bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and application of a livestock phenomics platform to enhance productivity and efficiency at pasture
Authors: Greenwood Paul L. , Bishop-Hurley Gregory J. , González Luciano A. , Ingham Aaron B.
Published: March 2016

Our capacity to measure performance- and efficiency-related phenotypes in grazing livestock in a timely manner, ideally in real-time without human interference, has been severely limited. Future demands and constraints on grazing livestock production will require a step change beyond our current approaches to obtaining phenotypic data. Animal phenomics is a relatively new term that describes the next generation of animal trait measurement, including methodologies and equipment used to acquire data on traits, and computational approaches required to turn data into phenotypic information. Phenomics offers a range of emerging opportunities to define new traits specific to grazing livestock, including intake and efficiency at pasture, and to measure many traits simultaneously or at a level of detail previously unachievable in the grazing environment. Application of this approach to phenotyping can improve the precision with which nutritional and other management strategies are applied, enable development of predictive biological traits, and accelerate the rate at which genetic gain is achieved for existing and new traits. In the present paper, we briefly outline the potential for livestock phenomics and describe (1) on-animal sensory-based approaches to develop traits diagnostic of productivity and efficiency, as well as resilience, health and welfare and (2) on-farm methods for data collection that drive management solutions to reduce input costs and accelerate genetic gain. The technological and analytical challenges associated with these objectives are also briefly considered, along with a brief overview of a promising field of work in which phenomics will affect animal agriculture, namely efficiency at pasture.
Practical Isolation of Asperuloside from Coprosma quadrifida via Rapid Pressurised Hot Water Extraction
Authors: Deans Bianca J. , Bissember Alex C. , Smith Jason A.
Published: March 2016

The valuable glycoside asperuloside was efficiently isolated in multigram quantities from Coprosma quadrifida employing a recently developed rapid pressurised hot water extraction (PHWE) method that utilises an unmodified household espresso machine. This study represents the first time C. quadrifida has been extracted and its major chemical components isolated and analysed. Our findings reveal that this species is a rich source of asperuloside (7.0 % yield w/w). Significantly, this represents one of the highest yields obtained of this glycoside from a Coprosma species, and the entire Rubiaceae family more generally.
An assessment of ‘turtle-friendly' lights on the sea-finding behaviour of loggerhead turtle hatchlings (Caretta caretta)
Authors: Robertson Katharine , Booth David T. , Limpus Colin J.
Published: March 2016

Context It is well established that artificial light can disrupt the sea-finding ability of sea turtle hatchlings, and some manufactures are now marketing ‘turtle-friendly’ lights that are supposed to be minimally disruptive to this sea-finding behaviour. However, there have been no studies that have tested whether ‘turtle-friendly’ lights are benign to hatchling sea turtle sea-finding ability. Aims We tested two different types of ‘turtle-friendly’ lights (LED amber-light peak intensity 620 nm and LED red-light peak intensity 640 nm) to see whether they are disruptive to the sea-finding ability of eastern-coast Australian loggerhead turtle hatchlings. Methods Using standard circular-arena experiments, we assessed the directional preference of newly emerged loggerhead turtle hatchlings from the Woongarra Coast of Queensland, Australia, during different moon phases without artificial lighting and in the presence of ‘turtle-friendly’ lights. Key results Contrary to expectations, sea-finding ability of hatchlings was disrupted by the amber lights, particularly in the absence of a moon. The less intense red lights were less disruptive to hatchlings; however, misorientation and disorientation events still occurred when lights were within 4 m of hatchlings. The disruptive impact on sea-finding ability increased with the cumulative impact of multiple lights increasing light intensity. Conclusions The ‘turtle-friendly’ lights we used disrupted the sea-finding ability of eastern-coast Australian loggerhead turtle hatchlings, with the most pronounced disruption occurring under moonless conditions. Implications The use of amber and red LED lights adjacent to the nesting beaches of loggerhead sea turtles should be managed because this lighting has the potential to disrupt the sea-finding ability of sea turtle hatchlings.
Identification of three LRR-RKs involved in perception of root meristem growth factor in
Arabidopsis
Authors: Shinohara Hidefumi , Mori Ayaka , Yasue Naoko , Sumida Kumiko , Matsubayashi Yoshikatsu
Published: March 2016

Significance

There is a growing awareness that receptor kinases (RKs) regulate various aspects of plant development in response to perception of specific ligands, but the highly redundant nature of this family's members often makes it difficult to identify their ligands by a conventional mutant screening approach. To sidestep gene redundancy problems, here we used a combination of a custom-made RK expression library and exhaustive photoaffinity labeling and identified three RKs that directly interact with root meristem growth factor (RGF), a peptide hormone regulating root meristem development. The receptor triple mutant was insensitive to externally applied RGF peptide and displayed a short root phenotype accompanied by a considerable decrease in meristematic cell number, representing a previously unidentified ligand–receptor system in plants.
XIBD: software for inferring pairwise identity by descent on the X chromosome
Authors: Henden Lyndal , Wakeham David , Bahlo Melanie
Published: March 2016

Summary: XIBD performs pairwise relatedness mapping on the X chromosome using dense single nucleotide polymorphism (SNP) data from either SNP chips or next generation sequencing data. It correctly accounts for the difference in chromosomal numbers between males and females and estimates global relatedness as well as regions of the genome that are identical by descent (IBD). XIBD also generates novel graphical summaries of all pairwise IBD tracts for a cohort making it very useful for disease locus mapping.

