bluuebunny/crossref_metadata_2025 huggingface dataset:
Stellar encounters with giant molecular clouds
Authors: Kokaia Giorgi , Davies Melvyn B
Published: April 2019

Giant molecular clouds (GMCs) are believed to affect the biospheres of planets as their host star passes through them. We simulate the trajectories of stars and GMCs in the Galaxy and determine how often stars pass through GMCs. We find a strong decreasing dependence with Galactocentric radius, and with the velocity perpendicular to the Galactic plane, V$\mathrm{ z}$. The XY-component of the kinematic heating of stars was shown to not affect the GMC hit rate, unlike the Z-dependence (V$\mathrm{ z}$) implies that stars hit fewer GMCs as they age. GMCs are locations of star formation, therefore we also determine how often stars pass near supernovae. For the supernovae the decrease with V$\mathrm{ z}$ is steeper as how fast the star passes through the GMC determines the probability of a supernova encounter. We then integrate a set of Sun-like trajectories to see the implications for the Sun. We find that the Sun hits 1.6 ± 1.3 GMCs per Gyr which results in 1.5 ± 1.1 or (with correction for clustering) 0.8 ± 0.6 supernova closer than 10 pc per Gyr. The different the supernova frequencies are from whether one considers multiple supernovae per GMC crossing (few Myr) as separate events. We then discuss the effect of the GMC hits on the Oort cloud, and the Earth’s climate due to accretion, we also discuss the records of distant supernova. Finally, we determine Galactic Habitable Zone using our model. For the thin disc, we find it to lie between 5.8 and 8.7 kpc and for the thick disc to lie between 4.5 and 7.7 kpc.
Alignment of a circumbinary disc around an eccentric binary with application to KH 15D
Authors: Smallwood Jeremy L , Lubow Stephen H , Franchini Alessia , Martin Rebecca G
Published: April 2019

We analyse the evolution of a mildly inclined circumbinary disc that orbits an eccentric orbit binary by means of smoothed particle hydrodynamics (SPH) simulations and linear theory. We show that the alignment process of an initially misaligned circumbinary disc around an eccentric orbit binary is significantly different than around a circular orbit binary and involves tilt oscillations. The more eccentric the binary, the larger the tilt oscillations and the longer it takes to damp these oscillations. A circumbinary disc that is only mildly inclined may increase its inclination by a factor of a few before it moves towards alignment. The results of the SPH simulations agree well with those of linear theory. We investigate the properties of the circumbinary disc/ring around KH 15D. We determine disc properties based on the observational constraints imposed by the changing binary brightness. We find that the inclination is currently at a local minimum and will increase substantially before settling to coplanarity. In addition, the nodal precession is currently near its most rapid rate. The recent observations that show a reappearance of star B impose constraints on the thickness of the layer of obscuring material. Our results suggest that disc solids have undergone substantial inward drift and settling towards to disc mid-plane. For disc masses ∼0.001 M⊙, our model indicates that the level of disc turbulence is low (α ≪ 0.001). Another possibility is that the disc/ring contains little gas.
Opacities for photon splitting and pair creation in neutron star magnetospheres
Authors: Hu Kun , Baring Matthew G , Wadiasingh Zorawar , Harding Alice K
Published: April 2019

Over the last four decades, persistent and flaring emission of magnetars observed by various telescopes has provided us with a suite of light curves and spectra in soft and hard X-rays, with no emission yet detected above around 1 MeV. Attenuation of such high-energy photons by magnetic pair creation and photon splitting is expected to be active in the magnetospheres of magnetars, possibly accounting for the paucity of gamma-rays in their signals. This paper explores polarization-dependent opacities for these two QED processes in static vacuum dipole magnetospheres of highly magnetized neutron stars, calculating attenuation lengths and determining escape energies, which are the maximum photon energies for transparency out to infinity. The numerical trajectory integral analysis in flat and curved space–times provides upper bounds of a few MeV or less to the visible energies for magnetars for locales proximate to the stellar surface. Photon splitting opacity alone puts constraints on the possible emission locales in their magnetospheres: regions within field loops of maximum altitudes $\, r_{{\rm max}}\sim 2\!-\!4\,$ stellar radii are not commensurate with maximum detected energies of around 250 keV. These constraints apply not only to magnetar flares but also to their quiescent hard X-ray tail emission. An exploration of photon splitting attenuation in the context of a resonant inverse Compton scattering model for the hard X-ray tails derives distinctive phase-resolved spectroscopic and polarimetric signatures, of significant interest for future MeV-band missions such as AMEGO and e-ASTROGAM.
Enrichment of Phosphatidylinositol 4,5-Bisphosphate in the Extra-Invasive Hyphal Membrane Promotes Colletotrichum Infection of Arabidopsis thaliana
Authors: Shimada Takashi L , Betsuyaku Shigeyuki , Inada Noriko , Ebine Kazuo , Fujimoto Masaru , Uemura Tomohiro , Takano Yoshitaka , Fukuda Hiroo , Nakano Akihiko , Ueda Takashi
Published: April 2019

