bluuebunny/crossref_metadata_2025 huggingface dataset:
A Nurse-Led Care Program for Breast Cancer Patients in a Chemotherapy Day Center
Authors: Lai Xiao Bin , Ching Shirley Siu Yin , Wong Frances Kam Yuet , Leung Carenx Wai Yee , Lee Lai Ha , Wong Jessica Shuk Yin , Lo Yim Fan
Published: September 2017

Background

Healthcare providers are facing the challenge of helping cancer patients cope with the impact of outpatient-based chemotherapy. A nurse-led care program was proposed to address this challenge.

Objective

The aim of this study was to examine the effects of a nurse-led care program for patients receiving outpatient-based chemotherapy.

Methods

This was a single-center, open-label, 2-arm parallel trial with equal randomization (NCT02228200). Breast cancer patients in Hong Kong were randomly allocated to the intervention arm or the control arm. The control arm received routine hospital care. The intervention arm received the nurse-led care plus the routine hospital care. The quality of life, self-efficacy, symptom distress levels, and satisfaction with care were evaluated with questionnaires before randomization (T0), in the middle of chemotherapy (T1), and 1 month after chemotherapy (T2). Individual interviews were conducted with some participants in the intervention arm at T2.

Results

The intervention arm participants reported significantly lower distress levels from oral problems, fatigue, peripheral neuropathy, distressful feelings, and higher satisfaction with care. According to the satisfaction evaluation and the interviews, the participants stated that the service was helpful in providing information and communication opportunities, filling the service gap after drug administration, providing psychological support, relieving discomfort, and building confidence.

Conclusion

Breast cancer patients received support from the provision of comprehensive, continuous, and individualized care.

Implications for Practice

The nurse-led care program could be applied to breast cancer patients in other hospitals in Hong Kong. Exploring its applicability to cancer settings in other countries is recommended.
Effectiveness of Early Warming With Self-Warming Blankets on Postoperative Hypothermia in Total Hip and Knee Arthroplasty
Authors: Koc Baris B. , Schotanus Martijn G. M. , Kollenburg Jean-Paul A. P. A. C. , Janssen Maurice J. A. , Tijssen Fabian , Jansen Edwin J. P.
Published: September 2017

BACKGROUND:

Hypothermia is an important complication in joint arthroplasty. Commonly, forced air warming (FAW) devices are used intraoperatively to maintain body temperature in patients undergoing surgery. However, it is believed that these convective warming systems could increase the risk of deep surgical site infections due to disruption of unidirectional downward laminar airflow. Conductive warming devices have no noticeable effect on ventilation airflow. Nevertheless, the effectiveness of the self-warming (SW) blanket, a novel conductive warming device, on postoperative hypothermia in elective joint arthroplasty is unknown.

PURPOSE:

The purpose of this study was to evaluate the effectiveness of early warming with SW blankets in the prevention of postoperative hypothermia in elective total hip (THA) and knee arthroplasty (TKA) compared with FAW devices.

METHODS:

Patients who underwent elective THA or TKA between May and June 2014 were assigned in the FAW or SW group. A total of 105 patients were enrolled into the study. In the FAW group, the FAW devices were applied after disinfection of the surgical site. In the SW group, the SW blankets were already applied in the orthopaedic department. The duration of warming with SW blankets before anesthetic induction was documented. The body temperature was measured preoperatively upon arrival in the orthopaedic department and postoperatively upon arrival in the postanesthesia care unit. The patient's body temperature was measured at the tympanic membrane, and hypothermia was defined as a body temperature of less than 35.5°C.

RESULTS:

The SW blankets were applied for a median of 86.8 minutes (78.8–94.8) before anesthetic induction. Postoperative hypothermia was observed in 15 (31.3%) and eight (14.0%) patients in the FAW group and the SW group, respectively (p = .029). The median postoperative body temperature was 35.59°C (35.44–35.74) and 35.95°C (35.83–36.06) in the FAW group and the SW group, respectively (p < .001).

CONCLUSION:

Early warming with SW blankets was more effective than FAW devices in the prevention of postoperative hypothermia in elective THA and TKA.
It's All in the Wrist
Authors: Durham Catherine O. , VanRavenstein Kathy
Published: September 2017

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy accounting for 90% of similar disorders, occurring in 3.8% of the population, common in adults aged 40–60 years, and is associated with an average 32 lost days of work and lost productivity. In addition to occupational exposure, there are several common chronic disorders that can preclude CTS, obesity, diabetes mellitus, rheumatoid arthritis, pregnancy, metabolic syndrome, and thyroid disorder, to name a few. Therefore, it is important for the primary care provider to have knowledge in this syndrome. The purpose of the article is to inform the provider about the etiology, presentation, diagnosis, and treatment of CTS, as well as the implications for job-associated CTS.
Variability in Usual Care Mechanical Ventilation for Pediatric Acute Respiratory Distress Syndrome: Time for a Decision Support Protocol?*
Authors: Newth Christopher J. L. , Sward Katherine A. , Khemani Robinder G. , Page Kent , Meert Kathleen L. , Carcillo Joseph A. , Shanley Thomas P. , Moler Frank W. , Pollack Murray M. , Dalton Heidi J. , Wessel David L. , Berger John T. , Berg Robert A. , Harrison Rick E. , Holubkov Richard , Doctor Allan , Dean J. Michael , Jenkins Tammara L. , Nicholson Carol E.
Published: September 2017

Objectives:

Although pediatric intensivists philosophically embrace lung protective ventilation for acute lung injury and acute respiratory distress syndrome, we hypothesized that ventilator management varies. We assessed ventilator management by evaluating changes to ventilator settings in response to blood gases, pulse oximetry, or end-tidal Co
2. We also assessed the potential impact that a pediatric mechanical ventilation protocol adapted from National Heart Lung and Blood Institute acute respiratory distress syndrome network protocols could have on reducing variability by comparing actual changes in ventilator settings to those recommended by the protocol.

