Miracle-dz/UniFAR-FTUs huggingface dataset:
How can we minimize bleeding complications in ABO‐incompatible kidney transplant recipients?

The use of ABO-incompatible (ABOi) donor organs is a possible solution for the shortage of donor organs for transplantation; however, naturally occurring antibodies (Abs) against blood group A or B (A/B) carbohydrate determinants in sera are a major impediment to achieving successful transplantation. The use of plasmapheresis (PP) has been shown to be a necessary preconditioning component in ABOi kidney transplant. Removal of pathologic anti-A and anti-B Abs has been accomplished with a variety of apheresis modalities including plasma exchange (PE), fractional PE, and immunoadsorption (IA) techniques. Using these modalities in conjunction with potent modern immunosuppression, ABO-incompatible kidney transplants have achieved graft and patient survivals similar to that seen in ABO-compatible (ABOc) transplants. de Weerd et al. in this issue [1] have performed a retrospective matched-cohort study to compare the incidence of intra-/postoperative bleeding complications in the two groups of patients submitted to ABOi kidney transplantation and to ABOc kidney transplantation. The preoperative desensitization regimen included PP, which was performed with a plasmafilter followed by IA of anti-ABO Abs, rituximab, tacrolimus, mycophenolate mofetil, prednisone, and immunoglobulins. In the cohort of 65 ABOi patients and 130 ABOc controls, they found that ABOi patients lost more blood intra-operatively than ABOc controls, received erythrocyte transfusions more than twice as frequently as the controls in the first 48 h postoperatively. From those findings, they conclude that antigen-specific IA prior to ABOi kidney transplantation exposes patients to a significantly higher bleeding risk than ABOc controls. The similar
Pulsatile hyperglycemia increases insulin secretion but not pancreatic β-cell mass in intrauterine growth-restricted fetal sheep

Abstract Impaired β-cell development and insulin secretion are characteristic of intrauterine growth-restricted (IUGR) fetuses. In normally grown late gestation fetal sheep pancreatic β-cell numbers and insulin secretion are increased by 7–10 days of pulsatile hyperglycemia (PHG). Our objective was to determine if IUGR fetal sheep β-cell numbers and insulin secretion could also be increased by PHG or if IUGR fetal β-cells do not have the capacity to respond to PHG. Following chronic placental insufficiency producing IUGR in twin gestation pregnancies (n=7), fetuses were administered a PHG infusion, consisting of 60 min, high rate, pulsed infusions of dextrose three times a day with an additional continuous, low-rate infusion of dextrose to prevent a decrease in glucose concentrations between the pulses or a control saline infusion. PHG fetuses were compared with their twin IUGR fetus, which received a saline infusion for 7 days. The pulsed glucose infusion increased fetal arterial glucose concentrations an average of 83% during the infusion. Following the 7-day infusion, a square-wave fetal hyperglycemic clamp was performed in both groups to measure insulin secretion. The rate of increase in fetal insulin concentrations during the first 20 min of a square-wave hyperglycemic clamp was 44% faster in the PHG fetuses compared with saline fetuses (P<0.05). There were no differences in islet size, the insulin+ area of the pancreas and of the islets, and β-cell mass between groups (P>0.23). Chronic PHG increases early phase insulin secretion in response to acute hyperglycemia, indicating that IUGR fetal β-cells are functionally responsive to chronic PHG.
Donor/recipient sex mismatch and survival after heart transplantation: only an issue in male recipients? An analysis of the Spanish Heart Transplantation Registry

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06–1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74–1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long‐term mortality (HR, 1.14; 95% CI 1.01–1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women.
Perioperative administration of high‐dose recombinant human erythropoietin for delayed graft function prevention in kidney transplantation: a meta‐analysis

Delayed graft function (DGF) due to ischemia–reperfusion injury is a major early complication of kidney transplantation (KT). Recombinant human erythropoietin (rHuEPO) has been shown to exert nephroprotective action in animal models. We conducted a meta‐analysis to explore the impact of rHuEPO on DGF in KT. Eligible studies comparing perioperative high‐dose rHuEPO with placebo or no therapy for prevention of DGF were identified through MEDLINE, CENTRAL, and Transplant Library. Their design and data were assessed by two independent reviewers. Among 737 examined studies, four randomized controlled trials, involving 356 recipients of kidney allografts from deceased donors, fulfilled inclusion criteria. Statistical heterogeneity across studies was not significant (P = 0.98, I2 = 0%). In a random effects model, no significant difference was found in the occurrence of DGF (odds ratio: 0,74, 95% CI: 0.47–1.18, P = 0.21). At 4 weeks after KT, the rHuEPO group exhibited higher systolic blood pressure (mean difference: 6.47 mmHg, 95% CI: 1.25–11.68, P = 0.02). Perioperative, high‐dose rHuEPO administration does not prevent DGF in deceased donor KT. Furthermore, it is associated with higher systolic blood pressure leading to safety concerns. Nonerythropoietic rHuEPO derivatives, designed for nephroprotective action without increasing cardiovascular risk, might prove an alternative but still are at early stages of development.
Time-Series Transcriptomics Reveals That AGAMOUS-LIKE22 Affects Primary Metabolism and Developmental Processes in Drought-Stressed Arabidopsis[CC-BY]

