bluuebunny/crossref_metadata_2025 huggingface dataset:
Concurrent Ipsilateral Tibial Shaft and Distal Tibial Fractures in Pediatric Patients: Risk Factors, Frequency, and Risk of Missed Diagnosis
Authors: Sheffer Benjamin W. , Villarreal Eric D. , Ochsner Mims G. , Sawyer Jeffrey R. , Spence David D. , Kelly Derek M.
Published: April 2019

Background:

The purpose of this study was to determine the frequency of concurrent ipsilateral distal tibial fractures with tibial shaft fractures in the pediatric population; to identify patient and fracture characteristics that increase the likelihood of a concurrent fracture; and determine if any of these concurrent distal tibial fractures were missed on initial radiographic examination.

Methods:

Retrospective chart review was done to identify patients 5 to 17 years old who were treated for a tibial shaft fracture at a large, Level 1 free-standing children’s hospital and an outpatient orthopaedic practice between 2008 and 2016. Patient and fracture characteristics were recorded.

Results:

Of 517 fractures (515 patients), 22 (4.3%) had concurrent ipsilateral distal tibial fractures: 11 triplane, 5 medial malleolar, 3 bimalleolar, and 2 Tillaux (Salter-Harris III) ankle fractures, and 1 Salter-Harris II distal tibial fracture. Age was the only patient characteristic significantly associated with a second, more distal fracture: patients with both fractures were older (12.7 y) than those with an isolated tibial shaft fracture (11 y). There was no difference in the rate of distal tibial fractures between high-energy and low-energy mechanisms of injury and no differences in the rate of open injuries or the presence of a fibular fracture. Patients with a tibial shaft fracture at the junction of the middle and distal thirds were significantly more likely to have a concurrent distal tibial fracture; oblique and spiral fracture patterns were more frequent in the group with concurrent distal tibial fractures than in the isolated tibial shaft fracture group.

Conclusions:

In our series, 36% of the concurrent distal tibial fractures were not diagnosed until chart review for this study, which suggests the need for ankle-specific imaging in certain patients. We recommend ankle-specific imaging when an oblique or spiral tibial shaft fracture is located at the junction of the middle and distal thirds of the tibia or in patients in whom a distal tibial fracture is suspected because of pain, swelling, or bruising.

Level of Evidence:

Level III—retrospective comparative study.
Tamoxifen use as a malignancy risk factor in postmenopausal women with endometrial polyps
Authors: Yela Daniela Angerame , Ikejiri Thales Akio , Machado Carolina Ribeiro , Mutta Danielle , Benetti-Pinto Cristina Laguna
Published: April 2019

Objective:

We analyzed tamoxifen use as a malignancy risk factor in women with endometrial polyps.

Methods:

This retrospective study included 675 women who underwent hysteroscopic polypectomy in 2010 to 2015 at the University of Campinas. Women were divided into tamoxifen use (n = 169) and no tamoxifen use (n = 506) groups. The primary outcome was endometrial cancer prevalence. Dependent variables included age, parity, years since menopause, presence of abnormal uterine bleeding, endometrial pattern on hysteroscopy, and endometrial thickness.

Results:

There were seven cases of endometrial cancer in the tamoxifen use group (4.14%) and 41 in the no tamoxifen use group (8.1%; P = 0.083). On performing multivariate analysis, tamoxifen use was not a risk factor for endometrial cancer (prevalence ratio 0.51, 95% confidence interval [CI] 0.23-1.14, P = 0.101). The no tamoxifen use group had an increased prevalence of malignancy when women presented with abnormal uterine bleeding (prevalence ratio 3.9, 95% CI 2.08-7.29, P < 0.001), age >60 years (prevalence ratio 2.1, 95% CI 1.12-3.93, P = 0.021), or nulliparous status (prevalence ratio 3.13, 95% CI 1.55-6.35, P = 0.002). The tamoxifen use group had increased prevalence of malignancy when women were >60 years (prevalence ratio 7.85, 95% CI 1.05-58.87, P = 0.006) or nulliparous (prevalence ratio 8.36, 95% CI 2.32-30.11, P < 0.001).