Design:

Prospective observational study.

Setting:

Eight tertiary care U.S. PICUs, October 2011 to April 2012.

Patients:

One hundred twenty patients (age range 17 d to 18 yr) with acute lung injury/acute respiratory distress syndrome.

Measurements and Main Results:

Two thousand hundred arterial and capillary blood gases, 3,964 oxygen saturation by pulse oximetry, and 2,757 end-tidal Co
2 values were associated with 3,983 ventilator settings. Ventilation mode at study onset was pressure control 60%, volume control 19%, pressure-regulated volume control 18%, and high-frequency oscillatory ventilation 3%. Clinicians changed Fio
2 by ±5 or ±10% increments every 8 hours. Positive end-expiratory pressure was limited at ~10 cm H2O as oxygenation worsened, lower than would have been recommended by the protocol. In the first 72 hours of mechanical ventilation, maximum tidal volume/kg using predicted versus actual body weight was 10.3 (8.5–12.9) (median [interquartile range]) versus 9.2 mL/kg (7.6–12.0) (p < 0.001). Intensivists made changes similar to protocol recommendations 29% of the time, opposite to the protocol’s recommendation 12% of the time and no changes 56% of the time.

Conclusions:

Ventilator management varies substantially in children with acute respiratory distress syndrome. Opportunities exist to minimize variability and potentially injurious ventilator settings by using a pediatric mechanical ventilation protocol offering adequately explicit instructions for given clinical situations. An accepted protocol could also reduce confounding by mechanical ventilation management in a clinical trial.
Temporal Changes in Prescription of Neuropharmacologic Drugs and Utilization of Resources Related to Neurologic Morbidity in Mechanically Ventilated Children With Bronchiolitis*
Authors: Shein Steven L. , Slain Katherine , Wilson-Costello Deanne , McKee Bryan , Rotta Alexandre T.
Published: September 2017

Objectives:

Critically ill children with bronchiolitis may require neuropharmacologic medications and support for neuro-functional sequelae, but current practices are not well described. We aimed to describe recent trends in neuropharmacology and utilization of neuro-rehabilitation resources in mechanically ventilated children with bronchiolitis.

Design:

Analysis of the multicenter Pediatric Health Information System database.

Setting:

Forty-seven U.S. children’s hospitals.

Patients:

PICU patients less than 2 years old with bronchiolitis undergoing mechanical ventilation between 2006 and 2015.

Interventions:

None. Annual rates of utilization of neuropharmacologic medications (sedatives, analgesics, etc) and of neuro-rehabilitation services (physical therapy, neurologic consultation, etc) over the 10-year study period were compared.

Measurements and Main Results:

Neuropharmacologic medications prescribed on greater than or equal to 2 days were extracted. Utilization of MRI of the brain, neurologic consultation, swallow evaluation, occupational therapy, and physical therapy was also extracted. Among 12,508 subjects, the median age was 2.8 months, ~50% had comorbid conditions, and the median duration of mechanical ventilation was 7 days. The percentage of children prescribed greater than or equal to five drugs/drug classes increased over the study period from 36.5% to 55.8% (p < 0.001). There were significant increases over time in utilization of 10 of the 15 individual drugs/drug classes analyzed. More than half of subjects (6,294 [50.3%]) received at least one service that evaluates/treats neurologic morbidity. There were significant increases in the use of greater than or equal to one service (36.3% in 2006 to 59.6% in 2015; p < 0.001) and in the use of greater than or equal to two services (20.8% to 34.8%; p < 0.001). Utilization of each of the five individual resources increased significantly during the study period, but use of vasoactive medications and mortality did not.

Conclusions:

Prescription of neuropharmacologic agents increased over time using metrics of both overall drug burden and specific drug usage. Concurrently, the utilization of services that evaluate and/or treat neurologic morbidity was common and also increased over time.
A Systematic Review and Meta-analysis of Efficacy and Safety of Novel Interleukin Inhibitors in the Management of Psoriatic Arthritis
Authors: Bilal Jawad , Riaz Irbaz Bin , Kamal Muhammad Umar , Elyan Mazen , Sudano Dominick , Khan Muhammad Asim
Published: September 2017

Objective

The aim of this study was to systemically review the efficacy and safety of inhibitors of interleukin 6 (IL-6): clazakizumab, IL-12/23: ustekinumab, and IL-17A: secukinumab, brodalumab, and ixekizumab in psoriatic arthritis (PsA).

