bluuebunny/crossref_metadata_2025_split huggingface dataset:
ALT flares during nucleotide analogue therapy are associated with HBsAg loss in genotype A HBeAg‐positive chronic hepatitis B
Authors: Wong Darren , Littlejohn Margaret , Edwards Rosalind , Jackson Kathy , Revill Peter , Gaggar Anuj , Kitrinos Kathryn , Subramanian Mani , Marcellin Patrick , Buti‐Ferret Maria , Janssen Harry , Gane Ed , Locarnini Stephen , Thompson Alexander 
Published: February 2018

AbstractBackgroundAlanine aminotransferase (ALT) flares during NA therapy are uncommon but occur. Evaluation of ALT flares during nucleos(t)ide analogue (NA) therapy is important as new immunomodulatory therapies for hepatitis B virus (HBV) are developed. We evaluated the association between ALT flares and HBsAg loss during long‐term therapy for genotype A CHB.MethodsThis analysis included genotype A subjects from a phase III study of tenofovir vs adefovir in HBeAg‐positive HBV. ALT flare was defined as (i) a rise in ALT >2x ULN from normal ALT levels; or (ii) a rise in ALT >2x baseline ALT level. HBsAg response at week 384 was recorded as one of HBsAg loss vs HBsAg decline (≥1 log10 IU/mL decline) vs non‐response. The primary analysis evaluated the association between ALT flare and HBsAg response.Results54 subjects were included. 23/54 (43%) subjects experienced an on‐treatment ALT flare. 45% achieved an HBsAg reduction ≥1 log10 IU/mL, and of these 67% achieved HBsAg loss at a median of 102 weeks [IQR: 64‐156]. Flare was associated with HBsAg decline vs non‐response (67% vs 23%, P = .002), and were more common in subjects who achieved HBsAg loss vs non‐response (56% vs 23%), P = .049). There was a median delay of 56 weeks [IQR: 40‐80] between a flare and HBsAg loss.ConclusionIn genotype A subjects undergoing long‐term NA therapy, ALT flares predict for HBsAg response. The delay between ALT flare and HBsAg loss has implications for clinical trial design for early phase development of immunomodulatory strategies aiming for HBsAg loss.
The ecosystem services of animal microbiomes
Authors: McKenney E. A. , Koelle K. , Dunn R. R. , Yoder A. D. 
Published: February 2018

AbstractMicrobiologists often evaluate microbial community dynamics by formulating functional hypotheses based on ecological processes. Indeed, many of the methods and terms currently used to describe animal microbiomes derive from ecology and evolutionary biology. As our understanding of the composition and functional dynamics of “the microbiome” grows, we increasingly refer to the host as an ecosystem within which microbial processes play out. Even so, an ecosystem service framework that extends to the context of the host has thus far been lacking. Here, we argue that ecosystem services are a useful framework with which to consider the value of microbes to their hosts. We discuss those “microbiome services” in the specific context of the mammalian gut, providing a context from which to develop new hypotheses and to evaluate microbial functions in future studies and novel systems.
Zebularine treatment is associated with deletion of FT‐B1 leading to an increase in spikelet number in bread wheat
Authors: Finnegan E. Jean , Ford Brett , Wallace Xiaomei , Pettolino Filomena , Griffin Patrick T. , Schmitz Robert J. , Zhang Peng , Barrero Jose M. , Hayden Matthew J. , Boden Scott A. , Cavanagh Colin A. , Swain Steve M. , Trevaskis Ben 
Published: February 2018

AbstractThe number of rachis nodes (spikelets) on a wheat spike is a component of grain yield that correlates with flowering time. The genetic basis regulating flowering in cereals is well understood, but there are reports that flowering time can be modified at a high frequency by selective breeding, suggesting that it may be regulated by both epigenetic and genetic mechanisms. We investigated the role of DNA methylation in regulating spikelet number and flowering time by treating a semi‐spring wheat with the demethylating agent, Zebularine. Three lines with a heritable increase in spikelet number were identified. The molecular basis for increased spikelet number was not determined in 2 lines, but the phenotype showed non‐Mendelian inheritance, suggesting that it could have an epigenetic basis. In the remaining line, the increased spikelet phenotype behaved as a Mendelian recessive trait and late flowering was associated with a deletion encompassing the floral promoter, FT‐B1. Deletion of FT‐B1 delayed the transition to reproductive growth, extended the duration of spike development, and increased spikelet number under different temperature regimes and photoperiod. Transiently disrupting DNA methylation can generate novel flowering behaviour in wheat, but these changes may not be sufficiently stable for use in breeding programs.
Epiphytic bromeliads in a changing world: the effect of elevated CO2 and varying water supply on growth and nutrient relations
Authors: Wagner K. , Zotz G. 
Published: February 2018

