bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium-dependent inactivation controls cardiac L-type Ca2+ currents under β-adrenergic stimulation
Authors: Morales Danna , Hermosilla Tamara , Varela Diego
Published: February 2019

The activity of L-type calcium channels is associated with the duration of the plateau phase of the cardiac action potential (AP) and it is controlled by voltage- and calcium-dependent inactivation (VDI and CDI, respectively). During β-adrenergic stimulation, an increase in the L-type current and parallel changes in VDI and CDI are observed during square pulses stimulation; however, how these modifications impact calcium currents during an AP remains controversial. Here, we examined the role of both inactivation processes on the L-type calcium current activity in newborn rat cardiomyocytes in control conditions and after stimulation with the β-adrenergic agonist isoproterenol. Our approach combines a self-AP clamp (sAP-Clamp) with the independent inhibition of VDI or CDI (by overexpressing CaVβ2a or calmodulin mutants, respectively) to directly record the L-type calcium current during the cardiac AP. We find that at room temperature (20–23°C) and in the absence of β-adrenergic stimulation, the L-type current recapitulates the AP kinetics. Furthermore, under our experimental setting, the activity of the sodium–calcium exchanger (NCX) does not affect the shape of the AP. We find that hindering either VDI or CDI prolongs the L-type current and the AP in parallel, suggesting that both inactivation processes modulate the L-type current during the AP. In the presence of isoproterenol, wild-type and VDI-inhibited cardiomyocytes display mismatched L-type calcium current with respect to their AP. In contrast, CDI-impaired cells maintain L-type current with kinetics similar to its AP, demonstrating that calcium-dependent inactivation governs L-type current kinetics during β-adrenergic stimulation.
Routine Solid Phase Multiplex Anti-HLA Antibody Tests Predict Platelet Refractoriness
Authors: Peña Jeremy Ryan A , Makar Robert S
Published: February 2019

Objectives

No validated screening methods identify patients at risk for human leukocyte antigen (HLA) alloimmune-mediated platelet refractoriness (alloPR). We determined if bead-based HLA antibody tests could predict risk of developing HLA alloPR.

Methods

Hematopoietic progenitor cell transplant patients screened for HLA antibodies without prior refractoriness were identified. Phenotype bead screening results were compared between patients who later did and did not develop alloPR.

Results

Seven of 27 patients identified subsequently developed alloPR. The panel reactive antibody (PRA) and mean fluorescence intensity (MFI) of the 10 most reactive beads in the initial screen were significantly higher among patients who later developed alloPR (P < .001). Specifically, PRA of more than 30% and mean MFI of 1,500 or more in the most reactive beads identified at-risk patients. Administration of HLA-compatible platelets yielded significant posttransfusion count increments compared with routine platelets.

Conclusions

HLA antibody screening by phenotype bead assay may prospectively identify at-risk patients for the development of alloPR. However, clinical trials are needed to validate these findings.
Robbers, pickpockets and average mutual firmness
Authors: Koscholke Jakob
Published: February 2019

Mark Siebel (2004) has presented a compelling argument against Branden Fitelson’s (2003) probabilistic measure of coherence. The present paper shows how Siebel’s argument can be strengthened and thereby extended to an argument against a huge class of coherence measures from the literature including William Roche’s (2013) average mutual firmness account, which has not been challenged up to now.
Genetic relatedness delineates the social structure of southern Australian bottlenose dolphins
Authors: Diaz-Aguirre Fernando , Parra Guido J , Passadore Cecilia , Möller Luciana
Published: February 2019

Social relationships represent an adaptive behavioral strategy that can provide fitness benefits to individuals. Within mammalian societies, delphinids are known to form diverse grouping patterns and show a variety of social systems. However, how ecological and intrinsic factors have shaped the evolution of such diverse societies is still not well understood. In this study, we used photo-identification data and biopsy samples collected between March 2013 and October 2015 in Coffin Bay, a heterogeneous environment in South Australia, to investigate the social structure of southern Australian bottlenose dolphins (Tursiops cf. australis). Based on the data from 657 groups of dolphins, we used generalized affiliation indices, and applied social network and modularity methods to study affiliation patterns among individuals and investigate the potential presence of social communities within the population. In addition, we investigated genetic relatedness and kinship relationships within and between the communities identified. Modularity analysis revealed that the Coffin Bay population is structured into 2 similar sized, mixed-sex communities which differed in ranging patterns, affiliation levels and network metrics. Lagged association rates also indicated that nonrandom affiliations persisted over the study period. The genetic analyses suggested that there was higher relatedness, and a higher proportion of inferred full-sibs and half-sibs, within than between communities. We propose that differences in environmental conditions between the bays and kinship relationships are important factors contributing to the delineation and maintenance of this social structure.
DECO: decompose heterogeneous population cohorts for patient stratification and discovery of sample biomarkers using omic data profiling
Authors: Campos-Laborie F J , Risueño A , Ortiz-Estévez M , Rosón-Burgo B , Droste C , Fontanillo C , Loos R , Sánchez-Santos J M , Trotter M W , De Las Rivas J
Published: February 2019

Motivation

Patient and sample diversity is one of the main challenges when dealing with clinical cohorts in biomedical genomics studies. During last decade, several methods have been developed to identify biomarkers assigned to specific individuals or subtypes of samples. However, current methods still fail to discover markers in complex scenarios where heterogeneity or hidden phenotypical factors are present. Here, we propose a method to analyze and understand heterogeneous data avoiding classical normalization approaches of reducing or removing variation.

