bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma microRNAs Are Potential Biomarkers of Acute Rejection After Hindlimb Transplantation in Rats
Authors: Oda Hiroki , Ikeguchi Ryosuke , Yurie Hirofumi , Kaizawa Yukitoshi , Ohta Souichi , Yamamoto Koji , Aoyama Tomoki , Matsuda Shuichi 
Published: October 2016

Background
The development of effective immunosuppressive regimens has resulted in many cases of successful hand transplantation. Visual skin inspection and histological evaluation are used to assess the rejection of hand transplants, but these methods are largely subjective. In this study, we aimed to determine the potential of microRNAs (miRNAs) as biomarkers for acute rejection in vascularized composite allotransplants.

Methods
In allograft group, 7 male Brown-Norway rats (RT1n) were used as donors and 13 male Lewis rats (RT1l) were used as recipients. In control group, 8 Lewis rats were used as donors and recipients. The hindlimbs of donor rats were transplanted orthotopically to recipient rats. Skin changes were noted daily. Skin biopsies were obtained from 5 recipients and evaluated histologically. Plasma samples were obtained from the other 8 recipients before transplant and 7, 10, and 14 days posttransplant and used to measure miRNA expression.

Results
Skin changes occurred at a mean of 11.0 days posttransplant. Rejection in most skin biopsies taken 7 and 10 days posttransplant was histologically classified as grade 0, whereas that in most biopsies taken 14 days posttransplant was classified as grade 3. We found that expression of miRNA-146a and miRNA-155 was significantly upregulated at 10 and 14 days posttransplant compared with that at 7 days posttransplant. In control group, there were no significant changes in plasma miRNAs expressions.

Conclusions
The upregulation of plasma miRNA-146a and miRNA-155 was detected before the histological evaluation methods could diagnose complete rejection in the rat hindlimb transplantation model. Plasma miRNA-146a and miRNA-155 may be potential biomarkers of acute rejection after vascularized composite allotransplantation.
Liberation From Renal Replacement Therapy After Cadaveric Liver Transplantation
Authors: Hilmi Ibtesam A. , Al-Khafaji Ali , Damian Daniela , Rosario-Rivera Bedda L. , Abdullah Ali , Kellum John A. 
Published: October 2016

Background
Renal failure requiring renal replacement therapy (RRT) is common in patients with end-stage liver disease (ESLD) and is associated with worse outcomes following liver transplantation (LT). We investigated the factors associated with liberation from posttransplant RRT and studied the impact of RRT on patient and graft outcomes.

Methods
A 5-year retrospective study of ESLD patients who received pretransplant RRT was conducted. Variables associated with liberation from RRT at 30 days and at 1-year posttransplant were analyzed. We used propensity matching to compare patient and graft outcomes in the study cohort to those of a control group who underwent LT but not pretransplant RRT.

Results
Sixty-four patients were included in the study. Twenty-four (38%) were liberated from RRT at 30 days posttransplant. Duration of pretransplant RRT (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-0.98) and severe postreperfusion syndrome (OR, 0.26; 95% CI, 0.08-0.87) were significantly associated with continued RRT at 1-month posttransplant. At one year, 34 (53%) patients were liberated from RRT. Age was significantly associated with lack of liberation from RRT (OR, 0.933; 95% CI, 0.875-0.995). Compared with propensity matched controls, patients who received RRT pretransplant had worse graft and patient survival at 1 year (52% vs 82%; P = 0.01, and 53% vs 83%; P = 0.003, respectively).

Conclusions
In ESLD patients who received pretransplant RRT, one third were liberated from RRT at 1 month, and half at 1 year. Longer duration of pretransplant RRT, postreperfusion syndrome, and older age were associated with lower likelihood of liberation from RRT. Patients who required pretransplant RRT had worse graft and patient survivals compared to matched patients who did not require RRT. Patients who were liberated from RRT post-LT had similar outcomes to patients who never required pre-LT RRT.
iCARE: R package to build, validate and apply absolute risk models
Authors: Choudhury Parichoy Pal , Maas Paige , Wilcox Amber , Wheeler William , Brook Mark , Check David , Garcia-Closas Montserrat , Chatterjee Nilanjan 
Published: October 2016

