristian Eduardo , Rodríguez Paula Juliana , Espitia Oscar Mauricio 
Published: September 2018

Abstract
Posterior reversible encephalopathy syndrome is a disorder of reversible subcortical vasogenic brain edema in the context of different diseases or exposure to cytotoxic drugs such as fludarabine. We present the case of a pediatric patient with β-thalassemia who develops a fludarabine-induced posterior reversible encephalopathy while he received an induction regimen to achieve an allogenic hematopoietic cell transplantation. The clinical presentation consists in altered mental state, headache, status epilepticus, visual disturbance, and hypertension. His treatment was carried out with the suspension of the medication and the control of hypertension and status epilepticus; the final outcome was positive without additional complications. There are published reports about fludarabine toxicity in the central nervous system with different doses of the drug in different clinical context. We also made a review of the literature available and conclude that fludarabine is not an extraordinary cause of posterior reversible encephalopathy syndrome.
Molecular basis of human asparagine synthetase inhibitor specificity
Authors: Zhu Wen , Radadiya Ashish , Bisson Claudine , Nordin Brian E. , Baumann Patrick , Imasaki Tsuyoshi , Wenzel Sabine A. , Sedelnikova Svetlana E. , Berry Alexandria H. , Nomanbhoy Tyzoon K. , Kozarich John W. , Jin Yi , Takagi Yuichiro , Rice David W. , Richards Nigel G. J. 
Published: September 2018

ABSTRACTExpression of the enzyme human asparagine synthetase (ASNS) promotes metastatic progression in breast cancer, which affects L-asparagine levels and tumor cell invasiveness. Human ASNS has therefore emerged as abona fidedrug target for cancer therapy. We have reported a slow-onset, tight binding ASNS inhibitor with nanomolar affinity, but our compound exhibits poor cell permeability. On the other hand, we show here that this inhibitor exhibits remarkable selectivity for the human ASNS in HCT-116 cell lysates. By determining the first high-resolution (1.85 Å) X-ray crystal structure for human ASNS, we have built a computational model of the enzyme complexed to our inhibitor, which provides the first insights into the intermolecular interactions mediating specificity. These findings should facilitate the development of a second generation of ASNS inhibitors, leading to the discovery of drugs to prevent metastasis.
Minimum Information for Reusable Arthropod Abundance Data (MIReAAD)
Authors: Rund Samuel , Braak Kyle , Cator Lauren , Copas Kyle , Emrich Scott J. , Giraldo-Calderón Gloria I. , Johansson Michael A. , Heydari Naveed , Hobern Donald , Kelly Sarah A. , Lawson Daniel , Lord Cynthia , MacCallum Robert M , Roche Dominique G. , Ryan Sadie J. , Schigel Dmitry , Vandegrift Kurt , Watts Matthew , Zaspel Jennifer M. , Pawar Samraat 
Published: September 2018

AbstractArthropods play a dominant role in natural and human-modified terrestrial ecosystem dynamics. Spatially-explicit population time-series are crucial for statistical or mathematical models of these dynamics and assessment of their veterinary, medical, agricultural, and ecological impacts. Arthropod data have been collected world-wide for over a century, but remain scattered and largely inaccessible. With the ever-present and growing threat of arthropod vectors of infectious diseases and pest species, there are enormous amounts of historical and ongoing surveillance. These data are currently reported in a wide variety of formats, typically lacking sufficient metadata to make reuse and re-analysis possible. We present the first minimum information standard for arthropod abundance. Developed with broad stakeholder collaboration, it balances sufficiency for reuse with the practicality of preparing the data for submission. It is designed to optimize data (re-)usability from the “FAIR,” (Findable, Accessible, Interoperable, and Reusable) principles of public data archiving (PDA). This standard will facilitate data unification across research initiatives and communities dedicated to surveillance for detection and control of vector-borne diseases and pests.