bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine Profiles in Children After Pediatric Kidney Transplantation With Acute Cellular Compared to Chronic Antibody-mediated Rejection and Stable Patients: A Pilot Study
Authors: Borsum Nadja , Verboom Murielle , Ahlenstiel-Grunow Thurid , Pape Lars 
Published: October 2019

Background.
Different patterns of plasma cytokines can be expected in the case of chronic active-antibody-mediated (cAMR) and acute cellular rejection (AR) after kidney transplantation (KTx).

Methods.
IL-2, 4, 6, 10, 17A, tumor necrosis factor alpha, and interferon gamma were measured in 51 pediatric KTx recipients at time of renal biopsy (17 AR, 14 cAMR, 20 normal). Patients were divided into a training (n = 30) and a validation (n = 21) set.

Results.
IL-6 was significantly higher in AR patients and significantly lower in the case of cAMR. In children with s-creatinine increase, IL-6 values were significantly different between AR and cAMR. IL-10 levels showed similar tendencies. For IL-2, 4, 17A, tumor necrosis factor alpha, and interferon gamma, no differences were found. In the independent validation cohort, the receiver operating characteristic area under the curve for IL-6 was 0.79 and 0.70 for AR and cAMR. In children with AR, an IL-6 <1141 fg/ml, and in those with cAMR, an IL-6 >721 fg/ml was associated with a specificity of 86%/76%, a sensitivity of 71%/80%, a positive predictive value of 56%/45%, and a negative predictive value of 92%/94%.

Conclusions.
In this pilot study, the plasma IL-6 level is a promising biomarker to identify pediatric kidney transplant recipients free from AR and cAMR and might help to distinguish between both entities, whereas there is only a nonsignificant trend toward the usability of IL-10. Validation in larger cohorts in combination with other biomarkers are warranted.
Insulin-Independent Reversal of Type-1 Diabetes Following Transplantation of Adult Brown Adipose Tissue Supplemented With IGF-1
Authors: Gunawardana Subhadra C. , Piston David W. 
Published: October 2019

Background.
As our previous publications show, it is feasible to reverse type 1 diabetes (T1D) without insulin in multiple mouse models, through transplantation of embryonic brown adipose tissue (BAT) in the subcutaneous space. Embryonic BAT transplants result in rapid and long-lasting euglycemia accompanied by decreased inflammation and regenerated healthy white adipose tissue, with no detectable increase in insulin. To translate this approach to human patients, it is necessary to establish practical alternatives for embryonic tissue. Adult adipose tissue transplants or BAT-derived stem cell lines alone fail to reverse T1D. A likely reason is transplant failure resulting from lack of growth factors abundant in embryonic tissue. Adding growth factors may enable transplants to survive and vascularize as well as stimulate adipogenesis and decrease inflammation in the surrounding host tissue. Previous data points to insulin like growth factor 1 (IGF-1) as the most likely candidate. Embryonic BAT abundantly expresses IGF-1, and embryonic BAT transplant recipients exhibit increased plasma levels of IGF-1. Therefore, we tested the ability of temporary administration of exogenous IGF-1 to enable adult BAT transplants to correct T1D.

Methods.
Fresh BAT from healthy adult CB7BL/6 donors were transplanted in the subcutaneous space of hyperglycemic nonobese diabetic recipients. Exogenous IGF-1 was administered daily for a week following transplant, at 100 µg/kg SC.

Results.
Adult BAT transplants with IGF-1 supplementation produced rapid long-lasting euglycemia at a 57% success rate, in contrast with no recovery in the control groups who received adult BAT alone, IGF-1 alone, or no treatment.

Conclusions.
Temporary supplementation with IGF-1 enables adult BAT transplants to correct T1D phenotypes independent of insulin, providing a possible route to translate this treatment to human patients.
Incidentally Detected Malignancies in Lung Transplant Explants
Authors: Amratia Dhruv A. , Hunt William R. , Neujahr David , Veeraraghavan Srihari 
Published: October 2019

