bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive-unlabeled ensemble learning for kinase substrate prediction from dynamic phosphoproteomics data
Authors: Yang Pengyi , Humphrey Sean J. , James David E. , Yang Yee Hwa , Jothi Raja 
Published: September 2015

Abstract
Motivation: Protein phosphorylation is a post-translational modification that underlines various aspects of cellular signaling. A key step to reconstructing signaling networks involves identification of the set of all kinases and their substrates. Experimental characterization of kinase substrates is both expensive and time-consuming. To expedite the discovery of novel substrates, computational approaches based on kinase recognition sequence (motifs) from known substrates, protein structure, interaction and co-localization have been proposed. However, rarely do these methods take into account the dynamic responses of signaling cascades measured from in vivo cellular systems. Given that recent advances in mass spectrometry-based technologies make it possible to quantify phosphorylation on a proteome-wide scale, computational approaches that can integrate static features with dynamic phosphoproteome data would greatly facilitate the prediction of biologically relevant kinase-specific substrates.
Results: Here, we propose a positive-unlabeled ensemble learning approach that integrates dynamic phosphoproteomics data with static kinase recognition motifs to predict novel substrates for kinases of interest. We extended a positive-unlabeled learning technique for an ensemble model, which significantly improves prediction sensitivity on novel substrates of kinases while retaining high specificity. We evaluated the performance of the proposed model using simulation studies and subsequently applied it to predict novel substrates of key kinases relevant to insulin signaling. Our analyses show that static sequence motifs and dynamic phosphoproteomics data are complementary and that the proposed integrated model performs better than methods relying only on static information for accurate prediction of kinase-specific substrates.
Availability and implementation: Executable GUI tool, source code and documentation are freely available at https://github.com/PengyiYang/KSP-PUEL.
Contact: pengyi.yang@nih.gov or jothi@mail.nih.gov
Supplementary information: Supplementary data are available at Bioinformatics online.
Association between malignancy and non-alcoholic Wernicke's encephalopathy: a case report and literature review
Authors: Choi Evan Y. , Gomes William A. , Haigentz Missak , Graber Jerome J. 
Published: September 2015

AbstractBackgroundWernicke's encephalopathy is a serious medical condition associated with high morbidity and mortality caused by deficiency of thiamine. This disease is classically associated with alcoholism, but is underappreciated in the nonalcoholic population. There is growing acknowledgement of the development of Wernicke's encephalopathy in patients with malignancies.MethodsWe conducted a literature review in PubMed for cases of Wernicke's encephalopathy occurring in patients with malignancy. We also present the case of a 47-year-old woman with recurrent laryngeal cancer and multiple hospital admissions for malnutrition. Neurological examination was notable for pendular nystagmus, severe gait ataxia, confusion, and poor memory consolidation. MRI of the brain was significant for T2-weighted fluid-attenuated inversion recovery hyperintensities in periaqueductal regions, medial thalami, and the tectal plate, typical for Wernicke's encephalopathy. She was treated with thiamine repletion, and had marked improvement in her mental status and some improvement in her vision problems and ataxia, although some nystagmus and significant short-term memory impairment persisted.ResultsThe literature review yielded dozens of case reports of Wernicke's encephalopathy in patients with malignancy, dominated by cases of patients with malignancies of the gastrointestinal system, followed by those with hematologic malignancies.ConclusionsMalignancy is an important risk factor for the development of Wernicke's encephalopathy. This diagnosis is underappreciated and difficult for the clinician to discern from multifactorial delirium. Clinicians should be aware to treat at-risk patients with thiamine immediately, especially if multiple risk factors are present.
Intensifying Antiretroviral Therapy With Raltegravir and Maraviroc During Early Human Immunodeficiency Virus (HIV) Infection Does Not Accelerate HIV Reservoir Reduction
Authors: Ostrowski Mario , Benko Erika , Yue Feng Yun , Kim Connie J. , Huibner Sanja , Lee Terry , Singer Joel , Pankovich Jim , Laeyendecker Oliver , Kaul Rupert , Kandel Gabor , Kovacs Colin 
Published: September 2015