Methods

The literature search was conducted using MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science. We included randomized controlled trials that assessed the efficacy of IL inhibitors and reported American College of Rheumatology 20 response at 24 weeks. Meta-analysis was done using random-effects model utilizing the DerSimonian and Laird method. Quality assessment was done using RobotReviewer Cochrane Risk-of-Bias Assessment Tool. Heterogeneity was assessed with Q statistic and quantified with I
2. Publication bias was assessed with a funnel plot.

Results

Eight studies including 2722 subjects demonstrate the efficacy of IL inhibitors clazakizumab, secukinumab, ixekizumab, brodalumab, and ustekinumab in the treatment of PsA. The American College of Rheumatology 20/50/70 risk ratios were 2.02 (95% confidence interval [CI], 1.65–2.47; P = 0.000), 2.95 (95% CI, 2.32–3.73; P = 0.00), and 5.14 (95% CI, 3.28–8.06; P = 0.00), respectively, in favor of treatment versus placebo. There was no evidence of significant heterogeneity between trials. Subgroup analysis showed efficacy in patients who were tumor necrosis factor naive, as well as tumor necrosis factor nonresponders or inadequate responders. The number of adverse events was higher in the treatment groups versus placebo, the majority were mild and did not require treatment adjustment (risk ratio, 1.17; 95% CI, 1.06–1.28; P = 0.001). There was no significant difference in drug withdrawals.

Conclusions

Our meta-analysis shows that the inhibitors of IL-6 (clazakizumab), IL-12/23 (ustekinumab), and IL-17A (secukinumab, brodalumab, ixekizumab) are efficacious and generally well tolerated when used to treat patients with PsA.
Role of Fat-Soluble Vitamins in Osteoarthritis Management
Authors: Zheng Xiao-yan , Liang Jun , Li Yu-sheng , Tu Min
Published: September 2017

Osteoarthritis (OA) is a chronic degenerative joint disease, in which metabolic imbalance in bone is observed. The pathological mechanism of metabolic imbalance is not clear yet, but the nutritional factors, particularly the vitamins, might be intrinsic to the development and progression of OA. In this review article, we have explored databases such as PubMed, Scopus, and Google Scholar articles until the beginning of 2017 and reviewed the role of fat-soluble vitamins in pathological and therapeutic aspects of OA. Vitamin D plays an important role in the development and maintenance of the skeleton, as well as bone and cartilage metabolism, and its deficiency is implicated in the pathological process of OA. Vitamin E enhances chondrocyte growth and exhibits an anti-inflammatory activity, as well as plays an important role in the prevention of cartilage degeneration. In human OA cartilage, vitamin K deficiency produces abnormal growth plate calcification and inappropriate mineralization of cartilage. Thus, these fat-soluble vitamins play a key role in the pathophysiology of OA, and supplementation of these vitamins may provide innovative approaches for OA management. However, vitamin A has a different role, which is a regulator of cartilage and skeletal formation. When metabolite levels of vitamin A are elevated in synovial fluid, they appear to drive OA development. The role of inhibitors of vitamin A here remains unclear. More investigations are needed to examine the effects of fat-soluble vitamins on the various molecular pathways of OA, as well as to assess the efficacy and safety of their usage clinically.
Two diseases, same person: moving towards a combined HIV and TB continuum of care
Authors: Granich Reuben , Gupta Somya
Published: September 2017

Setting

The Human Immunodeficiency Virus (HIV) andMycobacterium tuberculosissyndemic remains a global public health threat. Separate HIV and TB global targets have been set, however, success will depend on achieving combined disease control objectives and care continua.

Objective

Review available policy, budgets and data to re-conceptualize TB and HIV disease control objectives by combining HIV and TB care continua.

Methods

For 22 WHO TB and TB/HIV priority countries, we used 2014 and 2015 data from the HIV90-90-90watch website, UNAIDS Aidsinfo, and WHO 2016 Global TB Report. Global resources available in TB and HIV/TB activities for 2003-2017 was collected from publically available sources.

Results

In 22 high burden countries people living with HIV (PLHIV) on ART ranged from 9-70%; viral suppression was 38-63%. TB treatment success ranged from 34-94% with 13 (43% HIV/TB burden) countries above 80% TB treatment success. From 2003-2017, global international and domestic resources for HIV-associated TB and TB averaged $2.6 billion per year; the total for 2003-2017 was 39 billion dollars.

Conclusion

Reviewingcombined HIV and TB targets demonstrate disease control progress and challenges. Using an integrated HIV and TB continuum supports HIV and TB disease control efforts focused on improving both individual and public health.

Funding

None
Sociodemographic patterning in the oral microbiome of a diverse sample of New Yorkers
Authors: Renson Audrey , Jones Heidi E. , Beghini Francesco , Segata Nicola , Zolnik Christine P. , Usyk Mykhaylo , Moody Thomas U. , Thorpe Lorna , Burk Robert , Waldron Levi , Dowd Jennifer B.
Published: September 2017

1

1.1

Purpose

Variations in the oral microbiome are potentially implicated in social inequalities in oral disease, cancers, and metabolic disease. We describe sociodemographic variation of oral microbiomes in a diverse sample.

1.2

Methods

We performed 16S rRNA sequencing on mouthwash specimens in a subsample (n=282) of the 2013-14 population-based New York City Health and Nutrition Examination Study (NYC-HANES). We examined differential abundance of 216 operational taxonomic units (OTUs), and alpha and beta diversity by age, sex, income, education, nativity, and race/ethnicity. For comparison, we also examined differential abundance by diet, smoking status, and oral health behaviors.

