bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrin-associated EBV-positive Large B-Cell Lymphoma
Authors: Boyer Daniel F. , McKelvie Penelope A. , de Leval Laurence , Edlefsen Kerstin L. , Ko Young-Hyeh , Aberman Zachary A. , Kovach Alexandra E. , Masih Aneal , Nishino Ha T. , Weiss Lawrence M. , Meeker Alan K. , Nardi Valentina , Palisoc Maryknoll , Shao Lina , Pittaluga Stefania , Ferry Judith A. , Harris Nancy Lee , Sohani Aliyah R.
Published: February 2017

Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.5 years with a M:F ratio of 3. In all 12 cases, the lymphoma was an incidental microscopic finding involving atrial myxomas (n=3), thrombi associated with endovascular grafts (n=3), chronic hematomas (n=2), and pseudocysts (n=4). All cases tested were nongerminal center B-cell origin, type III EBV latency, and were negative for MYC rearrangements and alternative lengthening of telomeres by FISH. Most showed high CD30, Ki67, and PD-L1, and low to moderate MYC and p53 expression. Among 11 patients with detailed follow-up, 6 were treated surgically, 3 with cardiac or vascular lesions had persistent/recurrent disease at intravascular sites, and 4 died of causes not directly attributable to lymphoma. Reports of previously published fibrin-associated cases showed similar features, whereas traditional DLBCL-CI cases with a mass lesion had significantly higher lymphoma-associated mortality. Fibrin-associated EBV+ large B-cell lymphoma is clinicopathologically distinct from DLBCL-CI, warranting separate classification. Most cases, particularly those associated with pseudocysts, behave indolently with the potential for cure by surgery alone and may represent a form of EBV+ lymphoproliferative disease rather than lymphoma. However, primary cardiac or vascular disease may have a higher risk of recurrence despite systemic chemotherapy.
High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection
Authors: Kessing Cari F. , Spudich Serena , Valcour Victor , Cartwright Pearline , Chalermchai Thep , Fletcher James L. K. , Takata Hiroshi , Nichols Carmen , Josey Benjamin J. , Slike Bonnie , Krebs Shelly J. , Sailsuta Napapon , Lerdlum Sukalaya , Jagodzinski Linda , Tipsuk Somporn , Suttichom Duanghathai , Rattanamanee Somprartthana , Zetterberg Henrik , Hellmuth Joanna , Phanuphak Nittaya , Robb Merlin L. , Michael Nelson L. , Ananworanich Jintanat , Trautmann Lydie ,   on behalf of the RV254/SEARCH 010/011/013 Study Teams
Published: February 2017

Background:

Central nervous system (CNS) infiltration by CD8+T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8+T cells in the CNS during acute HIV infection (AHI) is unknown.

Methods:

We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8+T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8).

Results:

CSF CD8+T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8+T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8+T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8+T cells in AHI exhibited increased functional gene expression profiles associated with CD8+T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8+T cells directed to unique HIV epitopes compared with the periphery.

Conclusions:

These results suggest that CSF CD8+T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.
Longitudinal Assessment of Proximal Tubular Dysfunction in HIV Seropositive and Seronegative Persons: Correlates and Implications
Authors: Sheets Kerry M. , Atta Mohamed G. , Fine Derek M. , Zook Katie , Mcfall Allison M. , Estrella Michelle M. , Schwartz George J. , Lucas Gregory M.
Published: February 2017

Background:

Proximal tubular dysfunction (PTD) is common in HIV-positive persons and has been associated with tenofovir disoproxil fumarate (TDF). However, few studies have assessed the natural history PTD in HIV-positive and -negative individuals, or the association of PTD with the subsequent trajectory of directly measured glomerular filtration rate (mGFR).

Methods:

We followed 192 HIV-positive and 100 HIV-negative, nondiabetic participants for 3 years. We measured 3 PTD markers (normoglycemic glycosuria, fractional excretion of phosphorus, and tubular proteinuria) and mGFR (by iohexol disappearance from serum) annually. We used univariate and multivariate generalized estimating equation logistic regression to identify factors associated with PTD across all visits and linear mixed effects models to assess the association between baseline PTD and mGFR slope.

Results:

Compared with HIV-negative participants, HIV-positive persons that were not taking antiretroviral therapy were at increased risk of PTD (adjusted odds ratio 3.33; 95% confidence interval: 1.65 to 6.71), whereas those taking a TDF-based or a TDF-sparing regimen were not at significantly increased risk of PTD. Among HIV-positive participants, uncontrolled viremia was a strong correlate of PTD. Forty-nine of 55 (89%) participants with PTD at baseline had at least 1 subsequent visit without PTD. There was no association between baseline PTD and rate of decline in mGFR over time.