Availability and implementation: XIBD is written in R/Rcpp and executed from shell scripts that are freely available from http://bioinf.wehi.edu.au/software/XIBD along with accompanying reference datasets.

Contact:  henden.l@wehi.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
jSplice: a high-performance method for accurate prediction of alternative splicing events and its application to large-scale renal cancer transcriptome data
Authors: Christinat Yann , Pawłowski Rafał , Krek Wilhelm
Published: March 2016

Motivation: Alternative splicing represents a prime mechanism of post-transcriptional gene regulation whose misregulation is associated with a broad range of human diseases. Despite the vast availability of transcriptome data from different cell types and diseases, bioinformatics-based surveys of alternative splicing patterns remain a major challenge due to limited availability of analytical tools that combine high accuracy and rapidity.

Results: We describe here a novel junction-centric method, jSplice, that enables de novo extraction of alternative splicing events from RNA-sequencing data with high accuracy, reliability and speed. Application to clear cell renal carcinoma (ccRCC) cell lines and 65 ccRCC patients revealed experimentally validatable alternative splicing changes and signatures able to prognosticate ccRCC outcome. In the aggregate, our results propose jSplice as a key analytic tool for the derivation of cell context-dependent alternative splicing patterns from large-scale RNA-sequencing datasets.

Availability and implementation: jSplice is a standalone Python application freely available at http://www.mhs.biol.ethz.ch/research/krek/jsplice.

Contact:  wilhelm.krek@biol.ethz.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
MOLGENIS/connect: a system for semi-automatic integration of heterogeneous phenotype data with applications in biobanks
Authors: Pang Chao , van Enckevort David , de Haan Mark , Kelpin Fleur , Jetten Jonathan , Hendriksen Dennis , de Boer Tommy , Charbon Bart , Winder Erwin , van der Velde K. Joeri , Doiron Dany , Fortier Isabel , Hillege Hans , Swertz Morris A.
Published: March 2016

Motivation: While the size and number of biobanks, patient registries and other data collections are increasing, biomedical researchers still often need to pool data for statistical power, a task that requires time-intensive retrospective integration.

Results: To address this challenge, we developed MOLGENIS/connect, a semi-automatic system to find, match and pool data from different sources. The system shortlists relevant source attributes from thousands of candidates using ontology-based query expansion to overcome variations in terminology. Then it generates algorithms that transform source attributes to a common target DataSchema. These include unit conversion, categorical value matching and complex conversion patterns (e.g. calculation of BMI). In comparison to human-experts, MOLGENIS/connect was able to auto-generate 27% of the algorithms perfectly, with an additional 46% needing only minor editing, representing a reduction in the human effort and expertise needed to pool data.

Availability and Implementation: Source code, binaries and documentation are available as open-source under LGPLv3 from http://github.com/molgenis/molgenis and www.molgenis.org/connect.

Contact: m.a.swertz@rug.nl

Supplementary information:  Supplementary data are available at Bioinformatics online.
Opportunistically recorded acoustic data support Northeast Atlantic mackerel expansion theory
Authors: van der Kooij Jeroen , Fässler Sascha M.M. , Stephens David , Readdy Lisa , Scott Beth E. , Roel Beatriz A.
Published: March 2016

Fisheries independent monitoring of widely distributed pelagic fish species which conduct large seasonal migrations is logistically complex and expensive. One of the commercially most important examples of such a species in the Northeast Atlantic Ocean is mackerel for which up to recently only an international triennial egg survey contributed to the stock assessment. In this study, we explore whether fisheries acoustic data, recorded opportunistically during the English component of the North Sea International Bottom Trawl Survey, can contribute to an improved understanding of mackerel distribution and provide supplementary data to existing dedicated monitoring surveys. Using a previously published multifrequency acoustic mackerel detection algorithm, we extracted the distribution and abundance of schooling mackerel for the whole of the North Sea during August and September between 2007 and 2013. The spatio-temporal coverage of this unique dataset is of particular interest because it includes part of the unsurveyed summer mackerel feeding grounds in the northern North Sea. Recent increases in landings in Icelandic waters during this season suggested that changes have occurred in the mackerel feeding distribution. Thus far it is poorly understood whether these changes are due to a shift, i.e. mackerel moving away from their traditional feeding grounds in the northern North Sea and southern Norwegian Sea, or whether the species' distribution has expanded. We therefore explored whether acoustically derived biomass of schooling mackerel declined in the northern North Sea during the study period, which would suggest a shift in mackerel distribution rather than an expansion. The results of this study show that in the North Sea, schooling mackerel abundance has increased and that its distribution in this area has not changed over this period. Both of these findings provide, to our knowledge, the first evidence in support of the hypothesis that mackerel have expanded their distribution rather than moved away.
Risks and Benefits of Stress Ulcer Prophylaxis for Patients With Severe Sepsis*
Authors: Sasabuchi Yusuke , Matsui Hiroki , Lefor Alan K. , Fushimi Kiyohide , Yasunaga Hideo
Published: March 2016

Objectives:

The Surviving Sepsis Campaign Guidelines recommend stress ulcer prophylaxis for patients with severe sepsis who have bleeding risks. Although sepsis has been considered as a risk factor for gastrointestinal bleeding, the effect of stress ulcer prophylaxis has not been studied in patients with severe sepsis. Furthermore, stress ulcer prophylaxis may be associated with an increased risk of hospital-acquired pneumonia or Clostridium difficile infection. The aim of this study was to investigate the risks and benefits of stress ulcer prophylaxis for patients with severe sepsis.

