bluuebunny/crossref_metadata_2025 huggingface dataset:
Aortic dissection in children and young adults: diagnosis, patients at risk, and outcomes
Authors: Zalzstein Eli , Hamilton Robert , Zucker Nili , Diamant Samuel , Webb Gary
Published: April 2019

Objective: To heighten the awareness of pediatricians and pediatric cardiologists to aortic dissection, a potentially dangerous medical condition. Methods: We reviewed the charts of 13 patients, seen in four medical centers, who suffered acute or chronic aortic dissection over the period 1970 through 2000 whilst under the age of 25 years. Results: There were seven male and six female patients, with the mean age at diagnosis being 12.1 years, with a range from one day to 25 years. Congenital cardiac defects were present in five patients, and Marfan syndrome in four. In three of the patients with congenital cardiac defects, aortic dissection developed as a complication of medical procedures. In three patients, dissection followed blunt trauma to the chest. We could not identify any risk factors in one patient. The presenting symptoms included chest pain in four patients, abdominal pain and signs of ischemic bowel in two, non-palpable femoral pulses in one, and obstruction of the superior caval vein in one. Angiography and magnetic resonance imaging were the main diagnostic tools. Overall mortality was 38%. Only six patients had successful surgical outcomes. Conclusion: Due to the rarity of aortic dissection a high index of suspicion is required to reach the diagnosis in a timely manner. It should be considered in young patients complaining of chest pain in association with Marfan syndrome, anomalies of the aortic valve and arch, and chest trauma.
Exercise-induced left bundle branch block in a young female athlete
Authors: Giordano Ugo , Crosio Gaia , Calzolari Armando
Published: April 2019

An 11-year-old female, in apparent good health, was referred to our Institute because of exercise-induced left bundle branch block detected during a Master's step test performed to obtain the clearance for competitive sport. The tests that we performed to investigate the possible causes were all negative. We suspect, however, that the left bundle branch block is the initial sign of cardiomyopathy. If our suspicions are correct, close follow-up is important to chart the possible progression of the disease.
Reversible cardiomyopathy subsequent to perinatal infection with the human immunodeficiency virus
Authors: Diógenes Maria Suely Bezerra , Camargo Carvalho Antonio Carlos , de Menezes Succi Regina Célia
Published: April 2019

We describe a patient with advanced perinatal acquired immunodeficiency syndrome who had early clinical manifestation of severe dilated cardiomyopathy with congestive heart failure. The picture was completely reversed after six years treatment and follow-up, and the child is now doing well at the age of seven, with normal left ventricular dimension and contractility as shown by echodopplercardiography. To the best of our knowledge, this is the first reported case of full recovery from cardiomyopathy in children with perinatally acquired infection by the human immunodeficiency virus.
Abstracts for the British Congenital Cardiac Association Annual Meeting: The Barbican, London, 24–25 November 2005: Poster Presentations: Epoprostenol treatment in children with pulmonary arterial hypertension
Authors: Lammers A.E. , Hislop A. A. , Flynn Y. , Haworth S.G.
Published: April 2019

Background: Continuous intravenous Epoprostenol treatment has been shown to be beneficial in patients with severe pulmonary arterial hypertension (PAH). We report the experience of the UK Pulmonary Hypertension Service for Children treating 39 children with this therapy. Patients and methods: The patients were aged 4 months to 17 years (median 5.4 years), male: female ratio was 1: 1.2. Eleven children were treated with Epoprostenol alone. Twenty-eight were also treated with Sildenafil, Bosentan, Nifedipine or a combination of these. Twenty-five children had idiopathic PAH and 14 had PAH associated with congenital heart disease (9), connective tissue disease (2), chronic lung disease (2) or HIV (1). Cardiac catheter studies made before treatment began showed that in 26 patients the pulmonary artery pressure equalled or exceeded the systemic pressure. Thirty-four patients had a pulmonary vascular resistance (PVR) study with a mean PVR of 23 ± 12 units m2. After initial evaluation children were monitored by ECG, transthoracic echocardiography, weight, 6-minute-walk test and WHO functional class. Results: Follow-up was 1–90 months (mean 27). Twenty-four children remain stable and well, 8 have been transplanted and 7 died on treatment. There was no deterioration in the ECG; the 6-minute walk distance and right ventricular function assessed by echocardiography remained stable. WHO functional class improved from 3.6 to 2.6 during the first year (n = 38) (p < 0.001) and remained stable for up to 3 years (n = 17). Weight improved significantly (p < 0.05). A Kaplan Meier survival curve showed that survival was 94.4% at 1 year, 90.3% at 2 years and 83.9% at 3 years.

Conclusions: Epoprostenol treatment improved survival, clinical status and WHO functional class in children with severe PAH. Survival in the children on intravenous Epoprostenol with and without combination therapy was better than that described in adult studies (McLaughlin VV, et al. Circulation 2002; 106: 1477–1482).
Can sleep disturbance be a cue of mood spectrum comorbidity? A preliminary study in panic disorder
Authors: Miniati Mario , Palagini Laura , Maglio Alessandra , Marazziti Donatella , Dell’Osso Liliana
Published: April 2019

Objective.

To investigate if sleep disturbances may affect treatment outcomes of patients with panic disorder (PD).

Methods.