Background.Active malignancy diagnosed within 5 years is an absolute contraindication for lung transplantation. In this study, we evaluated the rate of incidental malignancies detected in explanted lungs at our institution and assessed the posttransplant survival in patients with nonsmall cell lung cancer (NSCLC).Methods.A retrospective chart review of lung transplant recipients at our institution from February 1999 to June 2017 was conducted. A literature review was performed to evaluate the prevalence and survival outcomes in patients with unexpected malignancies.Results.From 407 patients who underwent lung transplantation, 9 (2.2%) were discovered to have malignant neoplasms. There were 3 cases of adenocarcinoma, 3 cases of adenocarcinoma in situ, 2 cases of squamous cell carcinoma, and 1 case of metastatic renal cell carcinoma. An extensive literature review found 12 case reports or case series reporting malignancy discovered at the time of lung transplantation. The overall prevalence of incidental neoplasms among 6746 recipients is around 1.5% (n = 103). The most common neoplasms discovered included adenocarcinoma (n = 56, 54%) and squamous cell carcinoma (n = 29, 28%). The overall 3-year survival was 54.4% for patients with localized NSCLC compared to 5.7% for those with nonlocalized disease.Conclusions.Unidentified malignancies occur despite aggressive radiographic surveillance with poor posttransplant outcomes in patients with advanced malignancy. Malignancy-related radiographic findings may be missed pretransplant secondary to architectural distortion of lung parenchyma related to end-stage lung disease or because of the critical timing of surgery when donor lungs are available.
Comparison of Supraceliac and Infrarenal Aortic Conduits in Liver Transplantation: Is There a Difference in Patency and Postoperative Renal Dysfunction?
Authors: Livingston David , Lee David D. , Croome Sarah , Burcin Taner C. , Croome Kristopher P. 
Published: October 2019

Background.
Aorto-hepatic conduits can provide arterial inflow for liver transplants in cases where the native hepatic artery is unsuitable for use.

Methods.
Clinical outcomes of all patients undergoing liver transplantation (LT) with an aorto-hepatic conduit between 2000 and 2016 were included. Recipients were divided into 2 groups: those with a supraceliac (SC) aortic conduit (N = 22) and those with an infrarenal (IR) aortic conduit (N = 82).

Results.
There was no difference in calculated model for end-stage liver disease score between the 2 groups. The SC group received grafts with a higher mean donor risk index (1.69 versus 1.48; P = 0.02). Early allograft dysfunction was 18.2% in the SC group and 29.3% in the IR group (P = 0.30). In the SC group, 10.5% of patients required initiation of postoperative continuous renal replacement therapy compared to 12.1% of patients in the IR group (P = 0.69). No difference in the rate of postoperative acute kidney injury was seen between the 2 groups (P = 0.54). No significant difference in median creatinine at 1 year was seen between the SC (1.2 mg/dL; IQR 1–1.3) and IR (1.2 mg/dL; IQR 0.9–1.5) groups (P = 0.85). At a median follow-up of 5.3 years, thrombosis of the aortic conduit occurred in 0% of patients in the SC group and 6.1% of patients in the IR group (P = 0.24). Graft survival was not significantly different between the 2 groups (P = 0.47).

Conclusions.
No difference in renal dysfunction as demonstrated by need for post-LT continuous renal replacement therapy, acute kidney injury, or creatinine at 1 year post-LT was seen between SC and IR aortic conduits. A slight trend of higher conduit thrombosis rate was seen with IR compared to SC aortic conduits; however, this did not reach statistical significance. Both SC and IR aortic conduits represent reasonable options when the native hepatic artery is unsuitable for use.
Molecular point-of-care testing for influenza A/B and respiratory syncytial virus: comparison of workflow parameters for the ID Now and cobas Liat systems
Authors: Young Stephen , Phillips Jamie , Griego-Fullbright Christen , Wagner Aaron , Jim Patricia , Chaudhuri Sheena , Tang Shaowu , Sickler Joanna 
Published: October 2019