Design:

Retrospective cohort study.

Setting:

Five hundred twenty-six acute care hospitals in Japan.

Patients:

A total of 70,862 patients with severe sepsis.

Interventions:

None.

Measurements and Main Results:

One-to-one propensity score matching created 15,651 pairs of patients who received stress ulcer prophylaxis within 2 days of admission and those who did not. Patient characteristics were well balanced between the two groups. No significant differences were seen between the stress ulcer prophylaxis group and the control group with regard to gastrointestinal bleeding requiring endoscopic hemostasis (0.6% vs 0.5%; p = 0.208), 30-day mortality (16.4% vs 16.9%; p = 0.249), and Clostridium difficile infection (1.4% vs 1.3%; p = 0.588). The stress ulcer prophylaxis group had a significantly higher proportion of hospital-acquired pneumonia (3.9% vs 3.3%; p = 0.012) compared with the control group.

Conclusions:

Since the rate of gastrointestinal bleeding requiring endoscopic hemostasis is not different comparing patients with and without stress ulcer prophylaxis, and the increase in hospital-acquired pneumonia is significant, routine stress ulcer prophylaxis for patients with severe sepsis may be unnecessary.
Differential Diagnosis of Immunoglobulin G4-associated Cholangitis From Cholangiocarcinoma
Authors: Du Shunda , Liu Gang , Cheng Xinqi , Li Yue , Wang Qian , Li Ji , Lu Xin , Zheng Yongchang , Xu Haifeng , Chi Tianyi , Zhao Haitao , Xu Yiyao , Sang Xinting , Zhong Shouxian , Mao Yilei
Published: March 2016

Background and Aim:

Immunoglobulin G4-associated cholangitis (IAC) shares many similar symptoms with cholangiocarcinoma (CCA). However, the treatment and the prognosis are substantially different. This study aimed to identify the important markers for the differential diagnosis of these 2 diseases.

Methods:

Thirty IAC patients and 275 CCA patients were reviewed retrospectively for their clinical symptoms, serological tests, and imaging characteristics. Posttreatment responses were also studied.

Results:

IgG4 had 100% specificity for IAC at a cutoff of 6 times the upper normal limit. IAC patients had a significantly higher incidence of weight loss (P=0.025) and a higher level of weight loss (P=0.008) than CCA patients. The positive rates of biological markers CA199, CA242, and CEA in CCA and IAC were 81.5% versus 42.9%, 45.5% versus 4.5%, and 29.2% versus 7.1%, respectively. Levels of these tumor markers in CCA were significantly higher than in IAC (P<0.05). The thickened wall [17/18 (94.4%) vs. 3/10 (30%), P=0.001] and the occupying lesion on the bile duct [1/18 (5.6%) vs. 8/10 (80%), P<0.001] were found to be significantly different in IAC and CCA, respectively, by endoscopic ultrasonography. Autoimmune pancreatitis was the most frequently observed comorbidity of IAC (25/30). All IAC patients respond positively to steroid treatment.

Conclusions:

Increased tumor markers, 6-fold higher levels of serum IgG4, and other organs’ involvement could be the reference factors for a differential diagnosis of IAC and CCA. Endoscopic ultrasonography might be an effective imaging tool for diagnosis, although clinical signs and symptoms of IAC and CCA are similar. Experimental steroid treatment can be useful in the diagnosis for certain difficult cases.
Identification and Fibrosis Staging of Hepatitis C Patients Using the Electronic Medical Record System
Authors: Anand Vijay , Hyun Christian , Khan Qasim M. , Hall Curtis , Hessefort Norbert , Sonnenberg Amnon , Fimmel Claus J.
Published: March 2016

Background and Aims:

The aim of this study was to noninvasively assess the severity of chronic hepatitis C virus (HCV) in large patient populations. It would be helpful if fibrosis scores could be calculated solely on the basis of data contained in the patients’ electronic medical records (EMR). We performed a pilot study to identify all HCV-infected patients in a large health care system, and predict their fibrosis stage on the basis of demographic and laboratory data using common data from their EMR.

Materials and Methods:

HCV-infected patients were identified using the EMR. The liver biopsies of 191 HCV patients were graded using the Ishak and Metavir scoring systems. Demographic and laboratory data were extracted from the EMR and used to calculate the aminotransferase to platelet ratio index, Fib-4, Fibrosis Index, Forns, Göteborg University Cirrhosis Index, Lok Index, and Vira-HepC.

Results:

In total, 869 HCV-infected patients were identified from a population of over 1 million. In the subgroup of patients with liver biopsies, all 7 algorithms were significantly correlated with the fibrosis stage. The degree of correlation was moderate, with correlation coefficients ranging from 0.22 to 0.60. For the detection of advanced fibrosis (Metavir 3 or 4), the areas under the receiver operating characteristic curve ranged from 0.71 to 0.84, with no significant differences between the individual scores. Sensitivities, specificities, and positive and negative predictive values were within the previously reported range. All scores tended to perform better for higher fibrosis stages.