Results

DEcomposing heterogeneous Cohorts using Omic data profiling (DECO) is a method to find significant association among biological features (biomarkers) and samples (individuals) analyzing large-scale omic data. The method identifies and categorizes biomarkers of specific phenotypic conditions based on a recurrent differential analysis integrated with a non-symmetrical correspondence analysis. DECO integrates both omic data dispersion and predictor–response relationship from non-symmetrical correspondence analysis in a unique statistic (called h-statistic), allowing the identification of closely related sample categories within complex cohorts. The performance is demonstrated using simulated data and five experimental transcriptomic datasets, and comparing to seven other methods. We show DECO greatly enhances the discovery and subtle identification of biomarkers, making it especially suited for deep and accurate patient stratification.

Availability and implementation

DECO is freely available as an R package (including a practical vignette) at Bioconductor repository (http://bioconductor.org/packages/deco/).

Supplementary information

Supplementary data are available at Bioinformatics online.
Time-lapse imaging: the state of the art†
Authors: Gallego Raquel Del , Remohí José , Meseguer Marcos
Published: February 2019

The introduction of time-lapse imaging to clinical in vitro fertilization practice enabled the undisturbed monitoring of embryos throughout the entire culture period. Initially, the main objective was to achieve a better embryo development. However, this technology also provided an insight into the novel concept of morphokinetics, parameters regarding embryo cell dynamics. The vast amount of data obtained defined the optimal ranges in the cell-cycle lengths at different stages of embryo development. This added valuable information to embryo assessment prior to transfer. Kinetic markers became part of embryo evaluation strategies with the potential to increase the chances of clinical success. However, none of them has been established as an international standard. The present work aims at describing new approaches into time-lapse: progress to date, challenges, and possible future directions.
Tobacco chemical-induced mouse lung adenocarcinoma cell lines pin the prolactin orthologue proliferin as a lung tumour promoter
Authors: Kanellakis Nikolaos I , Giannou Anastasios D , Pepe Mario A A , Agalioti Theodora , Zazara Dimitra E , Giopanou Ioanna , Psallidas Ioannis , Spella Magda , Marazioti Antonia , Arendt Kristina A M , Lamort Anne Sophie , Champeris Tsaniras Spyridon , Taraviras Stavros , Papadaki Helen , Lilis Ioannis , Stathopoulos Georgios T
Published: February 2019

Lung adenocarcinoma (LADC) is the leading cause of cancer death worldwide. Nevertheless, syngeneic mouse models of the disease are sparse, and cell lines suitable for transplantable and immunocompetent mouse models of LADC remain unmet needs. We established multiple mouse LADC cell lines by repeatedly exposing two mouse strains (FVB, Balb/c) to the tobacco carcinogens urethane or diethylnitrosamine and by culturing out the resulting lung tumours for prolonged periods of time. Characterization of the resulting cell lines (n = 7) showed that they were immortal and phenotypically stable in vitro, and oncogenic, metastatic and lethal in vivo. The primary tumours that gave rise to the cell lines, as well as secondary tumours generated by transplantation of the cell lines, displayed typical LADC features, such as glandular architecture and mucin and thyroid transcription factor 1 expression. Moreover, these cells exhibited marked molecular similarity with human smokers’ LADC, including carcinogen-specific Kras point mutations (KrasQ61R in urethane- and KrasQ61H in diethylnitrosamine-triggered cell lines) and Trp53 deletions and displayed stemness features. Interestingly, all cell lines overexpressed proliferin, a murine prolactin orthologue, which functioned as a lung tumour promoter. Furthermore, prolactin was overexpressed and portended poor prognosis in human LADC. In conclusion, we report the first LADC cell lines derived from mice exposed to tobacco carcinogens. These cells closely resemble human LADC and provide a valuable tool for the functional investigation of the pathobiology of the disease.
Economic overview of a two-agent process for underground coal gasification with Fischer–Tropsch-based poly-generation
Authors: Brand Johan F , Van Dyk Johan C , Waanders Frans B
Published: February 2019