1.3

Results

69 OTUs were differentially abundant by any sociodemographic variable (false discovery rate < 0.01), including 27 by race/ethnicity, 21 by family income, 19 by education, three by sex. We also found 49 differentially abundant by smoking status, 23 by diet, 12 by oral health behaviors. Genera differing for multiple sociodemographic characteristics includedLactobacillus,Prevotella,Porphyromonas,Fusobacterium.

1.4

Conclusions

We identified oral microbiome variation consistent with health inequalities, with more taxa differing by race/ethnicity than diet, and more by SES variables than oral health behaviors. Investigation is warranted into possible mediating effects of the oral microbiome in social disparities in oral, metabolic and cancers.

Highlights

Most microbiome studies to date have had minimal sociodemographic variability, limiting what is known about associations of social factors and the microbiome.

We examined the oral microbiome in a population-based sample of New Yorkers with wide sociodemographic variation.

Numerous taxa were differentially abundant by race/ethnicity, income, education, marital status, and nativity.

Frequently differentially abundant taxa includePorphyromonas,Fusobacterium,Streptococcus, andPrevotella, which are associated with oral and systemic disease.

Mediation of health disparities by microbial factors may represent an important intervention site to reduce health disparities, and should be explored in prospective studies.
Pervasive contingency and entrenchment in a billion years of Hsp90 evolution
Authors: Starr Tyler N. , Flynn Julia M. , Mishra Parul , Bolon Daniel N. A. , Thornton Joseph W.
Published: September 2017

Interactions among mutations within a protein have the potential to make molecular evolution contingent and irreversible, but the extent to which epistasis actually shaped historical evolutionary trajectories is unclear. We addressed this question by identifying all amino acid substitutions that occurred during the billion-year evolutionary history of the heat shock protein 90 (Hsp90) ATPase domain beginning from a deep eukaryotic ancestor to modernSaccharomyces cerevisiaeand then precisely measuring their fitness effects when introduced into both extant and reconstructed ancestral Hsp90 proteins. We find a pervasive influence of epistasis: of 98 derived states that evolved during history, most were deleterious at times before they happened, and the vast majority also became subsequently entrenched, with the ancestral state becoming deleterious after its substitution. This epistasis was primarily caused by specific interactions among sites rather than a general permissive or restrictive effect on the protein’s tolerance to mutation. Our results show that epistasis continually opens and closes windows of mutational opportunity over evolutionary timescales, producing histories and biological states that reflect the transient internal constraints imposed by a protein’s fleeting sequence states.

Significance statement

When mutations within a protein change each other’s functional effects—a phenomenon called epistasis—the trajectories available to evolution at any moment in time depend on the specific set of changes that previously occurred in the protein. The extent to which epistasis has shaped historical evolutionary trajectories is unknown. Using a high-precision bulk fitness assay and ancestral protein reconstruction, we measured the fitness effects in ancestral and extant sequences of all historical substitutions that occurred during the billion-year trajectory of an essential protein. We found that most historical substitutions were contingent on prior epistatic substitutions and/or entrenched by subsequent changes. These results establish that epistasis caused widespread, consequential shifts in the site-specific fitness constraints that shaped the protein’s historical trajectory.
A closer look at cross-validation for assessing the accuracy of gene regulatory networks and models
Authors: Tabe-Bordbar Shayan , Emad Amin , Zhao Sihai Dave , Sinha Saurabh
Published: September 2017

Cross-validation (CV) is a technique to assess the generalizability of a model to unseen data. This technique relies on assumptions that may not be satisfied when studying genomics datasets. For example, random CV (RCV) assumes that a randomly selected set of samples, the test set, well represents unseen data. This assumption does not hold true where samples are obtained from different experimental conditions, and the goal is to learn regulatory relationships among the genes that generalize beyond the observed conditions. In this study, we investigated how the CV procedure affects the assessment of methods used to learn gene regulatory networks. We compared the performance of a regression-based method for gene expression prediction, estimated using RCV with that estimated using a clustering-based CV (CCV) procedure. Our analysis illustrates that RCV can produce over-optimistic estimates of generalizability of the model compared to CCV. Next, we defined the ‘distinctness’ of a test set from a training set and showed that this measure is predictive of the performance of the regression method. Finally, we introduced a simulated annealing method to construct partitions with gradually increasing distinctness and showed that performance of different gene expression prediction methods can be better evaluated using this method.
Gene-level differential analysis at transcript-level resolution
Authors: Yi Lynn , Pimentel Harold , Bray Nicolas L. , Pachter Lior
Published: September 2017

Gene-level differential expression analysis based on RNA-Seq is more robust, powerful and biologically actionable than transcript-level differential analysis. However aggregation of transcript counts prior to analysis results can mask transcript-level dynamics. We demonstrate that aggregating the results of transcript-level analysis allow for gene-level analysis with transcript-level resolution. We also show thatp-value aggregation methods, typically used for meta-analyses, greatly increase the sensitivity of gene-level differential analyses. Furthermore, such aggregation can be applied directly to transcript compatibility counts obtained during pseudoalignment, thereby allowing for rapid and accurate model-free differential testing. The methods are general, allowing for testing not only of genes but also of any groups of transcripts, and we showcase an example where we apply them to perturbation analysis of gene ontologies.
METHimpute: Imputation-guided construction of complete methylomes from WGBS data
Authors: Taudt Aaron , Roquis David , Vidalis Amaryllis , Wardenaar René , Johannes Frank , Colomé-Tatché Maria
Published: September 2017