AbstractThis report describes a R package, called the Individualized Coherent Absolute Risk Estimation (iCARE) tool, that allows researchers to build and evaluate models for absolute risk and apply them to estimate an individual’s risk of developing disease during a specified time interval based on a set of user defined input parameters. An attractive feature of the software is that it gives users flexibility to update models rapidly based on new knowledge on risk factors and tailor models to different populations by specifying three input arguments: (1) a model for relative risk, (2) an age-specific disease incidence rate, (3) the distribution of risk factors for the population of interest. The tool can handle missing information on risk factors for individuals for whom risks are to be predicted using a coherent approach where all estimates are derived from a single model after appropriate model averaging. The software allows single nucleotide polymorphisms (SNPs) to be incorporated into the model using published odds ratios and allele frequencies. The validation component of the software implements the methods for evaluation of model calibration, discrimination and risk-stratification based on independent validation datasets. We provide an illustration of the utility ofiCAREfor building, validating and applying absolute risk models using breast cancer as an example.
Giardia colonizes and encysts in high density foci in the murine small intestine
Authors: Barash NR , Nosala C , Pham JK , Mclnally SG , Gourguechon S , McCarthy-Sinclair B , Dawson SC 
Published: October 2016

AbstractGiardiais a highly prevalent, yet understudied protistan parasite causing diarrheal disease worldwide. Hosts ingestGiardiacysts from contaminated sources. In the gastrointestinal tract, cysts excyst to become motile trophozoites, colonizing and attaching to the gut epithelium. Trophozoites later differentiate into infectious cysts that are excreted and contaminate the environment. Due to the limited accessibility of the gut, the temporospatial dynamics of giardiasis in the host is largely inferred from laboratory culture and thus may not mirrorGiardiaphysiology in the host. Here we have developed bioluminescent imaging (BLI) to directly interrogate and quantify thein vivotemporospatial dynamics of giardiasis, thereby providing an improved murine model to evaluate anti-Giardiadrugs. Using BLI, we determined that parasites primarily colonize the proximal small intestine non-uniformly in high-density foci. By imaging encystation-specific bioreporters, we show that encystation initiates shortly after inoculation and continues throughout the entire duration of infection. Encystation also initiates in high-density foci in the proximal small intestine, and high-density laboratory cultures of parasites are also stimulated to encyst. This work overturns the assumption that parasites encyst later during infection as they are dislodged and travel through the colon. We suggest that these high-density regions of parasite colonization likely result in localized pathology to the epithelium, and encystation occurs when trophozoites reach a threshold density due to local nutrient depletion. This more accurate visualization of giardiasis redefines the dynamics ofin vivo Giardialife cycle, paving the way for future mechanistic studies of density-dependent parasitic processes in the host.SignificanceGiardiais a single-celled parasite causing both acute and chronic diarrheal disease in over one billion people worldwide. Due to limited access to the site of infection in the gastrointestinal tract, our understanding of the dynamics ofGiardiainfections in the host has remained limited, and largely inferred from laboratory culture. To better understand giardiasis in the host, we developed imaging methods to quantifyGiardiaexpressing bioluminescent physiological reporters in live mice. We discovered that parasites primarily colonize and encyst in the proximal small intestine in discrete, high-density foci. Furthermore, this work provides evidence of a parasite density-based threshold for the differentiation ofGiardiainto cysts in the host. These findings overturn existing paradigms of giardiasis infection dynamics in the host.
An Oscillatory Network Model of Head Direction, Spatially Periodic Cells and Place Cells Using Locomotor Inputs
Authors: Soman Karthik , Muralidharan Vignesh , Chakravarthy V. Srinivasa 
Published: October 2016

AbstractWe propose a computational modeling approach that explains the formation of a range of spatial cells like head direction cells, grid cells, border cells and place cells which are believed to play a pivotal role in the spatial navigation of an animal. Most existing models insert special symmetry conditions in the models in order to obtain such symmetries in the outcome; our models do not require such symmetry assumptions. Our modeling approach is embodied in two models: a simple one (Model #1) and a more detailed version (Model #2). In Model #1, velocity input is presented to a layer of Head Direction cells, with no special topology requirements, the outputs of which are presented to a layer of Path Integration neurons. A variety of spatially periodic responses resembling grid cells, are obtained using the Principal Components of Path Integration layer. In Model #2, the input consists of the locomotor rhythms from the four legs of a virtual animal. These rhythms are integrated into the phases of a layer of oscillatory neurons, whose outputs drive a layer of Head Direction cells. The Head Direction cells in turn drive a layer of Path Integration neurons, which in turn project to two successive layers of Lateral Anti Hebbian Networks (LAHN). Cells in the first LAHN resemble grid cells (with both hexagonal and square gridness), and border cells. Cells in the second LAHN exhibit place cell behaviour and a new cell type known as corner cell. Both grid cells and place cells exhibit phase precession in 1D and 2D spaces. The models outline the neural hierarchy necessary to obtain the complete range of spatial cell responses found in the hippocampal system.
Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank
Authors: Reus LM , Shen X , Gibson J , Wigmore E , Ligthart L , Adams MJ , Davies G , Cox SR , Hagenaars SP , Bastin ME , Deary IJ , Whalley HC , McIntosh AM 
Published: October 2016