Underground Coal Gasification (UCG) is a mining-gasification process that produces synthesis gas from in situ coal by injecting air (or oxygen and steam) and extracting the produced gas via boreholes. The resulting synthesis gas (‘syngas’) produced by UCG can be used directly as a fuel-gas or deep-cleaned to produce many other products like chemicals, liquid fuels, hydrogen and synthetic natural gas. UCG has significant environmental, safety and practical advantages over conventional coal mining and utilization, foremost being cost and emissions reductions. In South Africa, facilities of an industrial-scale Fischer–Tropsch (FT) have been operating for decades on coal-to-liquid and gas-to-liquid conversion. Oxygen-blown UCG produces syngas, which contains a mixture of carbon monoxide (CO) and hydrogen, and these molecules can be conditioned to serve as feed for synthetic-crude-oil (‘syncrude’) conversion technologies based on the FT process. African Carbon Energy (Pty) Ltd. (Africary) completed a study integrating its UCG technology with mini gas-to-liquids plant. Syngas from Africary’s Theunissen Underground Coal Gasification (TUCG) project will be used for power production and synthesis of liquid fuels in a unique poly-generation configuration. The TUCG process will consist of two parallel gasifiers, operated on different agents, making the component parts of UCG and coal-to-(any product) (CtX) tightly linked and interdependent, but reducing both cost and emissions. UCG-CtX offers a lower capital investment to conventional underground mining and surface gasification due to the removal of the surface gasifier and coal-mine operations. The gas clean-up systems will remove undesirable components from each gasifier and blend the cleaned syngas for H2:CO ratio control and provide implementation of carbon capture and sequestration. This study has minimized the complexity and optimized the process flow to provide own-use electricity and about 4000 barrels/day equivalent fuels at a capital cost estimate (2017) of about US$ 350 million and operating cost of around 28 US$/barrel.
KCC2 Manipulation Alters Features of Migrating Interneurons in Ferret Neocortex
Authors: Djankpa F T , Lischka F , Chatterjee M , Juliano S L
Published: February 2019

KCC2 is a brain specific chloride–potassium cotransporter affecting neuronal development including migration and cellular maturation. It modulates chloride homeostasis influencing the switch of GABA from depolarizing to hyperpolarizing, which contributes to the cues that influence the termination of neuronal migration. The expression of KCC2 during migration of interneurons, therefore, correlates with the ability of these cells to respond to GABA as a stop signal. Manipulation of KCC2 in development can affect various aspects of migrating neurons, including the speed. We describe the effect of KCC2 downregulation and inhibition on features of migrating interneurons of normal ferret kits and those treated with methylazoxymethanol acetate, which increases KCC2. Treatment of organotypic cultures with Bisphenol A, an environmental toxin that alters gene expression, also downregulates KCC2 protein. In organotypic slices treated with the KCC2 antagonist VU0240551, chloride imaging shows inhibition of KCC2 via blockade of chloride flux. Time-lapse video imaging of organotypic cultures treated with either drug, shows a significant increase in the average speed, step size, and number of turns made by migrating neurons leaving the ganglionic eminence. Our findings demonstrate the harmful effect of environmental toxins on brain development and potential consequences in the pathogenesis of neurodevelopmental disorders.
Children Use Regions in the Visual Processing and Executive Function Networks during a Subsequent Memory Reading Task
Authors: Farah Rola , Coalson Rebecca S , Petersen Steven E , Schlaggar Bradley L , Horowitz-Kraus Tzipi
Published: February 2019

Memory encoding is a critical process for memory function, which is foundational for cognitive functioning including reading, and has been extensively studied using subsequent memory tasks. Research in adults using such tasks indicates the participation of visual and cognitive-control systems in remembered versus forgotten words. However, given the known developmental trajectories of these systems, the functional neuroanatomy of memory encoding in children may be different than in adults. We examined brain activation for silent word reading and checkerboard viewing during an event-related reading task in 8–12 year-old children. Results indicate greater activation for checkerboard viewing than lexical processing in early visual regions, as well as for lexical processing versus checkerboard viewing in regions in left sensorimotor mouth, cingulo-opercular and dorsal-attention networks. Greater activation for remembered than forgotten words was observed in bilateral visual system and left lateralized regions within the ventral- and dorsal-attention, cingulo-opercular and fronto-parietal networks. These findings suggest a relatively mature reliance on the cognitive-control system, but greater reliance on the visual system in children when viewing words subsequently remembered. The location of regions with greater activity for remembered words reinforces the involvement of the attention and cognitive-control systems in subsequent memory in reading.
Widespread Use of High-dose Ceftriaxone Therapy for Uncomplicated Gonorrhea Without Reported Ceftriaxone Treatment Failure: Results From 5 Years of Multicenter Surveillance Data in China
Authors: Han Yan , Yin Yueping , Dai Xiuqin , Chen Shaochun , Yang Ligang , Zhu Bangyong , Zhong Na , Cao Wenling , Zhang Xiaohui , Wu Zhizhou , Yuan Liufeng , Zheng Zhongjie , Feng Lishan , Liu Jun , Chen Xiangsheng
Published: February 2019

Background

Antimicrobial resistance to Neisseria gonorrhoeae has emerged for each of the antibiotics recommended as first-line therapies following their introduction into clinical practice. To improve rational and effective clinical antibiotic treatment, we analyzed the prescription patterns of antibiotics and their therapeutic effect in the treatment of uncomplicated gonorrhea in China.

Methods

We obtained data from a follow-up multicenter surveillance program. Multinomial logistic regression analyses were conducted to explore the associations between demographic/clinical variables with the levels of sensitivity to ceftriaxone and prescription of high-dose ceftriaxone.