Conclusions:

Poorly controlled HIV may be a stronger risk factor for PTD than TDF use. The individual-level variability of the PTD markers over time was high, potentially limiting their usefulness for routine screening in unselected patients. Baseline PTD was not associated with subsequent mGFR slope.
Neutralizing and Targeting Properties of a New Set of α4β7-Specific Antibodies Are Influenced by Their Isotype
Authors: Girard Alexandre , Jelicic Katija , Van Ryk Don , Rochereau Nicolas , Cicala Claudia , Arthos James , Noailly Blandine , Genin Christian , Verrier Bernard , Laurant Stephanie , Razanajaoana-Doll Diane , Pin Jean-Jacques , Paul Stéphane
Published: February 2017

The homing of lymphocytes to the mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or inflammatory bowel diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7+ lymphocyte–specific monoclonal antibodies that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. First, 5 monoclonal antibodies (1 IgA, 1 IgM, and 4 IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells. Their ability to block gp120/α4β7 or MAdCAM-1/α4β7 interactions was then measured in vitro with human T and B lymphocytes. In vitro, the anti-α4β7 IgA isotype was found to have the highest affinity for the α4β7 heterodimer, and it significantly reduced HIV replication in retinoic acid–treated α4β7hi CD4+ human T cells. This α4β7-specific IgA also displayed a high avidity for human and mouse α4β7+ lymphocytes in both mouse and human inflammatory colitis tissues. These new antibodies, and in particular those with mucosa-targeting isotypes such as IgA, could therefore be potential novel therapeutic tools for treating HIV and inflammatory bowel disease.
Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study
Authors: Tenforde Mark W. , Yadav Ashish , Dowdy David W. , Gupte Nikhil , Shivakoti Rupak , Yang Wei-Teng , Mwelase Noluthando , Kanyama Cecilia , Pillay Sandy , Samaneka Wadzanai , Santos Breno , Poongulali Selvamuthu , Tripathy Srikanth , Riviere Cynthia , Berendes Sima , Lama Javier R. , Cardoso Sandra W. , Sugandhavesa Patcharaphan , Christian Parul , Semba Richard D. , Campbell Thomas B. , Gupta Amita ,   the NWCS319 and ACTG 5175 study team
Published: February 2017

Introduction:

Numerous micronutrients have immunomodulatory roles that may influence risk of tuberculosis (TB), but the association between baseline micronutrient deficiencies and incident TB after antiretroviral therapy (ART) initiation in HIV-infected individuals is not well characterized.

Methods:

We conducted a case-cohort study (n = 332) within a randomized trial comparing 3 ART regimens in 1571 HIV treatment-naive adults from 9 countries. A subcohort of 30 patients was randomly selected from each country (n = 270). Cases (n = 77; main cohort = 62, random subcohort = 15) included patients diagnosed with TB by 96 weeks post-ART initiation. We determined pretreatment concentrations of vitamin A, carotenoids, vitamin B6, vitamin B12, vitamin D, vitamin E, and selenium. We measured associations between pretreatment micronutrient deficiencies and incident TB using Breslow-weighted Cox regression models.

Results:

Median pretreatment CD4+ T-cell count was 170 cells/mm3; 47.3% were women; and 53.6% Black. In multivariable models after adjusting for age, sex, country, treatment arm, previous TB, baseline CD4 count, HIV viral load, body mass index, and C-reactive protein, pretreatment deficiency in vitamin A (adjusted hazard ratio, aHR 5.33, 95% confidence interval, CI: 1.54 to 18.43) and vitamin D (aHR 3.66, 95% CI: 1.16 to 11.51) were associated with TB post-ART.

Conclusions:

In a diverse cohort of HIV-infected adults from predominantly low- and middle-income countries, deficiencies in vitamin A and vitamin D at ART initiation were independently associated with increased risk of incident TB in the ensuing 96 weeks. Vitamin A and D may be important modifiable risk factors for TB in high-risk HIV-infected patients starting ART in resource-limited highly-TB-endemic settings.
Computed Tomography–Assisted Thoracoscopic Surgery
Authors: Kostrzewa Michael , Kara Kerim , Rathmann Nils , Tsagogiorgas Charalambos , Henzler Thomas , Schoenberg Stefan O. , Hohenberger Peter , Diehl Steffen J. , Roessner Eric D.
Published: February 2017

Objectives

Minimally invasive resection of small, deep intrapulmonary lesions can be challenging due to the difficulty of localizing them during video-assisted thoracoscopic surgery (VATS). We report our preliminary results evaluating the feasibility of an image-guided, minimally invasive, 1-stop-shop approach for the resection of small, deep intrapulmonary lesions in a hybrid operating room (OR).

Materials and Methods

Fifteen patients (5 men, 10 women; mean age, 63 years) with a total of 16 solitary, deep intrapulmonary nodules of unknown malignant status were identified for intraoperative wire marking. Patients were placed on the operating table for resection by VATS. A marking wire was placed within the lesion under 3D laser and fluoroscopic guidance using a cone beam computed tomography system. Then, wedge resection by VATS was performed in the same setting without repositioning the patient.

Results

Complete resection with adequate safety margins was confirmed for all lesions. Marking wire placement facilitated resection in 15 of 16 lesions. Eleven lesions proved to be malignant, either primary or secondary; 5 were benign. Mean lesion size was 7.7 mm; mean distance to the pleural surface was 15.1 mm (mean lesion depth–diameter ratio, 2.2). Mean procedural time for marking wire placement was 35 minutes; mean VATS duration was 36 minutes.