AbstractMajor depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data compromised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). Our, findings however, indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. In the current study, we found little or no evidence for genetic overlap between major psychiatric disorders and structural brain measures. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders.
A shared representation of order between encoding and recognition in visual short-term memory
Authors: Kalm Kristjan , Norris Dennis 
Published: October 2016

AbstractMost complex tasks require people to bind individual stimuli into a sequence in short term memory (STM). For this purpose information about the order of the individual stimuli in the sequence needs to be in active and accessible form in STM over a period of few seconds. Here we investigated how the temporal order information is shared between the presentation and response phases of an STM task. We trained a classification algorithm on the fMRI activity patterns from the presentation phase of the STM task to predict the order of the items during the subsequent recognition phase. While voxels in a number of brain regions represented positional information during either presentation and recognition phases, only voxels in the lateral prefrontal cortex (PFC) and the anterior temporal lobe (ATL) represented position consistently across task phases. A shared positional code in the ATL might reflect verbal recoding of visual sequences to facilitate the maintenance of order information over several seconds.
Genetic, transcriptome, proteomic and epidemiological evidence for blood brain barrier disruption and polymicrobial brain invasion as determinant factors in Alzheimer’s disease
Authors: Carter C.J. 
Published: October 2016

AbstractMultiple pathogens have been detected in Alzheimer’s disease (AD) brains. A bioinformatics approach was used to assess relationships between pathogens and AD genes (GWAS), the AD hippocampal transcriptome and plaque or tangle proteins. Host/pathogen interactomes (C.albicans,C.Neoformans, Bornavirus,B.Burgdorferri, cytomegalovirus, Ebola virus, HSV-1, HERV-W, HIV-1, Epstein-Barr, hepatitis C, influenza,C.Pneumoniae,P.Gingivalis,H.Pylori,T.Gondii,T.Cruzi) significantly overlap with misregulated AD hippocampal genes, with plaque and tangle proteins and, except Bornavirus, Ebola and HERV-W, with AD genes. Upregulated AD hippocampal genes match those upregulated by multiple bacteria, viruses, fungi or protozoa in immunocompetent blood cells. AD genes are enriched in bone marrow and immune locations and in GWAS datasets reflecting pathogen diversity, suggesting selection for pathogen resistance. The age of AD patients implies resistance to infections afflicting the younger. APOE4 protects against malaria and hepatitis C, and immune/inflammatory gain of function applies to APOE4, CR1, TREM2 and presenilin variants. 30/78 AD genes are expressed in the blood brain barrier (BBB), which is disrupted by AD risk factors (ageing, alcohol, aluminium, concussion, cerebral hypoperfusion, diabetes, homocysteine, hypercholesterolaemia, hypertension, obesity, pesticides, pollution, physical inactivity, sleep disruption and smoking). The BBB and AD benefit from statins, NSAIDs, oestrogen, melatonin and the Mediterranean diet. Polymicrobial involvement is supported by the upregulation of pathogen sensors/defenders (bacterial, fungal, viral) in the AD brain, blood or CSF. Cerebral pathogen invasion permitted by BBB inadequacy, activating a hyper-efficient immune/inflammatory system, betaamyloid and other antimicrobial defence may be responsible for AD which may respond to antibiotic, antifungal or antiviral therapy.
A risk stratification approach for improved interpretation of diagnostic accuracy statistics
Authors: Katki Hormuzd A. , Schiffman Mark 
Published: October 2016

AbstractDiagnostic accuracy statistics, including predictive values, risk-differences, Youden’s index and Area Under the Curve (AUC), assess the promise of novel biomarkers proposed as diagnostic tests. We reinterpret these statistics in light of risk-stratification (how well a biomarker separates those at higher risk from those at lower risk) to better understand their implications for public-health programs. We introduce an intuitively simple statistic, Mean Risk Stratification (MRS): the average change in risk (pre-test vs. post-test) revealed for tested individuals. High MRS implies better risk separation achieved by testing. MRS demonstrates that conventional predictive values can mislead because they do not account for disease prevalence or test-positivity rates. Little risk-stratification is possible for rare diseases, demonstrating a “high-bar” to justify population-based screening. Importantly, we demonstrate that the risk-difference, Youden’s index, and AUC measure only multiplicative relative gains in risk-stratification: AUC=0.6 achieves only 20% of maximum risk-stratification (AUC=0.9 achieves 80%). However, large relative gains in risk-stratification might not imply large absolute gains if disease is rare or if the test is rarely positive. We illustrate MRS by our experience comparing the performance of cervical cancer screening tests in China vs. the USA. The test with the worst AUC=0.72 in China (visual inspection with ascetic acid) provides twice the risk-stratification of the test with best AUC=0.83 in the USA (human papillomavirus and Pap cotesting) because China has three times more cervical precancer/cancer. MRS could be routinely calculated to better understand the clinical/public-health implications of standard diagnostic accuracy statistics.
Human anterolateral entorhinal cortex volumes are associated with preclinical cognitive decline
Authors: Olsen RK , Yeung L-K , Noly-Gandon A , D’Angelo MC , Kacollja A , Smith VM , Ryan JD , Barense MD 
Published: October 2016