ABSTRACTAimsPoint-of-care (POC) tests for influenza and respiratory syncytial virus (RSV) offer the potential to improve patient management and antimicrobial stewardship. Studies have focused on performance; however, no workflow assessments have been published comparing POC molecular tests. This study compared the Liat and ID Now systems workflow, to assist end-users in selecting an influenza and/or RSV POC test.MethodsStaffing, walk-away, and turnaround time (TAT) of the Liat and ID Now systems were determined using 40 nasopharyngeal samples, positive for influenza or RSV. The ID Now system requires separate tests for influenza and RSV, so parallel (two instruments) and sequential (one instrument) workflows were evaluated.ResultsThe ID Now ranged 4.1–6.2 minutes for staffing, 1.9–10.9 minutes for walk-away and 6.4–15.8 minutes for TAT per result. The Liat ranged 1.1–1.8 minutes for staffing, 20.0–20.5 minutes for walk-away and 21.3–22.0 minutes for TAT. Mean walk-away time comprised 38.0% (influenza positive) and 68.1% (influenza negative) of TAT for ID Now and 93.7% (influenza/RSV) for Liat. The ID Now parallel workflow resulted in medians of 5.9 minutes for staffing, 9.7 minutes for walk-away, and 15.6 minutes for TAT. Assuming prevalence of 20% influenza and 20% RSV, the ID Now sequential workflow resulted in medians of 9.4 minutes for staffing, 17.4 minutes for walk-away, and 27.1 minutes for TAT.ConclusionsThe ID Now and Liat systems offer different workflow characteristics. Key considerations for implementation include value of both influenza and RSV results, clinical setting, staffing capacity, and instrument(s) placement.
A Multiomics Approach to Heterogeneity in Alzheimer’s Disease: Focused Review and Roadmap
Authors: Badhwar AmanPreet , McFall G. Peggy , Sapkota Shraddha , Black Sandra E. , Chertkow Howard , Duchesne Simon , Masellis Mario , Li Liang , Dixon Roger A. , Bellec Pierre 
Published: October 2019

AbstractEtiological and clinical heterogeneity is increasingly recognized as a common characteristic of Alzheimer’s disease and related dementias. This heterogeneity complicates diagnosis, treatment, and the design and testing of new drugs. An important line of research is discovery of multimodal biomarkers that will facilitate the targeting of subpopulations with homogeneous pathophysiological signatures. High-throughput ‘omics’ are unbiased data driven techniques that probe the complex etiology of Alzheimer’s disease from multiple levels (e.g. network, cellular, and molecular) and thereby account for pathophysiological heterogeneity in clinical populations. This review focuses on data reduction analyses that identify complementary disease-relevant perturbations for three omics techniques: neuroimaging-based subtypes, metabolomics-derived metabolite panels, and genomics-related polygenic risk scores. Neuroimaging can track accrued neurodegeneration and other sources of network impairments, metabolomics provides a global small-molecule snapshot that is sensitive to ongoing pathological processes, and genomics characterizes relatively invariant genetic risk factors representing key pathways associated with Alzheimer’s disease. Following this focused review, we present a roadmap for assembling these multiomics measurements into a diagnostic tool highly predictive of individual clinical trajectories, to further the goal of personalized medicine in Alzheimer’s disease.
Depletion of erythropoietic miR-486-5p and miR-451a improves detectability of rare microRNAs in peripheral blood-derived small RNA sequencing libraries
Authors: Juzenas Simonas , Lindqvist Carl Mårten , Ito Go , Dolshanskaya Yewgenia , Halfvarson Jonas , Franke Andre , Hemmrich-Stanisak Georg 
Published: October 2019

AbstractErythroid-specific miR-451a and miR-486-5p are two of the most dominant microRNAs (miRNAs) in human peripheral blood. In small RNA sequencing libraries, their overabundance reduces diversity as well as complexity and consequently causes negative effects such as missing detectability and inaccurate quantification of low abundant miRNAs. Here we present a simple, cost-effective and easy to implement hybridization-based method to deplete these two erythropoietic miRNAs from blood-derived RNA samples. By utilization of blocking oligonucleotides, this method provides a highly efficient and specific depletion of miR-486-5p and miR-451a, which leads to a considerable increase of measured expression as well as detectability of low abundant miRNA species. The blocking oligos are compatible with common 5’ ligation-dependent small RNA library preparation protocols, including commercially available kits, such as Illumina TruSeq and Perkin Elmer NEXTflex. Furthermore, the here described method and oligo design principle can be easily adapted to target many other miRNA molecules, depending on context and research question.
The diversity and distribution of endophytes across biomes, plant phylogeny, and host tissues—how far have we come and where do we go from here?
Authors: Harrison Joshua G. , Griffin Eric A. 
Published: October 2019