Conclusions:

Our study demonstrates that HCV-infected patients can be identified and their fibrosis staged using commonly available EMR-based algorithms.
Outcomes of Seropositive Patients With Marsh 1 Histology in Clinical Practice
Authors: Singh Prashant , Lauwers Gregory Y. , Garber John J.
Published: March 2016

Goals:

We retrospectively studied all seropositive Marsh 1 patients seen at 2 tertiary care hospitals in the last 15 years to determine their clinical, serological, and histologic outcomes.

Background:

Patients with positive celiac serologies and Marsh 1 histology represent an understudied subgroup of patients, and it is unclear whether they should be advised to adopt a gluten-free diet (GFD).

Study:

Subjects were identified based on positive celiac serologies and Marsh 1 histology while on a full-gluten diet. Clinical presentation and baseline laboratory data were noted. Clinical course, repeat serologies, and histology were determined.

Results:

Of 620 patients with positive celiac serologies and abnormal duodenal histology, we identified 36 (5.8%) with positive tissue transglutaminase and/or antiendomysial antibodies and Marsh 1 lesions who had adequate follow-up. Abdominal pain was the commonest (47.2%) presenting symptom. Twenty-eight patients were advised to adopt GFD, whereas 8 were not. Among patients treated with GFD, 88.9% improved symptomatically and 95% normalized serology. In contrast, among patients who continued to consume gluten, 85.7% remained symptomatic and 80% had persistently positive serologies. Among the 8 patients on normal diet, 5 underwent repeat biopsy, and 4 of them had the same or worse histology, with 3 patients progressing to Marsh 3c. Among the 28 patients on GFD, 5 underwent repeat biopsy and all improved to normal histology.

Conclusions:

Most patients with positive celiac serology and Marsh 1 lesions benefit from GFD and, if not treated, a majority will continue to be symptomatic and remain at risk of progressing to villous atrophy.
Liver Failure in Early Infancy
Authors: Bitar Rana , Thwaites Rosemary , Davison Suzanne , Rajwal Sanjay , McClean Patricia
Published: March 2016

Objective:

Acute liver failure (ALF) in early infancy is rare and challenging to recognize and manage. We aim to describe the presentation and outcome of infants with ALF according to their final aetiology to elucidate features to facilitate early recognition leading to prompt diagnosis and management.

Methods:

All infants presenting within 120 days from birth with liver failure were included in a retrospective review over a 19‐year period. The aetiology, clinical features, presenting investigations, and outcome were collected.

Results:

Seventy‐eight young infants presented with ALF. The aetiology was established in 94% and included metabolic disease (36%), hypoxic‐ischaemic (HI) insult (19%), infection (17%), neonatal haemochromatosis (9%), and infiltrative disease (9%). Infections, infiltrative disease, and acute HI insult usually resulted in higher transaminases and international normalized ratio, whereas neonatal haemochromatosis and tyrosinaemia were characterized by lower or near normal transaminases. Overall jaundice was not visible in 24% of infants at presentation. Forty‐five (58%) infants were alive at discharge from hospital. Survival at 1 year was 53% and survival with native liver 50%. Later deaths occurred in infants with mitochondrial disease. Six infants received a liver transplant and 4 subsequently died from their underlying disease.

Conclusion:

ALF should be considered in any young infant with a coagulopathy as transaminases and/or bilirubin levels can be near normal at presentation. Better intensive care and the judicious use of liver transplantation may have contributed to the improved outcomes for this group compared with previous decades.
Transient Ocular Wavefront Data in Type 1 Diabetes Mellitus
Authors: Blendowske Ralf , Kalb Max
Published: March 2016

Purpose

We report transient ocular wavefront and blood glucose data for one patient with acute type 1 diabetes mellitus after the treatment with insulin has been initiated.

Case Report

The wavefront data for both eyes of a 34-year-old male patient were examined by a Hartmann-Shack wavefront sensor. Refraction data and higher-order aberrations were recorded during 130 days for eyes in natural conditions, without cycloplegia. At the beginning, we sampled data every 3 to 4 days and enlarged the intervals, when values settled. In total, we report 20 measurements and 1 baseline entry. Blood glucose levels were recorded at least six times a day during the complete period. For the equivalent sphere, we recorded a bilateral hyperopic shift of 5 D from −2.75 DS to +2.25 DS, followed by a reverse myopic shift of the same amount. The equivalent sphere peaked about 15 to 18 days after the treatment with insulin had begun. Cylinder values kept remarkably stable. Higher-order aberrations are dominated by the spherical aberration. The Zernike coefficient c
12 for both eyes changed substantially from OD 0.036 μm and OS 0.062 μm to OD 0.24 μm and OS 0.22 μm (5 mm pupil diameter) following the time pattern of the equivalent sphere. About 60 days after they had reached their peak, all refraction values and higher-order aberrations stabilized at their baseline levels. The baseline was defined by records taken 4 years before the treatment with insulin was commenced.

