bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of advection loss due to wind and estuarine circulation on the timing of the spring phytoplankton bloom in a fjord
Authors: Wolfe A. Megan , Allen Susan E. , Hodal Michal , Pawlowicz Rich , Hunt Brian P. V. , Tommasi Desiree 
Published: September 2015

AbstractA coupled biophysical model is used to explore the physical controls involved in the timing of the spring phytoplankton bloom in fjords. Observations from Rivers Inlet, British Columbia, are used to force and evaluate the model. It is found that the interannual variation in timing is due primarily to variations in retention, in particular, to variations in horizontal advection out of the fjord. The two dominant processes are (i) strong outflow winds rapidly advecting the surface layer and thus the phytoplankton population out of the fjord and (ii) losses due to high river flux increasing the estuarine circulation. Both processes delay the timing of spring bloom. Smaller effects on the interannual variation are due to increased wind mixing which deepens the mixing layer and reduces light to phytoplankton, and increased river flow which increases the stratification and decreases the mixing layer depth. Observed interannual variations in cloudiness were small. Strong outflow winds are common in winter along the British Columbia coast, but generally cease after the spring wind transition. Thus, observed interdecadal variations in the spring transition date probably imply strong variations in the timing of spring phytoplankton blooms in British Columbia fjords.
Regulatory B cells mediate tolerance to apoptotic self in health: implications for disease
Authors: Gray Mohini , Gray David 
Published: September 2015

AbstractB cells are able to regulate immune responses through the secretion of IL-10 and other inhibitory cytokines, though no transcription factor that can define ‘regulatory B cells’ as a separate lineage has yet been found. Instead it is likely that this function arises as a result of the immune context in which B cells find themselves and the stimuli they perceive. However, some B cells found within the B1a and the marginal zone subsets have a greater propensity to produce IL-10 than others. What are the natural stimuli for these cells to induce immune regulation? We discuss the role that the recognition of autoantigens exposed by apoptotic cells plays in stimulating IL-10 production in mouse and human studies. This mechanism involves the recognition and uptake of self-antigens by autoreactive BCRs, for delivery to endocytic compartments, where apoptosis-derived DNA binds to TLR9, driving IL-10 production. These ‘natural’ regulatory B cells represent a way of maintaining tolerance to self. We discuss how this may operate in inflammatory lesions where there is an excess of apoptotic leukocytes and how this impacts on our understanding of autoimmune disease.
A case study in open source innovation: developing the Tidepool Platform for interoperability in type 1 diabetes management
Authors: Neinstein Aaron , Wong Jenise , Look Howard , Arbiter Brandon , Quirk Kent , McCanne Steve , Sun Yao , Blum Michael , Adi Saleh 
Published: September 2015

Abstract
Objective Develop a device-agnostic cloud platform to host diabetes device data and catalyze an ecosystem of software innovation for type 1 diabetes (T1D) management.
Materials and Methods An interdisciplinary team decided to establish a nonprofit company, Tidepool, and build open-source software.
Results Through a user-centered design process, the authors created a software platform, the Tidepool Platform, to upload and host T1D device data in an integrated, device-agnostic fashion, as well as an application (“app”), Blip, to visualize the data. Tidepool’s software utilizes the principles of modular components, modern web design including REST APIs and JavaScript, cloud computing, agile development methodology, and robust privacy and security.
Discussion By consolidating the currently scattered and siloed T1D device data ecosystem into one open platform, Tidepool can improve access to the data and enable new possibilities and efficiencies in T1D clinical care and research. The Tidepool Platform decouples diabetes apps from diabetes devices, allowing software developers to build innovative apps without requiring them to design a unique back-end (e.g., database and security) or unique ways of ingesting device data. It allows people with T1D to choose to use any preferred app regardless of which device(s) they use.
Conclusion The authors believe that the Tidepool Platform can solve two current problems in the T1D device landscape: 1) limited access to T1D device data and 2) poor interoperability of data from different devices. If proven effective, Tidepool’s open source, cloud model for health data interoperability is applicable to other healthcare use cases.
Combining billing codes, clinical notes, and medications from electronic health records provides superior phenotyping performance
Authors: Wei Wei-Qi , Teixeira Pedro L , Mo Huan , Cronin Robert M , Warner Jeremy L , Denny Joshua C 
Published: September 2015