Eighty-five PD outpatients with no Axis I comorbidity for mood disorders completed a baseline assessment (T1) and were evaluated after 3 (T2), 6 (T3) and 12 months (T4), with the Panic Disorder Severity Scale (PDSS) total score as outcome measure during a 12-month naturalistic follow-up. Patients were assessed with the Mood Spectrum Self-Report (MOODS-SR, Lifetime Version), and the PDSS.

Results.

Forty-three patients (50.5%) met criteria for remission (PDSS<5) and 42 (49.5%) for no remission. In a logistic regression model withremissionas the dependent variable, MOODS-SRsleep disturbanceswas the only determinant for a lower likelihood of PD remission. The items accounting for this result were the following:Repeated difficulty falling asleep(chi-square = 4.4; df = 1;p= 0.036), andRepeatedly waking up in the middle of the night(chi-square = 5.2; df = 1;p= 0.022).

Conclusion.

Lifetime sleep disturbances would represent a cue of mood spectrum (in absence of overt affective comorbidity) that may impair remission in PD.
Trade-off between the conflicting planning goals in correlation with patient’s anatomical parameters for intensity-modulated radiotherapy of prostate cancer patients
Authors: Banaei Amin , Hashemi Bijan , Bakhshandeh Mohsen , Mofid Bahram
Published: April 2019

Aim

To quantify the relationship between the planning target volume (PTV) dose homogeneity and organs at risk (OARs) sparing in correlation with anatomical parameters in prostate intensity-modulated radiotherapy (IMRT).

Materials and methods

Nine IMRT plans with various target dose constraints’ priorities were created for 15 prostate cancer patients. Selected PTV and OARs parameters were calculated for the patients. A trade-off was assessed between homogeneity index (HI) and OAR sparing. Several anatomical parameters were evaluated to investigate their effects on the OAR sparing and HI.

Results

Inverse exponential relationships were found between the OAR sparing and HI (average R
2 of 0·983 and 0·994 for bladder and rectum, respectively). Decreasing the priority led to more OARs sparing (normal tissue complication probability reduction: 97·6 and 74·5%; mean dose reduction: 16·3 and 11·3% for bladder and rectum, respectively) and worsening of the HI (0·095–0·322) but with no significant effect on tumour control probability. Furthermore, OARs volumes, distances between OARs and PTV and their joint volumes had stronger correlations with OARs’ mean doses.

Conclusion

Enforcement of target dose constraints was more effective on the improvement of HIs for the patients with initial high HI values at low dose constraints’ priorities. Reducing the priority had more effects on the OARs sparing compared to HI, especially for the patients with high OAR doses in high priority plans. This can be attributed to smaller distances or greater joint volumes between the OARs and PTV.
ACEs: Evidence, Gaps, Evaluation and Future Priorities
Authors: Steptoe Andrew , Marteau Theresa , Fonagy Peter , Abel Kathryn
Published: April 2019

There is strong evidence linking adverse childhood experiences (ACEs) and poor outcomes in adulthood both in terms of mental and physical health. Gaps in both the evidence base and research priorities still exist. These include understanding how to identify and assess risk in children who have experienced ACEs, and also the development and, importantly, the evaluation of interventions. Outstanding gaps include whether there are sensitive periods during childhood, the role of resilience/protective factors, the causal relationships, biological mechanisms and relative risk of ACEs for particular negative outcomes. ACEs affect individual children differently and chronic exposure appears to increase the risk of poor outcomes in adulthood, meaning interventions should also be tailored to the individual children, families and communities. Generally, there needs to be better evaluation of interventions and dissemination of this information to ensure that their use is evidence based. More input from affected communities, clinicians, funding bodies and Government departments is required to identify research priorities and ensure gaps in the evidence base are addressed.
COHOMOLOGY AND OVERCONVERGENCE FOR REPRESENTATIONS OF POWERS OF GALOIS GROUPS
Authors: Pal Aprameyo , Zábrádi Gergely
Published: April 2019

We show that the Galois cohomology groups of$p$-adic representations of a direct power of$\operatorname{Gal}(\overline{\mathbb{Q}_{p}}/\mathbb{Q}_{p})$can be computed via the generalization of Herr’s complex to multivariable$(\unicode[STIX]{x1D711},\unicode[STIX]{x1D6E4})$-modules. Using Tate duality and a pairing for multivariable$(\unicode[STIX]{x1D711},\unicode[STIX]{x1D6E4})$-modules we extend this to analogues of the Iwasawa cohomology. We show that all$p$-adic representations of a direct power of$\operatorname{Gal}(\overline{\mathbb{Q}_{p}}/\mathbb{Q}_{p})$are overconvergent and, moreover, passing to overconvergent multivariable$(\unicode[STIX]{x1D711},\unicode[STIX]{x1D6E4})$-modules is an equivalence of categories. Finally, we prove that the overconvergent Herr complex also computes the Galois cohomology groups.
Culture and therapist self-disclosure
Authors: Phiri Peter , Rathod Shanaya , Gobbi Mary , Carr Hannah , Kingdon David
Published: April 2019