Conclusions

Wavefront aberrometry gives quantitative insights in the transient alteration and recovering of the eye’s optics whilst the therapy of acute type 1 diabetes mellitus is being initiated. The data of this case support the assumption that variations in the crystalline lens, most probably the modification of its refractive gradient index, as a cause for the transient behavior. An explanation is still missing.
Pharmacologic Management of Pressure-Induced Stromal Keratopathy after LASIK
Authors: Unlu Metin , Hondur Ahmet M. , Korkmaz Safak , Kumova Deniz , Yuksel Erdem
Published: March 2016

Purpose

To emphasize the importance of anticipation of pressure-induced stromal keratopathy (PISK) in eyes with a previous history of LASIK.

Case Report

A 40-year-old man developed LASIK-related pressure-induced stromal keratopathy after uneventful phacoemulsification (Phaco) and intraocular lens (IOL) implantation in his left eye. With immediate discontinuation of the steroid drops and initiation of antiglaucoma medication, his visual acuity, interface edema, and haze improved rapidly. One year later, during Phaco with IOL implantation in his other eye, with anticipation of a similar LASIK-related pressure-induced stromal keratopathy, a very brief course of soft steroid therapy was given together with antiglaucoma medication. Intraocular pressure elevation was avoided, and no interface edema or haze was observed.

Conclusions

This case illustrates that the risk for LASIK-related pressure-induced stromal keratopathy may be reduced with appropriate precautions.
Melanoma Extirpation with Immediate Reconstruction: The Oncologic Safety and Cost Savings of Single-Stage Treatment
Authors: Karanetz Irena , Stanley Sharon , Knobel Denis , Smith Benjamin D. , Bastidas Nicholas , Beg Mansoor , Kasabian Armen K. , Tanna Neil
Published: March 2016

Background:

The timing of reconstruction following melanoma extirpation remains controversial, with some advocating definitive reconstruction only when the results of permanent pathologic evaluation are available. The authors evaluated oncologic safety and cost benefit of single-stage neoplasm extirpation with immediate reconstruction.

Methods:

The authors reviewed all patients treated with biopsy-proven melanoma followed by immediate reconstruction during a 3-year period (January of 2011 to December of 2013). Patient demographic data, preoperative biopsies, operative details, and postoperative pathology reports were evaluated. Cost analysis was performed using hospital charges for single-stage surgery versus theoretical two-stage surgery.

Results:

During the study period, 534 consecutive patients were treated with wide excision and immediate reconstruction, including primary closure in 285 patients (55 percent), local tissue rearrangement in 155 patients (30 percent), and skin grafting in 78 patients (15 percent). The mean patient age was 67 years (range, 19 to 98 years), and the median follow-up time was 1.2 years. Shave biopsy was the most common diagnostic modality, resulting in tumor depth underestimation in 30 patients (6.0 percent). Nine patients (2.7 percent) had positive margins on permanent pathologic evaluation. The only variables associated with positive margins were desmoplastic melanoma (p = 0.004) and tumor location on the cheek (p = 0.0001). The mean hospital charge for immediate reconstruction was $22,528 compared with the theoretical mean charge of $35,641 for delayed reconstruction, leading to mean savings of 38.5 percent (SD, 7.9 percent).

Conclusion:

This large series demonstrates that immediate reconstruction can be safely performed in melanoma patients with an acceptable rate of residual tumor requiring reoperation and significant health care cost savings.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Fracture Prediction With Modified-FRAX in Older HIV-Infected and Uninfected Men
Authors: Yin Michael T. , Shiau Stephanie , Rimland David , Gibert Cynthia L. , Bedimo Roger J. , Rodriguez-Barradas Maria C. , Harwood Katherine , Aschheim Josh , Justice Amy C. , Womack Julie A.
Published: March 2016

Background:

FRAX is a validated, computer-based clinical fracture risk calculator that estimates the 10-year risk of major osteoporotic (clinical spine, forearm, hip, or shoulder) fracture, and hip fracture alone. It is widely used for decision making in fracture prevention, but it may underestimate the risk in HIV-infected individuals. Some experts recommend considering HIV as a cause of secondary osteoporosis when calculating FRAX in HIV-infected individuals.

Methods:

From the Veterans Aging Cohort Study Virtual Cohort, we included 24,451 HIV-infected and uninfected men aged 50–70 years with complete data in the year 2000 to approximate all but 2 factors (ie, history of secondary osteoporosis and parental hip fracture) for modified-FRAX calculation without bone density and 10-year observational data for incident fragility fracture. The accuracy of the modified-FRAX calculation was compared by the observed/estimated (O/E) ratios of fracture by HIV status.

Results:

The accuracy of modified-FRAX was less for HIV-infected [O/E = 1.62, 95% confidence interval (CI) 1.45 to 1.81] than uninfected men (O/E = 1.29, 95% CI: 1.19 to 1.40), but improved when HIV was included as a cause of secondary osteoporosis (O/E = 1.20, 95% CI: 1.08 to 1.34). However, only 3%–6% of men with incident fractures were correctly identified by the modified-FRAX using accepted FRAX thresholds for pharmacologic therapy.