Abstract
Objective To evaluate the phenotyping performance of three major electronic health record (EHR) components: International Classification of Disease (ICD) diagnosis codes, primary notes, and specific medications.
Materials and Methods We conducted the evaluation using de-identified Vanderbilt EHR data. We preselected ten diseases: atrial fibrillation, Alzheimer’s disease, breast cancer, gout, human immunodeficiency virus infection, multiple sclerosis, Parkinson’s disease, rheumatoid arthritis, and types 1 and 2 diabetes mellitus. For each disease, patients were classified into seven categories based on the presence of evidence in diagnosis codes, primary notes, and specific medications. Twenty-five patients per disease category (a total number of 175 patients for each disease, 1750 patients for all ten diseases) were randomly selected for manual chart review. Review results were used to estimate the positive predictive value (PPV), sensitivity, and F -score for each EHR component alone and in combination.
Results The PPVs of single components were inconsistent and inadequate for accurately phenotyping (0.06–0.71). Using two or more ICD codes improved the average PPV to 0.84. We observed a more stable and higher accuracy when using at least two components (mean ± standard deviation: 0.91 ± 0.08). Primary notes offered the best sensitivity (0.77). The sensitivity of ICD codes was 0.67. Again, two or more components provided a reasonably high and stable sensitivity (0.59 ± 0.16). Overall, the best performance ( F score: 0.70 ± 0.12) was achieved by using two or more components. Although the overall performance of using ICD codes (0.67 ± 0.14) was only slightly lower than using two or more components, its PPV (0.71 ± 0.13) is substantially worse (0.91 ± 0.08).
Conclusion Multiple EHR components provide a more consistent and higher performance than a single one for the selected phenotypes. We suggest considering multiple EHR components for future phenotyping design in order to obtain an ideal result.
The Associations Between Pain-related Beliefs, Pain Intensity, and Patient Functioning
Authors: Jensen Mark P. , Galer Peter D. , Johnson Linea L. , George Holly R. , Mendoza M. Elena , Gertz Kevin J. 
Published: September 2015

Objectives:
On the basis of the idea that thoughts held about pain may represent “self-suggestions” and evidence indicating that people with higher levels of trait hypnotizability are more responsive to suggestions, the current study evaluated hypothesized moderating effects of hypnotizability on the associations between pain-related thoughts and both pain intensity and pain interference.

Methods:
Eighty-five individuals with chronic pain were given measures of hypnotizability, pain intensity, pain interference, and pain-related thoughts (control beliefs, catastrophizing).

Results:
Analyses supported a moderating role of hypnotizability on the association between control beliefs and pain interference. Specifically, the negative association between pain control beliefs and pain interference were stronger among those with higher trait hypnotizability than between those with lower trait hypnotizability.

Discussion:
The study findings, if replicated in additional samples of individuals with chronic pain, have important clinical and theoretical implications. For example, if trait hypnotizability is found to predict an individual’s response to a particular technique of cognitive therapy—such as focusing on and repeating pain control belief self-statements—measures of hypnotizability could be used to identify individuals who might be most responsive to this technique. The current findings indicate that research to further examine this possibility is warranted.
Basal Ganglia Perfusion in Fibromyalgia is Related to Pain Disability and Disease Impact
Authors: Shokouhi Mahsa , Davis Karen D. , Moulin Dwight E. , Morley-Forster Pat , Nielson Warren R. , Bureau Yves , St. Lawrence Keith 
Published: September 2015

Objectives:
Pain disability is a major impediment to fibromyalgia (FM) patients’ quality of life. Neuroimaging studies have demonstrated abnormal pain processing in FM. However, it is not known whether there are brain abnormalities linked to pain disability. Understanding neural correlates of pain disability in FM, independent from pain intensity, could provide a framework to guide future more efficient therapy strategies to improve patients’ functional ability.

Methods:
We used arterial spin labeling to image cerebral blood flow (CBF) in 23 FM patients and 16 controls. Functional connectivity was also estimated using blood oxygenation level–dependent imaging to further investigate the possible underpinnings of the observed CBF changes.