Conclusions

Computed tomography–assisted thoracoscopic surgery is a new, safe, and effective procedure for minimally invasive resection of small, deeply localized intrapulmonary lesions. The benefits of computed tomography–assisted thoracoscopic surgery are 1. One-stop-shop procedure, 2. Lower risk for the patient (no patient relocation, no marking wire loss), and 3. No need to coordinate scheduling between the CT room and OR.
Time-Dependent Diffusion in Prostate Cancer
Authors: Lemberskiy Gregory , Rosenkrantz Andrew B. , Veraart Jelle , Taneja Samir S. , Novikov Dmitry S. , Fieremans Els
Published: February 2017

Objective

Prior studies in prostate diffusion-weighted magnetic resonance imaging (MRI) have largely explored the impact of b-value and diffusion directions on estimated diffusion coefficient D. Here we suggest varying diffusion time, t, to study time-dependent D(t) in prostate cancer, thereby adding an extra dimension in the development of prostate cancer biomarkers.

Methods

Thirty-eight patients with peripheral zone prostate cancer underwent 3-T MRI using an external-array coil and a diffusion-weighted image sequence acquired for b = 0, as well as along 12 noncollinear gradient directions for b = 500 s/mm2 using stimulated echo acquisition mode (STEAM) diffusion tensor imaging (DTI). For this sequence, 6 diffusion times ranging from 20.8 to 350 milliseconds were acquired. Tumors were classified as low-grade (Gleason score [GS] 3 + 3; n = 11), intermediate-grade (GS 3 + 4; n = 16), and high-grade (GS ≥4 + 3; n = 11). Benign peripheral zone and transition zone were also studied.

Results

Apparent diffusion coefficient (ADC) D(t) decreased with increasing t in all zones of the prostate, though the rate of decay in D(t) was different between sampled zones. Analysis of variance and area under the curve analyses suggested better differentiation of tumor grades at shorter t. Fractional anisotropy (FA) increased with t for all regions of interest. On average, highest FA was observed within GS 3 + 3 tumors.

Conclusions

There is a measurable time dependence of ADC in prostate cancer, which is dependent on the underlying tissue and Gleason score. Therefore, there may be an optimal selection of t for prediction of tumor grade using ADC. Controlling t should allow ADC to achieve greater reproducibility between different sites and vendors. Intentionally varying t enables targeted exploration of D(t), a previously overlooked biophysical phenomenon in the prostate. Its further microstructural understanding and modeling may lead to novel diffusion-derived biomarkers.
Aggressive Surgical Management of Congenital Diaphragmatic Hernia: Worth the Effort?
Authors: Harting Matthew T. , Hollinger Laura , Tsao Kuojen , Putnam Luke R. , Wilson Jay M. , Hirschl Ronald B. , Skarsgard Erik D. , Tibboel Dick , Brindle Mary E. , Lally Pamela A. , Miller Charles C. , Lally Kevin P.
Published: February 2017

Objective:

The objectives of this study were (i) to evaluate infants with congenital diaphragmatic hernia (CDH) that do not undergo repair, (ii) to identify nonrepair rate by institution, and (iii) to compare institutional outcomes based on nonrepair rate.

Background:

Approximately 20% of infants with CDH go unrepaired and the threshold to offer surgical repair is variable.

Methods:

Data were abstracted from a multicenter, prospectively collected database. Standard clinical variables, including repair (or nonrepair), and outcome were analyzed. Institutions were grouped based on volume and rate of nonrepair. Preoperative mortality predictors were identified using logistic regression, expected mortality for each center was calculated, and observed /expected (O/E) ratios were computed for center groups and compared by Kruskal-Wallis ANOVA.

Results:

A total of 3965 infants with CDH were identified and 691 infants (17.5%) were not repaired. Nonrepaired patients had lower Apgar scores (P < 0.05) and increased incidence of anomalies (P < 0.0001). Low-volume centers (“Lo”, n=44 total, < 10 CDH pts/yr) and high-volume centers (“Hi”, n = 21) had median nonrepair rates of 19.8% (range 0%–66.7%) and 16.7% (5.1%–38.5%), respectively. High-volume centers were further dichotomized by rate of nonrepair (HiLo = 5.1–16.7% and HiHi = 17.6–38.5%), leaving 3 groups: HiLo, HiHi, and Lo. Predictors of mortality were lower birth weight, lower Apgar scores, prenatal diagnosis, and presence of congenital anomalies. O/E ratios for mortality in the HiLo, HiHi, and Lo groups were 0.81, 0.94, and 1.21, respectively (P < 0.0001). For every 100 CDH patients, HiLo centers have 2.73 (2.4–3.1, 95% confidence interval) survivors beyond expectation.

Conclusions:

There are significant differences between repaired and nonrepaired CDH infants and significant center variation in rate of nonrepair exists. Aggressive surgical management, leading to a low rate of nonrepair, is associated with improved risk-adjusted mortality.
Modulating Portal Hemodynamics With Vascular Ring Allows Efficient Regeneration After Partial Hepatectomy in a Porcine Model
Authors: Bucur Petru O. , Bekheit Mohamed , Audebert Chloe , Othman Amnah , Hammad Seddik , Sebagh Mylene , Allard Marc-Antoine , Decante Benoît , Friebel Adrian , Miquelestorena-Standley Elodie , Drasdo Dirk , Hengstler Jan G. , Vignon-Clementel Irene E. , Vibert Eric
Published: February 2017

Objective:

To investigate safety and efficacy of temporary portal hemodynamics modulation with a novel percutaneously adjustable vascular ring (MID-AVR) onto a porcine model of 75% hepatectomy.