Pathogenic fungi from the genus Colletotrichum form invasive hyphae; the hyphae are surrounded by an extra-invasive hyphal membrane (EIHM), which is continuous with the plant plasma membrane. Although the EIHM plays a crucial role as the interface between plant and fungal cells, its precise function during Colletotrichum infection remains elusive. Here, we show that enrichment of phosphoinositides (PIs) has a crucial role in Colletotrichum infection. We observed the localization of PIs in Arabidopsis thaliana cells infected by A. thaliana-adapted Colletotrichum higginsianum (Ch), and found that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] was extremely enriched in the EIHM during Ch infection. We also found that phosphatidylinositol 4-phosphate-5 kinase (PIP5K), which catalyzes production of PI(4,5)P2, also accumulated at the EIHM. The overexpression of PIP5K3 in A. thaliana increased hyphal invasion by Ch. An exocytic factor, EXO84b, was targeted to the EIHM during Ch infection, although endocytic factors such as CLATHRIN LIGHT CHAIN 2 and FLOTILLIN 1 did not. Intriguingly, the interfacial membranes between A. thaliana and powdery mildew- or downy mildew-causing pathogens did not accumulate PI(4,5)P2. These results suggest that Ch could modify the PI(4,5)P2 levels in the EIHM to increase the exocytic membrane/protein supply of the EIHM for successful infection. Our results also suggest that PI(4,5)P2 biosynthesis is a promising target for improved defense against Colletotrichum infection.
Deposit Insurance, Bank Risk-Taking, and Failures: Evidence from Early Twentieth-Century State Deposit Insurance Systems
Authors: Aldunate Felipe
Published: April 2019

I use the introduction of deposit insurance in eight U.S. states in the early twentieth-century to study the effects of deposit insurance on the banking system. Using a triple difference approach exploiting regulatory differences between national and state banks and between states, I find that insured banks experienced higher deposit growth and decreased funding costs. I also observe a replacement of demand deposits by riskier time deposits. However, I find no aggregate effects on failure rates or risk-taking. Using hand-collected micro-level data, I show that small and large banks reacted differently and that banks facing funding problems especially benefited.

Received July 20, 2017; editorial decision November 12, 2018 by Editor Efraim Benmelech.
Health-Related Quality of Life With Ulipristal Acetate for Treatment of Uterine Leiomyomas
Authors: Lukes Andrea S. , Soper David , Harrington Amanda , Sniukiene Vilma , Mo Yifan , Gillard Patrick , Shulman Lee
Published: April 2019

OBJECTIVE:

To investigate effects of ulipristal acetate on health-related quality of life (QOL) and symptom severity in women with symptomatic uterine leiomyomas and abnormal uterine bleeding.

METHODS:

Women were randomized to ulipristal (5 mg, 10 mg) or placebo in two phase 3, multicenter, double-blind, placebo-controlled trials (VENUS I and II). Health-related QOL and symptom severity were assessed at baseline, and over one (VENUS I and II) and two (VENUS II) 12-week treatment courses using the Uterine Fibroid Symptom Health-Related Quality of Life questionnaire. In pooled VENUS I and II data, change from baseline to the end of the first course for each Uterine Fibroid Symptom Health-Related Quality of Life scale was analyzed, including a Revised Activities subscale that measured physical and social activities. The proportion of women achieving meaningful change in the Symptom Severity (20 or more points), Health-Related QOL Total (20 or more points), and Revised Activities (30 or more points) scales was calculated. In VENUS II data, change from baseline to the end of each course in each scale was analyzed for each treatment arm.

RESULTS:

In pooled analyses, the intent-to-treat population included 589 patients (placebo, n=169; ulipristal 5 mg, n=215; ulipristal 10 mg, n=205). Significantly greater improvements from baseline in all Uterine Fibroid Symptom Health-Related Quality of Life scales were observed with both ulipristal doses compared with placebo (P<.001). A meaningful change in Revised Activities was achieved by 51 patients receiving placebo (34.9%), compared with 144 (73.5%; OR 5.0 [97.5% CI 2.9–8.6]) and 141 (80.6%; OR 7.9 [97.5% CI 4.3–14.6]) patients receiving ulipristal 5 mg, and 10 mg, respectively. In VENUS II, at end of courses 1 and 2, both ulipristal doses demonstrated significant improvements from baseline compared with placebo for all Uterine Fibroid Symptom Health-Related Quality of Life scales (P<.01). Mean Revised Activities scores showed that beneficial ulipristal effects were maintained in course 2, and improvements occurred on switching to ulipristal; results for other scales were similar.

CONCLUSION:

Ulipristal was associated with significant improvements in health-related QOL and symptom severity compared with placebo for women with symptomatic uterine leiomyomas.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02147197 and NCT02147158.

FUNDING SOURCE:

Allergan plc, Dublin, Ireland.
Raynaud Phenomenon of the Nipple
Authors: Jansen Sierra , Sampene Katherine
Published: April 2019

BACKGROUND:

Obstetricians often feel ill-equipped to address the symptom of breast pain in pregnant and postpartum patients.

Cases:

In the first case, a 40-year-old woman in the second trimester of pregnancy reported nipple discoloration and severe pain. She was treated with nifedipine, and her symptoms decreased quickly and markedly. In the second case, a 32-year-old woman presented for a routine postpartum visit. She described breast pain and sporadic purple discoloration of the nipples, a finding confirmed on examination. Conservative measures of maintaining warmth were recommended.

CONCLUSION:

Raynaud phenomenon of the nipple is an underdiagnosed condition affecting women in both the prenatal and postpartum periods. A careful history and physical must be obtained in women presenting with breast pain, because diagnosis and treatment allows breastfeeding continuation and mitigation of symptoms.
Medication-Assisted Treatment Use Among Pregnant Women With Opioid Use Disorder
Authors: Krans Elizabeth E. , Kim Joo Yeon , James Alton Everette , Kelley David , Jarlenski Marian P.
Published: April 2019

OBJECTIVE:

To evaluate temporal trends in medication-assisted treatment use among pregnant women with opioid use disorder.