Abstract
Background.  Persistent human immunodeficiency virus (HIV) within the CD4+ T-cell reservoir is an obstacle to eradication. We hypothesized that adding raltegravir and maraviroc to standard combination antiretroviral therapy (cART) during early HIV infection could substantially reduce viral reservoirs as a step towards eradication.
Methods.  A prospective, randomized, double-blinded, placebo-controlled pilot trial enrolled 32 participants with documented early (&lt;6 months) HIV infection to either standard cART (emtricitabine/tenofovir/lopinavir/ritonavir) or intensive cART (standard regimen + raltegravir/maraviroc). Human immunodeficiency virus reservoirs were assessed at baseline and at 48 weeks by (1) proviral DNA, (2) cell-associated RNA, and (3) replication-competent virus, all from purified blood CD4+ T cells, and (4) gut proviral DNA. A multiassay algorithm (MAA) on baseline sera estimated timing of infection.
Results.  Thirty individuals completed the study to the 48-week endpoint. The reduction in blood proviral burden was −1.03 log DNA copies/106 CD4+ T cells versus −.84 log in the standard and intensive groups, respectively (P = .056). Overall, there was no significant difference in the rate of decline of HIV-associated RNA, replication-competent virus in blood CD4+ T cells, nor proviral gut HIV DNA to 48 weeks. Individuals who presented with more recent HIV infection had significantly lower virus reservoirs, and cART tended to reduce their reservoirs to a greater extent.
Conclusions.  Intensive cART led to no additional reduction in the blood virus reservoir at 48 weeks compared with standard cART. Human immunodeficiency virus reservoir size is smaller earlier in HIV infection. Other novel treatment strategies in combination with early cART will be needed to eliminate the HIV latent reservoir.
Secondary Epiretinal Membrane After Trabeculectomy
Authors: Vieira Luísa , Cabugueira Ana , Borges Bárbara , Carvalho Vanessa , Noronha Manuel , Abegão Pinto Luis , Reina Maria , Dutra Medeiros Marco 
Published: September 2015

Purpose:
To determine the frequency of epiretinal membranes (ERM) in eyes with primary open-angle glaucoma subjected to trabeculectomy.

Methods:
We conducted a retrospective study on patients subjected to trabeculectomy with at least a 6-month follow-up. Ophthalmologic examination and spectral-domain optical coherence tomography (SD-OCT) were analyzed. Eyes with previous surgical or laser treatments or other pathologies (other than glaucoma and ERM) were excluded.

Results:
A total of 50 eyes (40 patients) were included in this study. The mean follow-up time after surgery was 27.8 months. After surgery, 9 eyes (18%) had preretinal macular fibrosis and 19 eyes (38%) had cellophane macular reflex. Of the 16 eyes with a preoperative macular SD-OCT, 3 (18.8%) developed ERM and 4 (25%) progressed from cellophane macular reflex to preretinal macular fibrosis, after surgery. The ERM frequency did not differ significantly between eyes subjected to trabeculectomy with or without the use of antimetabolites (P=0.08), or between eyes subjected to simple or combined surgery (phacotrabeculectomy) (P=0.09).

Conclusion:
Trabeculectomy may predispose one to the appearance and progression of ERM. Further studies are needed to clarify this intriguing relation.
Lateral Canthal Tendon Disinsertion: Clinical Characteristics and Anatomical Correlates
Authors: Shriver Erin M. , Erickson Benjamin P. , Kossler Andrea L. , Tse David T. 
Published: September 2015

Purpose:
To highlight features of lateral canthal tendon disinsertion (LCTD), provide an algorithm for systematic assessment, and describe the anatomic genesis of signs and symptoms.

Methods:
Retrospective case series of consecutive patients with lateral canthal tendon disinsertion, who underwent lateral canthal tendon fixation by a single surgeon (DTT) between 2004 and 2011.