Cognitive behaviour therapy (CBT) as a treatment for schizophrenia and psychotic-related disorders has been shown to have significantly greater drop-out rates in clients of black and minority ethnic (BME) groups. This has resulted in poor outcomes in treatments. Our recent qualitative study thus aimed to develop culturally sensitive CBT for BME clients. The study consisted of individual in-depth 1:1 interviews with patients with a diagnosis of schizophrenia, schizo-affective, delusional disorders or psychosis (n = 15) and focus groups with lay members (n = 52), CBT therapists (n = 22) and mental health practitioners (n = 25) on a data set of 114 participants. Several themes emerged relating to therapist awareness on culturally derived behaviours, beliefs and attitudes that can influence client response and participation in therapy. The current paper aims to explore one of these themes in greater detail, i.e. client-initiated therapist self-disclosure (TSD). Using thematic analysis, the paper highlights key elements of TSD and how this could impact on therapist’s reactions towards TSD, the therapeutic alliance and ultimately, the outcomes of therapy. The findings appear to show that TSD has significant relevance in psychological practice today. Some BME client groups appear to test therapists through initiating TSD. It is not the content of TSD they are testing per se, but how the therapist responds. Consequently, this requires therapists’ cognisance and sensitive responses in a manner that will nurture trust and promote rapport. Further investigation in this area is suggested with a recommendation for guidelines to be created for clinicians and training.

Key learning aims

(1)

To develop a dialogue and practice with confidence when addressing issues of self-disclosure with diverse populations.

(2)

To appreciate the impact therapist self-disclosure has in early stages of engagement, in particular when working with patients from BME communities.

(3)

To understand the impact and role of self-disclosure as initiated by patients.

(4)

To increase therapist awareness on cultural differences in self-disclosure and develop ways to address this in therapy.

(5)

To challenge therapists to adapt psychological therapies to diverse cultures and be cognisant that ‘one size does not fit all’.
Case-control study of the low intensive autism-specific early behavioral intervention A-FFIP: Outcome after one year
Authors: Kitzerow Janina , Teufel Karoline , Jensen Katrin , Wilker Christian , Freitag Christine M.
Published: April 2019

Abstract. ﻿Abstracts:﻿ ﻿Objective:﻿ In current international research, early intervention in children with autism-spectrum disorder (ASD) focuses on naturalistic developmental behavioral interventions (NDBI). The manualized Frankfurt Early Intervention Program for preschool-aged children with ASD (A-FFIP) implements NDBI principles within a low-intensity approach of 2 h intervention/week. The present case-control study established effect sizes of change in autistic symptoms, comorbid behavioral problems as well as IQ after one year. ﻿Methodology:﻿ An intervention group (﻿N﻿ = 20; age: 3.4–7.9 years) and a treatment-as-usual control group (﻿N﻿ = 20; age: 3.2–7.3 years) of children with ASD were matched for developmental and chronological age. The outcome measures used were the ADOS severity score, the Child Behavior Checklist, and cognitive development. ﻿Results:﻿ After one year, the A-FFIP group showed a trend towards greater improvement in autistic symptoms (η﻿2﻿ = .087 [95 %-CI: .000–.159]) and significantly greater improvements in cognitive development (η﻿2﻿ = .206 [CI: .012–.252]) and global psychopathology (η﻿2﻿ = .144 [CI: .001–.205]) compared to the control group. ﻿Conclusion:﻿ The efficacy of A-FFIP should be established in a larger, sufficiently powered, randomized controlled study.
Praxislernen im Pflegestudium
Authors: Jakob Nane , Kaiser Anna , Schell Helga , Herold-Majumdar Astrid , Milla Günter
Published: April 2019

Zusammenfassung. Im nachfolgenden Artikel wird aus zwei Perspektiven der Frage nachgegangen, wie Praxislernen im Pflegestudium gelingen kann. Die Arbeit von Tutoren im Rahmen praktischer Einsätze von Bachelorstudierenden und ein Modell zum besseren Theorie-Praxis-Theorie-Transfer werden beschrieben, und deren Wirkung ausgeleuchtet.
Das „Boot Camp“ – Eine didaktische Methode zum Einstieg in den	Schreibprozess einer Bachelorarbeit
Authors: Büker Christa , Mertin Matthias , Müller Irene , Röding Dominik
Published: April 2019

Zusammenfassung. An der Fachhochschule Bielefeld wird seit einigen Jahren im dualen Bachelorstudiengang Gesundheits- und Krankenpflege zur Vorbereitung auf die Bachelorarbeit ein dreitägiges Kompaktseminar – genannt „Boot Camp“ – durchgeführt. Der Beitrag widmet sich dem Hintergrund, den Zielen und Inhalten des Seminars.
A Mechanistic Model of Microbially Mediated Soil Biogeochemical Processes: A Reality Check
Authors: Fatichi Simone , Manzoni Stefano , Or Dani , Paschalis Athanasios
Published: April 2019

Present gaps in the representation of key soil biogeochemical processes such as the partitioning of soil organic carbon among functional components, microbial biomass and diversity, and the coupling of carbon and nutrient cycles present a challenge to improving the reliability of projected soil carbon dynamics. We introduce a new soil biogeochemistry module linked with a well‐tested terrestrial biosphere model T&C. The module explicitly distinguishes functional soil organic carbon components. Extracellular enzymes and microbial pools are differentiated based on the functional roles of bacteria, saprotrophic, and mycorrhizal fungi. Soil macrofauna is also represented. The model resolves the cycles of nitrogen, phosphorus, and potassium. Model simulations for 20 sites compared favorably with global patterns of litter and soil stoichiometry, microbial and macrofaunal biomass relations with soil organic carbon, soil respiration, and nutrient mineralization rates. Long‐term responses to bare fallow and nitrogen addition experiments were also in agreement with observations. Some discrepancies between predictions and observations are appreciable in the response to litter manipulation. Upon successful model reproduction of observed general trends, we assessed patterns associated with the carbon cycle that were challenging to address empirically. Despite large site‐to‐site variability, fine root, fungal, bacteria, and macrofaunal respiration account for 33%, 40%, 24%, and 3% on average of total belowground respiration, respectively. Simulated root exudation and carbon export to mycorrhizal fungi represent on average about 13% of plant net primary productivity. These results offer mechanistic and general estimates of microbial biomass and its contribution to respiration fluxes and to soil organic matter dynamics.
Controlling Factors of Seismicity and Geometry in Double Seismic Zones
Authors: Florez M. A. , Prieto G. A.
Published: April 2019