METHODS:

We conducted a retrospective cohort study using Pennsylvania Medicaid administrative data. Trends in medication-assisted treatment use, opioid pharmacotherapy (methadone and buprenorphine) and behavioral health counselling, were calculated using pharmacy records and procedure codes. Cochrane-Armitage tests evaluated linear trends in characteristics of pregnant women using methadone compared with buprenorphine.

RESULTS:

In total, we evaluated 12,587 pregnancies among 10,741 women with opioid use disorder who had a live birth between 2009 and 2015. Across all years, 44.1% of pregnant women received no opioid pharmacotherapy, 27.1% used buprenorphine, and 28.8% methadone. Fewer than half of women had any behavioral health counseling during pregnancy. The adjusted prevalence of methadone use declined from 31.6% (95% CI 29.3–33.9%) in 2009 to 25.2% (95% CI 23.3–27.1%) in 2015, whereas the adjusted prevalence of buprenorphine use increased from 15.8% (95% CI 13.9–17.8%) to 30.9% (95% CI 28.8–33.0%). Greater increases in buprenorphine use were found in geographic regions with large metropolitan centers, such as the Southwest (plus 24.9%) and the Southeast (plus 12.0%), compared with largely rural regions, such as the New West (plus 5.2%). In 2015, the adjusted number of behavioral health counseling visits during pregnancy was 3.4 (95% CI 2.6–4.1) among women using buprenorphine, 4.0 (95% CI 3.3–4.7) among women who did not use pharmacotherapy, and 6.4 (95% CI 4.9–7.9) among women using methadone.

CONCLUSION:

Buprenorphine use among Medicaid-enrolled pregnant women with opioid use disorder increased significantly over time, with a small concurrent decline in methadone use. Behavioral health counseling use was low, but highest among women using methadone.
Industry Payments to Pediatric Orthopaedic Surgeons Reported by the Open Payments Database: 2014 to 2017
Authors: Pathak Neil , Mets Elbert J. , Mercier Michael R. , Galivanche Anoop R. , Bovonratwet Patawut , Smith Brian G. , Grauer Jonathan N.
Published: April 2019

Background:

The Open Payments Database (OPD), mandated by the Sunshine Act, is a national registry of physician-industry transactions. Payments are reported as either General, Research, or Ownership payments. The current study aims to investigate trends in OPD General payments reported to pediatric orthopaedic surgeons from 2014 to 2017.

Methods:

General industry payments made to pediatric orthopaedic surgeons (as identified by OPD) were characterized by median payment, payment subtype, and census region. As fewer Research and Ownership payments were made, only payment totals for these categories were determined. General payment data were analyzed for trends using the nonparametric Mann-Whitney U test.

Results:

For General payments, there was an increase in the number of compensated pediatric orthopaedists from 2014 to 2017 (324 vs. 429). Of those compensated, there was no significant change in median payment per compensated surgeon ($201 vs. $197; P=0.82). However, a large percentage of total General payment dollars in pediatric orthopaedics were made to the top 5% of compensated pediatric orthopaedists each year (average 71% of total General industry compensation). For this top 5% group, median General payment per compensated surgeon increased from 2014 ($14,624) to 2017 ($32,752) (P=0.006). A significant increase in median subtype aggregate payment per surgeon was observed in the education (P<0.001) and royalty/license (P=0.031) subtypes; a significant decrease was observed for travel/lodging payments (P=0.01). Midwest pediatric orthopaedists received the highest median payment across all years studied. Few payments for research and ownership were made to pediatric orthopaedists. Four-year aggregate payment totals were $18,151 and $3,223,554 for Research and Ownership payments, respectively.

Conclusions:

Many expected payments to surgeons to decrease when put under the public scrutiny of the OPD. Not only was this decrease not observed for General payments to pediatric orthopaedic surgeons during the 2014 to 2017 period, but also the median General payment to the top 5% increased. These findings are important to note in the current era of increased transparency.

Level of Evidence:

Level III.
Fluoroscopy as Definitive Postreduction Imaging of Pediatric Wrist and Forearm Fractures Is Safe and Saves Time
Authors: Goodman Avi D. , Walsh Devin F. , Zonfrillo Mark R. , Eberson Craig P. , Cruz Aristides I.
Published: April 2019

Background:

Recent studies indicate that formal postreduction radiographs may be unnecessary for closed, isolated pediatric wrist, and forearm when mini C-arm fluoroscopy is used for reduction. Our institution changed the Emergency Department (ED) management protocol to reflect this by allowing orthopaedic providers to determine if fluoroscopy was acceptable to assess fracture reduction. We hypothesized that using fluoroscopy as definitive postreduction imaging would decrease total encounter time, without an increase in the rate of rereduction or surgery.

Methods:

Patients with closed, isolated distal radius/distal ulna (DR/DU) or both bone forearm (BBFA) fractures that required sedation and reduction under mini C-arm fluoroscopy at our Level 1 pediatric ED were reviewed for 6 months both before and after this policy change. Before, all patients had formal postreduction radiographs; after, the decision was left to the orthopaedic physician. Timestamp data were collected, as was the need for rereduction or surgery. In addition to descriptive statistics, between-group differences were analyzed with the Student t test, χ2 test, and multivariable regression as appropriate.