Abstract

Global climate change is likely to impact all plant life. Vascular epiphytes represent a life form that may be affected more than any other by possible changes in precipitation leading to water shortage, but negative effects of drought may be mitigated through increasing levels of atmospheric CO2.

We studied the response of three epiphytic Aechmea species to different CO2 and watering levels in a full‐factorial climate chamber study over 100 days. All species use crassulacean acid metabolism (CAM). Response variables were relative growth rate (RGR), nocturnal acidification and foliar nutrient levels (N, P, K, Mg).

Both elevated CO2 and increased water supply stimulated RGR, but the interaction of the two factors was not significant. Nocturnal acidification was not affected by these factors, indicating that the increase in growth in these CAM species was due to higher assimilation in the light. Mass‐based foliar nutrient contents were consistently lower under elevated CO2, but most differences disappeared when expressed on an area basis.

Compared to previous studies with epiphytes, in which doubling of CO2 increased RGR, on average, by only 14%, these Aechmea species showed a relatively strong growth stimulation of up to +61%. Consistent with earlier findings with other bromeliads, elevated CO2 did not mitigate the effect of water shortage.
Assessing ocular activity during performance of motor skills using electrooculography
Authors: Gallicchio Germano , Cooke Andrew , Ring Christopher 
Published: February 2018

AbstractEye‐tracking research has revealed that, compared to novices, experts make longer ocular fixations on the target of an action when performing motor skills; that is, they have a longer quiet eye. Remarkably, the reason why a longer quiet eye aids movement has yet to be established. There is a need for interdisciplinary research and new measures to accelerate progress on the mechanistic understanding of the phenomenon. With the aim to provide researchers with new tools, we assessed the utility of electrooculography (EOG) to examine ocular activity while 10 experts and 10 novices putted golf balls. We measured quiet eye durations, distinguishing its pre‐ and postmovement initiation components, and developed a novel time‐varying index of ocular activity, eye quietness, computed as the variability of the EOG in short time intervals: lower values correspond with greater quietness. Finally, we measured movement durations using a combination of infrared and sound sensors. Experts had longer postmovement initiation quiet eye compared to novices; however, total and premovement quiet eye durations did not differ between groups. Eye quietness was inversely correlated with quiet eye duration, and was greatest immediately after movement initiation. Importantly, movement duration correlated positively with postmovement initiation quiet eye and negatively with eye quietness shortly after movement initiation. This study demonstrates the utility of assessing ocular activity during performance of motor skills using EOG. Additionally, these findings provide evidence that expert–novice differences in ocular activity may reflect differences in the kinematics (e.g., movement duration) of how experts and novices execute motor skills.
Cardiorespiratory fitness not sedentary time or physical activity is associated with cardiometabolic risk in active older adults
Authors: Pollock R. D. , Duggal N. A. , Lazarus N. R. , Lord J. M. , Harridge S. D. R. 
Published: February 2018

Sedentary time (ST) and moderate‐to‐vigorous physical activity (MVPA) are associated with cardiometabolic health. Cardiorespiratory fitness (CRF) is also implicated but often overlooked in health recommendations. This study assessed the relationships between ST, MVPA, CRF, and cardiometabolic health in highly active older individuals. 125 healthy amateur cyclists aged 55 to 79 years had their ST and MVPA levels assessed by actigraphy over a 7‐day period. CRF was assessed using a maximal effort cycle ergometry test to determine VO2max with results normalized to both body mass and fat‐free mass measured by DXA. Markers of cardiometabolic risk (blood glucose, triglycerides, cholesterol, HDL, LDL, Insulin, HOMA IR, blood pressure, and body fat) were assessed and used to determine cumulative cardiometabolic risk. Multiple linear regression was used to assess ST, MVPA, and CRF associations with cardiometabolic health with the relationship between activity levels and CRF determined. CRF was associated with training volume (P = .003), but not ST or MVPA. A high CRF was associated with lower cumulative cardiometabolic risk, body fat percentage, triglyceride, and HDL levels (P < .05 in all cases). MVPA was negatively associated with body fat percentage, while ST was not associated with any marker of cardiometabolic risk when adjusting for activity levels. An association between CRF and cardiometabolic risk even in a group of older individuals with high fitness levels highlights the importance that CRF may have in maintaining health.
Noninvasive quantitative analysis of ceramide in skin of healthy Chinese population
Authors: Cheng S.‐S. , Chang Y.‐L. , Fei W.‐M. , Zhai W.‐F. , Cheng H. , Yang S. , Zhang X.‐J. 
Published: February 2018