Results:
Among patients, CBF in the basal ganglia correlated negatively with pain disability index and positively with the overall impact of FM (Fibromyalgia Impact Questionnaire) but did not correlate with pain intensity. Whole-brain analysis revealed no CBF differences between the 2 groups; however, post hoc analysis in the basal ganglia showed CBF reductions mainly in the right putamen and right lateral globus pallidus in patients, likely reflecting the negative correlation with the pain disability index. However, the connectivity of the corresponding corticobasal ganglia-thalamus loop, that is, motor network (the connection between supplementary motor area, putamen, and thalamus) remained intact.

Discussion:
Basal ganglia perfusion reflects long-term symptoms, including somatic and psychological components of FM rather than pain intensity. These CBF findings may reflect differences in behavioral and psychological responses between patients.
A New Fitting Approach for Providing Adequate Comfort and Visual Performance in Keratoconus: Soft HydroCone (Toris K) Lenses
Authors: Gumus Koray , Kahraman Nisa 
Published: September 2015

Objective:
To evaluate the comfort and visual performance of soft HydroCone (Toris K) silicone hydrogel lenses in keratoconus patients.

Methods:
Fifty eyes of 50 keratoconic patients who were fitted with the Toris K lens were included in the study. All patients were evaluated at baseline and after 2 weeks of lens wear. Uncorrected and best-corrected visual acuities were measured. Corneal topography, ocular aberrations, and point spread function (PSF) were obtained using NIDEK-OPD Scan. Comfort level and visual performance in daytime and nighttime conditions were scored from 0 to 5 after 2 weeks of lens wear.

Results:
Best-corrected visual acuity was significantly better with the Toris K lens (P<0.001). Mean increase in visual acuity with the lens was 4.5 lines. Mean K1, K2, and Kmax values significantly decreased with the lens (P<0.001). Both total and higher-order root-mean-square errors were significantly corrected with the Toris K lens (P<0.001 and P=0.038, respectively). A significant correction of total coma and trefoil aberrations was achieved with the lens. Also, PSF values were significantly increased with the lens (P<0.001). Although comfort scores in 46 eyes (92.0%) were classified as good/excellent, only 4 eyes (8.0%) had moderate comfort scores. Visual acuity was classified as good/excellent in 46 eyes (92.0%) in daytime and in 38 eyes (76%) in nighttime conditions.

Conclusions:
Soft HydroCone silicone hydrogel keratoconus lenses should be considered as alternative visual correction for keratoconus patients. The soft and full-custom design provides optimal comfort and visual performance for the patients' daily requirements.
Endoscopic Surveillance After Repair of Oesophageal Atresia
Authors: Koivusalo Antti I. , Pakarinen Mikko P. , Lindahl Harry G. , Rintala Risto J. 
Published: September 2015

ABSTRACTAim:After repair of oesophageal atresia (OA), the need for endoscopic follow‐up (EFU) remains unclear. To end this, we assessed the trends of oesophageal mucosal changes in successive follow‐up biopsies.Methods:EFU records of 264 patients including histological grades of oesophagitis (from 0 to III), gastric (GM) or intestinal (IM) metaplasia and dysplasia (mild to severe) at 1, 3, 5 10, 15, and >15 years after repair of OA were reviewed.Results:Included were 209 patients with 616 biopsies. A total of 60 patients had undergone antireflux surgery and 24 had long‐gap OA (LG). Median follow‐up was 12 (range 1–17) years with 3 (1–6) endoscopies per patient. Highest grade of oesophagitis was Gr 0 (no oesophagitis) in 47%, Gr I in 37%, and Gr II or III in 16%. Metaplasia, GM (n = 31), IM (n = 4), occurred in 17% of patients and reached 15% prevalence by 15 years. Dysplasia and cancer were not found. From 1 to 15 years after repair grade of histological oesophagitis often fluctuated between Gr 0 and Gr I, but further progression was unlikely, hazard ratio = 0.2–3.4 (95% confidence interval 0.0–29), P = 0.06–0.87. LG and antireflux surgery predicted early detection of metaplasia (P < 0.001). Only 9% of patients with metaplasia and 32% with Gr II oesophagitis were symptomatic. A total of 6 (3%) patients had a symptomatic anastomotic stenosis at 1 year.Conclusions:EFU revealed frequent oesophagitis and metaplasia, but no dysplasia or cancer. Routine endoscopic surveillance had limited benefit and seems unnecessary during childhood after repair of OA.
Psittacosis associated with pet bird ownership: a concern for public health
Authors: Ferreira Vivian Lindmayer , Silva Marcos Vinícius , Nascimento Rodrigo Delfino , Raso Tânia Freitas 
Published: September 2015