Temporal transcriptome analysis during drought stress coupled with Bayesian network modeling reveals early drought signaling events and identifies AGL22 as a regulator of primary metabolism. In Arabidopsis thaliana, changes in metabolism and gene expression drive increased drought tolerance and initiate diverse drought avoidance and escape responses. To address regulatory processes that link these responses, we set out to identify genes that govern early responses to drought. To do this, a high-resolution time series transcriptomics data set was produced, coupled with detailed physiological and metabolic analyses of plants subjected to a slow transition from well-watered to drought conditions. A total of 1815 drought-responsive differentially expressed genes were identified. The early changes in gene expression coincided with a drop in carbon assimilation, and only in the late stages with an increase in foliar abscisic acid content. To identify gene regulatory networks (GRNs) mediating the transition between the early and late stages of drought, we used Bayesian network modeling of differentially expressed transcription factor (TF) genes. This approach identified AGAMOUS-LIKE22 (AGL22), as key hub gene in a TF GRN. It has previously been shown that AGL22 is involved in the transition from vegetative state to flowering but here we show that AGL22 expression influences steady state photosynthetic rates and lifetime water use. This suggests that AGL22 uniquely regulates a transcriptional network during drought stress, linking changes in primary metabolism and the initiation of stress responses.
Anti‐HLA sensitization in extensively burned patients: extent, associated factors, and reduction in potential access to vascularized composite allotransplantation

Extensively burned patients receive iterative blood transfusions and skin allografts that often lead to HLA sensitization, and potentially impede access to vascularized composite allotransplantation (VCA). In this retrospective, single‐center study, anti‐HLA sensitization was measured by single‐antigen‐flow bead analysis in patients with deep, second‐ and third‐degree burns over ≥40% total body surface area (TBSA). Association of HLA sensitization with blood transfusions, skin allografts, and pregnancies was analyzed by bivariate analysis. The eligibility for transplantation was assessed using calculated panel reactive antibodies (cPRA). Twenty‐nine patients aged 32 ± 14 years, including 11 women, presented with a mean burned TBSA of 54 ± 11%. Fifteen patients received skin allografts, comprising those who received cryopreserved (n = 3) or glycerol‐preserved (n = 7) allografts, or both (n = 5). An average 36 ± 13 packed red blood cell (PRBC) units were transfused per patient. In sera samples collected 38 ± 13 months after the burns, all patients except one presented with anti‐HLA antibodies, of which 13 patients (45%) had complement‐fixing antibodies. Eighteen patients (62%) were considered highly sensitized (cPRA≥85%). Cryopreserved, but not glycerol‐preserved skin allografts, history of pregnancy, and number of PRBC units were associated with HLA sensitization. Extensively burned patients may become highly HLA sensitized during acute care and hence not qualify for VCA. Alternatives to skin allografts might help preserve their later access to VCA.
Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells

VISUAL, an ectopic induction system for phloem differentiation in Arabidopsis, allows the molecular mechanism underlying this crucial process to be analyzed, opening up new avenues of research. Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL. Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells.
The Global Burden of Disease 2010 update: keeping mental health in the spotlight

Epidemiology and Psychiatric Sciences / Volume 23 / Issue 03 / September 2014, pp 255 257 DOI: 10.1017/S2045796014000316, Published online: 03 June 2014 Link to this article: http://journals.cambridge. org/abstract_S2045796014000316 How to cite this article: Scott B. Patten (2014). The Global Burden of Disease 2010 update: keeping mental health in the spotlight. Epidemiology and Psychiatric Sciences, 23, pp 255-257 doi:10.1017/S2045796014000316 Request Permissions : Click here
Simultaneous determination of naphthalene and anthraquinone derivatives in Rumex nepalensis Spreng. roots by HPLC: comparison of different extraction methods and validation.