Background:

Postoperative liver failure is a leading cause of mortality after major hepatectomy. Portal flow modulation is an increasingly accepted concept to prevent postoperative liver failure. Nonetheless, the current strategies have shortcomings.

Methods:

Resection was performed under hemodynamic monitoring in 17 large, white pigs allocated into 2 groups. Eight pigs had ring around the portal vein for 3 days with the aim of reducing changes in hemodynamics due to hepatectomy. Analysis of hemodynamics, laboratory, and histopathological parameters was performed.

Results:

Percutaneous inflation, deflation, and removal of the MID-AVR were safe. Two (25%) pigs in the MID-AVR group and 4 (45%) controls died before day 3 (P = NS). A moderate increase of portal flow rate per liver mass after resection was associated with better survival (P = 0.017). The portocaval pressure gradient was lower after hepatectomy in the MID-AVR group (P = 0.001). Postoperative serum bilirubin levels were lower in the MID-AVR group (P = 0.007 at day 5). In the MID-AVR group, the Ki67 index was significantly higher on day 3 (P = 0.043) and the architectural derangement was lower (P < 0.05). Morphometric quantification of the bile canaliculi revealed a significantly lower number of intersection branches (P < 0.05) and intersection nodes (P < 0.001) on day 7 compared with the preoperative specimen, in the control group. These differences were not found in the ring group.

Conclusions:

MID-AVR is safe for portal hemodynamics modulation. It might improve liver regeneration by protecting liver microarchitecture.
Survival Outcomes for Patients With Indeterminate 18FDG-PET Scan for Extrahepatic Disease Before Liver Resection for Metastatic Colorectal Cancer
Authors: Wong Geoffrey Yuet Mun , Kumar Rajiv , Beeke Carol , Ullah Shahid , Chen John , Karapetis Christos , Price Timothy , Padbury Rob
Published: February 2017

Objective:

The aim of this study was to evaluate overall survival (OS) and cancer recurrence for patients with indeterminate positron emission tomography (PET) scan for extrahepatic disease (EHD) before liver resection (LR) for colorectal liver metastases (CLMs).

Summary of Background Data:

Indeterminate EHD as determined by PET imaging indicates a probability of extrahepatic malignancy and potentially excludes patients from undergoing LR for CLM.

Methods:

In a retrospective analysis of prospectively collected data from February 2006 to December 2014, OS for patients with indeterminate EHD on 18FDG-PET scan before LR for CLM was performed using standard survival analysis methods, including Kaplan-Meier estimator and Cox proportional hazard models for multivariate analyses. Postoperative imaging was used as reference to evaluate the association between indeterminate EHD and recurrence.

Results:

Of 267 patients with PET scans before LR, 197 patients had no EHD and 70 patients had indeterminate EHD. Median follow-up was 33 months. The estimated 5-year OS was 60.8% versus 59.4% for indeterminate and absent EHD, respectively (P = 0.625). Disease-free survival was comparable between both groups (P = 0.975) and overall recurrence was 57.1% and 59.5% for indeterminate and absent EHD, respectively (P = 0.742). About 16.9% of recurrence was associated with the site of indeterminate EHD, with 80% of associated recurrence occurring in the thorax.

Conclusions:

The site of indeterminate EHD appears to have a predictive value for recurrence, with indeterminate EHD in the thorax having a higher probability of malignancy. The evidence in this report supports the critical evaluation of PET scan results and that patients are not denied potential curative LR unless the evidence for unresectable EHD is certain.
Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors
Authors: Locke Jayme E. , Sawinski Deirdre , Reed Rhiannon D. , Shelton Brittany , MacLennan Paul A. , Kumar Vineeta , Mehta Shikha , Mannon Roslyn B. , Gaston Robert , Julian Bruce A. , Carr John J. , Terry James G. , Kilgore Meredith , Massie Allan B. , Segev Dorry L. , Lewis Cora E.
Published: February 2017

Objective:

The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors.

Summary of Background Data:

Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs).

Methods:

We identified a cohort of young adults (18–30 years) with no absolute contraindication to kidney donation from the longitudinal cohort study Coronary Artery Risk Development in Young Adults. Risk associations for CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) were identified and assigned weighted points to calculate risk scores.

Results:

A total of 3438 healthy adults were identified [mean age 24.8 years; 48.3% AA; median follow-up 24.9 years (interquartile range: 24.5–25.2)]. For 18-year olds, 25-year projected CKD risk varied by ethnicity and sex even without baseline clinical and genetic abnormalities; risk was 0.30% for European American (EA) women, 0.52% for EA men, 0.52% for AA women, 0.90% for AA men. Among 18-year-old AAs with apolipoprotein L1 gene (APOL1) renal-risk variants without baseline abnormalities, 25-year risk significantly increased: 1.46% for women and 2.53% for men; among those with 2 APOL1 renal-risk variants and baseline abnormalities, 25-year risk was higher: 2.53% to 6.23% for women and 4.35% to 10.58% for men.