Double seismic zones are ubiquitous features of subduction zones, where seismicity is distributed along two layers separated by a region with significantly less seismic activity. Dehydration embrittlement is thought to be responsible for earthquakes in the subducting crust (upper layer), but the case for it in the lithospheric mantle (lower layer) is less clear. We apply a recently developed relative relocation technique to characterize seismicity in 32 slab segments. The high‐precision hypocentral depths allow us to assign events to either the upper or lower layer and to separately estimate frequency size distributions for each plane. We find consistently larger b values, correlating with slab age, for the upper layer and roughly constant values for the lower. We also show that thermal parameter and plate age are the key controls on double seismic zone geometry. Our results point to a relatively dry lower layer and suggest a fundamentally different mechanism for lithospheric mantle earthquakes.
Tracking Open Versus Closed‐Canopy Boreal Forest Using the Geochemistry of Lake Sediment Deposits
Authors: Bastianelli C. , Ali A. A. , Bergeron Y. , Hély C. , Paré D.
Published: April 2019

Identifying geochemical paleo‐proxies of vegetation type in watersheds could become a powerful tool for paleoecological studies of ecosystem dynamics, particularly when commonly used proxies, such as pollen grains, are not suitable. In order to identify new paleological proxies to distinguish ecosystem types in lake records, we investigated the differences in the sediment geochemistry of lakes surrounded by two boreal forest ecosystems dominated by the same tree species: closed‐canopy black spruce‐moss forests (MF) and open‐canopy black spruce‐lichen woodlands (LW). This study was designed as a first calibration step between terrestrial modern soils and lacustrine sediments (0–1000 cal yr BP) on six lake watersheds. In a previous study, differences in the physical and geochemical properties of forest soils had been observed between these two modern ecosystems. Here we show that the geochemical properties of the sediments varied between the six lakes studied. While we did not identify geochemical indicators that could solely distinguish both ecosystem types in modern sediments, we observed intriguing differences in concentrations of C:N ratio, carbon isotopic ratio, and aluminum oxide species, and in the stabilization of their geochemical properties with depth. The C accumulation rates at millennial scale were significantly higher in MF watersheds than in LW watersheds. We suggest that these variations could result from organic matter inflows that fluctuate depending on forest density and ground vegetation cover. Further investigations on these highlighted geochemistry markers need to be performed to confirm whether they can be used to detect shifts in vegetation conditions that have occurred in the past.
King of the Tyrannosaurs Goes on Display
Authors: Morton Mary
Published: April 2019

The biggest, oldest T. rex found to date shows how big tyrannosaurs could get.
Statistical Results of the Power Gap Between Lower‐Band and Upper‐Band Chorus Waves
Authors: Gao Xinliang , Chen Lunjin , Li Wen , Lu Quanming , Wang Shui
Published: April 2019

The primary power gap of chorus waves is statistically investigated using 7‐year waveform data from THEMIS probes for the first time. Overall, ~2/3 of chorus events have a power gap between the lower and upper bands. Both the gap frequency and the frequency bandwidth of the gap have a broad distribution, which peaks at frequencies of ~0.49fce and ~0.07fce, respectively. The gap frequency tends to increase with increasing |MLAT| (magnetic latitude), while the frequency width gradually increases with L‐shell. In most of banded events, the peak frequency of upper band is roughly twice that of lower band. Two types of events are studied. For Type I events, one population is located around Pup/Plow = 10−1, and the other is around Pup/Plow = 10−3. However, Type II events are roughly concentrated around Pup/Plow = 10−3. The gap frequency positively correlates with the frequency of upper band. Our study provides detailed observational constraints on potential mechanisms of the power gap formation.
The Influence of Tropical Forecast Errors on Higher Latitude Predictions
Authors: Dias Juliana , Kiladis George N.
Published: April 2019

The atmospheric response to variations in tropical latent heating extends well beyond its source region, and therefore it is thought that a reduction of tropical forecast errors should also benefit subsequent forecasts over the extratropics. This relationship is evaluated using a conditional skill analysis applied to subseasonal reforecasts from the National Centers for Environmental Prediction Coupled Forecast System and the European Centre for Medium‐Range Weather Forecasts Integrated Forecast System. It is shown that there is enhanced or attenuated skill in Northern Hemisphere Weeks 2–4 forecasts when tropical short range precipitation forecasts are “good” or “poor,” respectively. This conditional skill is modulated by both El Ni
o Southern Oscillation and the Madden and Julian Oscillation, particularly in the Integrated Forecast System. The results presented here indicate that midlatitude Weeks 2–4 predictive skill would benefit from improvements in Week 1 tropical performance, particularly for the National Centers for Environmental Prediction system.
Multidisciplinary perspectives to prevent occupational health-related conditions among dental practitioners
Authors: Moodley Rajeshree , Van Wyk J.
Published: April 2019

Introduction

The prevalence of occupational health conditions is high among dental practitioners and this study investigated the role which occupational health plays in dental training.