Results:
One hundred and seventeen eyes in 90 patients underwent lateral canthal tendon fixation. Average age was 69.3 ± 17.9 years. Twenty-three percentage of eyes had undergone lower eyelid blepharoplasty and 52% had undergone lateral canthal tightening; 35% had no previous periocular surgery. Patients with purely involutional lateral canthal tendon disinsertion were significantly older (76.1 ± 7.8 years of age; p < 0.03). Six key features associated with lateral canthal tendon disinsertion were identified. On static evaluation: 1) a blunted or vertically displaced lateral canthal angle; 2) a narrow horizontal fissure with reduced temporal scleral triangle; and 3) pseudo eyelid retraction. On dynamic evaluation with attempted closure: 4) medial and inferior movement of the lateral commissure; 5) incomplete apposition of the eyelid margins in the absence of anterior lamellar shortage; and 6) temporal eyelid imbrication. Improved blink dynamics with manual lateral canthal tendon complex repositioning (“the thumb test”) predicted a favorable outcome with surgical tightening in 95.7% of cases.

Conclusions:
Lateral canthal tendon disinsertion results in altered eyelid fissure symmetry, blink dynamics, and lacrimal pump function. The authors recommend the mnemonic—A.B.C.: for Aperture configuration, Blink dynamics, and eyelid Closure—to structure the examination of all symptomatic patients. Manual restoration of the disinserted lateral canthal tendon with the “thumb test” predicts favorable outcomes with surgical fixation.
Pseudomonas Aeruginosa: A Masquerader in Sino-Orbital Infections
Authors: Chen Xi , Bleier Benjamin S. , Lefebvre Daniel R. , Lee Nahyoung Grace 
Published: September 2015

Purpose:
To report 2 immunocompromised patients with sino-orbital necrotizing pseudomonas infections and review the literature.

Methods:
This is a noncomparative, retrospective case series, and review. The clinical data of 2 patients with histopathologic and microbiologic diagnoses of pseudomonas sinus infections causing orbital cellulitis were obtained from medical records. A retrospective literature review was performed on all reported cases of periorbital pseudomonas infections.

Results:
One patient with acquired immune deficiency syndrome was noted to have orbital cellulitis with clear visualization of eschar in the middle turbinate on nasal endoscopy. A second patient also had orbital cellulitis with ophthalmoplegia and presence of eschar in the sinus. Both patients had some degree of erosion through the lamina papyracea found on orbital imaging and both had intact vision without optic neuropathy. Pseudomonas infection was confirmed in both cases with permanent histopathology and cultures from conservative sinus debridement.

Conclusions:
Pseudomonas sino-orbital infections must be considered in the differential diagnosis in cases of eschar and orbital wall erosion especially when vision is preserved in immunocompromised individuals. This finding obviates the need for radical debridement including orbital exenteration, which can be indicated in cases of invasive fungal disease.
Local Resection and Brachytherapy for Primary Orbital Rhabdomyosarcoma: Outcome and Failure Pattern Analysis
Authors: Schoot Reineke A. , Saeed Peerooz , Freling Nicole J. , Blank Leo E. C. M. , Pieters Bradley R. , van der Grient Johan N. B. , Strackee Simon D. , Bras Johannes , Caron Huib N. , Merks Johannes H. M. 
Published: September 2015

Purpose:
Survival in patients with orbital rhabdomyosarcoma (RMS) is excellent. Therefore, new local treatment modalities, such as brachytherapy, have been developed to minimize adverse events. Since 1990, patients with orbital RMS and a residual tumor after induction chemotherapy were eligible for resection and brachytherapy. Otherwise patients received external beam radiotherapy. In this study, the authors describe the outcome for 20 patients with primary orbital RMS. The aim was to assess risk factors for treatment failure in this single center cohort.

Methods:
In this retrospective cohort study, the authors reviewed imaging studies, surgery reports, histology reports, and radiotherapy plans in a multidisciplinary setting. The authors included 20 consecutive patients with orbital RMS, treated between 1990 and 2007, (median age: 7.4 years, range: 0.7–16.1; median follow up: 11.5 years).

Results:
After induction chemotherapy, 12 patients were treated with surgery and brachytherapy, 2 with external beam radiotherapy, and in 5 patients who achieved complete remission, local treatment was withheld. In 1 patient, brachytherapy was incorrectly withheld after delayed surgery. Seven patients relapsed (no local treatment, N = 2; surgery and brachytherapy, N = 2; external beam radiotherapy, N = 2; surgery only, N = 1). The authors found no patient, tumor, or treatment characteristics that predisposed for treatment failure. Ten-year-overall survival and event-free survival were 89% and 65%, respectively.