Whole-genome Bisulfite sequencing (WGBS) has become the standard method for interrogating plant methylomes at base resolution. However, deep WGBS measurements remain cost prohibitive for large, complex genomes and for population-level studies. As a result, most published plant methylomes are sequenced far below saturation, with a large proportion of cytosines having either missing data or insufficient coverage. Here we present METHimpute, a Hidden Markov Model (HMM) based imputation algorithm for the analysis of WGBS data. Unlike existing methods, METHimpute enables the construction of complete methylomes by inferring the methylation status and level of all cytosines in the genome regardless of coverage. Application of METHimpute to maize, rice and Arabidopsis shows that the algorithm infers cytosine-resolution methylomes with high accuracy from data as low as 6X, compared to data with 60X, thus making it a cost-effective solution for large-scale studies. Although METHimpute has been extensively tested in plants, it should be broadly applicable to other species.
An extensive enhancer-promoter map generated by genome-scale analysis of enhancer and gene activity patterns
Authors: Hait Tom Aharon , Amar David , Shamir Ron , Elkon Ran
Published: September 2017

Massive efforts have documented hundreds of thousands of putative enhancers in the human genome. A pressing genomic challenge is to identify which of these enhancers are functional and map them to the genes they regulate. We developed a novel method for inferring enhancer-promoter (E-P) links based on correlated activity patterns across many samples. Our method, calledFOCS, uses rigorous statistical validation tailored for zero-inflated data, identifying the most important E-P links in each gene model. We applied FOCS to the wide epigenomic and transcriptomic datasets recorded by theENCODE,Roadmap EpigenomicsandFANTOM5projects, together covering 2,630 samples of human primary cells, tissues and cell lines. In addition, building on expression of enhancer RNAs (eRNAs) as an exquisite mark of enhancer activity and on the robust detection of eRNAs by the GRO-seq technique, we compiled a compendium of eRNA and gene expression profiles based on public GRO-seq data from 245 samples and 23 human cell types. Applying FOCS to this compendium further expanded the coverage of our inferred E-P map. Benchmarking against gold standard E-P links from ChIA-PET and eQTL data, we demonstrate that FOCS prediction of E-P links outperforms extant methods. Collectively, we inferred >300,000 cross-validated E-P links spanning~16K known genes. Our study presents an improved method for inferring regulatory links between enhancers and promoters, and provides an extensive resource of E-P maps that could greatly assist the functional interpretation of the noncoding regulatory genome. FOCS and our predicted E-P map are publicly available athttp://acgt.cs.tau.ac.il/focs.
The differentially expressed translationally controlled tumor proteins TCTP1 and TCTP2 inTrypanosoma brucei
Authors: Jojic Borka , Amodeo Simona , Ochsenreiter Torsten
Published: September 2017

1.

InTrypanosoma bruceiwe identified two TCTP genes differentially expressed during the parasite life cycle and discovered the mechanism by which this expression is controlled. Furthermore, we demonstrate that TCTP is important for cell growth as well as proper cell and organelle morphology in the insect form of the parasite.

2.

TCTP is a highly conserved protein ubiquitously expressed in eukaryotes. Studies have reported TCTP to be involved in growth and development, cell cycle progression, protection against cellular stresses and apoptosis, indicating the multifunctional role of the protein. Here, for the first time we characterize the expression and function of TCTP in the unicellular parasiteTrypanosoma brucei. We identified two paralogue TCTP genes, which we named TbTCTP1 and TbTCTP2. They have identical 5’UTRs and only ten single nucleotide polymorphisms in the open reading frames (ORFs). However, the 3’UTRs differ dramatically in sequence and length. We found that the two TCTP mRNAs are differentially expressed duringT. bruceilife cycle. While procyclic form trypanosomes (PCF) express TCTP1, the bloodstream form trypanosomes (BSF), express TCTP2. We link the differential expression to the distinct 3’UTRs of the paralogues. In PCF cells, the protein appears to localize in the cytosol. We show that TCTP1 is essential for normal cell growth and has pleiotropic effects on the cells including aberrant cell morphology, enlarged and reduced number of acidocalcisomes and appearance of accumulations in the mitochondria.
ABLE: an Activity-Based Level Set Segmentation Algorithm for Two-Photon Calcium Imaging Data
Authors: Reynolds Stephanie , Abrahamsson Therese , Schuck Renaud , Jesper Sjöström P. , Schultz Simon R. , Dragotti Pier Luigi
Published: September 2017

We present an algorithm for detecting the location of cells from two-photon calcium imaging data. In our framework, multiple coupled active contours evolve, guided by a model-based cost function, to identify cell boundaries. An active contour seeks to partition a local region into two subregions, a cell interior and ex-terior, in which all pixels have maximally ‘similar’ time courses. This simple, local model allows contours to be evolved predominantly independently. When contours are sufficiently close, their evolution is coupled, in a manner that permits overlap. We illustrate the ability of the proposed method to demix overlapping cells on real data. The proposed framework is flexible, incorporating no prior information regarding a cell’s morphology or stereotypical temporal activity, which enables the detection of cells with diverse properties. We demonstrate algorithm performance on a challenging mousein vitrodataset, containing synchronously spiking cells, and a manually labelled mousein vivodataset, on which ABLE achieves a 67.5% success rate.