INTRODUCTION Rumex nepalensis contains mainly anthraquinone and naphthalene derivatives. Although HPLC methods have been reported for the analysis of anthraquinones, neither a phytochemical analysis of Rumex species nor the simultaneous determination of anthraquinone and naphthalene derivatives in other samples has been reported so far. OBJECTIVE To develop and validate a HPLC method for the simultaneous determination of anthraquinone and naphthalene derivatives in R. nepalensis roots. METHODOLOGY Anthraquinones and naphthalenes were extracted from R. nepalensis roots by three methods (reflux, ultrasonication and pressurized liquid extraction) using methanol. Separation was achieved on an RP C₁₈ column with a gradient mobile phase consisting of 0.05% orthophosphoric acid in water (solvent A) and methanol (solvent B) using a UV detector (254 nm). RESULTS Small differences were observed in the contents of anthraquinone and naphthalene derivatives extracted by the three methods. Chrysophanol-8-O-β-D-glucopyranoside and nepodin were detected as major constituents. The method showed a good linearity (r² > 0.9992), high precision (RSD < 5%) and a good recovery (97-105%) of the compounds. The lowest detection limit was found to be 0.97 ng and the method was found to be robust. CONCLUSION Reflux and ultrasonication were found to be the best suited methods for the extraction of glycosides and aglycones, respectively. The developed and validated HPLC method is simple, precise and accurate; and can hence be recommended as the method of choice for the analysis of anthraquinones and naphthalenes in R. nepalensis and other Rumex species for both quality control as well as routine analytical purposes.
MUGBAS: a species free gene-based programme suite for post-GWAS analysis

UNLABELLED Genome Wide Association Studies between molecular markers and phenotypes are now routinely run in model and non-model species. However, tools to estimate the probability of association of functional units (e.g. genes) containing multiple markers are not developed for species other than humans. Here we introduce MUGBAS (MUlti species Gene-Based Association Suite), software that estimates the P-value of a gene using information on annotation, single marker GWA results and genotype. The software is species and annotation independent, fast, highly parallelized and ready for high-density marker studies. AVAILABILITY AND IMPLEMENTATION https://bitbucket.org/capemaster/mugbas
Strategies to improve the performance of rare variant association studies by optimizing the selection of controls

MOTIVATION When analyzing a case group of patients with ultra-rare disorders the ethnicities are often diverse and the data quality might vary. The population substructure in the case group as well as the heterogeneous data quality can cause substantial inflation of test statistics and result in spurious associations in case-control studies if not properly adjusted for. Existing techniques to correct for confounding effects were especially developed for common variants and are not applicable to rare variants. RESULTS We analyzed strategies to select suitable controls for cases that are based on similarity metrics that vary in their weighting schemes. We simulated different disease entities on real exome data and show that a similarity-based selection scheme can help to reduce false positive associations and to optimize the performance of the statistical tests. Especially when data quality as well as ethnicities vary a lot in the case group, a matching approach that puts more weight on rare variants shows the best performance. We reanalyzed collections of unrelated patients with Kabuki make-up syndrome, Hyperphosphatasia with Mental Retardation syndrome and Catel-Manzke syndrome for which the disease genes were recently described. We show that rare variant association tests are more sensitive and specific in identifying the disease gene than intersection filters and should thus be considered as a favorable approach in analyzing even small patient cohorts. AVAILABILITY AND IMPLEMENTATION Datasets used in our analysis are available at ftp://ftp.1000genomes. ebi.ac. uk. /vol1/ftp/ CONTACT : peter.krawitz@charite.de SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Does the meld system provide equal access to liver transplantation for patients with different ABO blood groups?

This study investigates the relationship between blood group and waiting time until transplantation or death on the waiting list. All patients listed for liver transplantation in the Netherlands between 15 December 2006 and 31 December 2012, were included. Study variables were gender, age, year of listing, diagnosis, previous transplantations, blood group, urgency, and MELD score. Using a competing risks analysis, separate cumulative incidence curves were constructed for death on the waiting list and transplantation and used to evaluate outcomes.In 517 listings, the mean death rate per 100 patient‐years was 10.4. A total of 375 (72.5% of all listings) were transplanted. Of all transplantations, 352 (93.9%) were ABO‐identical and 23 (6.1%) ABO‐compatible. The 5‐year cumulative incidence of death was 11.2% (SE 1.4%), and of transplantation 72.5% (SE 2.0%). Patient blood group had no multivariate significant impact on the hazard of dying on the waiting list nor on transplantation. Age, MELD score, and urgency status were significantly related to the death on the waiting list and transplantation. More recent listing had higher probability of being transplanted. In the MELD era, patient blood group status does not have a significant impact on liver transplant waiting list mortality nor on waiting time for transplantation.
The Deubiquitinating Enzymes UBP12 and UBP13 Positively Regulate MYC2 Levels in Jasmonate Responses