Conclusions:

Young AAs were at highest risk for CKD, and APOL1 renal-risk variants drove some of this risk. Understanding the genetic profile of young AA potential living kidney donors in the context of baseline health characteristics may help to inform candidate selection and counseling.
En Bloc Cadaver Kidney Transplantation From a 9-Month-Old Donor to an Adult Recipient: Maturation of Glomerular Size and Podocyte in the Recipient
Authors: Hirukawa Takashi , Suzuki Hajime , Niimura Fumio , Fukagawa Masafumi , Kakuta Takatoshi
Published: February 2017

Background

Favorable outcomes of en bloc pediatric donor kidney transplantation to adult recipients are attributed primarily to grafting of twice the nephron mass of a single kidney.

Methods

The kidneys of a 9-month-old male infant were transplanted en bloc in a 56-year-old man. Biopsies were performed 1 hour postreperfusion, 6 months and 3.5 years posttransplant.

Results

Warm and cold ischemia times were 21 and 426 minutes, respectively. The recipient was released from hemodialysis 10 days posttransplant and discharged 91 days posttransplant when serum creatinine was 0.9 mg/dL. At 4 years and 9 months posttransplant, serum creatinine was 1.0 mg/dL, and estimated glomerular filtration rate was 58.0 mL/min per 1.73 m2. The grafts increased in size until they reached adult size by 3 months posttransplant. The glomerular area and volume, respectively, increased from 5.9 × 103 μm2 and 0.34 × 106 μm3 at 1 hour postreperfusion to 14.9 × 103 μm2 and 1.27 × 106 μm3 at 3.5 years posttransplant, both of which were less than half of adult size. At 1 hour postreperfusion, podocytes were structurally immature. At 6 months posttransplant, podocyte immaturity was still evident. At 3.5 years posttransplant, podocytes were mature.

Conclusions

These findings suggest that podocytes and glomerular size of pediatric donor kidneys can continue to mature in adult recipients at rates appropriate for donor age when transplanted en bloc. The maturational levels of podocytes and glomeruli may also be a factor involved in favorable outcomes of en bloc pediatric donor kidney transplantation.
Acute Rejection Phenotypes in the Current Era of Immunosuppression: A Single-Center Analysis
Authors: Wehmeier Caroline , Amico Patrizia , Hirt-Minkowski Patricia , Georgalis Argyrios , Höenger Gideon , Menter Thomas , Mihatsch Michael , Burkhalter Felix , Steiger Juerg , Dickenmann Michael , Hopfer Helmut , Schaub Stefan
Published: February 2017

Background

Besides ‘definitive rejection’, the Banff classification includes categories for ‘suspicious for rejection’ phenotypes. The aim of this study was to determine the frequency and phenotypes of rejection episodes in 316 consecutive renal transplants from 2009 to 2014 grouped into patients without/with pretransplant HLA-DSA (ptDSAneg, n = 251; ptDSApos, n = 65).

Methods

All adequate indication (n = 125) and surveillance biopsies (n = 538) performed within the first year posttransplant were classified according to the current Banff criteria.

Results

‘Suspicious for rejection’ phenotypes were 3 times more common than ‘definitive rejection’ phenotypes in biopsies from ptDSAneg patients (35% vs 11%) and equally common in biopsies from ptDSApos patients (25% vs 27%). In both groups, ‘suspicious for rejection’ phenotypes were more frequent in surveillance than in indication biopsies (28% vs 16% in ptDSAneg patients, and 37% vs 29% in ptDSApos patients). ‘Borderline changes: ‘Suspicious' for acute T-cell mediated rejection’ (91%) were the dominant ‘suspicious for rejection’ phenotype in ptDSAneg patients, whereas ‘borderline changes’ (58%) and ‘suspicious for acute/active antibody-mediated rejection’ (42%) were equally frequent in biopsies from ptDSApos patients. Inclusion of ‘suspicious for rejection’ phenotypes increased the 1-year incidence of clinical (ptDSAneg patients: 18% vs 8%, P = 0.0005; ptDSApos patients: 24% vs 18%, P = 0.31) and (sub)clinical rejection (ptDSAneg patients: 59% vs 22%, P < 0.0001; ptDSApos patients: 68% vs 40%, P = 0.004).

Conclusions

‘Suspicious for rejection’ phenotypes are very common in the current era and outnumber the frequency of ‘definitive rejection’ within the first year posttransplant.
Tumoral Presentation of Homonymous Hemianopia and Prosopagnosia in Cerebral Amyloid Angiopathy–Related Inflammation
Authors: Hainline Clotilde , Rucker Janet C. , Zagzag David , Golfinos John G. , Lui Yvonne W. , Liechty Benjamin , Warren Floyd A. , Balcer Laura J. , Galetta Steven L.
Published: February 2017

While cerebral amyloid angiopathy is a common cause of lobar hemorrhage, rarely it may be associated with an inflammatory response, thought to be incited by amyloid deposits. We report a 73-year-old woman with an extensive cancer history who presented with tumor-like lesions and symptoms of homonymous hemianopia and prosopagnosia. Found to have cerebral amyloid angiopathy–related inflammation proven by brain biopsy, she was treated successfully with immunosuppression.
A target-specific assay for rapid and quantitative detection of Mycobacterium chimaera DNA in environmental and clinical specimens
Authors: Zozaya-Valdés Enrique , Porter Jessica L. , Coventry John , Fyfe Janet A. M. , Carter Glen P. , Gonçalves da Silva Anders , Seemann Torsten , Johnson Paul D. R. , Stewardson Andrew James , Bastian Ivan , Roberts Sally A. , Howden Benjamin P. , Williamson Deborah A. , Stinear Timothy P.
Published: February 2017