Significance statement

Two-photon calcium imaging enables the study of brain activity during learning and behaviour at single-cell resolution. To decode neuronal spiking activity from the data, algorithms are first required to detect the location of cells in the video. It is still common for scientists to perform this task manually, as the heterogeneity in cell shape and frequency of cellular overlap impede automatic segmentation algorithms. We developed a versatile algorithm based on a popular image segmentation approach (the Level Set Method) and demonstrated its capability to overcome these challenges. We include no assumptions on cell shape or stereotypical temporal activity. This lends our framework the flexibility to be applied to new datasets with minimal adjustment.
A Yeast Global Genetic Screen Reveals that Metformin Induces an Iron Deficiency-Like State
Authors: Stynen B. , Abd-Rabbo D. , Kowarzyk J. , Miller-Fleming L. , Ralser M. , Michnick S.W.
Published: September 2017

We report here a simple and global strategy to map out gene functions and target pathways of drugs, toxins or other small molecules based on “homomer dynamics” Protein-fragment Complementation Assays (hdPCA).hdPCA measures changes in self-association (homomerization) of over 3,500 yeast proteins in yeast grown under different conditions.hdPCA complements genetic interaction measurements while eliminating confounding effects of gene ablation. We demonstrate thathdPCA accurately predicts the effects of two longevity and health-span-affecting drugs, immunosuppressant rapamycin and type II diabetes drug metformin, on cellular pathways. We also discovered an unsuspected global cellular response to metformin that resembles iron deficiency. This discovery opens a new avenue to investigate molecular mechanisms for the prevention or treatments of diabetes, cancers and other chronic diseases of aging.
Symbiodiniumfunctional diversity and clade specificity under global change stressors
Authors: Davies S.W. , Ries J.B. , Marchetti A , Granzotti Rafaela , Castillo K.D.
Published: September 2017

Coral bleaching episodes are increasing in frequency, demanding examination of the physiological and molecular responses of corals and theirSymbiodiniumto climate change. Here we quantify bleaching andSymbiodiniumphotosynthetic performance ofSiderastrea sidereafrom two reef zones after long-term exposure to thermal and CO2-acidification stress. Molecular response ofin hospite Symbiodiniumto these stressors was interrogated with RNAseq. Elevated temperatures reduced photosynthetic efficiency, which was highly correlated with bleaching status. However, photosynthetic efficiencies of forereef symbionts were more negatively affected by thermal stress than nearshore symbionts, indicating greater thermal tolerance in nearshore corals. At control temperatures, CO2-acidification had little effect on symbiont physiology, although forereef symbionts exhibited greater photosynthetic efficiencies than nearshore symbionts. Transcriptome profiling revealed thatS. sidereawere dominated by clade CSymbiodinium, except under thermal stress, which caused shifts to thermotolerant clade D. Comparative transcriptomics of conserved genes across symbiotic partners revealed few differentially expressedSymbiodiniumgenes when compared to corals. Instead of responding to stress, clade C transcriptomes varied by reef zone, with forereefSymbiodiniumexhibiting enrichment of genes associated with photosynthesis. Our findings suggest that functional variation in photosynthetic architecture exists between forereef and nearshoreSymbiodiniumpopulations.
Influential parameters for the analysis of intracellular parasite metabolomics
Authors: Carey Maureen A. , Covelli Vincent , Brown Audrey , Medlock Gregory L. , Haaren Mareike , Cooper Jessica G. , Papin Jason A. , Guler Jennifer L.
Published: September 2017

Metabolomics is increasingly popular for the study of many pathogens. For the malaria parasite,Plasmodium falciparum, both targeted and untargeted metabolite detection has improved our understanding of pathogenesis, host-parasite interactions, and antimalarial drug treatment and resistance. However, purification and analysis procedures for performing metabolomics on intracellular pathogens have not been explored. Here, we investigate the impact of host contamination on the metabolome when preparing samples using standard methods. We purifiedin vitrogrown ring stage intra-erythrocyticP. falciparumparasites for untargeted metabolomics studies; the small size of this developmental stage amplifies the challenges associated with metabolomics studies as the ratio between host and parasite biomass is maximized. Following metabolite identification and data preprocessing, we investigated whether host contributions could be corrected post hoc using various normalization approaches (including double stranded DNA, total protein, or parasite number). We conclude that normalization parameters have large effects on differential abundance analysis and recommend the thoughtful selection of these parameters. However, normalization does not remove the contribution from the parasite’s extracellular environment (culture media and host erythrocyte). In fact, we found that extra-parasite material is as influential on the metabolome as treatment with a potent antimalarial drug with known metabolic effects (artemisinin). Because of this influence, we could not detect significant changes associated with drug treatment. Instead, we identified metabolites predictive of host and media contamination that can be used to assess sample purification. Our findings provide a basis for development of improved experimental and analytical methods for future metabolomics studies of intracellular organisms.
A brain wide circuit model of heat evoked swimming behavior in larval zebrafish
Authors: Haesemeyer Martin , Robson Drew N , Li Jennifer M , Schier Alexander F , Engert Florian
Published: September 2017