The deubiquitinating enzymes UBP12 and UBP13 positively regulate JA responses by rescuing MYC2 from destruction. The transcription factor MYC2 has emerged as a master regulator of jasmonate (JA)-mediated responses as well as crosstalk among different signaling pathways. The instability of MYC2 is in part due to the action of PUB10 E3 ligase, which can polyubiquitinate this protein. Here, we show that polyubiquitinated MYC2 can be deubiquitinated by UBP12 and UBP13 in vitro, suggesting that the two deubiquitinating enzymes can counteract the effect of PUB10 in vivo. Consistent with this view, UBP12 and UBP13 associate with MYC2 in the nucleus. Transgenic Arabidopsis thaliana plants deficient in UBP12 and UBP13 show accelerated decay of MYC2 and are hyposensitive to JA, whereas plants overexpressing UBP12 or UBP13 have prolonged MYC2 half-life and are hypersensitive to JA. Our results suggest that there is a genetic link between UBP12, UBP13, and MYC2. Our results identify UBP12 and UBP13 as additional positive regulators of JA responses and suggest that these enzymes likely act by stabilizing MYC2.
Qualitative and semi-quantitative analysis of phenolics in Eucalyptus globulus leaves by high-performance liquid chromatography coupled with diode array detection and electrospray ionisation mass spectrometry.

INTRODUCTION Eucalyptus species are widely cultivated in Mediterranean regions. Moreover, plants of this family have been utilized for medicinal purposes. A number of studies have been devoted to the identification of eucalypt phenolics, all of them have focused on specific families of compounds, and no exhaustive profiling has been reported in leaves of this plant. OBJECTIVE To develop methods that allows the identification and quantification of different classes of phenolics in Eucalyptus globulus leaf. METHODOLOGY Acetonic extract was fractionated by chromatography on a Sephadex LH-20 column using consecutive elution with ethanol, methanol and aqueous acetone (60%). High-performance liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (HPLC-DAD-ESI/MS) were applied to determine the structure of different compounds. Quantities were evaluated from peak areas in the HPLC profile, using external calibration curves. RESULTS Fractionation of acetonic extract yielded three fractions: F1, F2 and F3. In total 39 phenolic compounds are detected. Among them: 16 hydrolyzable tannins, 3 terpenyl derivatives, 12 ellagic acid derivatives, 5 flavonols, 2 hydroxybenzoic acids and 1 formylated phloroglucinol. 26 compounds described in this study have not previously detected in leaves of this plant and this is the first report of quercetin 3-O-β-galactoside-6"-O-gallate and cypellogin A and B, in E. globulus plant. Quantitatively, ellagic acid derivatives and sideroxylonal A or B are largely predominant. CONCLUSION Fractionation of crude extract by chromatography on Sephadex LH-20 was efficient to separate different molecular weight compounds. HPLC-DAD-ESI/MS enabled detection of gallotannin, ellagitannin and flavonol derivatives, in leaves of E. globulus.
Economic evidence for the clinical management of major depressive disorder: a systematic review and quality appraisal of economic evaluations alongside randomised controlled trials

Aims. The aim of this systematic review of economic evaluations alongside randomised controlled trials (RCTs) was to provide a comprehensive overview of the evidence concerning cost-effectiveness analyses of common treatment options for major depression. Methods. An existing database was used to identify studies reporting cost-effectiveness results from RCTs. This database has been developed by a systematic literature search in the bibliographic databases of PubMed, PsychINFO, Embase and Cochrane library from database inception to December 2014. We evaluated the quality of economic evaluations using a 10-item short version of the Drummond checklist. Results were synthesised narratively. The risk of bias of the included RCTs was assessed, based on the Cochrane risk of bias assessment tool. Results. Fourteen RCTs were included from the 5580 articles screened on titles and abstracts. The methodological quality of the health economic evaluations was relatively high and the majority of the included RCTs had low risk of bias in most of Cochrane items except blinding of participants and personnel. Cognitive behavioural therapy was examined in seven trials as part of a variety of treatment protocols and seems cost-effective compared with pharmacotherapy in the long-term. However cost-effectiveness results for the combination of psychotherapy with pharmacotherapy are conflicting and should be interpreted with caution due to limited comparability between the examined trials. For several treatments, only a single economic evaluation was reported as part of a clinical trial. This was the case for comparisons between different classes of antidepressants, for several types of psychotherapy (behavioural activation, occupational therapy, interpersonal psychotherapy, short-term psychotherapy, psychodynamic psychotherapy, rational emotive behavioural therapy, solution focused therapy), and for transcranial magnetic stimulation v. electroconvulsive therapy. The limited evidence base for these interventions means generalisations, based on economic evaluation alongside clinical trials, cannot easily be made. Conclusions. There is some economic evidence underpinning many of the common treatment options for major depression. Wide variability was observed in study outcomes, probably attributable to differences in population, interventions or follow-up periods. For many interventions, only a single economic evaluation alongside clinical trials was identified. Thus, significant economic evidence gaps remain in the area of major depressive disorder.