bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programmed Cell Death-Ligand 1 (PD-L1) Expression in Anal Cancer
Authors: Govindarajan Rangaswamy , Gujja Swetha , Siegel Eric R. , Batra Anu , Saeed Anwaar , Lai Keith , James Jennifer D. , Fogel Bradley J. , Williamson Stephen 
Published: November 2016

Objective:
To evaluate the expression of programmed cell death-ligand 1 (PD-L1) in anal cancer.

Patients and Methods:
In a retrospective cohort analysis, subjects with squamous cell carcinoma of the anal canal were tested for PD-L1 expression, then followed for recurrence and survival. Crude recurrence rates (CRRs), crude mortality rates (CMRs), and crude event rates (CERs) were assessed for PD-L1-dependent differences using Poisson regression. All 3 types of crude rate were expressed as the number that occurred per hundred person-years (hPY) of follow-up.

Results:
Samples from 41 subjects were evaluated for PD-L1 expression; 23 (56%) were positive. Subjects with PD-L1-expressing versus PD-L1-negative tumors respectively had CRRs of 30.8 versus 12.1 recurrences/hPY (P=0.082), CMRs of 16.7 versus 12.0 deaths/hPY (P=0.47), and CERs of 39.2 versus 16.9 events/hPY (P=0.069).

Conclusions:
PD-L1 positivity was associated with worse CRR and CER, and marginally worse CMR. The effect on progression-free and overall survival needs to be validated in a study with a larger sample size.
A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer
Authors: Iyer Renuka V. , Pokuri Venkata K. , Groman Adrienne , Ma Wen W. , Malhotra Usha , Iancu Dan M. , Grande Catherine , Saab Tanios B. 
Published: November 2016

Objectives:
Vascular endothelial growth factor overexpression, seen in 42% to 76% of biliary tract cancers (BTCs), correlates with poor survival. We explored the safety/efficacy and potential biomarkers for bevacizumab in combination with gemcitabine-capecitabine in advanced BTCs.

Patients and Methods:
Inoperable stage III/IV BTC patients in our prospective study were given 1000 mg/m2 of gemcitabine (on days 1, 8), 650 mg/m2 of capecitabine (on days 1 to 14), and 15 mg/kg of bevacizumab (on day 1) in 21-day cycles. Circulating tumor cells and quality of life were assessed at baseline and before cycle 2 and 3.

Results:
In total, 50 patients with gallbladder cancer (22%), intrahepatic (58%), and extrahepatic (20%) cholangiocarcinoma, received a median of 8 treatment cycles for median treatment duration of 5.8 months. Common grade 3/4 toxicities were neutropenia (36%), thrombocytopenia (16%), fatigue (20%), infections (14%), and hand-foot syndrome (10%). There were 12 partial response (24%), 24 stable disease (48%) with clinical benefit rate of 72%. Median progression-free survival was 8.1 months (95% confidence interval, 5.3-9.9). Median overall survival was 10.2 months (95% confidence interval, 7.5-13.7). Circulating tumor cells were identified at baseline in 21/46 patients (46%), who had lower median overall survival compared with those without (9.4 vs. 13.7 mo; P=0.29). Patients with quality of life scores greater than the group median by the end of first cycle of treatment had improved survival compared with those who did not (13.3 vs. 9.4 mo; P=0.39).

Conclusions:
Addition of bevacizumab to gemcitabine/capecitabine did not improve outcome in an unselected group of patients with advanced BTC compared with historical controls. The selective benefit of vascular endothelial growth factor inhibition in BTC remains to be explored.
Can the Risks of Cerebrospinal Fluid Leak After Vestibular Schwannoma Surgery Be Predicted?
Authors: Russel Adrien , Hoffmann Charles P. , Nguyen Duc T. , Beurton Renaud , Parietti-Winkler Cécile 
Published: November 2016

Objective:
Identifying predictive factors of cerebrospinal fluid (CSF) leak after translabyrinthine approach (TLA) for vestibular schwannoma.

Design:
Retrospective study.

Setting:
Tertiary care center.

Patients:
All patients (n = 275) operated for a vestibular schwannoma by TLA between 2004 and 2013 were included.

Intervention:
Vestibular schwannoma surgery by TLA.