Mycobacterium chimaerais an opportunistic environmental mycobacterium, belonging to theMycobacterium intracellularecomplex. Although most commonly associated with pulmonary disease, there has been growing awareness of invasiveM. chimaerainfections following cardiac surgery. Investigations suggest world-wide spread of a specificM. chimaeraclone, associated with contaminated hospital heater-cooler units used during the surgery. Given the global dissemination of this clone, its potential to cause invasive disease, and the laboriousness of current culture-based diagnostic methods, there is a pressing need to develop rapid and accurate diagnostic assays, specific forM. chimaera. Here, we assessed 354 mycobacterial genome sequences and confirmed thatM. chimaerais a phylogenetically coherent group.In silicocomparisons indicated six DNA regions present only inM. chimaera. We targeted one of these regions and developed a TaqMan qPCR assay forM. chimaerawith a detection limit of 10 CFU in whole blood.In vitroscreening against DNA extracted from 40 other mycobacteria and 22 bacterial species from 21 diverse genera confirmedin silicopredicted specificity forM. chimaera. Screening 33 water samples from heater cooler units with this assay highlighted the increased sensitivity of PCR compared to culture, with 15 of 23 culture negative samples positive byM. chimaeraqPCR. We have thus developed a robust molecular assay that can be readily and rapidly deployed to screen clinical and environmental specimens forM. chimaera.
The Social Genome of Friends and Schoolmates in the National Longitudinal Study of Adolescent to Adult Health
Authors: Domingue Benjamin W. , Belsky Daniel W. , Fletcher Jason M. , Conley Dalton , Boardman Jason D. , Harris Kathleen Mullan
Published: February 2017

Humans tend to form social relationships with others who resemble them. Whether this sorting of like with like arises from historical patterns of migration, meso-level social structures in modern society, or individual-level selection of similar peers remains unsettled. Recent research has evaluated the possibility that unobserved genotypes may play an important role in the creation of homophilous relationships. We extend this work by using data from 9,500 adolescents from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine genetic similarities among pairs of friends. While there is some evidence that friends have correlated genotypes, both at the whole-genome level as well as at trait-associated loci (via polygenic scores), further analysis suggests that meso-level forces, such as school assignment, are a principal source of genetic similarity between friends. We also observe apparent social-genetic effects in which polygenic scores of an individual’s friends and schoolmates predict the individual’s own educational attainment. In contrast, an individual’s height is unassociated with the height genetics of peers.

Significance

Our study reported significant findings of a “social genome” that can be quantified and studied to understand human health and behavior. In a national sample of more than 9,000 American adolescents, we found evidence of social forces that act to make friends and schoolmates more genetically similar to one another as compared to random pairs of unrelated individuals. This subtle genetic similarity was observed across the entire genome and at sets of genomic locations linked with specific traits—educational attainment and body-mass index—a phenomenon we term “social-genetic correlation.” We also find evidence of a “social-genetic effect” such that the genetics of a person’s friends and schoolmates influenced their own education, even after accounting for the person’s own genetics.
Pairwise comparisons across species are problematic when analyzing functional genomic data
Authors: Dunn Casey W. , Zapata Felipe , Munro Catriona , Siebert Stefan , Hejnol Andreas
Published: February 2017

There is considerable interest in comparing functional genomic data across species. One goal of such work is to provide an integrated understanding of genome and phenotype evolution. Most comparative functional genomic studies have relied on multiple pairwise comparisons between species, an approach that does not incorporate information about the evolutionary relationships among species. The statistical problems that arise from not considering these relationships can lead pairwise approaches to the wrong conclusions, and are a missed opportunity to learn about biology that can only be understood in an explicit phylogenetic context. Here we examine two recently published studies that compare gene expression across species with pairwise methods, and find reason to question the original conclusions of both. One study interpreted pairwise comparisons of gene expression as support for the ortholog conjecture, the hypothesis that orthologs tend to be more similar than paralogs. The other study interpreted pairwise comparisons of embryonic gene expression across distantly related animals as evidence for a distinct evolutionary process that gave rise to phyla. In each study, distinct patterns of pairwise similarity among species were originally interpreted as evidence of particular evolutionary processes, but instead we find they reflect species relationships. These reanalyses concretely demonstrate the inadequacy of pairwise comparisons for analyzing functional genomic data across species. It will be critical to adopt phylogenetic comparative methods in future functional genomic work. Fortunately, phylogenetic comparative biology is also a rapidly advancing field with many methods that can be directly applied to functional genomic data.