Purpose/objectives

This study was conducted to explore occupational health and to determine the topics to include from an occupational health perspective into the dental curriculum.

Methods

A descriptive qualitative study was conducted to explore the perceptions of dental practitioners, dental academics, physiotherapists, occupational therapists, occupational health specialists, ergonomists, optometrists and audiologists about dental training from an occupational health perspective in KwaZulu- Natal, South Africa. The interdisciplinary and multidisciplinary approach was used in this study.

Results

Three main themes became evident that hinged on varying understanding of occupational health-related conditions to dental practice, how practitioners experience practising in the resource-poor settings and its impact on the dental practice. There was also a lack of awareness of the occupational health policies and practices, which could inform safe dental practice.

Conclusion

Dental academics should gain input from a multidisciplinary team. An occupational health course with a student-centred approach would enrich the dental curriculum and make dental practitioners more aware of occupational health issues.
Dentinogenesis imperfecta in Osteogenesis imperfecta type XI in South Africa: a genotype–phenotype correlation
Authors: Chetty M. , Roberts T. , Shaik S. , Beighton P.
Published: April 2019

Background

The maxillofacial and dental manifestations of Osteogenesis imperfecta (OI) have significant implications in terms of management. Although the occurrence of abnormal dentine in some forms of OI is well documented, there is scant information on the association of abnormal dentine in the Black African persons with phenotypic OI III and genotypic OI XI in South Africa.

Methods

This was a cross-sectional analytic study. A series of 64 Black South African individuals with a confirmed phenotypic diagnosis of OI III, ages ranging from 3 months to 29 years, were assessed clinically, radiographically, and at a molecular level.

Results

A total number of 64 saliva samples were analyzed and 3 DNA variations were identified in exon 5 of the FKBP10 gene. The homozygous mutation, c.[831dupC]; [831dupC], was identified in 23 affected persons who had no clinically obvious features of DI in their primary and secondary teeth. Radiologically, mild features of DI were evident in 10 persons in whom radiographic images were obtained and were given a Clinical–radiological score of 2. A compound heterozygous mutation, c. [831delC]; [831dupC], was identified in three siblings. An intraoral examination of these affected persons revealed no clinically apparent features of DI in their primary and secondary teeth. Due to the lack of radiological facilities, the presence or absence of DI could not be confirmed or negated. A second compound heterozygous mutation, c.[831dupC]; [1400-4C>G], was identified in a female of 29 years belonging to the Xhosa linguistic group. Her teeth appeared clinically normal but it was not possible to obtain radiographs. In 37 affected individuals, no disease-causing mutations were identified.

Conclusion

Black African individuals in SA with the homozygous mutation in the FKBP10 gene have clinically unaffected teeth yet exhibited radiographic features of DI to varying degrees. This characterization is suggestive of a relationship between the genetic abnormality and the clinical manifestations of DI. The authors suggest that this diagnosis must include teeth that are clinically and/or radiologically aberrant, and should not exclude the presence of other, milder, dentinal aberrations associated with OI. There was no correlation between severity of OI and DI in this cohort of individuals.
The homeobox transcription factor MEIS2 is a regulator of cancer cell survival and IMiDs activity in Multiple Myeloma: modulation by Bromodomain and Extra-Terminal (BET) protein inhibitors
Authors: Abruzzese Maria Pia , Bilotta Maria Teresa , Fionda Cinzia , Zingoni Alessandra , Soriani Alessandra , Petrucci Maria Teresa , Ricciardi Maria Rosaria , Molfetta Rosa , Paolini Rossella , Santoni Angela , Cippitelli Marco
Published: April 2019

The transcription factor Myeloid Ecotropic Insertion Site 2 (MEIS2) has been identified as a cellular substrate of the E3-ubiquitin ligase complex CRL4-cereblon (CRL4CRBN) in crystal structure and by biochemical screen. Emerging evidence suggests that IMiDs can block MEIS2 from binding to CRBN facilitating the subsequent activation of a CRL4CRBNIMiD-E3-ubiquitin ligase activity and proteasome-mediated degradation of critical substrates regulators of Multiple Myeloma (MM) cell survival and proliferation. Bromodomain and Extra-Terminal (BET) family of proteins are important epigenetic regulators involved in promoting gene expression of several oncogenes, and many studies have revealed important anticancer activities mediated by BET inhibitors (BETi) in hematologic malignancies including MM. Here, we investigated MEIS2 in MM, the role of this protein as a modulator of IMiDs activity and the ability of BETi to inhibit its expression. Our observations indicate that inhibition of MEIS2 in MM cells by RNA interference correlates with reduced growth, induction of apoptosis and enhanced efficacy of different anti-MM drugs. In addition, MEIS2 regulates the expression of Cyclin E/CCNE1 in MM and induction of apoptosis after treatment with the CDK inhibitor Seliciclib/Roscovitine. Interestingly, modulation of MEIS2 can regulate the expression of NKG2D and DNAM-1 NK cell-activating ligands and, importantly, the activity of IMiDs in MM cells. Finally, BETi have the ability to inhibit the expression of MEIS2 in MM, underscoring a novel anticancer activity mediated by these drugs. Our study provides evidence on the role of MEIS2 in MM cell survival and suggests therapeutic strategies targeting of MEIS2 to enhance IMiDs anti-myeloma activity.
Electrical polarization induced by atomically engineered compositional gradient in complex oxide solid solution
Authors: Wu Ping-Chun , Huang Rong , Hsieh Ying-Hui , Wang Bo , Yen Min , Ho Sheng-Zhu , Kumamoto Akihito , Zhong Chaorong , Song Haili , Chen Yi-Chun , Chen Long-Qing , Duan Chun-Gang , Ikuhara Yuichi , Chu Ying-Hao
Published: April 2019