Main Outcomes and Measures:
The rate of postoperative CSF leak considering the age, sex, body mass index (BMI), tumor staging, and duration of surgical procedure. A logistic regression model was used to identify the predictors and compute a biometric predictive model of CSF leak.

Results:
Thirty-three patients (12.0%) developed a CSF leak after surgery. In a multivariable model, an increased risk of CSF leak was found for younger patients (OR 0.95, 95% CI 0.92–0.98), longer duration of surgery (OR 1.85, 95% CI 1.12–3.05), and the male sex (0 = male; 1 = female; OR 0.22, 95% CI 0.09–0.54), while also adjusting for BMI. The probability of developing a CSF leak after vestibular schwannoma surgery was calculated using a statistical prediction model, with a percentage of false negative of 7.0% and an overall correct prediction of 88.4%.

Conclusion:
The predictors of CSF leak after TLA for vestibular schwannoma are young age, male sex, longer duration of surgery, which adjusting for BMI. In this regard, the surgical team should adapt its management during pre- and postoperative period to decrease the likelihood of a leak.
Alcohol Use and Activity Limitations in Gout Patients
Authors: Harding Mariann 
Published: November 2016

BACKGROUND
Few studies have evaluated whether patients with a diagnosis of gout adhere to alcohol use recommendations and the relationship between adherence and activity limitations.

PURPOSE:
The purpose of this study was to determine adherence to American College of Rheumatology (ACR) alcohol use recommendations and evaluate the relationship between alcohol use and activity limitations in persons with gout.

METHOD:
A secondary analysis was performed with a sample of 298 persons with gout from the 2008 National Health Interview Survey.

RESULTS:
In all, 22.8% of persons with gout were nonadherent to alcohol use recommendations. Males, those aged 41–60 years, and those not receiving healthcare for joint symptoms were most likely to be nonadherent. In all, 39.9% reported that joint symptoms interfered with activity in the preceding 30 days. Those who were adherent were more likely to report limitations (χ2 = 6.788, p = .03).

CONCLUSIONS:
To promote optimal patient outcomes, more attention needs to be devoted to individualized patient education and self-management interventions that follow ACR recommendations.
Increased Survival Among HIV-Infected PWID Receiving a Multi-Level HIV Risk and Stigma Reduction Intervention: Results From a Randomized Controlled Trial
Authors: Go Vivian F. , Frangakis Constantine , Le Minh Nguyen , Ha Tran Viet , Latkin Carl A. , Sripaipan Teerada , Zelaya Carla E. , Davis Wendy W. , Celentano David D. , Quan Vu Minh 
Published: November 2016

Objective:
In Vietnam, where 58% of prevalent HIV cases are attributed to people who inject drugs, we evaluated whether a multi-level intervention could improve care outcomes and increase survival.

Methods:
We enrolled 455 HIV-infected males who inject drugs from 32 communes in Thai Nguyen Province. Communes were randomized to a community stigma reduction intervention or standard of care and then within each commune, to an individual enhanced counseling intervention or standard of care, resulting into 4 arms: Arm 1 (standard of care); Arm 2 (community intervention alone); Arm 3 (individual intervention alone); and Arm 4 (community + individual interventions). Follow-up was conducted at 6, 12, 18, and 24 months to assess survival.

Results:
Overall mortality was 23% (n = 103/455) more than 2 years. There were no losses to follow-up for the mortality endpoint. Survival at 24 months was different across arms: Arm 4 (87%) vs Arm 1 (82%) vs Arm 2 (68%) vs Arm 3 (73%); log-rank test for comparison among arms: P = 0.001. Among those with CD4 cell count <200 cells/mm3 and not on antiretroviral therapy at baseline (n = 162), survival at 24 months was higher in Arm 4 (84%) compared with other arms (Arm 1: 61%; Arm 2: 50%; Arm 3: 53%; P-value = 0.002). Overall, Arm 4 (community + individual interventions) had increased uptake of antiretroviral therapy compared with Arms 1, 2, and 3.