Results:

A total of 243 patients (119 before, 124 after) had 165 DR/DU and 78 BBFA fractures. Demographic data were similar before and after. After protocol implementation, univariable analysis (Student t test) showed that sedation times were longer, while total ED time and the time from sedation beginning to discharge were similar. The proportion of patients requiring rereduction or surgery were similar.

After multivariable regression, “fluoroscopy as definitive imaging” was the only independent determinant of the time intervals compared with using conventional radiography. Sedation was an average of 13.8 minutes longer (P<0.001), while the interval from sedation beginning to discharge was 15.8 minutes shorter (P=0.007), and total ED time was 33.0 minutes shorter (P=0.018). Fluoroscopy as definitive imaging was not a predictor of surgery (odds ratio=0.63, P=0.520), although having a BBFA increased the likelihood (odds ratio=4.50, P=0.008).

Conclusions:

Implementing a protocol in which the provider could use mini C-arm fluoroscopy for definitive postreduction imaging did not result in increased rates remanipulation or need for surgery. Regression analysis further demonstrated time savings associated with foregoing conventional radiographs.

Level of Evidence:

Level III—therapeutic.
Prevalence of Clostridium difficile infection among hospitalized inflammatory bowel disease patients in Greece
Authors: Viazis Nikos , Pontas Christos , Karmiris Konstantinos , Dimas Ioannis , Fragaki Maria , Paspatis Gregorios , Drygiannakis Ioannis , Koutroubakis Ioannis E. , Moschovis Dimitris , Tzouvala Maria , Theocharis Georgios , Tsolias Chrysostomos , Thomopoulos Konstantinos , Zampeli Evanthia , Axiaris Georgios , Michopoulos Spyros , Belesiotou Eleni , Banasa Maria , Maraki Sofia , Kouskoumpekou Fotini , Apostolopoulos Georgios , Stamouli Vasiliki , Prifti Heleni , Mantzaris Gerasimos J.
Published: April 2019

Background

Inflammatory bowel disease (IBD) is an independent risk factor for Clostridium difficile infection (CDI), which is associated significantly with disease severity. We aimed to determine the rates of CDI among hospitalized IBD patients in major tertiary referral hospitals in Greece.

Patients and methods

A retrospective analysis was carried out of stool cultures from hospitalized patients investigated for diarrhea, during 2016, tested for CDI with glutamate dehydrogenase (GDH) and toxins A and B.

Results

In total, 6932 patients were tested for CDI; 894 were positive for GDH (12.89%) and 339 were also positive for C. difficile toxin (4.89%). The prevalence of CDI among all hospitalized patients was 1.6/1000 patient-days. Among these, there were 401 IBD patients, and 62 were positive for GDH (15.46%) and 30 were also positive for C. difficile toxin (7.48%). The prevalence of CDI in IBD patients was 2.5/1000 patient-days, significantly higher than in non-IBD hospitalized patients (30/401 vs. 309/6531, P=0.013). Among the 30 IBD patients (ulcerative colitis=18, Crohn’s disease=12) with CDI, six were receiving biologics, three were on corticosteroids [one combined with azathioprine (AZA) and one combined with 5-ASA], nine were on AZA monotherapy and 12 were on 5-ASA monotherapy. The prevalence of CDI among patients receiving AZA monotherapy was significantly higher than in patients receiving other medications (9/68 vs. 21/333, P=0.047). Mild CDI (n=28) was treated with metronidazole and/or vancomycin, whereas severe CDI (n=2) was treated with vancomycin.

Conclusion

The prevalence of CDI is higher in hospitalized IBD patients than those without IBD and AZA monotherapy increases the risk of CDI.
Osteopoikilosis With Germline LEMD3 Mutation Mimicking Bone Metastases in a Girl With a Concurrent Secreting Mixed Germ Cell Tumor
Authors: Correa Llano Maria G. , Mora Jaume , Torner Ferran , Inarejos Emilio , Cruz Ofelia
Published: April 2019

Osteopoikilosis (OPK) is a rare, benign, asymptomatic bone disease causing dense bone lesions, which could be interpreted as bone metastasis. The symmetric distribution, lack of bone destruction, and location differentiate OPK from metastatic disease. It is essential to be aware of this benign condition to prevent diagnostic errors. We present the case of a 10-year-old female patient with the concurrent diagnosis of secreting mixed germ cell tumor with Yolk Salk Tumor compound and OPK. Physical examination disclosed an abdominal mass, and blood tests showed increased alfa-fetoprotein and human chorionic gonadotropin levels. Computed tomography revealed a pelvic tumor associated with multiple radiodense lesions distributed throughout the bone skeleton. Lesions were inactive on scintigraphy and FDG-PET. Pathology of the bone showed normal bone tissue and ruled out metastasis. The patient achieved complete remission after chemotherapy and surgery and remains in continued complete remission 28 months from diagnosis. The genetic analysis confirmed the LEMD3 germline mutation confirming OPK.
Late Recurrence of Wilms Tumor After 17 Years: A Case Report
Authors: Park Woo Young , Hong Kyung Taek , Ahn Hong Yul , Choi Jung Yoon , Kang Hyoung Jin , Park Sung Hye , Shin Hee Young
Published: April 2019