AbstractObjectiveThe objective of this study was to make noninvasive quantitative analysis of ceramide (CER) in skin of healthy Chinese population by high performance liquid chromatography tandem mass spectrometry.MethodsSeven healthy subjects were selected and the stratified skin samples were available using cyanoacrylate adhesion method. High performance liquid chromatography tandem mass spectrometry, use ceramide Subclass Standard C42H85NO3 Quantification of the 12 corresponding ceramide subclass in the epidermis on the 7 skin samples, which cannot get all the standard of ceramides subclass since the stratum corneum ceramide is complex and diverse. Data were collected and analyzed using full‐flow lipid analysis software (LipidSearch).ResultsAll the seven skin samples contained 12 subclasses of ceramide and the samples were quantitated with ceramide C42H85NO3 standard. The average contents were 33.63, 27.59, 108.57, 220.75, 149.20, 43.06, and 22.78 μg/mL, respectively.ConclusionCeramide is an important lipid in the epidermis and is closely related to the skin barrier function. There are 12 subtypes of ceramide detected in the skin of Chinese healthy people, and there is a difference in the concentration between individuals. The difference may be associated with the skin barrier condition, and may also be related to the unavoidable error in the process of sampling, treatment, and detection.
Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients
Authors: Dubberke E.R. , Reske K.A. , Olsen M.A. , Bommarito K. , Cleveland A.A. , Silveira F.P. , Schuster M.G. , Kauffman C.A. , Avery R.K. , Pappas P.G. , Chiller T.M. 
Published: February 2018

AbstractBackgroundClostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described.MethodsWe performed a prospective, multicenter study of CDI within 365 days post‐allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post‐transplant and while hospitalized and contacted monthly up to 18 months post‐transplantation.ResultsSix sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post‐index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post‐index date (HR = 4.7, P = .09).ConclusionsThe epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post‐transplant period.
Risk factors for Clostridium difficile infection in intestinal transplant recipients during the first year post‐transplant
Authors: Guzman L. , Qiu F. , Kalil A.C. , Mercer D.F. , Langnas A. , Florescu D.F. 
Published: February 2018

AbstractBackgroundClostridium difficile is the most common cause of healthcare‐associated infectious diarrhea. Risk factors for C. difficile infections (CDI) in intestinal transplant recipients (ITR) are not well‐defined. The aim of our study was to assess specific risk factors for CDI in ITR.MethodsThis is a 1:3 case–control study that included 29 ITR who developed CDI (cases) and 87 ITR without CDI (controls) observed during the first year post‐transplantation. Wilcoxon rank sum and Fisher's exact tests were used to compare variables. Univariate and multivariable conditional logistic regressions analysis were performed to identify risk factors for CDI.ResultsThe multivariable conditional logistic regression analysis showed that proton pump inhibitors (PPI) administration (odds ratio [OR] = 0.06; 95% confidence interval [CI]: 0.007‐0.52; P = .01) was the only factor associated with lower rates of CDI. Outcomes for cases vs controls: rejection episodes 24.14% vs 20.69% (P = .7), graft loss 0% vs 2.3% (P = .99), and survival rate 1 year post‐transplantation 79.3% (59.6‐90.1%) vs 87.2% (78.1‐92.7%) (P = .38).ConclusionsProton pump inhibitor administration might be protective for CDI in ITR. Risks factors for CDI might be different in ITR compared to other populations; anatomical differences and medications administered in the post‐transplantation period may affect intestinal microbiota.
Interleukin‐8 mediates neutrophil‐endothelial interactions in pig‐to‐human xenogeneic models
Authors: French Beth M. , Sendil Selin , Sepuru Krishna Mohan , Ranek Jolene , Burdorf Lars , Harris Donald , Redding Emily , Cheng Xiangfei , Laird Christopher T. , Zhao Yuming , Cerel Benjamin , Rajarathnam Krishna , Pierson Richard N. , Azimzadeh Agnes M. 
Published: February 2018