AbstractThe interiors of plants are colonized by diverse microorganisms that are referred to as endophytes. Endophytes have received much attention over the past few decades, yet many questions remain unanswered regarding patterns in their biodiversity at local to global scales. To characterize research effort to date, we synthesized results from ∼600 published studies. Our survey revealed a global research interest and highlighted several gaps in knowledge. For instance, of the seventeen biomes encompassed by our survey, seven were understudied and together composed only 7% of the studies that we considered. We found that fungal endophyte diversity has been characterized in at least one host from 30% of embryophyte families, while bacterial endophytes have been surveyed in hosts from only 10.5% of families. We complimented our survey with a vote counting procedure to determine endophyte richness patterns among plant tissue types. We found that variation in endophyte assemblages in above-ground tissues varied with host growth habit. Stems were the richest tissue in woody plants, whereas roots were the richest tissue in graminoids. For forbs, we found no consistent differences in relative tissue richness among studies. We propose future directions to fill the gaps in knowledge we uncovered and inspire further research.Originality-Significance StatementMuch remains to be learned regarding the biodiversity and distribution of the microbes that colonize the interiors of plants. Here, we surveyed approximately 600 publications to characterize gaps in knowledge and provide a roadmap for future research. We compared biomes, plant families, and geographical regions in terms of the research interest that they have garnered. Additionally, we synthesized published results and report that variation in endophyte richness among plant tissue types is a function of host growth habit. Stems were the richest tissue in woody plants, whereas roots were the richest tissue in graminoids. We hope to inspire research to fill the gaps in knowledge that we uncovered.
HSP110 dependent HSP70 disaggregation machinery mediates prion-like propagation of amyloidogenic proteins in metazoa
Authors: Tittelmeier Jessica , Sandhof Carl Alexander , Ries Heidrun Maja , Druffel-Augustin Silke , Mogk Axel , Bukau Bernd , Nussbaum-Krammer Carmen 
Published: October 2019

ABSTRACTThe gradual accumulation and prion-like propagation of α-synuclein and other amyloidogenic proteins is associated with devastating neurodegenerative diseases. The metazoan disaggregation machinery, a specific combination of HSP70 and its co-chaperones, is able to disassemble α-synuclein fibrils in vitro, but the physiological consequence in vivo is unknown. To explore this, we used Caenorhabditis elegans models that exhibit pathological features of α-synuclein, such as misfolding, intercellular spreading and toxicity. We inhibited the HSP70 disaggregase by depleting the crucial component HSP-110 and monitored the effect on α-synuclein related phenotypes. The knockdown of HSP-110 not only impaired HSP70 disaggregation activity and prevented the resolubilization of amorphous heat shock induced firefly luciferase aggregates, but also compromised the cellular folding capacity. In stark contrast, HSP-110 depletion reduced α-synuclein foci formation, cell-to-cell transmission and toxicity. Similar effects were observed for a polyQ model substrate, confirming that inhibition of HSP70 disaggregation function mitigates amyloid toxicity. These data demonstrate that the metazoan HSP70 disaggregation complex plays a critical role in the prion-like propagation of amyloid-type conformers. Therefore, the HSP70 disaggregation activity is a double-edged sword as it is essential for the maintenance of cellular proteostasis while being involved in the generation of toxic amyloid-type protein species.
SalmonellaEnhances Osteogenic Differentiation in Adipose-Derived Mesenchymal Stem Cells
Authors: Foutouhi Soraya H. , Mohamad-Fauzi Nuradilla , Storey Dylan Bobby , Foutouhi Azarene A. , Kong Nguyet , Kol Amir , Borjesson Dori , Desai Prerak , Shah Jigna , Murray James D. , Weimer Bart C. 
Published: October 2019

AbstractThe potential of mesenchymal stem cells (MSCs) for tissue repair and regeneration has garnered great attention. While MSC interaction with microbes at sites of tissue damage and inflammation is likely, especially in the gut, the consequences of bacterial association have yet to be elucidated. This study investigated the effect ofSalmonella entericasspentericaserotype Typhimurium on MSC trilineage differentiation path and mechanism. Through examination of key markers of differentiation, immunomodulatory regulators, and inflammatory cytokines, we demonstrated thatSalmonellaaltered osteogenic and chondrogenic differentiation pathways in human and goat adipose-derived MSCs. Gene expression profiles defined signaling pathway alterations in response toSalmonellaassociation not observed in epithelial cells. We uncovered significant differential expression (P< 0.05) of genes associated with anti-apoptotic and pro-proliferative responses in MSCs duringSalmonellachallenge. These observations led us to conclude that bacteria, specificallySalmonella,induce pathways that influence functional differentiation trajectories in MSCs, thus implicating substantial microbial influence on MSC physiology and immune activity.
Recurrent neural network models of multi-area computation underlying decision-making
Authors: Kleinman Michael , Chandrasekaran Chandramouli , Kao Jonathan C. 
Published: October 2019