Wilms tumor is the most common renal malignancy in children. Most of Wilms tumor recurrences occur within 2 years of the first diagnosis. Relapse after 5 years after the first diagnosis is called “late recurrence” and is rare in Wilms tumor. There are few case reports or small series of late recurrence of Wilms tumor. Because of the rarity of late recurrence of Wilms tumor, there is no clear guideline for its management. We describe a case of late recurrence of Wilms tumor as a remote metastasis in the lung at 18 years after the first diagnosis and 17 years after the second remission, which was achieved by radiotherapy and high-dose chemotherapy with autologous stem cell rescue. After late recurrence, the patient was treated by surgery and adjuvant chemotherapy, and remained disease-free for 11 months. Several very late recurrences of Wilms tumor in the literature are reviewed.
Why Some Walk and Others Don't: Neighborhood Safety and the Sociodemographic Variation Effect on Walking for Leisure and Transportation
Authors: Aliyas Zeinab
Published: April 2019

Objective:

The study was aimed at assessing the association of all components of safety (crime, traffic, social, and physical) and general safety with walking for leisure and transportation among Iranian adults. In this regard, sociodemographic factors as potential effect modifiers on walking behavior and the association of neighborhood safety with the level of walking were explored.

Method:

A total of 1300 questionnaires were distributed among respondents residing in 8 neighborhoods in Bandar Abbas city, among which 1132 qualified for use in further analysis. Using a binary logistic regression method, differences in walking behavior and perceived safety to walk were evaluated across sociodemographic characteristics.

Results:

The results showed that the walking rate is higher among older adults, married people, and adults with lower education and a higher length of residency. An increase in neighborhood safety from crime, traffic, social disorders, and overall safety associates with increased leisure walking among all populations. Further, overall neighborhood safety and safety from crime and traffic positively correlate with the level of transportation walking among all respondents. For both types of walking, this association varies in sociodemographic groups.

Conclusion:

The study suggests that an increase in the safety of a neighborhood contributes to a higher level of leisure and transportation walking; however, it varies in different subgroups. This study provides the knowledge needed to consider all aspects of neighborhood safety to measure walking behavior level.
Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity
Authors: Heden Timothy D. , Johnson Jordan M. , Ferrara Patrick J. , Eshima Hiroaki , Verkerke Anthony R. P. , Wentzler Edward J. , Siripoksup Piyarat , Narowski Tara M. , Coleman Chanel B. , Lin Chien-Te , Ryan Terence E. , Reidy Paul T. , de Castro Brás Lisandra E. , Karner Courtney M. , Burant Charles F. , Maschek J. Alan , Cox James E. , Mashek Douglas G. , Kardon Gabrielle , Boudina Sihem , Zeczycki Tonya N. , Rutter Jared , Shaikh Saame R. , Vance Jean E. , Drummond Micah J. , Neufer P. Darrell , Funai Katsuhiko
Published: April 2019

Exercise capacity is a strong predictor of all-cause mortality. Skeletal muscle mitochondrial respiratory capacity, its biggest contributor, adapts robustly to changes in energy demands induced by contractile activity. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are regulated. Herein, we show that exercise training or muscle disuse alters mitochondrial membrane phospholipids including phosphatidylethanolamine (PE). Addition of PE promoted, whereas removal of PE diminished, mitochondrial respiratory capacity. Surprisingly, skeletal muscle-specific inhibition of mitochondrial-autonomous synthesis of PE caused a respiratory failure due to metabolic insults in the diaphragm muscle. While mitochondrial PE deficiency coincided with increased oxidative stress, neutralization of the latter did not rescue lethality. These findings highlight the previously underappreciated role of mitochondrial membrane phospholipids in dynamically controlling skeletal muscle energetics and function.
Random forest-based modelling to detect biomarkers for prostate cancer progression
Authors: Toth Reka , Schiffmann Heiko , Hube-Magg Claudia , Büscheck Franziska , Höflmayer Doris , Weidemann Sören , Lebok Patrick , Fraune Christoph , Minner Sarah , Schlomm Thorsten , Sauter Guido , Plass Christoph , Assenov Yassen , Simon Ronald , Meiners Jan , Gerhäuser Clarissa
Published: April 2019

The clinical course of prostate cancer (PCa) is highly variable, demanding an individualized approach to therapy and robust prognostic markers for treatment decisions. We present a random forest-based classification model to predict aggressive behaviour of PCa. DNA methylation changes between PCa cases with good or poor prognosis (discovery cohort with n=70) were used as input. The model was validated with data from two large independent PCa cohorts from the “International Cancer Genome Consortium” (ICGC) and “The Cancer Genome Atlas” (TCGA). Ranking of cancer progression-related DNA methylation changes allowed selection of candidate genes for additional validation by immunohistochemistry. We identified loss of ZIC2 protein expression, mediated by alterations in DNA methylation, as a promising novel prognostic biomarker for PCa in >12,000 tissue micro-array tumors. The prognostic value of ZIC2 proved to be independent from established clinico-pathological variables including Gleason grade, tumor stage, nodal stage and PSA. In summary, we have developed a PCa classification model, which either directly orviaexpression analyses of the identified top ranked candidate genes might help in decision making related to the treatment of prostate cancer patients.
Meiotic Cellular Rejuvenation is Coupled to Nuclear Remodeling in Budding Yeast
Authors: King Grant A. , Goodman Jay S. , Chetlapalli Keerthana , Schick Jennifer G. , Jorgens Danielle M. , McDonald Kent L. , Ünal Elçin
Published: April 2019