Significance

Comparisons of genome function between species are providing important insight into the evolutionary origins of diversity. Here we demonstrate that comparative functional genomics studies can come to the wrong conclusions if they do not take the relationships of species into account and instead rely on pairwise comparisons between species, as is common practice. We re-examined two previously published studies and found problems with pairwise comparisons that draw both their original conclusions into question. One study had found support for the ortholog conjecture and the other had concluded that the evolution of gene expression was different between animal phyla than within them. Our results demonstrate that to answer evolutionary questions about genome function, it is critical to consider evolutionary relationships.
A scalable method for parameter-free simulation and validation of mechanistic cellular signal transduction network models
Authors: Romers Jesper , Thieme Sebastian , Münzner Ulrike , Krantz Marcus
Published: February 2017

The metabolic modelling community has established the gold standard for bottom-up systems biology with reconstruction, validation and simulation of mechanistic genome-scale models. Similar methods have not been established for signal transduction networks, where the representation of internal states leads to scalability issues in both model formulation and execution. While rule- and agent-based methods allow efficient model definition and execution, respectively, model parametrisation introduces an additional layer of uncertainty due to the sparsity of reliably measured parameters. Here, we present a scalable method for parameter-free simulation of mechanistic signal transduction networks. It is based on rxncon and uses a bipartite Boolean logic with separate update rules for reactions and states. Using two generic update rules, we enable translation of any rxncon model into a unique Boolean model, which can be used for network validation and simulation - allowing the prediction of system level function directly from molecular mechanistic data. Through scalable model definition and simulation, and the independence of quantitative parameters, it opens up for simulation and validation of mechanistic genome-scale models of signal transduction networks.
PhyD3: a phylogenetic tree viewer with extended phyloXML support for functional genomics data visualization
Authors: Kreft Łukasz , Botzki Alexander , Coppens Frederik , Vandepoele Klaas , Van Bel Michiel
Published: February 2017

Motivation:

Comparative and evolutionary studies utilise phylogenetic trees to analyse and visualise biological data. Recently, several web-based tools for the display, manipulation, and annotation of phylogenetic trees, such as iTOL and Evolview, have released updates to be compatible with the latest web technologies. While those web tools operate an open server access model with a multitude of registered users, a feature-rich open source solution using current web technologies is not available.

Results:

Here, we present an extension of the widely used PhyloXML standard with several new options to accommodate functional genomics or annotation datasets for advanced visualization. Furthermore, PhyD3 has been developed as a lightweight tool using the JavaScript library D3.js to achieve a state-of-the-art phylogenetic tree visualisation in the web browser, with support for advanced annotations. The current implementation is open source, easily adaptable and easy to implement in third parties’ web sites.

Availability:

More information about PhyD3 itself, installation procedures, and implementation links are available athttp://phyd3.bits.vib.beand athttp://github.com/vibbits/phyd3/.

Contact:

bits@vib.be
Thermal expansion of deuterated monoclinic natrojarosite; a combined neutron–synchrotron powder diffraction study
Authors: Brand Helen E. A. , Scarlett Nicola V. Y. , Knight Kevin S.
Published: February 2017

A combination of time-of-flight neutron diffraction and synchrotron X-ray powder diffraction has been used to investigate the thermal expansion of a synthetic deuterated natrojarosite from 80 to 440 K under ambient-pressure conditions. The variation in unit-cell volume for monoclinic jarosite over this temperature range can be well represented by an Einstein expression of the form V = 515.308 (5) + 8.5 (4)/{exp[319 (4)/T] − 1}. Analysis of the behaviour of the polyhedra and hydrogen-bond network suggests that the strength of the hydrogen bonds connected to the sulfate tetrahedra is instrumental in determining the expansion of the structure, which manifests primarily in the c-axis direction.
Organisational change towards servitization: a theoretical framework
Authors: Ziaee Bigdeli Ali , Baines Tim , Bustinza Oscar F. , Guang Shi Victor
Published: February 2017

Purpose

The need for a holistic framework for studying organisational transformation towards Servitization is implicit. This is particularly relevant as Servitization demands consideration of both business model and organisational change. The purpose of this paper is, therefore, to provide an integrative framework that systematically captures and evaluate existing literature on Servitization.

Design/methodology/approach

The aim of the paper has been achieved through three main objectives; comprehensively examine the literature in organisational change management that would assist with the selection of the most effective evaluation framework, classify previous studies against the proposed framework through a systematic literature review methodology and analyse the selected papers and propose research questions/propositions based on the identified gaps.

Findings

Results indicate that there are two somewhat macro opportunities for the Servitization community, namely, stronger infusion of generic theory into the Servitization debate and exploring Servitization in action through the lens of the theoretical framework.

Practical implications

The findings of the paper demonstrate the gaps in the Servitization literature, which indeed require further theoretical/empirical research.

Originality/value

It is discussed the usefulness and practicality of viewing research contributions that are setting out to be either “descriptive” or “prescriptive”. Consequently, the authors have proposed several avenues for future research based on these two viewpoints.
Numerical study of nanofluid flow and heat transfer over a rotating disk using Buongiorno’s model
Authors: Khan Junaid Ahmad , Mustafa M. , Hayat T. , Turkyilmazoglu Mustafa , Alsaedi A.
Published: February 2017

Purpose

The purpose of the present study is to explore a three-dimensional rotating flow of water-based nanofluids caused by an infinite rotating disk.

Design/methodology/approach

Mathematical formulation is performed using the well-known Buongiorno model which accounts for the combined influence of Brownian motion and thermophoresis. The recently suggested condition of passively controlled wall nanoparticle volume fraction has been adopted.