Conclusions:
Overall survival in this cohort of orbital RMS patients was good, including surgery and brachytherapy as treatment modality for orbital RMS resulted in an effective local treatment approach with fewer adverse events than external beam radiotherapy. The authors could not identify factors predisposing for treatment failure.
Sustained fitness gains and variability in fitness trajectories in the long-term evolution experiment withEscherichia coli
Authors: Lenski Richard E. , Wiser Michael J. , Ribeck Noah , Blount Zachary D. , Nahum Joshua R. , Morris J. Jeffrey , Zaman Luis , Turner Caroline B. , Wade Brian D. , Maddamsetti Rohan , Burmeister Alita R. , Baird Elizabeth J. , Bundy Jay , Grant Nkrumah A. , Card Kyle J. , Rowles Maia , Weatherspoon Kiyana , Papoulis Spiridon E. , Sullivan Rachel , Clark Colleen , Mulka Joseph S. , Hajela Neerja 
Published: September 2015

AbstractMany populations live in environments subject to frequent biotic and abiotic changes. Nonetheless, it is interesting to ask whether an evolving population’s mean fitness can increase indefinitely, and potentially without any limit, even in a constant environment. A recent study showed that fitness trajectories ofEscherichia colipopulations over 50,000 generations were better described by a power-law model than by a hyperbolic model. According to the power-law model, the rate of fitness gain declines over time but fitness has no upper limit, whereas the hyperbolic model implies a hard limit. Here, we examine whether the previously estimated power-law model predicts the fitness trajectory for an additional 10,000 generations. To that end, we conducted more than 1100 new competitive fitness assays. Consistent with the previous study, the power-law model fits the new data better than the hyperbolic model. We also analysed the variability in fitness among populations, finding subtle, but significant, heterogeneity in mean fitness. Some, but not all, of this variation reflects differences in mutation rate that evolved over time. Taken together, our results imply that both adaptation and divergence can continue indefinitely— or at least for a long time—even in a constant environment.
Purification, crystallization and X-ray crystallographic analysis of human RAB11(S20V), a constitutively active GTP-binding form
Authors: Kim Chang Min , Choi Jae Young , Yoon Jong Hwan , Park Hyun Ho 
Published: September 2015

RAB11, a member of the Ras superfamily of small G proteins, is involved in the regulation of vesicle trafficking during endosome recycling. Substitution of Ser20 by Val20 in Rab11 [RAB11(S20V)] inhibits its GTP hydrolysis activity and produces a constitutively active GTP-binding form. In this study, the RAB11(S20V) mutant was overexpressed inEscherichia coliwith an engineered C-terminal His tag. RAB11(S20V) was then purified to homogeneity and was crystallized at 293 K. X-ray diffraction data were collected to a resolution of 2.4 Å from a crystal belonging to space groupI4, with unit-cell parametersa = 74.11,b= 74.11,c= 149.44 Å. The asymmetric unit was estimated to contain two molecules of RAB11(S20V).
Home is where the shell is: predicting turtle home range sizes
Authors: Slavenko Alex , Itescu Yuval , Ihlow Flora , Meiri Shai 
Published: September 2015

Summary

Home range is the area traversed by an animal in its normal activities. The size of home ranges is thought to be tightly linked to body size, through size effect on metabolic requirements. Due to the structure of Eltonian food pyramids, home range sizes of carnivores are expected to exceed those of herbivorous species. The habitat may also affect home range size, with reduced costs of locomotion or lower food abundance in, for example, aquatic habitats selecting for larger home ranges. Furthermore, home range of males in polygamous species may be large due to sexual selection for increased reproductive output.

Comparative studies on home range sizes have rarely been conducted on ectotherms. Because ectotherm metabolic rates are much lower than those of endotherms, energetic considerations of metabolic requirements may be less important in determining the home range sizes of the former, and other factors such as differing habitats and sexual selection may have an increased effect.

We collected literature data on turtle home range sizes. We used phylogenetic generalized least squares analyses to determine whether body mass, sex, diet, habitat and social structure affect home range size.

Turtle home range size increases with body mass. However, body mass explains relatively little of the variation in home range size. Aquatic turtles have larger home ranges than semiaquatic species. Omnivorous turtles have larger home ranges than herbivores and carnivores, but diet is not a strong predictor. Sex and social structure are unrelated to home range size.