Introduction:
Psittacosis is a zoonotic infectious disease caused by Chlamydia psittaci and most cases involve avian contact history. In humans, psittacosis induces symptoms ranging from mild ‘flu-like’ symptoms to serious atypical pneumonia. Unless specifically thought of, the diagnosis of psittacosis can be missed and the disease is usually treated as atypical pneumonia. Here, we detail cases of psittacosis related to pet birds.

Case presentation:
A 16-year-old male was admitted with fever and persistent cough. The patient reported previous treatment with broad-spectrum antibiotics that led to limited improvement of his condition, and owning pet birds; thus, psittacosis was suspected. Serum samples from the patient were obtained and tested using a microimmunofluorescence assay, revealing an IgG titre of 64. An epidemiological investigation was conducted in five family members related to the patient; two possessed anti-C. psittaci antibodies (IgG titre = 64 and IgM titre = 20; IgG titre = 128 and IgA titre = 20). Additionally, C. psittaci DNA was detected by PCR carried out on the family's pet birds.

Conclusion:
Psittacosis probably occurs more often than reported. Individuals with milder cases may not seek medical attention, and physicians may not inquire about bird exposure. There is a need for awareness campaigns directed at health workers and birds owners.
Small Heat Shock Proteins and Eicosanoid Pathways Modulate Caspase-1 Activity in the Fat Bodies ofAntheraea pernyi
Authors: Zhang Congfen , Wang Lei , Wei Guoqing , Qian Cen , Dai Lishang , Sun Yu , Zhu Baojian , Liu Chaoliang 
Published: September 2015

AbstractAfter heat shock injury, a group of proteins that regulate protein-folding processes are synthesised to prevent damage. Caspase is an enzyme responsible for the execution ostress-induced apoptosis. Heat shock proteins (Hsp) are capable of modulating caspase activity. In addition to changes in protein synthesis, heat shock causes the release of arachidonic acid (AA) from plasma membranes and the subsequent synthesis of eicosanoids, i.e., activation of the AA pathways. The development of cytoprotective strategies might depend on whether caspase-1 activity is affected by heat shock preconditioning and the associated pharmacological modulations after heat shock injury. Therefore, we studied the effects of heat shock preconditioning and modulations of the eicosanoid pathways onAp-sHSP20.8and on the final apoptotic effector enzyme caspase-1 to clarify whether these effects were modulated in the fat bodies ofAntheraea pernyiinjured by heat shock. We concluded that eicosanoid biosynthesis inhibitors might be utilised to simultaneously decrease Hsp 20.8 synthesis and to increase caspase-1 activity. Modifications of the eicosanoid pathways might also be used to mediate caspase-1 activity under hyperthermic conditions, suggesting a novel mechanism for regulation of caspase-1 in the fat bodies ofA. pernyi
A Comparison of Methods: Normalizing High-Throughput RNA Sequencing Data
Authors: Reddy Rahul 
Published: September 2015

ABSTRACTAs RNA-Seq and other high-throughput sequencing grow in use and remain critical for gene expression studies, technical variability in counts data impedes studies of differential expression studies, data across samples and experiments, or reproducing results. Studies likeDillies et al. (2013)compare several between-lane normalization methods involving scaling factors, whileHansen et al. (2012)andRisso et al. (2014)propose methods that correct for sample-specific bias or use sets of control genes to isolate and remove technical variability. This paper evaluates four normalization methods in terms of reducingintra-group, technical variability and facilitating differential expression analysis or other research where the biological,inter-groupvariability is of interest. To this end, the four methods were evaluated in differential expression analysis between data fromPickrell et al. (2010)andMontgomery et al. (2010)and between simulated data modeled on these two datasets. Though the between-lane scaling factor methods perform worse on real data sets, they are much stronger for simulated data. We cannot reject the recommendation of Dillies et al. to use TMM and DESeq normalization, but further study of power to detect effects of different size under each normalization method is merited.
Genetic evidence challenges the native status of a threatened freshwater fish (Carassius carassius) in England
Authors: Jeffries Daniel L , Copp Gordon H , Handley Lori Lawson , Sayer Carl D , Hänfling Bernd 
Published: September 2015