AbstractBackgroundHuman neutrophils are sequestered by pig lung xenografts within minutes during ex vivo perfusion. This phenomenon is not prevented by pig genetic modifications that remove xeno‐antigens or added human regulatory molecules intended to down‐regulate activation of complement and coagulation pathways. This study investigated whether recipient and donor interleukin‐8 (IL‐8), a chemokine known to attract and activate neutrophils during inflammation, is elaborated in the context of xenogeneic injury, and whether human or pig IL‐8 promote the adhesion of human neutrophils in in vitro xenograft models.MethodsPlasma levels of pig, human or non‐human primate (NHP) IL‐8 from ex vivo pig lung perfusion experiments (n = 10) and in vivo pig‐to‐baboon lung transplantation in baboons (n = 22) were analysed by ELISA or Luminex. Human neutrophils stimulated with human or pig IL‐8 were analysed for CD11b expression, CD18 activation, oxidative burst and adhesion to resting or TNF‐activated endothelial cells (EC) evaluated under static and flow (Bioflux) conditions. For some experiments, human neutrophils were incubated with Reparixin (IL‐8/CXCL8 receptor blocker) and then analysed as in the in vitro experiments mentioned above.ResultsPlasma levels of pig IL‐8 (~6113 pg/mL) increased more than human (~1235 pg/mL) between one and four hours after initiation of ex vivo lung perfusion. However, pig IL‐8 levels remained consistently low (<60 pg/mL) and NHP IL‐8 plasma levels increased by ~2000 pg/mL after four hours in a pig‐to‐baboon lung xenotransplantation. In vitro, human neutrophils’ CD11b expression, CD18 activation and oxidative burst all increased in a dose‐dependent manner following exposure to either pig or human IL‐8, which also were associated with increased adhesion to EC in both static and flow conditions. Reparixin inhibited human neutrophil activation by both pig and human IL‐8 in a dose‐dependent fashion. At 0.1 mg/mL, Reparixin inhibited the adhesion of IL‐8‐activated human neutrophils to pAECs by 84 ± 2.5%.ConclusionsPig IL‐8 increased in an ex vivo model of pig‐to‐human lung xenotransplantation but is not detected in vivo, whereas human or NHP IL‐8 is elevated to a similar degree in both models. Both pig and human IL‐8 activate human neutrophils and increase their adhesion to pig aortic ECs, a process significantly inhibited by the addition of Reparixin to human neutrophils. This work implicates IL‐8, whether of pig or human origin, as a possible factor mediating in lung xenograft inflammation and injury and supports the evaluation of therapeutic targeting of this pathway in the context of xenotransplantation.
UBC‐Nepal expedition: The use of oral antioxidants does not alter cerebrovascular function at sea level or high altitude
Authors: Hansen Alexander B. , Hoiland Ryan L. , Lewis Nia C. S. , Tymko Michael M. , Tremblay Joshua C. , Stembridge Michael , Nowak‐Flück Daniela , Carter Howard H. , Bailey Damian M. , Ainslie Philip N. 
Published: February 2018

New Findings
What is the central question of the study?
Does the use of antioxidants alter cerebrovascular function and blood flow at sea level (344 m) and/or high altitude (5050 m)?

What is the main finding and its importance?
This is the first study to investigate whether antioxidant administration alters cerebrovascular regulation and blood flow in response to hypercapnia, acute hypoxia and chronic hypoxia in healthy humans. We demonstrate that an acute dose of antioxidants does not alter cerebrovascular function and blood flow at sea level (344 m) or after 12 days at high altitude (5050 m).