Results

In this study, 1686 patients infected with N. gonorrhoeae were recruited in a surveillance network during 1 January 2013 through 31 December 2017 in 7 hospitals distributed in 5 provinces. The prevalence of isolates with decreased susceptibility to ceftriaxone was 9.8% (131/1333), fluctuating between 5.6% and 12.1%. Injectable ceftriaxone was chosen as the first-line treatment among 83.1% of patients, and most of them (72.7% [1018/1401]) received >1000 mg dosage. Patients who were previously infected with gonorrhea or other sexually transmitted infections (adjusted odds ratio [AOR], 1.618 [95% confidence interval {CI}, 1.11–2.358]; AOR, 2.08 [95% CI, 1.41–3.069]) or who already used antibiotics for this infection (AOR, 1.599 [95% CI, 1.041–2.454]) were associated with a higher prescribed ceftriaxone dosage. All of the patients recruited in this study were cured regardless of the isolates’ susceptibility to ceftriaxone or the dosage of ceftriaxone they received.

Conclusions

No ceftriaxone treatment failure for uncomplicated gonorrhea was reported in China; however, high-dose ceftriaxone was widely used in China. Its impacts need further study.
A One Health Study of the Genetic Relatedness of Klebsiella pneumoniae and Their Mobile Elements in the East of England
Authors: Ludden Catherine , Moradigaravand Danesh , Jamrozy Dorota , Gouliouris Theodore , Blane Beth , Naydenova Plamena , Hernandez-Garcia Juan , Wood Paul , Hadjirin Nazreen , Radakovic Milorad , Crawley Charles , Brown Nicholas M , Holmes Mark , Parkhill Julian , Peacock Sharon J
Published: February 2019

Background

Klebsiella pneumoniae is a human, animal, and environmental commensal and a leading cause of nosocomial infections, which are often caused by multiresistant strains. We evaluate putative sources of K. pneumoniae that are carried by and infect hospital patients.

Methods

We conducted a 6-month survey on 2 hematology wards at Addenbrooke’s Hospital, Cambridge, United Kingdom, in 2015 to isolate K. pneumoniae from stool, blood, and the environment. We conducted cross-sectional surveys of K. pneumoniae from 29 livestock farms, 97 meat products, the hospital sewer, and 20 municipal wastewater treatment plants in the East of England between 2014 and 2015. Isolates were sequenced and their genomes compared.

Results

Klebsiella pneumoniae was isolated from stool of 17/149 (11%) patients and 18/922 swabs of their environment, together with 1 bloodstream infection during the study and 4 others over a 24-month period. Each patient carried 1 or more lineages that was unique to them, but 2 broad environmental contamination events and patient–environment transmission were identified. Klebsiella pneumoniae was isolated from cattle, poultry, hospital sewage, and 12/20 wastewater treatment plants. There was low genetic relatedness between isolates from patients/their hospital environment vs isolates from elsewhere. Identical genes encoding cephalosporin resistance were carried by isolates from humans/environment and elsewhere but were carried on different plasmids.

Conclusion

We identified no patient-to-patient transmission and no evidence for livestock as a source of K. pneumoniae infecting humans. However, our findings reaffirm the importance of the hospital environment as a source of K. pneumoniae associated with serious human infection.
Prognostic significance of sarcopenia in patients undergoing esophagectomy for superficial esophageal squamous cell carcinoma
Authors: Oguma J , Ozawa S , Kazuno A , Yamamoto M , Ninomiya Y , Yatabe K
Published: February 2019

Nononcological prognostic factors in superficial esophageal squamous cell carcinoma (SESCC) patients remain unclear. The aim of this study is to evaluate the relationship between sarcopenia and surgical outcome in patients with SESCC who had undergone definitive surgery. A total of 194 SESCC patients who had undergone thoracic esophagectomy with three-field lymphadenectomy without neoadjuvant therapy at Tokai University Hospital between January 2006 and December 2015 were analyzed retrospectively. Manual tracing using CT imaging was used to measure the cross-sectional areas of the skeletal muscle mass. The cutoff values for the skeletal muscle index used to define sarcopenia were based on the results of a previous study. Twenty-eight patients (14.4%) had sarcopenia, while the remaining 166 patients (85.6%) did not. A multivariate analysis suggested that sarcopenia was an independent risk factor for postoperative pulmonary complications (OR = 3.232, P = 0.026). The overall survival rate and the disease-free survival rate were both significantly worse in the sarcopenia group than in the nonsarcopenia group (P < 0.001). In a multivariate analysis, sarcopenia was an independent prognostic factor affecting overall survival (HR = 7.121, P < 0.001) and disease-free survival (HR = 6.000, P < 0.001). Patients with sarcopenia and lymph node metastasis (n = 18) had a worse outcome than the other patients (P < 0.001). This study suggests that the alleviation of sarcopenia through nutritional support and rehabilitation in SESCC patients scheduled to undergo surgery might help to prevent postoperative pulmonary complications and to improve the long-term outcome.
Survival probability of dental autotransplantation of 366 teeth over 34 years within a hospital setting in the United Kingdom
Authors: Abela Stefan , Murtadha Linda , Bister Dirk , Andiappan Manoharan , Kwok Jerry
Published: February 2019

Introduction

The purpose of this retrospective study was to evaluate 34 years’ experience of autotransplantation of teeth during orthodontic treatment.

Methodology

Treatment was completed at Queen Mary’s Hospital, Sidcup, Kent, UK, during the period 1969–2003. A total of 366 teeth were transplanted in 314 patients.