Control of inhomogeneity in materials in order to avoid unexpected effects to the system remains a challenge. In this study, we seek to engineer inhomogeneity in materials and anticipate new properties. Through precise control of composition at the atomic scale, an electrical polarization is induced in the composition-graded LaAlO3–SrTiO3 solid solution epitaxially deposited on NdGaO3 substrates. By tailoring the direction of compositional gradient, the relationship between structure and electrical polarization is simulated via phase-field modeling and revealed by a combination of scanning transmission electron microscopy and scanning probe microscopy. The analysis of the results indicates that the induced polarization is due to the flexoelectric effect in the compositional gradient system. The results of this study provide a new pathway for obtaining a new material genome. Moreover, by a suitable design of the new genome, that is, by using different combinations of compositional gradient geometries, local conduction can be obtained and manipulated, providing a new approach to obtain the desired properties.
Y-chromosomal analysis of clan structure of Kalmyks, the only European Mongol people, and their relationship to Oirat-Mongols of Inner Asia
Authors: Balinova Natalia , Post Helen , Kushniarevich Alena , Flores Rodrigo , Karmin Monika , Sahakyan Hovhannes , Reidla Maere , Metspalu Ene , Litvinov Sergey , Dzhaubermezov Murat , Akhmetova Vita , Khusainova Rita , Endicott Phillip , Khusnutdinova Elza , Orlova Keemya , Bakaeva Elza , Khomyakova Irina , Spitsina Nailya , Zinchenko Rena , Villems Richard , Rootsi Siiri
Published: April 2019

Kalmyks, the only Mongolic-speaking population in Europe, live in the southeast of the European Plain, in Russia. They adhere to Buddhism and speak a dialect of the Mongolian language. Historical and linguistic evidence, as well a shared clan names, suggests a common origin with Oirats of western Mongolia; yet, only a limited number of genetic studies have focused on this topic. Here we compare the paternal genetic relationship of Kalmyk clans with ethnographically related groups from Mongolia, Kyrgyzstan and China, within the context of their neighbouring populations. A phylogeny of 37 high-coverage Y-chromosome sequences, together with further genotyping of larger sample sets, reveals that all the Oirat-speaking populations studied here, including Kalmyks, share, as a dominant paternal lineage, Y-chromosomal haplogroup C3c1-M77, which is also present in several geographically distant native Siberian populations. We identify a subset of this clade, C3c1b-F6379, specifically enriched in Kalmyks as well as in Oirat-speaking clans in Inner Asia. This sub-clade coalesces at around 1500 years before present, before the Genghis Khan era, and significantly earlier than the split between Kalmyks and other Oirat speakers about 400 years ago. We also show that split between the dominant hg C variant among Buryats—C3-M407—and that of C3-F6379, took place in the Early Upper Palaeolithic, suggesting an extremely long duration for the dissipation of hg C3-M217 carriers across northern Eurasia, which cuts through today’s major linguistic phyla.
Quantifying economic resilience from input–output susceptibility to improve predictions of economic growth and recovery
Authors: Klimek Peter , Poledna Sebastian , Thurner Stefan
Published: April 2019

Modern macroeconomic theories were unable to foresee the last Great Recession and could neither predict its prolonged duration nor the recovery rate. They are based on supply−demand equilibria that do not exist during recessionary shocks. Here we focus on resilience as a nonequilibrium property of networked production systems and develop a linear response theory for input−output economics. By calibrating the framework to data from 56 industrial sectors in 43 countries between 2000 and 2014, we find that the susceptibility of individual industrial sectors to economic shocks varies greatly across countries, sectors, and time. We show that susceptibility-based growth predictions that take sector- and country-specific recovery into account, outperform—by far—standard econometric models. Our results are analytically rigorous, empirically testable, and flexible enough to address policy-relevant scenarios. We illustrate the latter by estimating the impact of recently imposed tariffs on US imports (steel and aluminum) on specific sectors across European countries.
Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation
Authors: Rogers Corey , Erkes Dan A. , Nardone Alexandria , Aplin Andrew E. , Fernandes-Alnemri Teresa , Alnemri Emad S.
Published: April 2019

Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells. GSDME deficiency also accelerates cell growth in culture and in a mouse model of melanoma. Phosphomimetic mutation of the highly conserved phosphorylatable Thr6 residue of GSDME, inhibits its pore-forming activity, thus uncovering a potential mechanism by which GSDME might be regulated. Like GSDME-N, inflammasome-generated gasdermin D-N (GSDMD-N), can also permeabilize the mitochondria linking inflammasome activation to downstream activation of the apoptosome. Collectively, our results point to a role of gasdermin proteins in targeting the mitochondria to promote cytochrome c release to augment the mitochondrial apoptotic pathway.
Catalytic asymmetric acetalization of carboxylic acids for access to chiral phthalidyl ester prodrugs
Authors: Liu Yingguo , Chen Qiao , Mou Chengli , Pan Lutai , Duan Xiaoyong , Chen Xingkuan , Chen Hongzhong , Zhao Yanli , Lu Yunpeng , Jin Zhichao , Chi Yonggui Robin
Published: April 2019