AbstractCognition emerges from coordinated computations across multiple brain areas. However, elucidating these computations within and across brain regions is challenging because intra- and inter-area connectivity are typically unknown. To study coordinated computation, we trained multi-area recurrent neural networks (RNNs) to discriminate the dominant color of a checker-board and output decision variables reflecting a direction decision, a task previously used to investigate decision-related dynamics in dorsal premotor cortex (PMd) of monkeys. We found that multi-area RNNs, trained with neurophysiological connectivity constraints and Dale’s law, recapitulated decision-related dynamics observed in PMd. The RNN solved this task by a dynamical mechanism where the direction decision was computed and outputted, via precisely oriented dynamics, on an axis that was nearly orthogonal to checkerboard color inputs. This orthogonal direction information was preferentially propagated through alignment with inter-area connections; in contrast, color information was filtered. These results suggest that cortex uses modular computation to generate minimal sufficient representations of task information. Finally, we used multi-area RNNs to produce experimentally testable hypotheses for computations that occur within and across multiple brain areas, enabling new insights into distributed computation in neural systems.
Phenotypic differences in reversible attachment behavior reveal distinctP. aeruginosasurface colonization strategies
Authors: Lee Calvin K. , Vachier Jérémy , Anda Jaime de , Zhao Kun , Baker Amy E. , Bennett Rachel R. , Armbruster Catherine R. , Lewis Kimberley A. , Tarnopol Rebecca L. , Lomba Charles J. , Hogan Deborah A. , Parsek Matthew R. , O’Toole George A. , Golestanian Ramin , Wong Gerard C. L. 
Published: October 2019

AbstractDespite possessing the machinery to sense, adhere to, and proliferate on surfaces, it is commonly observed that bacteria initially have a difficult time attaching to a surface. Before forming a bacterial biofilm, planktonic bacteria exhibit a random period of transient surface attachment known as “reversible attachment” which is poorly understood. Using community tracking methods at single-cell resolution, we examine how reversible attachment progresses during initial stages of surface sensing.Pseudomonas aeruginosastrains PAO1 and PA14, which exhibit similar exponential trends of surface cell population increase, show unanticipated differences when the behavior of each cell was considered at the full lineage level and interpreted using the unifying quantitative framework of an exactly solvable stochastic model. Reversible attachment comprises two regimes of behavior, processive and nonprocessive, corresponding to whether cells of the lineage stay on the surface long enough to divide, or not, before detaching. Stark differences between PAO1 and PA14 in the processive regime of reversible attachment suggest the existence of two complementary surface colonization strategies, which are roughly analogous to “immediate-” vs “deferred-gratification” in a prototypical cognitive-affective processing system. PAO1 lineages commit relatively quickly to a surface compared to PA14 lineages. PA14 lineages allow detaching cells to retain memory of the surface so that they are primed for improved subsequent surface attachment. In fact, it is possible to identify motility suppression events in PA14 lineages in the process of surface commitment. We hypothesize that these contrasting strategies are rooted in downstream differences between Wsp-based and Pil-Chp-based surface sensing systems.
Smoothened receptor Signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex
Authors: Delmotte Quentin , Medina Igor , Hamze Mira , Buhler Emmanuelle , Zhang Jinwei , Belgacem Yesser H. , Porcher Christophe 
Published: October 2019

ABSTRACTSonic Hedgehog (Shh) and its patched-smoothened receptor complex control a variety of functions in the developing central nervous system (CNS) such as neural cell proliferation and differentiation. Recently, Shh signaling components have been found to be expressed at the synaptic level in the postnatal brain, suggesting a potential role in the regulation of synaptic transmission. Usingin uteroelectroporation of constitutively active and dominant-negative forms of the Shh co-receptor smoothened (Smo), we studied the role of Smo signaling in the development and maturation of GABAergic transmission in the somatosensory cortex. Our results show that enhancing Smo activity during development accelerates the shift from depolarizing to hyperpolarizing GABA in dependence on functional expression of potassium-chloride cotransporter type 2 (KCC2). On the other hand, blocking Smo activity maintains GABA response in a depolarizing state in mature cortical neurons resulting in altered chloride homeostasis and increased seizure susceptibility. This study reveals an unexpected function of Smo signaling on the regulation of chloride homeostasis through the control of KCC2 cell surface stability and on the timing of the GABA inhibitory/excitatory shift in brain maturation.Summary statementThe smoothened receptor controls the time course of inhibitory transmission through the stability of the potassium-chloride cotransporter type 2 at the plasma membrane.