Conclusions:

Modified-FRAX underestimated the fracture rates more in older HIV-infected than in otherwise similar uninfected men. The accuracy improved when HIV was included as a cause of secondary osteoporosis, but it still performed poorly for case finding. Further studies are necessary to determine how to use FRAX or define an HIV-specific index to risk stratify for screening and treatment in older HIV-infected individuals.
FOXP3+Helios+ Regulatory T Cells, Immune Activation, and Advancing Disease in HIV-Infected Children
Authors: Khaitan Alka , Kravietz Adam , Mwamzuka Mussa , Marshed Fatma , Ilmet Tiina , Said Swalehe , Ahmed Aabid , Borkowsky William , Unutmaz Derya
Published: March 2016

Regulatory T cells (Tregs) are functionally suppressive CD4 T cells, critical for establishing peripheral tolerance and controlling inflammatory responses. Previous reports of Tregs during chronic HIV disease have conflicting results with higher or lower levels compared with controls. Identifying true Tregs with suppressive activity proves challenging during HIV infection, as traditional Treg markers, CD25 and FOXP3, may transiently upregulate expression as a result of immune activation (IA). Helios is an Ikaros family transcription factor that marks natural Tregs with suppressive activity and does not upregulate expression after activation. Coexpression of FOXP3 and Helios has been suggested as a highly specific marker of “bona fide” Tregs. We evaluated Treg subsets by FOXP3 coexpressed with either CD25 or Helios and their association with HIV disease progression in perinatally infected HIV-positive children. Identifying Tregs by FOXP3 coexpression with Helios rather than CD25 revealed markedly higher Treg frequencies, particularly in HIV+ children. Regardless of antiretroviral therapy, HIV-infected children had a selective expansion of memory FOXP3+Helios+ Tregs. The rise in memory Tregs correlated with declining HIV clinical status, indicated by falling CD4 percentages and CD4:CD8 ratios and increasing HIV plasma viremia and IA. In addition, untreated HIV+ children exhibited an imbalance between the levels of Tregs and activated T cells. Finally, memory Tregs expressed IA markers CD38 and Ki67 and exhaustion marker, PD-1, that tightly correlated with a similar phenotype in memory CD4 T cells. Overall, HIV-infected children had significant disruptions of memory Tregs that associated with advancing HIV disease.
Magnetic Resonance Elastography of the Liver
Authors: Wagner Mathilde , Besa Cecilia , Bou Ayache Jad , Yasar Temel Kaya , Bane Octavia , Fung Maggie , Ehman Richard L. , Taouli Bachir
Published: March 2016

Objective

The aim of this study was to compare 2-dimensional (2D) gradient recalled echo (GRE) and 2D spin echo echoplanar imaging (SE-EPI) magnetic resonance elastography (MRE) sequences of the liver in terms of image quality and quantitative liver stiffness (LS) measurement.

Materials and Methods

This prospective study involved 50 consecutive subjects (male/female, 33/17; mean age, 58 years) who underwent liver magnetic resonance imaging at 3.0 T including 2 MRE sequences, 2D GRE, and 2D SE-EPI (acquisition time 56 vs 16 seconds, respectively). Image quality scores were assessed by 2 independent observers based on wave propagation and organ coverage on the confidence map (range, 0–15). A third observer measured LS on stiffness maps (in kilopascal). Mean LS values, regions of interest size (based on confidence map), and image quality scores between SE-EPI and GRE-MRE were compared using paired nonparametric Wilcoxon test. Reproducibility of LS values between the 2 sequences was assessed using intraclass coefficient correlation, coefficient of variation, and Bland-Altman limits of agreement. T2* effect on image quality was assessed using partial Spearman correlation.

Results

There were 4 cases of failure with GRE-MRE and none with SE-EPI-MRE. Image quality scores and region of interest size were significantly higher using SE-EPI-MRE versus GRE-MRE (P < 0.0001 for both measurements and observers). Liver stiffness measurements were not significantly different between the 2 sequences (3.75 ± 1.87 kPa vs 3.55 ± 1.51 kPa, P = 0.062), were significantly correlated (intraclass coefficient correlation, 0.909), and had excellent reproducibility (coefficient of variation, 10.2%; bias, 0.023; Bland-Altman limits of agreement, −1.19; 1.66 kPa). Image quality scores using GRE-MRE were significantly correlated with T2* while there was no correlation for SE-EPI-MRE.

Conclusions

Our data suggest that SE-EPI-MRE may be a better alternative to GRE-MRE. The diagnostic performance of SE-EPI-MRE for detection of liver fibrosis needs to be assessed in a future study.
Multifrequency Magnetic Resonance Elastography for the Assessment of Renal Allograft Function
Authors: Marticorena Garcia Stephan Rodrigo , Fischer Thomas , Dürr Michael , Gültekin Emin , Braun Jürgen , Sack Ingolf , Guo Jing
Published: March 2016

Objective

The aim of this study was to apply multifrequency magnetic resonance elastography (MMRE) for assessment of kidney function based on renal stiffness of allografts in transplant recipients and native kidneys in controls.

Methods

In this prospective study, MMRE was used to measure stiffness in transplant kidneys in 22 recipients (age range, 23–73 years; 7 females) and in native kidneys in 11 controls (age range, 26–55 years; 4 females) after internal review board approval. The MMRE was performed on a 1.5 T magnetic resonance imaging scanner using 4 vibration frequencies from 40 to 70 Hz. Stiffness maps were computed by multifrequency reconstruction of the magnitude shear modulus (|G*|). Clinical markers such as glomerular filtration rate (GFR) and resistive index (RI) were acquired. Differences in renal stiffness among groups were compared by Mann-Whitney U test. Correlations were tested using Pearson correlation.