Results

Canines totalled 78 per cent of all autotransplanted teeth; mean age of patient was 19.4 years. Survival probability for the first 5 years post-autotransplantation was 95 per cent, 94 per cent for the subsequent 5 years, and 88 per cent after 15 years. The maximum observation period was 34 years, the median was 2.0 years, and the mean was 3.51 (standard deviation = 3.68) years. Of the observed teeth, 10 failed and these were lost due to unsuccessful periodontal ligament regeneration and persistent mobility grade III (or greater). Apical pathology was observed in 16 per cent of all autotransplanted teeth. In 79 per cent of this subgroup, apical pathology was evident in the first 3 years post-operatively. Seventy per cent of all external resorption also occurred within the first 3 years. Internal resorption was rare but its occurrence was mostly observed between the second and sixth year post-transplantation. A minority of autotransplanted teeth [14 per cent (n = 51)] needed root canal therapy, and this was completed within the first 6 months post-transplantation.

Conclusions

Autotransplantation can be a justified procedure with good survival probability. It can be considered an alternative to other treatments, such as prosthodontic replacement of teeth.
Torsional Alfvén waves in a dipolar magnetic field: experiments and simulations
Authors: Tigrine Z , Nataf H-C , Schaeffer N , Cardin P , Plunian F
Published: February 2019

The discovery of torsional Alfvén waves (geostrophic Alfvén waves) in the Earth’s core (Gillet et al. 2010) calls for a better understanding of their properties. We present the first experimental observations of torsional Alfvén waves, performed in the DTS-Ω set-up. In this set-up, 50 L of liquid sodium are confined between an inner sphere (ri = 74 mm) and an outer shell (ro = 210 mm). The inner sphere houses a permanent magnet, imposing a dipolar magnetic field (Bmax = 345 mT). Both the inner sphere and the outer shell can rotate around the vertical axis. Alfvén waves are triggered by a sudden jerk of the inner sphere. We study the propagation of these waves when the fluid is initially at rest, and when it spins at a rotation rate up to 15 Hz. We measure the azimuthal magnetic field of the wave at different radii inside the fluid with magnetometers installed in a sleeve. We also record the electric potential signature on the outer shell at several latitudes. Besides, we probe the associated azimuthal velocity field using ultrasound Doppler velocimetry. With a 15 Hz rotation rate, the dynamical regimes we achieve are characterized by dimensionless numbers in the following ranges: Lundquist number 0.5 < Lu < 12, Lehnert number 0.01 < Le < 0.26, Rossby number Ro ∼ 0.1.

We observe that the magnetic signal propagates away from the inner sphere, strongly damped by magnetic diffusion. Rotation affects the magnetic signature in a subtle way. Its effect is more pronounced on the surface electric potentials, which are sensitive to the actual fluid velocity of the wave. The ultrasound Doppler probes provide the first experimental measurement of the fluid velocity of an Alfvén wave.

To complement these observations, we ran numerical simulations, using the XSHELLS pseudospectral code with parameters as close as possible to the experimental ones. The synthetic magnetic and electric signals match our measurements. The meridional snapshots of the synthetic azimuthal velocity field reveal the formation of geostrophic cylinders expected for torsional Alfvén waves.

We establish scaling laws for the magnetic and kinetic energies of Alfvén waves with and without rotation. In both cases, we find that the magnetic energy EM saturates at a level proportional to $Rm_{\rm jerk}^2$, where Rmjerk = Ujerkro/η is the magnetic Reynolds number built with the maximum azimuthal velocity of the inner sphere during the jerk. The $E_K^{\rm max}/E_M^{\rm max}$ ratio (where $E_K^{\rm max}$ is the maximum kinetic energy), close to 1 for very quick jerks, increases linearly with the jerk duration.
Efficacy of Vedolizumab for Refractory Pouchitis of the Ileo-anal Pouch: Results From a Multicenter US Cohort
Authors: Gregory Martin , Weaver Kimberly N , Hoversten Patrick , Hicks Stephen Bradley , Patel Devin , Ciorba Matthew A , Gutierrez Alexandra M , Beniwal-Patel Poonam , Palam Sowmya , Syal Gaurav , Herfarth Hans H , Christophi George , Raffals Laura , Barnes Edward L , Deepak Parakkal
Published: February 2019

Background and Aims

Inflammation of the pouch after ileal pouch-anal anastomosis (IPAA) can significantly impact quality of life and be difficult to treat. We assessed the effectiveness and safety of vedolizumab in Crohn’s disease (CD) of the pouch and chronic antibiotic-dependent or antibiotic-refractory pouchitis.

Methods

This was a retrospective, multicenter cohort study at 5 academic referral centers in the United States. Adult patients with endoscopic inflammation of the pouch who received vedolizumab were included. The primary outcome was clinical response at any time point. Secondary outcomes included clinical remission, endoscopic response, and remission. Univariate analysis and multivariate analysis were performed for the effect of the following variables on clinical response: fistula, onset of pouchitis less than 1 year after IPAA, younger than 35 years old, gender, previous tumor necrosis factor inhibitor-alpha use, and BMI >30.