Thermosensation provides crucial information but it is poorly understood how temperature representation is transformed from sensation to behavior. Here, we report a preparation that allows control of heat delivery to zebrafish larvae while monitoring motor output and imaging whole-brain calcium signals, thereby uncovering algorithmic and computational rules that couple dynamics of heat modulation, neural activity and swimming behavior. This approach identifies a critical step in the transformation of temperature representation between the sensory trigeminal ganglia and the hindbrain: A simple sustained trigeminal stimulus representation is transformed into a representation of absolute temperature as well as temperature changes in the hindbrain that explains the observed motor output. An activity constrained dynamic circuit model captures the most prominent aspects of these sensori-motor transformations and predicts both behavior and neural activity in response to novel heat stimuli. These findings provide the first algorithmic description of heat processing from sensory input to behavioral output.
STAT1 modulates tissue wasting or overgrowth downstream from PDGFRβ
Authors: He Chaoyong , Medley Shayna C. , Kim Jang , Sun Chengyi , Kwon Hae Ryong , Sakashita Hiromi , Pincu Yair , Yao Longbiao , Eppard Danielle , Dai Bojie , Berry William L. , Griffin Timothy M. , Olson Lorin E.
Published: September 2017

Platelet-derived growth factor (PDGF) acts through two conserved receptor tyrosine kinases: PDGFRα and PDGFRβ. Gain-of-function mutations in humanPDGFRBhave been linked recently to genetic diseases characterized by connective tissue wasting (Penttinen syndrome) or overgrowth (Kosaki overgrowth syndrome), but it is unclear whetherPDGFRBmutations alone are responsible. Mice with constitutive PDGFRβ signaling caused by a kinase domain mutation (D849V) develop lethal autoinflammation. Here we used a genetic approach to investigate the mechanism of autoinflammation inPdgfrb+/D849Vmice and test the hypothesis that signal transducer and activator of transcription 1 (STAT1) mediates this phenotype. We show thatPdgfrb+/D849Vmice withStat1knockout (Stat1−/−Pdgfrb+/D849V) are rescued from autoinflammation and have improved life span compared withStat1+/−Pdgfrb+/D849Vmice. Furthermore, PDGFRβ–STAT1 signaling suppresses PDGFRβ itself. Thus,Stat1−/−Pdgfrb+/D849Vfibroblasts exhibit increased PDGFRβ signaling, and mice develop progressive overgrowth, a distinct phenotype from the wasting seen inStat1+/−Pdgfrb+/D849Vmice. Deletion of interferon receptors (Ifnar1orIfngr1) does not rescue wasting inPdgfrb+/D849Vmice, indicating that interferons are not required for autoinflammation. These results provide functional evidence that elevated PDGFRβ signaling causes tissue wasting or overgrowth reminiscent of human genetic syndromes and that the STAT1 pathway is a crucial modulator of this phenotypic spectrum.
Timber under real fire conditions – the influence of oxygen content and gas velocity on the charring behavior
Authors: Schmid Joachim , Santomaso Alessandro , Brandon Daniel , Wickström Ulf , Frangi Andrea
Published: September 2017

Purpose

The purpose of this study is to investigate the influencing factors on the charring behaviour of timber, the char layer and the charring depth in non-standard fires.

Design/methodology/approach

This paper summarizes outcomes of tests, investigating the influences on the charring behavior of timber by varying the oxygen content and the gas velocity in the compartment. Results show that charring is depending on the fire compartment temperature, but results show further that at higher oxygen flow, char contraction was observed affecting the protective function of the char layer.

Findings

In particular, in the cooling phase, char contraction should be considered which may have a significant impact on performance-based design using non-standard temperature fire curves where the complete fire history including the cooling phase has to be taken into account.

Originality/value

Up to now, some research on non-standard fire exposed timber member has been performed, mainly based on standard fire resistance tests where boundary conditions as gas flow and oxygen content especially in the decay phase are not measured or documented. The approach presented in this paper is the first documented fire tests with timber documenting the data required.
Rewilded mammal assemblages reveal the missing ecological functions of granivores
Authors: Mills Charlotte H. , Gordon Christopher E. , Letnic Mike
Published: September 2017

Rewilding is a strategy for ecological restoration that uses reintroductions of animals to re‐establish the ecological functions of keystone species. Globally, rewilding efforts have focused primarily on reinstating the ecological functions of charismatic megafauna. In Australia, rewilding efforts have focused on restoring the ecological functions of herbivorous and omnivorous rodents and marsupials weighing between 30 and 5,000 g inside of predator‐proof exclosures.

In many arid ecosystems, mammals are considered the dominant seed predators. In Australian deserts, ants are considered to be the primary removers and predators of seeds and mammals unimportant removers and predators of seeds. However, most research on granivory in Australian deserts has occurred in areas where native mammals were functionally extinct.