Results

Functioning transplants had higher stiffness (|G*| = 9.00 ± 1.71 kPa) than nonfunctioning transplants (|G*| = 5.88 ± 1.71 kPa, P < 0.001) and native kidneys (|G*| = 6.63 ± 1.63 kPa, P < 0.01). A cutoff value of 7.04 kPa provided sensitivity (83.33%) and specificity (86.67%) for detecting renal allograft dysfunction with an area under the receiver operating characteristic curve value of 0.9278 (95% confidence interval, 0.83–1.00). |G*| correlated positively with GFR (r = 0.52, P = 0.015) and negatively with RI (r = −0.52, P = 0.016).

Conclusions

Multifrequency magnetic resonance elastography has good diagnostic accuracy in detecting renal allograft dysfunction. Renal stiffness is significantly lower in recipients with nonfunctioning transplant kidneys and correlates with clinical markers such as GFR and RI.
Application of the thermofluor PaSTRy technique for improving foot-and-mouth disease virus vaccine formulation
Authors: Kotecha Abhay , Zhang Fuquan , Juleff Nicholas , Jackson Terry , Perez Eva , Stuart Dave , Fry Elizabeth , Charleston Bryan , Seago Julian
Published: March 2016

Foot-and-mouth disease (FMD) has a major economic impact throughout the world and is a considerable threat to food security. Current FMD virus (FMDV) vaccines are made from chemically inactivated virus and need to contain intact viral capsids to maximize efficacy. FMDV exists as seven serotypes, each made up by a number of constantly evolving subtypes. A lack of immunological cross-reactivity between serotypes and between some strains within a serotype greatly complicates efforts to control FMD by vaccination. Thus, vaccines for one serotype do not afford protection against the others, and multiple-serotype-specific vaccines are required for effective control. The FMDV serotypes exhibit variation in their thermostability, and the capsids of inactivated preparations of the O, C and SAT serotypes are particularly susceptible to dissociation at elevated temperature. Methods to quantify capsid stability are currently limited, lack sensitivity and cannot accurately reflect differences in thermostability. Thus, new, more sensitive approaches to quantify capsid stability would be of great value for the production of more stable vaccines and to assess the effect of production conditions on vaccine preparations. Here we have investigated the application of a novel methodology (termed PaSTRy) that utilizes an RNA-binding fluorescent dye and a quantitative (q)PCR machine to monitor viral genome release and hence dissociation of the FMDV capsid during a slow incremental increase in temperature. PaSTRy was used to characterize capsid stability of all FMDV serotypes. Furthermore, we have used this approach to identify stabilizing factors for the most labile FMDV serotypes.
A neural basis for the spatial suppression of visual motion perception
Authors: Liu Liu D. , Haefner Ralf M. , Pack Christopher C.
Published: March 2016

In theory, sensory perception should be more accurate when more neurons contribute to the representation of a stimulus. However, psychophysical experiments that use larger stimuli to activate larger pools of neurons sometimes report impoverished perceptual performance. To determine the neural mechanisms underlying these paradoxical findings, we trained monkeys to discriminate the direction of motion of visual stimuli that varied in size across trials, while simultaneously recording from populations of motion-sensitive neurons in cortical area MT. We used the resulting data to constrain a computational model that explained the behavioral data as an interaction of three main mechanisms: noise correlations, which prevented stimulus information from growing with stimulus size; neural surround suppression, which decreased sensitivity for large stimuli; and a read-out strategy that emphasized neurons with receptive fields near the stimulus center. These results suggest that paradoxical percepts reflect tradeoffs between sensitivity and noise in neuronal populations.
Genome-Wide Analysis of Single Non-Templated Nucleotides in Plant Endogenous siRNAs and miRNAs
Authors: Wang Feng , Johnson Nathan R. , Coruh Ceyda , Axtell Michael J.
Published: March 2016

Plant small RNAs are subject to various modifications. Previous reports revealed widespread 3' modifications (truncations and non-templated tailing) of plant miRNAs when the 2'-C-methyltransferase HEN1 is absent. However, non-templated nucleotides in plant heterochromatic siRNAs have not been deeply studied, especially in wild-type plants. We systematically studied non-templated nucleotide patterns in plant small RNAs by analyzing small RNA sequencing libraries from Arabidopsis. tomato, Medicago, rice, maize, and Physcomitrella. Elevated rates of non-templated nucleotides were observed at the 3' ends of both miRNAs and endogenous siRNAs from wild-type specimens of all species. 'Off-sized' small RNAs, such as 25 and 23 nt siRNAs arising from loci dominated by 24 nt siRNAs, often had very high rates of 3'-non-templated nucleotides. The same pattern was observed in all species that we studied. Further analysis of 24 nt siRNA clusters in Arabidopsis revealed distinct patterns of 3'-non-templated nucleotides of 23 nt siRNAs arising from heterochromatic siRNA loci. This pattern of non-templated 3' nucleotides on 23 nt siRNAs is not affected by loss of known small RNA 3'-end modifying enzymes, and may result from modifications added to longer heterochromatic siRNA precursors.
Synchrotron-radiation-based X-ray micro-computed tomography reveals dental bur debris under dental composite restorations
Authors: Hedayat Assem , Nagy Nicole , Packota Garnet , Monteith Judy , Allen Darcy , Wysokinski Tomasz , Zhu Ning
Published: March 2016