Findings

The results reveal that temperature decreases with an increase in thermophoresis parameter, whereas it is negligibly affected with a variation in the Brownian motion parameter. Axial velocity is negative because of the downward flow in the vertical direction.

Originality/value

Two- and three-dimensional streamlines are also sketched and discussed. The computations are found to be in very good agreement with the those of existing studies in the literature for pure fluid.
Unsteady mixed convection stagnation-point flow over a plate moving along the direction of flow impingement
Authors: Muhad Saleh Siti Hidayah , Md. Arifin Norihan , Nazar Roslinda , Pop Ioan
Published: February 2017

Purpose

The purpose of this paper is to present the results of an analysis performed to study unsteady mixed convection at the stagnation point flow over a plate moving along the direction of flow impingement. The similarity transformations are used to transform the governing nonlinear partial differential equation to a system of an ordinary differential equation.

Design/methodology/approach

The transformed equations are then solved numerically by a shooting technique together with bvp4c function.

Findings

The numerical results are compared with the corresponding results from previous researchers. The effects of the unsteadiness Parameter A, Prandtl number Pr, mixed convection parameter λ for plane (m = 0) and axisymmetric (m = 1) flow on the shear stress or the skin friction and heat transfer coefficients, as well as the velocity and temperature profiles, are presented and discussed.

Originality/value

Dual solutions for the opposing flow and multiple solutions for the assisting flow are found.
Heat and mass transfer analysis in natural convection flow of nanofluid over a vertical cone with chemical reaction
Authors: Reddy P. Sudarsana , Chamkha A.
Published: February 2017

Purpose

In recent years, nanofluids are being widely used in many thermal systems because of their higher thermal conductivity and heat transfer rate. The higher thermal conductivity depends on many parameters such as size, shape and volume and the Brownian motion and thermophoresis of added nanoparticles. The purpose of this paper is to analyze the influence of the Brownian motion and thermophoresis on natural convection heat and mass transfer boundary layer flow of nanofluids over a vertical cone with radiation.

Design/methodology/approach

Using similarity variables, the non-linear partial differential equations, which represent momentum, energy and diffusion, are transformed into ordinary differential equations. The transformed conservation equations are solved numerically subject to the boundary conditions by using versatile, extensively validated, variational finite-element method.

Findings

The sway of significant parameters such as magnetic field (M), buoyancy ratio parameter (Nr), Brownian motion parameter (Nb), thermophoresis parameter (Nt), thermal radiation (R), Lewis number (Le) and chemical reaction parameter (Cr) on velocity, temperature and concentration evaluation in the boundary layer region is examined in detail. The results are compared with previously published work and are found to be in agreement. The velocity distributions are reduced, while temperature and concentration profiles elevate with a higher (M). With the improving values of (R), the velocity and temperature sketches improve, while concentration distributions are lowered in the boundary layer region. The temperature and concentration profiles are elevated in the boundary layer region for higher values of (Nt). With the increasing values of (Nb), temperature profiles are enhanced, whereas concentration profiles get depreciated in the flow region.

Social implications

In recent years, it has been found that magneto-nanofluids are significant in many areas of science and technology. It has applications in optical modulators, magnetooptical wavelength filters, tunable optical fiber filters and optical switches. Magnetic nanoparticles are especially useful in biomedicine, sink float separation, cancer therapy, etc. Specific biomedical applications involving nanofluids include hyperthermia, magnetic cell separation, drug delivery and contrast enhancement in magnetic resonance imaging.

Originality/value

To the best of the authors’ knowledge, no studies have assessed the impact of the two slip effects, namely, Brownian motion and thermophoresis, on the natural convection of electrically conducted heat and mass transfer to the nanofluid boundary layer flow over a vertical cone in the presence of radiation and chemical reaction; therefore, this problem has been addressed in this study. Comparison of the results of this study’s with those of previously published work was found to be in good agreement.
Environmental literacy of business students in Ghana
Authors: Owusu Godfred Matthew Yaw , Ossei Kwakye Teddy , Welbeck Edem Emerald , Ofori Charles Gyamfi
Published: February 2017

Purpose

This study examines the multidimensionality of the environmental literacy concept among university business students in Ghana. The study also investigates the relationship between students’ interests in environmental issues and knowledge levels of environment and assesses how these two constructs influence students overall environmental behaviour and actions.

Design/methodology/approach

Using a total of 591 business students from the University of Ghana Business School, the study uses exploratory factor analysis to examine the multidimensionality of environmental literacy concept. A structural equation modelling-based approach was used to examine the relationship among the study constructs.

Findings

Based on the factor analysis results, the study documents that environmental literacy concept can be grouped under four distinct factors (general environmental factors; industry-related factors; environmental assessment factors; and accounting-related factors). The regression results indicate a direct and positive relationship between students’ interest in environmental issues and their environmental literacy level. Also, students’ interest and their knowledge levels of environmental issues were found to be good predictors of actual students’ involvement in activities that promote sustainable environment.

Research limitations/implications

The conclusions of the study are based on only data from one public university, which limits the generalizability of the findings.

Originality/value

The study is unique as it is the first empirical study to investigate environmental literacy levels in higher education in the Ghanaian setting.