Results

Eighty-three patients were treated with vedolizumab for inflammation of the pouch between January 2014 and October 2017. Median follow-up was 1.3 years (interquartile range 0.7–2.1). The proportion of patients that achieved at least a clinical response was 71.1%, with 19.3% achieving clinical remission. Of the 74 patients with a follow-up pouchoscopy, the proportion of patients with endoscopic response and mucosal healing was 54.1% and 17.6%, respectively. Patients who developed pouchitis symptoms less than 1 year after undergoing IPAA were less likely to respond to vedolizumab, even after controlling for other risk factors.

Conclusions

Vedolizumab is safe and effective in the management of CD of the pouch and chronic pouchitis. Further studies are needed to compare vedolizumab with other biologic therapies for pouchitis and CD of the pouch.
Job Flexibility and Occupational Selection in Ghana: An Application of Maximum Simulated Likelihood†
Authors: Lain Jonathan
Published: February 2019

In many African labour markets, the vast majority of self-employed workers are female. It is often hypothesised that self-employment enables workers to balance income-generation with caring for children and other domestic tasks and, since responsibility for these activities is divided unequally in the household, this effect is stronger for women than men. However, testing whether ‘job flexibility’ matters is difficult because variables that proxy for domestic obligations—such as the number of dependents in the household—may be endogenous to occupational choice. In this paper, we build a new estimator using maximum simulated likelihood that allows us to use selection on observables as a guide to selection on unobservables within the multinomial choice problem individuals face when deciding their occupation. We apply this approach to detailed cross-sectional data from Ghana. Our results show that having extra dependents in the household pushes women towards own account self-employment substantially more than men, even under more conservative assumptions about the extent of endogeneity.
Crystal structure of bacterial cyclopropane-fatty-acyl-phospholipid synthase with phospholipid
Authors: Ma Yulong , Pan Chunli , Wang Qihai
Published: February 2019

The lipids containing cyclopropane-fatty-acid (CFA) protect bacteria from adverse conditions such as acidity, freeze-drying desiccation and exposure to pollutants. CFA is synthesized when cyclopropane-fatty-acyl-phospholipid synthase (CFA synthase, CFAS) transfers a methylene group from S-adenosylmethionine (SAM) across the cis double bonds of unsaturated fatty acyl chains. Here, we reported a 2.7-Å crystal structure of CFAS from Lactobacillus acidophilus. The enzyme is composed of N- and C-terminal domain, which belong to the sterol carrier protein and methyltransferase superfamily, respectively. A phospholipid in the substrate binding site and a bicarbonate ion (BCI) acting as a general base in the active site were discovered. To elucidate the mechanism, a docking experiment using CFAS from L. acidophilus and SAM was carried out. The analysis of this structure demonstrated that three groups, the carbons from the substrate, the BCI and the methyl of S(CHn)3 group, were close enough to form a cyclopropane ring with the help of amino acids in the active site. Therefore, the structure supports the hypothesis that CFAS from L. acidophilus catalyzes methyl transfer via a carbocation mechanism. These findings provide a structural basis to more deeply understand enzymatic cyclopropanation.
Response to a Synthetic Pheromone Source by OX4319L, a Self-Limiting Diamondback Moth (Lepidoptera: Plutellidae) Strain, and Field Dispersal Characteristics of its Progenitor Strain
Authors: Bolton Michael , Collins Hilda L , Chapman Tracey , Morrison Neil I , Long Stefan J , Linn Charles E , Shelton Anthony M
Published: February 2019

The diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae), is a global pest that infests vegetable and field crops within the Brassica family. A genetically engineered strain of P. xylostella, OX4319L, carrying a ‘self-limiting’ gene, has shown potential for managing P. xylostella populations, using sustained releases of OX4319L male moths. In order for such a strain to provide control, the transgenic individuals must exhibit attraction to female P. xylostella sex pheromone and adequate dispersal in the field. In this study, we tested these key traits. First, we compared the responses of the OX4319L male moths to a synthetic female sex pheromone source in wind tunnel trials to those of males from three other strains. We found that OX4319L males responded comparably to strains of non-engineered males, with all males flying upwind towards the pheromone source. Second, we used mark-release-recapture studies of a wildtype P. xylostella strain, from which the OX4319L strain was originally developed, to assess dispersal under field conditions. Released males were recaptured using both pheromone-baited and passive traps within a 2.83 ha circular cabbage field, with a recapture rate of 7.93%. Males were recaptured up to the boundary of the field at 95 m from the central release point. The median dispersal of males was 14 m. These results showed the progenitor strain of OX4319L retained its ability to disperse within a host field. The results of these experiments are discussed in relation to the potential for the effective use of engineered male-selecting P. xylostella strains under field conditions.
How Efficient Is Fertilization by Traumatic Insemination in Orius insidiosus (Hemiptera: Anthocoridae)?
Authors: Vacacela Ajila Henry E , Michaud J P , Abdelwahab Ahmed H , Kuchta Sara V , Stowe Hannah E
Published: February 2019