AbstractHypoxia is associated with an increase in systemic and cerebral formation of free radicals and associated reactants that may be linked to impaired cerebral vascular function and neurological sequelae. To what extent oral antioxidant prophylaxis impacts cerebrovascular function in humans throughout the course of acclimatization to the hypoxia of terrestrial high altitude has not been examined. Thus, the purpose of the present study was to examine the influence of orally ingested antioxidants at clinically relevant doses (vitamins C and E and α‐lipoic acid) on cerebrovascular regulation at sea level (344 m; n = 12; female n = 2 participants) and at high altitude (5050 m; n = 9; female n = 2) in a randomized, placebo‐controlled and double‐blinded crossover design. Hypercapnic and hypoxic cerebrovascular reactivity tests of the internal carotid artery (ICA) were conducted at sea level, and global and regional cerebral blood flow (CBF; i.e. ICA and vertebral artery) were assessed 10–12 days after arrival at 5050 m. At sea level, acute administration of antioxidants did not alter cerebral hypoxic cerebrovascular reactivity (pre versus post: 1.5 ± 0.7 versus 1.2 ± 0.8%∆CBF/−%∆; P = 0.96) or cerebral hypercapnic cerebrovascular reactivity (pre versus post: 5.7 ± 2.0 versus 5.8 ± 1.9%∆CBF/∆mmHg; P = 0.33). Furthermore, global CBF (P = 0.43) and cerebral vascular conductance (ICA P = 0.08; vertebral artery P = 0.32) were unaltered at 5050 m after antioxidant administration. In conclusion, these data show that an oral antioxidant cocktail known to attenuate systemic oxidative stress failed to alter cerebrovascular function at sea level and CBF during acclimatization to high altitude.
Injury, repair, inflammation and metaplasia in the stomach
Authors: Meyer Anne R. , Goldenring James R. 
Published: February 2018

AbstractThe development of intestinal‐type gastric cancer is preceded by the emergence of metaplastic cell lineages in the gastric mucosa. In particular, intestinal metaplasia and spasmolytic polypeptide‐expressing metaplasia (SPEM) have been associated with the pathological progression to intestinal‐type gastric cancer. The development of SPEM represents a physiological response to damage that recruits reparative cells to sites of mucosal injury. Metaplastic cell lineages are characterized by mucus secretion, adding a protective barrier to the epithelium. Increasing evidence indicates that the influence of alarmins and cytokines is required to initiate the process of metaplasia development. In particular, IL‐33 derived from epithelial cells stimulates IL‐13 production by specialized innate immune cells to induce chief cell transdifferentiation into SPEM following the loss of parietal cells from the corpus of the stomach. While SPEM represents a physiological healing response to acute injury, persistent injury and chronic inflammation can perpetuate a recurring pattern of reprogramming and metaplasia that is a risk factor for gastric cancer development. The transdifferentiation of zymogen secreting cells into mucous cell metaplasia may represent both a general repair mechanism in response to mucosal injury in many epithelia as well as a common pre‐neoplastic pathway associated with chronic injury and inflammation.
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Phase 1 Study To Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Oral Doses of DS-2969b, a Novel GyrB Inhibitor, in Healthy Subjects
Authors: Vandell Alexander G. , Inoue Satoshi , Dennie Justin , Nagasawa Yasuo , Gajee Roohi , Pav Joe , Zhang George , Zamora Cynthia , Masuda Nobuhisa , Senaldi Giorgio 
Published: February 2018

ABSTRACT

DS-2969b is a novel GyrB inhibitor in development for the treatment of
Clostridium difficile
infection (CDI). The aim of this study was to assess the safety, tolerability, pharmacokinetics, and effects on the normal gastrointestinal microbiota of multiple daily oral ascending doses of DS-2969b in healthy subjects. The study enrolled three sequential ascending-dose cohorts (60 mg, 200 mg, and 400 mg). In each cohort, subjects received an oral dose of DS-2969b or placebo (six subjects received DS-2969b, and two received placebo) each morning for 14 days. DS-2969b was safe and well tolerated at all dose levels examined. All adverse events related to DS-2969b were mild and predominantly related to the gastrointestinal tract. DS-2969a (free form of DS-2969b) plasma concentrations increased with increasing doses; however, both the maximum concentration of drug in serum (
C
max
) and the area under the concentration-time curve (AUC) increased less than dose proportionally. In all cohorts, sufficient fecal levels of DS-2969a were achieved within 24 h following the administration of the first dose and maintained for at least 17 days. Following treatment with DS-2969b, clear reductions in the populations of
Clostridium coccoides
and
Bifidobacterium
groups were observed. However, populations of three other bacterial groups examined (
Bacteroides fragilis
,
Clostridium leptum
, and
Prevotella
) were not affected. Data from this study support and encourage the further development of DS-2969b as a novel treatment for CDI.