Production of healthy gametes in meiosis relies on the quality control and proper distribution of both nuclear and cytoplasmic contents. Meiotic differentiation naturally eliminates age-induced cellular damage by an unknown mechanism. Using time-lapse fluorescence microscopy in budding yeast, we found that nuclear senescence factors – including protein aggregates, extrachromosomal ribosomal DNA circles, and abnormal nucleolar material – are sequestered away from chromosomes during meiosis II and subsequently eliminated. A similar sequestration and elimination process occurs for the core subunits of the nuclear pore complex in both young and old cells. Nuclear envelope remodeling drives the formation of a membranous compartment containing the sequestered material. Importantly,de novogeneration of plasma membrane is required for the sequestration event, preventing the inheritance of long-lived nucleoporins and senescence factors into the newly formed gametes. Our study uncovers a new mechanism of nuclear quality control and provides insight into its function in meiotic cellular rejuvenation.
West Nile Virus Subverts T Cell Stimulatory Capacity of Human Dendritic Cells
Authors: Zimmerman Matthew G. , Bowen James R. , McDonald Circe E. , Pulendran Bali , Suthar Mehul S.
Published: April 2019

West Nile virus (WNV) is a neurotropic flavivirus and the leading cause of mosquito-borne encephalitis in the United States. Recent studies in humans have found that dysfunctional T cell responses strongly correlate with development of severe WNV neuroinvasive disease. However, the contributions of human dendritic cells (DCs) in priming WNV-specific T cell immunity remains poorly understood. Here, we demonstrate that human monocyte-derived DCs (moDCs) support productive viral replication following infection with a pathogenic strain of WNV. Antiviral effector gene transcription was strongly induced during the log-phase viral growth, while secretion of type I interferons (IFN) occurred with delayed kinetics. Activation of RIG-I like receptor (RLR) or type I IFN signaling prior to log-phase viral growth significantly diminished viral replication, suggesting that activation of antiviral programs early can block WNV infection. In contrast to the induction of antiviral responses, WNV infection did not promote transcription or secretion of pro-inflammatory (IL-6, GM-CSF, CCL3, CCL5, CXCL9) or T cell modulatory cytokines (IL-4, IL-12, IL-15). There was also minimal induction of molecules associated with antigen presentation and T cell priming, including the co-stimulatory molecules CD80, CD86, and CD40. Functionally, WNV-infected moDCs dampened allogenic CD4 and CD8 T cell activation and proliferation. Combined, we propose a model where WNV subverts human DC activation to compromise priming of WNV-specific T cell immunity.

Importance

West Nile virus (WNV) is an encephalitic flavivirus that remains endemic in the United States. Previous studies have found dysfunctional T cell responses correlate to severe disease outcomes during human WNV infection. Here, we sought to better understand the ability of WNV to program human dendritic cells (DCs) to prime WNV-specific T cell responses. While productive infection of monocyte-derived DCs activated antiviral and type I interferon responses, molecules associated with inflammation and programming of T cells were minimally induced. Functionally, WNV-infected DCs dampened T cell activation and proliferation during an allogeneic response. Combined, our data supports a model where WNV infection of human DCs compromises WNV-specific T cell immunity.
Genomic Selection in Rubber Tree Breeding: A Comparison of Models and Methods for dealing with G × E
Authors: Souza L.M. , Francisco F.R. , Gonçalves P.S. , Scaloppi Junior E.J. , Le Guen V. , Fritsche-Neto R. , Souza A.P
Published: April 2019

Several genomic prediction models incorporating genotype × environment (G×E) interactions have recently been developed and used in genomic selection (GS) in plant breeding programs. G×E interactions decrease selection accuracy and limit genetic gains in plant breeding. Two genomic data sets were used to compare the prediction ability of multi-environment G×E genomic models and two kernel methods (a linear kernel (genomic best linear unbiased predictor, GBLUP) (GB) and a nonlinear kernel (Gaussian kernel, GK)) and prediction accuracy (PA) of five genomic prediction models: (1) one without environmental data (BSG); (2) a single-environment, main genotypic effect model (SM); (3) a multi-environment, main genotypic effect model (MM); (4) a multi-environment, single variance GxE deviation model (MDs); and (5) a multi-environment, environment-specific variance GxE deviation model (MDe). We evaluated the utility of GS with 435 rubber tree individuals in two sites and genotyped the individuals with genotyping-by-sequencing (GBS) of single-nucleotide polymorphisms (SNPs). Prediction models were estimated for diameter (DAP) and height (AP) at different ages, with a heritability ranging from 0.59 to 0.75 for both traits. Applying the model (BSG, SM, MM, MDs, and MDe) and kernel method (GBLUP and GK) combinations to rubber tree data showed that models with the nonlinear GK and linear GBLUP kernel had similar PAs. Multi-environment models were superior to single-environment genomic models regardless the kernel (GBLUP or GK), suggesting that introducing interactions between markers and environmental conditions increases the proportion of variance explained by the model and, more importantly, the PA. In the best scenario (well-watered (WW / GK), an increase of 6.7 and 8.7 fold of genetic gain can be obtained for AP and DAP, respectively, with multi-environment GS (MM, MDe and MDS) than by conventional genetic breeding model (CBM). Furthermore, GS resulted in a more balanced selection response in DAP and AP and if used in conjunction with traditional genetic breeding programs will contribute to a reduction in selection time. With the rapid advances in and declining costs of genotyping methods, balanced against the overall costs of managing large progeny trials and potential increased gains per unit time, we are hopeful that GS can be implemented in rubber tree breeding programs.
Deciphering the mechanoresponsive role of β-catenin in Keratoconus epithelium
Authors: Amit Chatterjee , Padmanabhan Prema , Narayanan Janakiraman
Published: April 2019