Traumatic insemination (TI) can be injurious to females, and females have evolved various paragenital structures to mitigate these impacts. We examined the mating behavior of Orius insidiosus (Say) and the consequences of single and double matings for female fitness. A total of 100 virgin females (4–6-d old) were directly observed while they mated with virgin males. Some of these females were mated a second time with a different, nonvirgin male 3–5 d later, after they oviposited in sunflower stems. Females were held in isolation, fed eggs of Ephestia kuehniella Zeller, and reproductive success was tracked for 30 d. Six females died during their first copulation (6%), and another within 48 h, without laying eggs. Four percent of the females died during their second copulations. Copulations lasting less than 90 s usually did not result in successful fertilization, and duration of copula was positively correlated with egg fertility in singly-mated females. Duration of copula was more than halved in second matings, twice as variable, and negatively correlated with 30 d fecundity. Thirty-seven percent of singly-mated females and 31% of twice-mated females were infertile, with fewer than half of all females producing 88% of all eggs. We conclude that O. insidiosus females are likely monandrous in the wild, and that TI in this species is inefficient, contributing to high variation in female fitness. Thus, mating involves a significant mortality risk for females, despite their possession of complex paragenital structures that ostensibly mitigate copulatory injury.
The prognostic signature of the somatic mutations in Ewing sarcoma: from a network view
Authors: Zhang Yuehui , Song Jia , Shi Qili , Song Xupu , Shen Libing , Zhou Jingqi , Shao Jiang
Published: February 2019

Background

Ewing sarcoma is a malignant bone tumor mainly affecting teenagers and young adults. Its main driver mutation, the EWS-FLI1 fusion gene, has been identified more than 20 years ago, whereas its other somatic mutations have been just recently reported.

Methods

In this study, we organized the somatic mutations from 216 Ewing sarcoma cases into 216 individual protein–protein interaction networks by using interactome information. These mutation networks were then classified into five different clusters based on their structural similarities. The prognostic effect of mutation genes was evaluated according to their network features.

Results

The cases in cluster two exhibited remarkably high metastasis and mortality rates, and STAG2, TP53 and TTN were the three most significantly mutated genes in this cluster. Microarray data demonstrate that the expression of STAG2, TP53 and TTN are down-regulated in the EWS-FLI1-knockdown Ewing sarcoma cells. However, the mutation effect analysis shows that the somatic mutations in TTN are less damaging than those in STAG2 and TP53. The analyses of functional network modules further revealed that STAG2, TP53 and their interacting gene partners participate in the oncogenic-related biological modules such as cell cycle and regulation of transcription from RNA polymerase II promoter while TTN, TP53 and their interacting gene partners constitute the modules less relevant to oncogenesis. The results of Gene Ontology analyses demonstrated that the uniquely mutated genes associated with poor prognosis in Clusters 1, 4 and 5 were distinctively enriched in epidermal growth factor-related functions and phosphoproteins.

Conclusions

Our study identified the highly lethal mutation combination cases and characterized the possible prognostic genes in Ewing sarcoma from a network perceptive.
Practical method of cell segmentation in electron microscope image stack using deep convolutional neural network☆
Authors: Konishi Kohki , Mimura Masafumi , Nonaka Takao , Sase Ichiro , Nishioka Hideo , Suga Mitsuo
Published: February 2019

Segmentation of three-dimensional (3D) electron microscopy (EM) image stacks is an arduous and tedious task. Deep convolutional neural networks (CNNs) work well to automate the segmentation; however, they require a large training dataset, which is a major impediment. In order to solve this issue, especially for sparse segmentation, we used a CNN with a minimal training dataset. We segmented a Cerebellar Purkinje cell from an image stack of a mouse Cerebellum cortex in less than two working days, which is much shorter than that of the conventional method. We concluded that we can reduce the total labor time for the sparse segmentation by reducing the training dataset.
Structural biology of plant sulfur metabolism: from sulfate to glutathione
Authors: Jez Joseph M
Published: February 2019

Sulfur is an essential element for all organisms. Plants must assimilate this nutrient from the environment and convert it into metabolically useful forms for the biosynthesis of a wide range of compounds, including cysteine and glutathione. This review summarizes structural biology studies on the enzymes involved in plant sulfur assimilation [ATP sulfurylase, adenosine-5'-phosphate (APS) reductase, and sulfite reductase], cysteine biosynthesis (serine acetyltransferase and O-acetylserine sulfhydrylase), and glutathione biosynthesis (glutamate-cysteine ligase and glutathione synthetase) pathways. Overall, X-ray crystal structures of enzymes in these core pathways provide molecular-level information on the chemical events that allow plants to incorporate sulfur into essential metabolites and revealed new biochemical regulatory mechanisms, such as structural rearrangements, protein–protein interactions, and thiol-based redox switches, for controlling different steps in these pathways.
Perioperative Renal Protection
Authors: Shah Sapna , Lapsia Vijay
Published: February 2019

Acute kidney injury (AKI) is a serious postoperative complication with significant implications on morbidity and mortality. Estimated to occur in 5% of all hospital admissions, postoperative AKI is the second most common cause of renal injury among all hospitalized patients. With the increasing incidence and prevalence of chronic kidney disease, it is therefore important to clearly understand risk prior to surgery through detailed risk assessment and preoperative laboratory testing. This chapter discusses preoperative risk factors contributing to AKI, presents strategies to prevent postoperative AKI, and considers available options to protect perioperative renal function to prevent acute complications and long-term renal injury.
Renal Protection in Critically Ill Patients
Authors: Haines Ryan W. , Prowle John R.
Published: February 2019