Dental burs are used extensively in dentistry to mechanically prepare tooth structures for restorations (fillings), yet little has been reported on the bur debris left behind in the teeth, and whether it poses potential health risks to patients. Here it is aimed to image dental bur debris under dental fillings, and allude to the potential health hazards that can be caused by this debris when left in direct contact with the biological surroundings, specifically when the debris is made of a non-biocompatible material. Non-destructive micro-computed tomography using the BioMedical Imaging & Therapy facility 05ID-2 beamline at the Canadian Light Source was pursued at 50 keV and at a pixel size of 4 µm to image dental bur fragments under a composite resin dental filling. The bur's cutting edges that produced the fragment were also chemically analyzed. The technique revealed dental bur fragments of different sizes in different locations on the floor of the prepared surface of the teeth and under the filling, which places them in direct contact with the dentinal tubules and the dentinal fluid circulating within them. Dispersive X-ray spectroscopy elemental analysis of the dental bur edges revealed that the fragments are made of tungsten carbide–cobalt, which is bio-incompatible.
Crystal structure and bonding analysis of the first dinuclear calcium(II)–proton-pump inhibitor (PPI) `butterfly molecule': a combined microcrystal synchrotron and DFT study
Authors: Cong Hengjiang
Published: March 2016

Proton-pump inhibitors (PPI) are prodrugs used widely to treat acid-related diseases since the late 1980s. After an extensive research effort it has become clear that the fundamental interactions between metal atoms and PPIs are of paramount importance for both drug release and long-term therapeutic safety. Unfortunately, until now, very little information has been available on this topic. In this paper, we report the crystal structure analysis of a novel calcium–PPI compound incorporating bridging and terminal deprotonated (R)-rabeprazole tricyclic ligands (L), namely bis[μ-(R)-2-({[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl}sulfinyl)-6,7-dihydro-3H-benzofuro[5,6-d]imidazol-1-ido]bis{dimethanol[(R)-2-({[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methyl}sulfinyl)-6,7-dihydro-3H-benzofuro[5,6-d]imidazol-1-ido]calcium(II)} methanol hexasolvate, [Ca2(C20H22N3O4S)4(CH3OH)4]·6CH3OH or [Ca2(L)4(CH3OH)4]·6CH3OH, which crystallizes from methanol in the polarC2 space group. Using low-temperature microcrystal synchrotron radiation, we demonstrate that this compound is in the form of a beautiful `butterfly molecule', consisting of aC2-symmetric dinuclear (CH3OH)2LCaII(μ2-L)2CaIIL(HOCH3)2framework. A large amount of disorder is found within the bridgingLligand and the conformation of the fused tetrahydrofuran ring exhibits great variety. All the sulfinyl groups remain intact and the nonbonded Ca...Ca distance is significantly longer than in other calcium dimers, indicating steric hindrance in the bridging ligands. Considerable hydrogen bonding and aromatic C—H...π interactions co-operate to stabilize the whole complex, as well as to facilitate supramolecular assembly. Additional investigations into the bond nature were made using density functional theory (DFT) methods at the B3LYP/6-31G(d) level; geometry optimization, Mulliken atomic charges, MEP (molecular electrostatic potential), HOMO–LUMO (highest occupied molecular orbital–lowest unoccupied molecular orbital), TDOS (total density of states), PDOS (partial density of states), COOP (crystal orbital overlap population) and vibrational spectra were calculated/recorded and assessed carefully.
Crystal structure of bis(2-aminoanilinium) hydrogen phosphate
Authors: Ittyachan Reena , Ahigna Melesuparambil Sundaram , Jagan Rajamony
Published: March 2016

The asymmetric unit of the title compound, 2C6H9N2+·HPO42−, comprises two 2-aminoanilinium cations and one hydrogen phosphate dianion. In the crystal, the HPO42−dianions are linked by O—H...O hydrogen bonds into chains along [100]. The inorganic anionic chains and organic cations are linked by N—H...O and N—H...N hydrogen bonds, forming a two-dimensional supramolecular network extending parallel to (001).
Big Data and consumer behavior: imminent opportunities
Authors: Hofacker Charles F. , Malthouse Edward Carl , Sultan Fareena
Published: March 2016

Purpose

– The purpose of this paper is to assess how the study of consumer behavior can benefit from the presence of Big Data.

Design/methodology/approach

– This paper offers a conceptual overview of potential opportunities and changes to the study of consumer behavior that Big Data will likely bring.

Findings

– Big Data have the potential to further our understanding of each stage in the consumer decision-making process. While the field has traditionally moved forward using a priori theory followed by experimentation, it now seems that the nature of the feedback loop between theory and results may shift under the weight of Big Data.

Research limitations/implications

– A new data culture is now represented in marketing practice. The new group advocates inductive data mining and A/B testing rather than human intuition harnessed for deduction. The group brings with it interest in numerous secondary data sources. However, Big Data may be limited by poor quality, unrepresentativeness and volatility, among other problems.

Practical implications

– Managers who need to understand consumer behavior will need a workforce with different skill sets than in the past, such as Big Data consumer analytics.

Originality/value

– To the authors ' knowledge, this is one of the first articles to assess how the study of consumer behavior can evolve in the context of the Big Data revolution.