Keratoconus (KC) a disease with established biomechanical instability of the corneal stroma, is an ideal platform to identify key proteins involved in mechanosensing. This study aims to investigate the possible role of β-catenin as mechanotransducer in KC epithelium. KC patients were graded as mild, moderate or severe using Amsler Krumeich classification. Immunoblotting and tissue immunofluorescence studies were performed on KC epithelium to analyze the expression and localization of β-catenin, E-cadherin, ZO1, α-catenin, Cyclin D1, α-actinin, RhoA, Rac123. Co-immunoprecipitation (Co-IP) of β-catenin followed by mass spectrometry of mild KC epithelium was performed to identify its interacting partners. This was further validated by using epithelial tissues grown on scaffolds of different stiffness. We observed down regulation of E-cadherin, α-catenin, ZO1 and upregulation of Cyclin D1, α-actinin and RhoA in KC corneal epithelium. β-catenin Co-IP from mild KC epithelium identified new interacting partners such as StAR-related lipid transfer protein3, Dynamin-1-like protein, Cardiotrophin-1,Musculin, Basal cell adhesion molecule and Protocadherin Fat 1.β-catenin localization was altered in KC which was validatedin vitro, using control corneal epithelium grown on different substrate stiffness. β-catenin localization is dependent upon the elastic modulus of the substrate and acts as mechanotransducer by altering its interaction and regulating the barrier function in corneal epithelium.
Crystal structure and Hirshfeld surface analysis of (E)-2-[1-hydroxy-2-(pyridin-2-yl)ethyl]-4-[2-(4-methoxyphenyl)diazen-1-yl]phenol
Authors: Faizi Md. Serajul Haque , Sen Pratik , Saxena Gyanesh Kumar , Golenya Irina A.
Published: April 2019

In the title compound, C20H19N3O3, the configuration about the azo N=N bond is E, and the central benzene ring is inclined to the pyridine ring by 31.43 (8)° and to the 4-methoxyphenyl ring by 4.73 (8)°. In the crystal, molecules are linked by pairs of O—H...N hydrogen bonds, forming inversion dimers with an R
2
2(12) ring motif. The dimers are linked by O—H...O and C—H...O hydrogen bonds, forming layers parallel to the ac plane. There are C—H...π interactions present within the layers and between the layers, leading to the formation of a supramolecular framework. The layers are also linked by offset π–π interactions, with an interplanar distance of 3.416 (2) Å.
Sonochemical synthesis and crystal structure of dimethylammonium bis[3-carboxy-2-(dimethylamino)propanoato-κ2
N,O
1]chloridochromium(II) monohydrate
Authors: Saidi Meriem , Giorgi Michel , Boukli-hacene Leila
Published: April 2019

The title complex, [(CH3)2NH2][Cr(C6H10NO4)2Cl]·H2O, was synthesized sonochemically. The complex anion consists of a chromium(II) ion ligated by two 3-carboxy-2-(dimethylamino)propanoate anions. They coordinate in a bidentate manner, with a carboxylate oxygen atom and the nitrogen atom cis to each other in the equatorial plane, while the apical position is occupied by a Cl− ion. Hence, the chromium(II) ion is five-coordinate with a quasi-ideal square-pyramidal geometry; τ5 parameter = 0.01. The complex crystallizes as a monohydrate and in the crystal, the water molecule and the dimethylammonium counter-ion link the complex cations via N—H...O, N—H...Cl, Owater—H...O, O—H...Owater and O—H...O hydrogen bonds, forming a supramolecular framework. There are also a number of C—H...O hydrogen bonds present that reinforce the framework structure. The crystal studied was refined as a racemic twin.
The sensory school: working with teachers, parents and pupils to create good sensory conditions
Authors: Martin Nicola , Milton Damian Elgin Maclean , Krupa Joanna , Brett Sally , Bulman Kim , Callow Danielle , Copeland Fiona , Cunningham Laura , Ellis Wendy , Harvey Tina , Moranska Monika , Roach Rebecca , Wilmot Seanne
Published: April 2019

Purpose

An alliance of schools and researchers formed a collaborative community of practice in order to understand and improve the sensory school environment for pupils on the autistic spectrum, and incorporate the findings into school improvement planning. The paper aims to discuss this issue.

Design/methodology/approach

Representatives of special and mainstream schools in South London and a team of researchers formed the project team, including an autistic researcher. The researchers and a named staff member from each of the schools met regularly over the course of 18 months in order to work on an iterative process to improve the sensory experience pupils had of the school environment. Each school completed sensory audits and observations, and was visited by members of the research team. Parents were involved via meetings with the research team and two conferences were organised to share findings.

Findings

Useful outcomes included: developing and sharing of good practice between schools; opportunities for parents of autistic pupils to discuss their concerns, particularly with someone with insider perspective; and exploration of creative ways to achieve pupil involvement and the idea that good autism practice has the potential to benefit all pupils. A resource pack was produced for the schools to access. Plans are in place to revisit the initiative in 12 months’ time in order to ascertain whether there have been long-term benefits.