Here, we compare rates of seed removal by mammals and ants on shrub seeds and abundance of shrub seedlings in two rewilded desert ecosystems (Arid Recovery Reserve and Scotia Wildlife Sanctuary) with adjacent areas possessing depauperate mammal faunas. We used foraging trays containing seeds of common native shrubs (Acacia ligulata and Dodonaea viscosa) to examine rates of seed removal by ants and mammals. We quantified the abundance of A. ligulata and D. viscosa seedlings inside and outside of rewilded areas along belt transects.

By excluding ants and mammals from foraging trays, we show that ants removed more seeds than mammals where mammal assemblages were depauperate, but mammals removed far more seeds than ants in rewilded areas. Shrub seedlings were more abundant in areas with depauperate mammal faunas than in rewilded areas.

Our study provides evidence that rewilding of desert mammal assemblages has restored the hitherto unappreciated ecological function of omnivorous rodents and bettongs as seed predators. We hypothesize that the loss of omnivorous mammals may be a factor that has facilitated shrub encroachment in arid Australia.

We contend that rewilding programs aimed at restoring ecological processes should not ignore consumers with relatively lower per capita consumptive effects. This is because consumers with low per capita consumptive effects often occur at high population densities or perform critical ecological functions and thus may have significant population level impacts that can be harnessed for ecological restoration.

A plain language summary is available for this article.
Extended reflectivity method for modelling the propagation of diffusive–viscous wave in dip‐layered media
Authors: Zhao Haixia , Gao Jinghuai , Peng Jigen
Published: September 2017

The reflectivity method plays an important role in seismic modelling. It has been used to model different types of waves propagating in elastic and anelastic media. The diffusive–viscous wave equation was proposed to investigate the relationship between frequency dependence of reflections and fluid saturation. It is also used to describe the attenuation property of seismic wave in a fluid‐saturated medium. The attenuation of diffusive–viscous wave is mainly characterised by the effective attenuation parameters in the equation. Thus, it is essential to obtain those parameters and further characterise the features of the diffusive–viscous wave. In this work, we use inversion method to obtain the effective attenuation parameters through quality factor to investigate the characteristics of diffusive–viscous wave by comparing with those of the viscoacoustic wave. Then, the reflection/transmission coefficients in a dip plane‐layered medium are studied through coordinate transform and plane‐wave theory. Consequently, the reflectivity method is extended to compute seismograms of diffusive–viscous wave in a dip plane multi‐layered medium. Finally, we present two models to simulate the propagation of diffusive–viscous wave in a dip plane multi‐layered medium by comparing the results with those in a viscoacoustic medium. The numerical results demonstrate the validity of our extension of reflectivity method to the diffusive–viscous medium. The numerical examples in both time domain and time–frequency domain show that the reflections from a dip plane interface have significant phase shift and amplitude change compared with the results of horizontal plane interface due to the differences in reflection/transmission coefficients. Moreover, the modelling results show strong attenuation and phase shift in the diffusive–viscous wave compared to those of the viscoacoustic wave.
Strategies for stable attenuation compensation in reverse‐time migration
Authors: Sun Junzhe , Zhu Tieyuan
Published: September 2017

Attenuation in seismic wave propagation is a common cause for poor illumination of subsurface structures. Attempts to compensate for amplitude loss in seismic images by amplifying the wavefield may boost high‐frequency components, such as noise, and create undesirable imaging artefacts. In this paper, rather than amplifying the wavefield directly, we develop a stable compensation operator using stable division. The operator relies on a constant‐Q wave equation with decoupled fractional Laplacians and compensates for the full attenuation phenomena by performing wave extrapolation twice. This leads to two new imaging conditions to compensate for attenuation in reverse‐time migration. A time‐dependent imaging condition is derived by applying Q‐compensation in the frequency domain, whereas a time‐independent imaging condition is formed in the image space by calculating image normalisation weights. We demonstrate the feasibility and robustness of the proposed methods using three synthetic examples. We found that the proposed methods are capable of properly compensating for attenuation without amplifying high‐frequency noise in the data.
Patterns of Collaboration among Health Care and Social Services Providers in Communities with Lower Health Care Utilization and Costs
Authors: Brewster Amanda L. , Brault Marie A. , Tan Annabel X. , Curry Leslie A. , Bradley Elizabeth H.
Published: September 2017

Objective

To understand how health care providers and social services providers coordinate their work in communities that achieve relatively low health care utilization and costs for older adults.

Study Setting

Sixteen Hospital Service Areas (HSAs) in the United States.

Study Design

We conducted a qualitative study of HSAs with performance in the top or bottom quartiles nationally across three key outcomes: ambulatory care sensitive hospitalizations, all‐cause risk‐standardized readmission rates, and average reimbursements per Medicare beneficiary. We selected 10 higher performing HSAs and six lower performing HSAs for inclusion in the study.

Data Collection

To understand patterns of collaboration in each community, we conducted site visits and in‐depth interviews with a total of 245 representatives of health care organizations, social service agencies, and local government bodies.

Principal Findings

Organizations in higher performing communities regularly worked together to identify challenges faced by older adults in their areas and responded through collective action—in some cases, through relatively unstructured coalitions, and in other cases, through more hierarchical configurations. Further, hospitals in higher performing communities routinely matched patients with needed social services.

Conclusions

The collaborative approaches used by higher performing communities, if spread, may be able to improve outcomes elsewhere.