Conclusions:
This multi-level behavioral intervention seemed to increase survival of HIV-infected participants more than a 2-year period. Relative to the standard of care, the greatest intervention effect was among those with lower CD4 cell counts.
Pneumonia, Intake Problems, and Survival Among Nursing Home Residents With Variable Stages of Dementia in the Netherlands
Authors: Hendriks Simone A. , Smalbrugge Martin , van Gageldonk-Lafeber Arianne B. , Galindo-Garre Francisca , Schipper Maarten , Hertogh Cees M.P.M. , van der Steen Jenny T. 
Published: November 2016

Objectives:We explored how pneumonia and intake problems affect survival in nursing home residents in variable stages of dementia.Methods:In a longitudinal observational study (372 residents) with up to 3.5 years of follow-up, we examined relationships between dementia severity, the development of pneumonia, intake problems, and mortality using joint modeling, Cox models, and mediation analyses. Dementia severity was measured semiannually with the Bedford Alzheimer Nursing Severity-Scale (BANS-S).Results:The median BANS-S score at baseline was 13 (range, 7 to 28). Pneumonia occurred in 103 (28%) and intake problems in 126 (34%) of 367 residents with complete registration of pneumonia and intake problems. Compared with dementia severity, incident pneumonia and, even more so, incident intake problems were more strongly associated with mortality risk. Pneumonia and intake problems both mediated the relationship between more severe dementia and mortality.Discussion:Developing pneumonia and intake problems affects survival, and this is not limited to advanced dementia. The occurrence of pneumonia and intake problems are important signals to consider a palliative care approach in nursing home residents with dementia, and an active focus on advance care planning is needed. Future studies should investigate whether this is also relevant for patients in primary care.
Biased gene conversion drives codon usage in human and precludes selection on translation efficiency
Authors: Pouyet Fanny , Mouchiroud Dominique , Duret Laurent , Sémon Marie 
Published: November 2016

AbstractIn humans, as in other mammals, synonymous codon usage (SCU) varies widely among genes. In particular, genes involved in cell differentiation or in proliferation display a distinct codon usage, suggesting that SCU is adaptively constrained to optimize translation efficiency in distinct cellular states. However, in mammals, SCU is known to correlate with large-scale fluctuations of GC-content along chromosomes, caused by meiotic recombination, via the non-adaptive process of GC-biased gene conversion (gBGC). To disentangle and to quantify the different factors driving SCU in humans, we analyzed the relationships between functional categories, base composition, recombination, and gene expression. We first demonstrate that SCU is predominantly driven by large-scale variation in GC-content and is not linked to constraints on tRNA abundance, which excludes an effect of translational selection. In agreement with the gBGC model, we show that differences in SCU among functional categories are explained by variation in intragenic recombination rate, which, in turn, is strongly negatively correlated to gene expression levels during meiosis. Our results indicate that variation in SCU among functional categories (including variation associated to differentiation or proliferation) result from differences in levels of meiotic transcription, which interferes with the formation of crossovers and thereby affects gBGC intensity within genes. Overall, the gBGC model explains 70% of the variance in SCU among genes. We argue that the strong heterogeneity of SCU induced by gBGC in mammalian genomes precludes any optimization of the tRNA pool to the demand in codon usage.
Nitrogen cost minimization is promoted by structural changes in the transcriptome of N deprivedProchlorococcuscells
Authors: Read Robert W. , Berube Paul M. , Biller Steven J. , Neveux Iva , Cubillos-Ruiz Andres , Chisholm Sallie W. , Grzymski Joseph J. 
Published: November 2016

AbstractProchlorococcusis a globally abundant marine cyanobacterium with many adaptations that reduce cellular nutrient requirements, facilitating growth in its nutrient-poor environment. One such genomic adaptation is the preferential utilization of amino acids containing fewer N-atoms, which minimizes cellular nitrogen requirements. We predicted that transcriptional regulation might be used to further reduce cellular N budgets during transient N limitation. To explore this, we compared transcription start sites (TSSs) inProchlorococcusMED4 under N-deprived and N-replete conditions. Of 64 genes with primary and internal TSSs in both conditions, N-deprived cells initiated transcription downstream of primary TSSs more frequently than N-replete cells. Additionally, 117 genes with only an internal TSS demonstrated increased internal transcription under N-deprivation. These shortened transcripts encode predicted proteins with ~5-20% less N content compared to full-length transcripts. We hypothesized that low translation rates, which afford greater control over protein abundances, would be beneficial to relatively slow-growing organisms likeProchlorococcus. Consistent with this idea, we found thatProchlorococcusexhibits greater usage of glycine-glycine motifs, which cause translational pausing, when compared to faster growing microbes. Our findings indicate that structural changes occur within theProchlorococcusMED4 transcriptome during N-deprivation, potentially altering the size and structure of proteins expressed under nutrient limitation.
Optical-flow analysis toolbox for characterization of spatiotemporal dynamics in mesoscale optical imaging of brain activity
Authors: Afrashteh Navvab , Inayat Samsoon , Mohsenvand Mostafa , Mohajerani Majid H. 
Published: November 2016