AbstractWe investigated whether older adults without subjective memory complaints, but who present with cognitive decline in the laboratory, demonstrate atrophy in medial temporal lobe (MTL) subregions associated with Alzheimer's disease. Forty community-dwelling older adults were categorized based on Montreal Cognitive Assessment (MoCA) performance. Total grey/white matter, cerebrospinal fluid, and white matter hyperintensity load were quantified from whole-brain T1-weighted and FLAIR magnetic resonance imaging scans, while hippocampal subfields and MTL cortical subregion volumes (CA1, dentate gyrus/CA2/3, subiculum, anterolateral and posteromedial entorhinal, perirhinal, and parahippocampal cortices) were quantified using high-resolution T2-weighted scans. Cognitive status was evaluated using standard neuropsychological assessments. No significant differences were found in the whole-brain measures. However, MTL volumetry revealed that anterolateral entorhinal cortex (alERC) volume -- the same region in which Alzheimer's pathology originates -- was strongly associated with MoCA performance. This is the first study to demonstrate that alERC volume is related to cognitive decline in preclinical, community-dwelling older adults.
Rapid evolution of primate type 2 immune response factors linked to asthma susceptibility
Authors: Barber Matthew F. , Lee Elliot M. , Griffin Hayden , Elde Nels C. 
Published: October 2016

ABSTRACTHost immunity pathways evolve rapidly in response to antagonism by pathogens. Microbial infections can also trigger excessive inflammation that contributes to diverse autoimmune disorders including asthma, lupus, diabetes, and arthritis. Definitive links between immune system evolution and human autoimmune disease remain unclear. Here we provide evidence that several components of the type 2 immune response pathway have been subject to recurrent positive selection in the primate lineage. Notably, rapid evolution of the central immune regulatorIL13corresponds to a polymorphism linked to asthma susceptibility in humans. We also find evidence of accelerated amino acid substitutions as well as repeated gene gain and loss events among eosinophil granule proteins, which act as toxic antimicrobial effectors that promote asthma pathology by damaging airway tissues. These results support the hypothesis that evolutionary conflicts with pathogens promote tradeoffs for increasingly robust immune responses during animal evolution. Our findings are also consistent with the view that natural selection has contributed to the spread of autoimmune disease alleles in humans.
Reversible Leaf Xylem Collapse: A Potential “Circuit Breaker” against Cavitation
Authors: Zhang Yong-Jiang , Rockwell Fulton E. , Graham Adam C. , Alexander Teressa , Holbrook N. Michele 
Published: October 2016

AbstractWe report a novel form of xylem dysfunction in angiosperms: reversible collapse of the xylem conduits of the smallest vein orders that demarcate and intrusively irrigate the areoles of red oak (Quercus rubra) leaves. Cryo-scanning electron microscopy revealed gradual increases in collapse from approximately −2 MPa down to −3 MPa, saturating thereafter (to −4 MPa). Over this range, cavitation remained negligible in these veins. Imaging of rehydration experiments showed spatially variable recovery from collapse within 20 s and complete recovery after 2 min. More broadly, the patterns of deformation induced by desiccation in both mesophyll and xylem suggest that cell wall collapse is unlikely to depend solely on individual wall properties, as mechanical constraints imposed by neighbors appear to be important. From the perspective of equilibrium leaf water potentials, petioles, whose vessels extend into the major veins, showed a vulnerability to cavitation that overlapped in the water potential domain with both minor vein collapse and buckling (turgor loss) of the living cells. However, models of transpiration transients showed that minor vein collapse and mesophyll capacitance could effectively buffer major veins from cavitation over time scales relevant to the rectification of stomatal wrong-way responses. We suggest that, for angiosperms, whose subsidiary cells give up large volumes to allow large stomatal apertures at the cost of potentially large wrong-way responses, vein collapse could make an important contribution to these plants’ ability to transpire near the brink of cavitation-inducing water potentials.