Carboxylic acids are common moieties in medicines. They can be converted to phthalidyl esters as prodrugs. Unfortunately, phthalidyl esters are now mostly prepared in racemic forms. This is not desirable because the two enantiomers of phthalidyl esters likely have different pharmacological effects. Here we address the synthetic challenges in enantioselective modification of carboxylic acids via asymmetric acetalizations. The key reaction step involves asymmetric addition of a carboxylic acid to the catalyst-bound intermediate. This addition step enantioselectively constructs a chiral acetal unit that lead to optically enriched phthalidyl esters. A broad range of carboxylic acids react effectively under mild and transition metal-free conditions. Preliminary bioactivity studies show that the two enantiomers of chlorambucil phthalidyl esters exhibit different anti-cancer activities to inhibit the growth of Hela cells. Our catalytic strategy of asymmetric acetalizations of carboxylic acids shall benefit future development of chiral phthalidyl ester prodrugs and related molecules.
Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα
Authors: Liang Ning , Damdimopoulos Anastasius , Goñi Saioa , Huang Zhiqiang , Vedin Lise-Lotte , Jakobsson Tomas , Giudici Marco , Ahmed Osman , Pedrelli Matteo , Barilla Serena , Alzaid Fawaz , Mendoza Arturo , Schröder Tarja , Kuiper Raoul , Parini Paolo , Hollenberg Anthony , Lefebvre Philippe , Francque Sven , Van Gaal Luc , Staels Bart , Venteclef Nicolas , Treuter Eckardt , Fan Rongrong
Published: April 2019

Obesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central role in these alterations and accelerates the progression of NAFLD towards non-alcoholic steatohepatitis (NASH). Hepatocyte-specific Gps2 knockout in mice alleviates the development of diet-induced steatosis and fibrosis and causes activation of lipid catabolic genes. Integrative cistrome, epigenome and transcriptome analysis identifies the lipid-sensing peroxisome proliferator-activated receptor α (PPARα, NR1C1) as a direct GPS2 target. Liver gene expression data from human patients reveal that Gps2 expression positively correlates with a NASH/fibrosis gene signature. Collectively, our data suggest that the GPS2-PPARα partnership in hepatocytes coordinates the progression of NAFLD in mice and in humans and thus might be of therapeutic interest.
Dissecting the role of H3K27 acetylation and methylation in PRC2 mediated control of cellular identity
Authors: Lavarone Elisa , Barbieri Caterina M. , Pasini Diego
Published: April 2019

The Polycomb repressive complexes PRC1 and PRC2 act non-redundantly at target genes to maintain transcriptional programs and ensure cellular identity. PRC2 methylates lysine 27 on histone H3 (H3K27me), while PRC1 mono-ubiquitinates histone H2A at lysine 119 (H2Aub1). Here we present engineered mouse embryonic stem cells (ESCs) targeting the PRC2 subunits EZH1 and EZH2 to discriminate between contributions of distinct H3K27 methylation states and the presence of PRC2/1 at chromatin. We generate catalytically inactive EZH2 mutant ESCs, demonstrating that H3K27 methylation, but not recruitment to the chromatin, is essential for proper ESC differentiation. We further show that EZH1 activity is sufficient to maintain repression of Polycomb targets by depositing H3K27me2/3 and preserving PRC1 recruitment. This occurs in the presence of altered H3K27me1 deposition at actively transcribed genes and by a diffused hyperacetylation of chromatin that compromises ESC developmental potential. Overall, this work provides insights for the contribution of diffuse chromatin invasion by acetyltransferases in PRC2-dependent loss of developmental control.
Modulating the mechanism of electrocatalytic CO2 reduction by cobalt phthalocyanine through polymer coordination and encapsulation
Authors: Liu Yingshuo , McCrory Charles C. L.
Published: April 2019

The selective and efficient electrochemical reduction of CO2 to single products is crucial for solar fuels development. Encapsulating molecular catalysts such as cobalt phthalocyanine within coordination polymers such as poly-4-vinylpyridine leads to dramatically increased activity and selectivity for CO2 reduction. In this study, we use a combination of kinetic isotope effect and proton inventory studies to explain the observed increase in activity and selectivity upon polymer encapsulation. We provide evidence that axial-coordination from the pyridyl moieties in poly-4-vinylpyridine to the cobalt phthalocyanine complex changes the rate-determining step in the CO2 reduction mechanism accounting for the increased activity in the catalyst-polymer composite. Moreover, we show that proton delivery to cobalt centers within the polymer is controlled by a proton relay mechanism that inhibits competitive hydrogen evolution. These mechanistic findings provide design strategies for selective CO2 reduction electrocatalysts and serve as a model for understanding the catalytic mechanism of related heterogeneous systems.
A requirement for STAG2 in replication fork progression creates a targetable synthetic lethality in cohesin-mutant cancers
Authors: Mondal Gourish , Stevers Meredith , Goode Benjamin , Ashworth Alan , Solomon David A.
Published: April 2019