AbstractA fundamental consideration for the conservation of a species is the extent of its native range, however defining a native range is often challenging as changing environments drive shifts in species distributions over time. The crucian carp,Carassius carassius(L.) is a threatened freshwater fish native to much of Europe, however the extent of this range is ambiguous. One particularly contentious region is England, in whichC. carassiusis currently considered native on the basis of anecdotal evidence. Here, we use 13 microsatellite loci, population structure analyses and approximate bayesian computation (ABC), to empirically test the native status ofC. carassiusin England. Contrary to the current consensus, ABC yields strong support for introduced origins ofC. carassiusin England, with posterior distribution estimates placing their introduction in the 15th century, well after the loss of the doggerland landbridge. This result brings to light an interesting and timely debate surrounding our motivations for the conservation of species. We discuss this topic, and make arguments for the continued conservation ofC. carassiusin England, despite its non-native origins.
Cationic Peptides Facilitate Iron-induced Mutagenesis in Bacteria
Authors: Rodríguez-Rojas Alexandro , Makarova Olga , Müller Uta , Rolff Jens 
Published: September 2015

AbstractPseudomonas aeruginosais the causative agent of chronic respiratory infections and is an important pathogen of cystic fibrosis patients. Adaptive mutations play an essential role for antimicrobial resistance and persistence. The factors that contribute to bacterial mutagenesis in this environment are not clear. Recently it has been proposed that cationic antimicrobial peptides such as LL-37 could act as a mutagen inP. aeruginosa. Here we provide experimental evidence that mutagenesis is the product of a joint action of LL-37 and free iron. By estimating mutation rate, mutant frequencies and assessing mutational spectra inP. aeruginosatreated either with LL-37, iron or a combination of both we demonstrate that mutation rate and mutant frequency were increased only when free iron and LL-37 were present simultaneously. The addition of an iron chelator completely abolished this mutagenic effect, suggesting that LL-37 enables iron to enter the cells resulting in DNA damage by Fenton reactions. This was also supported by the observation that the mutational spectrum of the bacteria under LL-37-iron regime showed one of the characteristic Fenton reaction fingerprints: C to T transitions. Free iron concentration in nature and within hosts is kept at a very low level, but the situation in infected lungs of cystic fibrosis patients is different. Intermittent bleeding and damage to the epithelial cells in lungs may contribute to the release of free iron that in turn leads to generation of reactive oxygen species and deterioration of the respiratory tract, making it more susceptible to the infection.Author SummaryCationic antimicrobial peptides (cAMPs) are small proteins naturally produced by the immune system to limit bacterial growth mainly through pore formation in the membrane. It has recently been suggested that sub-inhibitory concentrations of cAMPs promote bacterial mutagenesis, similarly to antibiotics. However, we previously reported that cAMPs do not increase mutation rate and do not activate bacterial stress responses. Here we resolve this contradiction. We report that free iron in the culture medium increases mutagenesis in the presence of cAMPs. We show that sub-inhibitory concentrations of cAMPs facilitate entry of free iron into bacterial cells, where it interacts with hydrogen peroxide, thereby resulting in production of DNA-damaging reactive oxygen species and increased mutagenesis. Moreover, these results may have clinically-relevant implications: while very little free iron is normally present in healthy individuals, this is not the case in patients suffering from cystic fibrosis, where elevated bacterial mutagenesis promotes antibiotic resistance and contributes to persistence and severity of infection. Thus, an intervention aimed at reduction of free iron in the lungs could reduce the cAMPs-facilitation of iron-mediated mutagenesis; hence antibiotic resistance and pathoadaptation.