We conclude that energetic constraints are not the primary factor that determines home range size in turtles, and energetic costs of locomotion in different habitats probably play a major role.
Ecological traits affect the sensitivity of bees to land‐use pressures in European agricultural landscapes
Authors: De Palma Adriana , Kuhlmann Michael , Roberts Stuart P.M. , Potts Simon G. , Börger Luca , Hudson Lawrence N. , Lysenko Igor , Newbold Tim , Purvis Andy 
Published: September 2015

Summary

Bees are a functionally important and economically valuable group, but are threatened by land‐use conversion and intensification. Such pressures are not expected to affect all species identically; rather, they are likely to be mediated by the species' ecological traits.

Understanding which types of species are most vulnerable under which land uses is an important step towards effective conservation planning.

We collated occurrence and abundance data for 257 bee species at 1584 European sites from surveys reported in 30 published papers (70 056 records) and combined them with species‐level ecological trait data. We used mixed‐effects models to assess the importance of land use (land‐use class, agricultural use‐intensity and a remotely‐sensed measure of vegetation), traits and trait × land‐use interactions, in explaining species occurrence and abundance.

Species' sensitivity to land use was most strongly influenced by flight season duration and foraging range, but also by niche breadth, reproductive strategy and phenology, with effects that differed among cropland, pastoral and urban habitats.

Synthesis and applications. Rather than targeting particular species or settings, conservation actions may be more effective if focused on mitigating situations where species' traits strongly and negatively interact with land‐use pressures. We find evidence that low‐intensity agriculture can maintain relatively diverse bee communities; in more intensive settings, added floral resources may be beneficial, but will require careful placement with respect to foraging ranges of smaller bee species. Protection of semi‐natural habitats is essential, however; in particular, conversion to urban environments could have severe effects on bee diversity and pollination services. Our results highlight the importance of exploring how ecological traits mediate species responses to human impacts, but further research is needed to enhance the predictive ability of such analyses.
The development and pilot testing of an occupational therapy group participation rating scale for inpatient mental health settings
Authors: Scanlan Justin Newton , Argent Stacey , Ayling Brooke , Mouawad Arianne , Woodward Mary 
Published: September 2015

IntroductionAlthough group facilitation is a common task for occupational therapists in inpatient mental health settings and groups provide excellent opportunities to observe functioning, it can be difficult to report this information efficiently and effectively. To overcome these challenges, a group participating rating scale was developed. The scale was printed onto stickers so that upon completion, it could be placed directly into the medical record. This pilot study was undertaken to explore the measurement properties and construct validity of the rating scale.MethodData were extracted from 528 rating scales completed for 51 individuals admitted to the inpatient unit where the study was conducted. Many‐faceted Rasch analysis was used to examine several aspects of validity: rating scale validity; item functioning and person performance validity; statistical validity; and overall construct validity. In addition, to explore the capacity of the scale to detect change over time, the data were explored for differences in ratings over the course of individuals’ admissions.ResultsRating scale functioning, item functioning and person performance validity were generally acceptable and statistical validity was good. Overall construct validity was generally acceptable, although there was a substantial ‘ceiling effect’ present. There were significant differences between ratings for individuals over time, suggesting that the scale may be effective in detecting change over time.ConclusionThe rating scale has two main benefits: improving the quality and consistency of reporting of group participation assessment findings and the potential ability to track the quality (and quantity) of group participation over time. Other, secondary benefits included recognition of occupational therapy and reduced documentation time.
The Essays of Patrick Collinson: Or, Politics with the Religion Put Back
Authors: Shagan Ethan H. 
Published: September 2015

AbstractThis essay analyses Patrick Collinson's contributions as an essayist and writer of short‐form historical articles, with special attention to his concept of the ‘monarchical republic’ but more broadly focused on his vision of the interplay between religion and politics throughout his long career. It argues that Collinson saw politics as fundamentally a struggle of ideas, especially religious ideas, but that he downplayed the potential instability or violence of religious politics by emphasizing the sincerity with which early modern figures sought to reform their world. This might, the article concludes, be giving religious politics just a bit too much credit.