Originality/value

Projects building communities of practice involving autistic people as core team members are rare, yet feedback from those involved in the project showed this to be a key aspect of shared learning.
What would people do with their money if they were rich? A search for Hofstede dimensions across 52 countries
Authors: Minkov Michael , Dutt Pinaki , Schachner Michael , Jandosova Janar , Khassenbekov Yerlan , Morales Oswaldo , Blagoev Vesselin
Published: April 2019

Purpose

The purpose of this paper is to test the replicability of Hofstede’s value-based dimensions – masculinity–femininity (MAS–FEM) and individualism–collectivism (IDV–COLL) – in the field of consumer behavior, and to compare cultural prioritizations with respect to disposable income budgets across the world.

Design/methodology/approach

The authors asked 51,529 probabilistically selected respondents in 52 countries (50 nationally representative consumer panels and community samples from another two countries) what they would do with their money if they were rich. The questionnaire items targeted Hofstede’s MAS–FEM and IDV–COLL as well as a wider range of options deemed sufficiently meaningful, ethical and moral across the world.

Findings

The authors obtained two main dimensions. The first contrasts self-enhancing and altruistic choices (status and power-seeking spending vs donating for healthcare) and is conceptually similar to MAS–FEM. However, it is statistically related to Hofstede’s fifth dimension, or monumentalism–flexibility (MON–FLX), not to MAS–FEM. The second dimension contrasts conservative-collectivist choices and modern-hedonistic concerns (donating for religion and sports vs preserving nature and travel abroad for pleasure) and is a variant of COLL–IDV.

Research limitations/implications

The authors left out various potential consumer choices as they were deemed culturally incomparable or unacceptable in some societies. Nevertheless, the findings paint a sufficiently rich image of worldwide value differences underpinning idealized consumer behavior prioritizations.

Practical implications

The study could be useful to international marketing and consumer behavior experts.

Social implications

The study contributes to the understanding of modern cultural differences across the world.

Originality/value

This is the first large cross-cultural study that reveals differences in values through a novel approach: prioritizations of consumer choices. It enriches the understanding of IDV–COLL and MON–FLX, and, in particular, of the value prioritizations of the East Asian nations. The study provides new evidence that Hofstede’s MAS–FEM is a peculiarity of his IBM database with no societal analogue. Some of the so-called MAS–FEM values are components of MON–FLX, which is statistically unrelated to Hofstede’s MAS–FEM.
(Un)Sanctioned: young adult literature as meaningful sponsor for writing teacher education
Authors: Sams Brandon L. , Cook Mike P.
Published: April 2019

Purpose

The purpose of this paper is to examine youth literacy and writing practices in select, contemporary young adult literature (YAL), especially how and why literate activity is sponsored, negotiated or occluded by teachers and schools.

Design/methodology/approach

The authors position young adult fiction as case studies of youth composing in and out of school. Drawing on Stake's (1995) features of case study research in education, the authors present readings ofGabi, a Girl in Piecesby Isabel Quintero andThe Vigilante Poets of Selwyn Academyby Kate Hattemer that highlight particular problems and insights about youth literacy practices that are worth extended examination and reflection.

Findings

Both novels feature youth engaging in powerful literacy and writing practices across a range of modes to critically read and write their worlds. These particular texts – and other YAL featuring youth composing – offer teacher educators and pre-service teachers opportunities for critical reflection on their evolving stances on literacy instruction; identities as writing and literacy educators; and pedagogies that enable robust literate activity.

Originality/value

In the US educational context, teacher education programs are required to provide pre-service teachers numerous opportunities to observe and participate as teachers in public school classrooms. YAL offers a unique setting of experience that can be productively paired with more traditional field placements to complement pre-service writing teacher education. Reading YAL featuring youth composing can serve as a useful occasion of reflection on pedagogies that limit and/or make possible students’ meaningful engagement with words and the world.
Parents’ and teachers’ critique of nutrition education in Indian secondary schools
Authors: Rathi Neha , Riddell Lynn , Worsley Anthony
Published: April 2019

Purpose

Nutrition education plays a significant role in inculcating lifelong healthy dietary behaviours among adolescents. The purpose of this paper is to understand the opinions of parents and teachers regarding nutrition education in private Indian secondary schools.

Design/methodology/approach

A cross-sectional, self-administered, paper-based survey comprising both closed- and open-ended questions was completed by 32 teachers and 280 parents who were recruited from five private English-speaking secondary schools in Kolkata, India. Descriptive and cross-tabulation analyses were conducted to compare the responses of teachers and parents. Thematic data analysis informed by template analysis technique was performed to evaluate the qualitative data.

Findings

While the curriculum was considered interesting and easy to understand, the gendered nature of the curriculum, excessive rote learning and lack of synchrony between the curriculum and school food services were highlighted as shortcomings of the existing curriculum. The need for the dissemination of food skills either through a compulsory food and nutrition curriculum or through extra-mural activities was expressed by most respondents. Both these ideas were indicative of strong support and motivation for modification in the current curriculum.

Practical implications

These findings emphasise the support for a skills-focussed food and nutrition curriculum to inculcate experiential culinary skills and comprehensive nutrition knowledge in Indian adolescents, thus improving their nutritional and health profiles.

Originality/value

This is the first cross-sectional survey to investigate the views of parents and teachers about the status of food and nutrition education in private Indian secondary schools.