Acute kidney injury complicates over 50% of critical care admissions and is associated with both increased short and long-term mortality and the development or acceleration of chronic kidney disease. While in certain settings, such as cardiac surgery, primary prevention of AKI is possible, in most cases AKI is present or evolving at intensive care unit admission and the main clinical focus is secondary prevention of further kidney injury. In the absence of evidence for specific AKI-targeted therapies, high quality supportive care to maximize hemodynamic stability and avoidance of secondary sources of kidney injury are the cornerstones of renal protection. Fluid overload is particularly associated with adverse outcomes in critical illness complicated by AKI. Continuous methods of renal replacement therapy may promote hemodynamic stability and have been associated with better longer term renal outcomes.
Tubulointerstitial Nephropathies
Authors: Koratala Abhilash , Singhania Girish , Ejaz A. Ahsan
Published: February 2019

Tubulointerstitial nephropathies encompass diverse disease processes involving the part of the renal parenchyma that consists of the tubules and interstitium. Tubulointerstitial diseases can occur as primary or secondary (to a systemic disease) processes, and patients can present with either acute or chronic disease. Depending on the offending agent, the disease may have a particular predilection for the proximal tubules, the distal tubules, or both. Definitive diagnosis is by renal biopsy, which typically reveals variable degrees of cellular infiltration of the interstitium, tubular atrophy, and fibrosis, depending on the chronicity. There are several causes, including drugs, infections, environmental toxins, and immunologic processes. This chapter classifies tubulointerstitial nephropathies and briefly discusses the important individual entities. In addition, an approach for renoprotection in these cases based on the available data is suggested.
Neurological Disorders
Authors: Schwartz Margaret A.
Published: February 2019

Many diseases are accompanied by neurological sequelae. Palliative care nurses must arm themselves with knowledge of common neurological symptoms in order to properly assess the patient, advise the patient and family/caregivers, and address these symptoms. Additionally, neurological diseases are common and may come with a heavy symptom burden. As evidence evolves, so must our clinical practice. This chapter will introduce the palliative care nurse to several neurological diseases requiring intervention for symptoms palliation. Additionally, this chapter will suggest appropriate, evidence-based interventions for broad symptom categories for treating the patient with a variety of neurological disturbances.
Anxiety and Depression
Authors: Salman Jaroslava , Wolfe Emma , Patel Sunita K.
Published: February 2019

Patients with advanced, incurable disease are vulnerable to emotional distress. While some level of psychological struggle is expected and understandable, the distinction between appropriate reaction to functional decline and dying and more serious psychiatric condition is often challenging. Depressive and anxiety symptoms are common but can be misunderstood, underdiagnosed, and untreated if not properly recognized and distinguished from milder forms of emotional reactions. For patients who are suffering, there are different modalities of treatment that can be used effectively, whether it is psychotropic medications; nonpharmacological interventions, such as psychotherapy or alternative supportive interventions; or some combination of the above. Providing patients and their families with education on psychological distress and ways to manage it can help empower them and relieve their suffering.
Cultural Considerations in Palliative Care
Authors: Cormack Carrie , Mazanec Polly , Panke Joan T.
Published: February 2019

This chapter defines culture and the complexity of its components as they relate to palliative care. It emphasizes how recognizing one’s own values, practices, and beliefs impacts the care of others. Key palliative care concepts and issues heavily influenced by culture are discussed throughout. This chapter is not intended to define behaviors and practices of different cultures as they relate to palliative care but rather to raise awareness of the significance of cultural considerations in palliative care. It is essential that nurses consider the role that culture or subcultures may play in patient and family choice and decision-making during difficult times involving serious illness and end of life.
Who Are Informal Cancer Caregivers?
Authors: Kent Erin E. , Longacre Margaret L. , Sylvia Chou Wen-Ying , Mollica Michelle A.
Published: February 2019

Informal cancer caregivers are family members, partners, or friends who provide care that is typically uncompensated, at home, and often intensive for individuals with cancer. Estimates vary, but approximately 2 to 6 million American adults are currently serving as a caregiver for an adult with cancer. Most adult cancer caregivers are female, and the median age of caregivers is 52. The growth in prevalence of cancer and move to more outpatient care has placed an increasing burden on informal caregivers. This chapter reviews the prevalence, characteristics, tasks, and impact of caregiving on both caregivers and patients, with implications and future directions for research, practice, and policy.
The Burden of Cancer Caregivers
Authors: Given Barbara A. , Given Charles W.
Published: February 2019

Caregiver burden is the “stress” perceived by family caregivers who care for patients and results from the imbalance between demands (objective and subjective) and their coping resources. Approximately 1.7 million Americans are diagnosed with cancer each year. There are an estimated 4 million caregivers of cancer patients in the United States. This chapter focuses on caregiver burden stemming from family caregivers’ negative appraisals (burden) of the care they provide to patients with cancer. This resulting burden may threaten the patient-caregiver dyadic relationship and result in negative physical, psychological, and social outcomes for the caregiver as well as negatively impact the patient. The balance between demands and resources determines the level of burden and the consequences on the care situation.