AbstractWide-field optical imaging techniques constitute powerful tools to sample and study mesoscale neuronal activity. The sampled data constitutes a sequence of image frames in which one can perceive the flow of brain activity starting and terminating at source and sink locations respectively. The most common data analyses include qualitative assessment to identify sources and sinks of activity as well as their trajectories. The quantitative analyses is mostly based on computing the temporal variation of the intensity of pixels while a few studies have also reported estimates of wave motion using optical-flow techniques from computer vision. A comprehensive toolbox for the quantitative analyses of mesoscale brain activity data however is still missing. We present a graphical-user-interface based Matlab®toolbox for investigating the spatiotemporal dynamics of mesoscale brain activity using optical-flow analyses. The toolbox includes the implementation of three optical-flow methods namely Horn-Schunck, Combined Local-Global, and Temporospatial algorithms for estimating velocity vector fields of perceived flow in mesoscale brain activity. From the velocity vector fields we determine the locations of sources and sinks as well as the trajectories and temporal velocities of activity flow. Using our toolbox, we compare the efficacy of the three optical-flow methods for determining spatiotemporal dynamics by using simulated data. We also demonstrate the application of optical-flow methods onto sensory-evoked calcium and voltage imaging data. Our results indicate that the combined local-global method we employ, yields results that correlate with the manual assessment. The automated approach permits rapid and effective quantification of mesoscale brain dynamics and may facilitate the study of brain function in response to new experiences or pathology.Conflicts of InterestnoneAuthor contribution statementMHM, MM, NV, and SI designed the study. NA and SI wrote Matlab®code for the toolbox and designed the simulated data. MHM, and NA performed the experiments. NA and SI analyzed the data. SI, NA, and MHM wrote the manuscript.
Modulation of Body Mass Composition using Vestibular Nerve Stimulation
Authors: McGeoch Paul D. , McKeown Jason , Peterson Hans , Ramachandran V.S. 
Published: November 2016

AbstractThere is increasing evidence of a “set-point” for body weight in the brain, that is regulated by the hypothalamus. This system modifies feeding behavior and metabolic rate, to keep body fat within predetermined parameters. It is also known that animals subjected to chronic centrifugation show a reduction in body fat. Experiments with mutant mice found that this loss of fat appears to be mediated by a vestibulo-hypothalamic pathway. Vestibular nerve stimulation (VeNS), also known as galvanic vestibular stimulation, involves non-invasively stimulating the vestibular system by applying a small electrical current between two electrodes placed over the mastoid processes. We suggest that any means of repeatedly stimulating the otolith organs in humans would cause a reduction in total body fat, and that VeNS would be a useful technique to use in this regard. Below we provide pilot data to support this idea.
Problems with Estimating Anthesis Phenology Parameters inZea mays: Consequences for Combining Ecophysiological Models with Genetics
Authors: Lamsal Abhishes , Welch Stephen M. , White Jeffrey W. , Thorp Kelly R. , Bello Nora 
Published: November 2016

AbstractEcophysiological crop models encode intra-species behaviors using constant parameters that are presumed to summarize genotypic properties. Accurate estimation of these parameters is crucial because much recent work has sought to link them to genotypes. The original goal of this study was to fit the anthesis date component of the CERES-Maize model to 5266 genetic lines grown at 11 site-years and genetically map the resulting parameter estimates. Although the resulting estimates had high predictive quality, numerous artifacts emerged during estimation. The first arose in situations where the model was unable to express the observed data for many lines, which ended up sharing the same parameter value. In the second (2254 lines), the model reproduced the data but there were often many parameter sets that did so equally well (equifinality). These artifacts made genetic mapping impossible, thus, revealing cautionary insights regarding a major current paradigm for linking process based models to genetics.
Cytokine and cellular responses to human herpesvirus‐6B in patients with B‐acute lymphoblastic leukemia
Authors: Nefzi Faten , Lambert Claude , Gautheret‐Dejean Agnès , Fisson Sylvain , Khebizi Quentin , Khelif Abderrahim , Agut Henri , Aouni Mahjoub 
Published: November 2016