Cohesin is a multiprotein ring that is responsible for cohesion of sister chromatids and formation of DNA loops to regulate gene expression. Genomic analyses have identified that the cohesin subunit STAG2 is frequently inactivated by mutations in cancer. However, the reason STAG2 mutations are selected during tumorigenesis and strategies for therapeutically targeting mutant cancer cells are largely unknown. Here we show that STAG2 is essential for DNA replication fork progression, whereby STAG2 inactivation in non-transformed cells leads to replication fork stalling and collapse with disruption of interaction between the cohesin ring and the replication machinery as well as failure to establish SMC3 acetylation. As a consequence, STAG2 mutation confers synthetic lethality with DNA double-strand break repair genes and increased sensitivity to select cytotoxic chemotherapeutic agents and PARP or ATR inhibitors. These studies identify a critical role for STAG2 in replication fork procession and elucidate a potential therapeutic strategy for cohesin-mutant cancers.
Formation of colloidal alloy semiconductor CdTeSe magic-size clusters at room temperature
Authors: Gao Dong , Hao Xiaoyu , Rowell Nelson , Kreouzis Theo , Lockwood David J. , Han Shuo , Fan Hongsong , Zhang Hai , Zhang Chunchun , Jiang Yingnan , Zeng Jianrong , Zhang Meng , Yu Kui
Published: April 2019

Alloy semiconductor magic-size clusters (MSCs) have received scant attention and little is known about their formation pathway. Here, we report the synthesis of alloy CdTeSe MSC-399 (exhibiting sharp absorption peaking at 399 nm) at room temperature, together with an explanation of its formation pathway. The evolution of MSC-399 at room temperature is detected when two prenucleation-stage samples of binary CdTe and CdSe are mixed, which are transparent in optical absorption. For a reaction consisting of Cd, Te, and Se precursors, no MSC-399 is observed. Synchrotron-based in-situ small angle X-ray scattering (SAXS) suggests that the sizes of the two samples and their mixture are similar. We argue that substitution reactions take place after the two binary samples are mixed, which result in the formation of MSC-399 from its precursor compound (PC-399). The present study provides a room-temperature avenue to engineering alloy MSCs and an in-depth understanding of their probable formation pathway.
A statistical atlas of cerebral arteries generated using multi-center MRA datasets from healthy subjects
Authors: Mouches Pauline , Forkert Nils D.
Published: April 2019

Magnetic resonance angiography (MRA) can capture the variation of cerebral arteries with high spatial resolution. These measurements include valuable information about the morphology, geometry, and density of brain arteries, which may be useful to identify risk factors for cerebrovascular and neurological diseases at an early time point. However, this requires knowledge about the distribution and morphology of vessels in healthy subjects. The statistical arterial brain atlas described in this work is a free and public neuroimaging resource that can be used to identify vascular morphological changes. The atlas was generated based on 544 freely available multi-center MRA and T1-weighted MRI datasets. The arteries were automatically segmented in each MRA dataset and used for vessel radius quantification. The binary segmentation and vessel size information were non-linearly registered to the MNI brain atlas using the T1-weighted MRI datasets to construct atlases of artery occurrence probability, mean artery radius, and artery radius standard deviation. This public neuroimaging resource improves the understanding of the distribution and size of arteries in the healthy human brain.
High resolution paddy rice maps in cloud-prone Bangladesh and Northeast India using Sentinel-1 data
Authors: Singha Mrinal , Dong Jinwei , Zhang Geli , Xiao Xiangming
Published: April 2019

Knowledge of where, when, and how much paddy rice is planted is crucial information for understating of regional food security, freshwater use, climate change, and transmission of avian influenza virus. We developed seasonal paddy rice maps at high resolution (10 m) for Bangladesh and Northeast India, typical cloud-prone regions in South Asia, using cloud-free Synthetic Aperture Radar (SAR) images from Sentinel-1 satellite, the Random Forest classifier, and the Google Earth Engine (GEE) cloud computing platform. The maps were provided for all the three distinct rice growing seasons of the region: Boro, Aus and Aman. The paddy rice maps were evaluated against the independent validation samples, and compared with the existing products from the International Rice Research Institute (IRRI) and the analysis of Moderate Resolution Imaging Spectroradiometer (MODIS) data. The generated paddy rice maps were spatially consistent with the compared maps and had a satisfactory accuracy over 90%. This study showed the potential of Sentinel-1 data and GEE on large scale paddy rice mapping in cloud-prone regions like tropical Asia.
Biodiversity loss in a Mediterranean ecosystem due to an extreme warming event unveils the role of an engineering gorgonian species
Authors: Verdura Jana , Linares Cristina , Ballesteros Enric , Coma Rafel , Uriz María J. , Bensoussan Nathaniel , Cebrian Emma
Published: April 2019

Stochastic perturbations can trigger major ecosystem shifts. Marine systems have been severely affected in recent years by mass mortality events related to positive thermal anomalies. Although the immediate effects in the species demography affected by mortality events are well known, information on the mid- to long-term effects at the community level is much less documented. Here, we show how an extreme warming event replaces a structurally complex habitat, dominated by long-lived species, by a simplified habitat (lower species diversity and richness) dominated by turf-forming species. On the basis of a study involving the experimental manipulation of the presence of the gorgonian Paramuricea clavata, we observed that its presence mitigated the effects of warming by maintaining the original assemblage dominated by macroinvertebrates and delaying the proliferation and spread of the invasive alga Caulerpa cylindracea. However, due to the increase of sediment and turf-forming species after the mortality event we hypothesize a further degradation of the whole assemblage as both factors decrease the recruitment of P.clavata, decrease the survival of encrusting coralligenous-dwelling macroinvertebrates and facilitate the spreading of C. cylindracea.