ABSTRACTPrimary infection with human herpesvirus‐6 (HHV‐6), is followed by its lifelong persistence in the host. Most T‐cell responses to HHV‐6 have been characterized using peripheral blood from healthy adults; however, the role of HHV‐6 infection in immune modulation has not been elucidated for some diseases. Therefore, in this study the immune response to HHV‐6 infection in patients with B‐acute lymphoblastic leukemia (B‐ALL) was analyzed. HHV‐6 load was quantified in blood samples taken at the time of diagnosis of leukemia and on remission. The same concentrations of anti‐ and pro‐inflammatory cytokines (IL‐4, IL‐1, IL‐6, IL‐8, IL‐12p70, IL‐17a, TNF‐α and IFN‐γ) were detected in plasma samples from 20 patients with and 20 without detectable HHV‐6 virus loads in blood. Characterization of T‐cell responses to HHV‐6 showed low specific T‐cells frequencies of 2.08% and 1.46% in patients with and without detectable viral loads, respectively. IFN‐γ‐producing T cells were detected in 0.03%–0.23% and in 0%–0.2% of CD4+T cells, respectively. Strong production of IL‐6 was detected in medium supernatants of challenged T‐cells whatever the HHV‐6 status of the patients (973.51 ± 210.06 versus 825.70 ± 210.81 pg/mL). However, concentrations of TNF‐α and IFN‐γ were low. Thus, no association between plasma concentrations of cytokines and detection of HHV‐6 in blood was identified, suggesting that HHV‐6 is not strongly associated with development of B‐ALL. The low viral loads detected may correspond with latently infected cells. Alternatively, HHV‐6B specific immune responses may be below the detection threshold of the assays used.
The missing link in grassland restoration: arbuscular mycorrhizal fungi inoculation increases plant diversity and accelerates succession
Authors: Koziol Liz , Bever James D. 
Published: November 2016

Summary

Because soil microbial communities are often altered by anthropogenic disturbance, successful plant community restoration may require the restoration of beneficial soil microbes, such as arbuscular mycorrhizal (AM) fungi. Recent evidence suggests that later successional grassland species are more strongly affected by AM fungi relative to early successional plants and that late successional plants consistently benefit from some AM fungi but not other AM fungal species. Many of these late successional species are also often missing in restorations despite being heavily seeded.

To assess the effects of AM fungal composition within grassland restorations, we inoculated plots with six different AM fungal community treatments including one of four different AM fungal species isolated from a prairie, a mixture of all four fungal species, and a non‐inoculated control. AM fungi were introduced by planting 16 different inoculated nurse plants into replicated plots. We also seeded the restoration with a diverse, 54 species prairie seed mixture.

We found that AM fungal inoculation drove plant community composition; plots inoculated with certain AM fungal treatments were dominated by desirable prairie plants, whereas plots inoculated with other AM fungal species and the non‐inoculated control were dominated by non‐desirable plants including weeds and exotic species. Specifically, we found that many early successional species established well regardless of AM fungal inoculation, whereas the establishment and growth of many late successional species was strongly dependent on the presence of specific AM fungal species. Many conservative late successional species did not occur without inoculation. Overall, total plant community richness, diversity, and Floristic Quality Index were all significantly improved with AM fungal inoculation, whereas we observed that non‐desirable plant abundance was significantly greater in the non‐inoculated plots.

Synthesis and applications. Our results suggest that the lack of late successional establishment reported in many previous restorations may be due to ineffective arbuscular mycorrhizal fungal communities at these sites. We conclude that the reintroduction of arbuscular mycorrhizal fungi from reference prairie environments could improve restoration outcomes by promoting plant diversity and richness, especially for desirable later successional plant species, while simultaneously inhibiting less desirable weedy plants.