Conclusion:

Tamoxifen use was not related with a higher prevalence of endometrial cancer in women with endometrial polyps. Abnormal uterine bleeding, age > 60 years, and nulliparous status were associated with malignancy.
Recurrent Skin Langerhan Cell Histiocytosis Successfully Treated With Indomethacin Monotherapy
Authors: Dhir Aditi , Kelly David R. , Watts Raymond G. , Kutny Matthew A.
Published: April 2019

Langerhans cell histiocytosis (LCH) often has a recurrent and refractory course despite multiagent treatment modalities. Common relapse treatments include intense or prolonged cytotoxic chemotherapy regimens. There are a few prior reports that the nonsteroidal anti-inflammatory drug indomethacin demonstrated activity against bone LCH. Here we report indomethacin as a successful treatment for a case of chronic skin LCH that failed multiple prior chemotherapy regimens. This experience supports the need for trials to investigate indomethacin as a treatment for LCH both in the relapsed or refractory setting as well as potential combination or maintenance therapy in newly diagnosed patients.
Effect of Sickle Cell Anemia Therapies on the Natural History of Growth and Puberty Patterns
Authors: Nagalapuram Vishnu , Kulkarni Varsha , Leach Justin , Aban Inmaculada , Sirigaddi Krishnaveni , Lebensburger Jeffrey D. , Iyer Pallavi
Published: April 2019

As pediatric patients with sickle cell anemia (SCA) have impaired growth and puberty patterns, we studied the effect of disease-modifying therapies on growth and puberty patterns for patients with SCA receiving hydroxyurea (HU), transfusions, or no therapy. We performed a retrospective study of children with SCA in whom anthropometric measurements and therapy type were recorded. Penalized smoothing splines were fitted to estimate growth curves and growth velocity, and linear mixed models were used to examine differences across treatment groups. Across group analyses were divided into early childhood (4.0 to 7.9 y) and peripubertal (8.0 to 12.0 y). We analyzed growth data on 157 SCA patients. From 8.0 to 12.0 years, girls on transfusion therapy were significantly taller than girls on HU (range, 5.7 to 7.2 cm; P-value range 0.002 to 0.01). From 10.0 to 12.0 years, boys on transfusion therapy were significantly taller than boys on HU (range, 4.1 to 9.4 cm; P-value range <0.0001 to 0.04). In addition, boys on transfusion therapy had an earlier peak height velocity as compared with boys on either HU or no therapy. In conclusion, children receiving transfusions tended to be taller than children on HU or no therapy. Children on HU did not demonstrate superior growth pattern when compared with children on no therapy in the peripubertal years.
Neuroblastoma in Adolescents and Children Older than 10 Years: Unusual Clinicopathologic and Biologic Features
Authors: McCarthy Laura C. , Chastain Katherine , Flatt Terrie G. , Taboada Eugenio , Garola Robert , Herriges John , Cooley Linda D. , Ahmed Atif A.
Published: April 2019

Neuroblastoma (NB) in children older than 10 years is rare. We reviewed our archives for patients with NB aged 10 to 18 years and summarized their clinicopathologic/genetic records. Of 96 patients, 4 patients were identified in this age group. Four tumors were abdominal; 1 patient had 2 tumors at diagnosis, one of which was presacral. Tumor sizes ranged from 3 to 20 cm. All tumors were high risk at clinical stages 3 and 4, with metastasis to bone marrow and other areas. Four tumors were poorly differentiated with unfavorable histology and one patient with bilateral adrenal disease had an intermixed ganglioneuroblastoma on one side. Another tumor exhibited pheochromocytoma-like morphology. MYCN amplification was present in bone marrow metastasis in one case. Complex chromosomal gains and 19p deletions were common. Exome sequencing revealed ALK variants in 2 cases and previously unreported MAGI2, RUNX1, and MLL mutations. All patients received standard chemotherapy and 2 patients received ALK-targeted trial therapy. Three patients died of disease, ranging 18 to 23 months after diagnosis. One patient has active disease and is receiving trial therapy. In conclusion, NB in children older than 10 years may exhibit unusual clinicopathologic and genetic features with large tumors, bilateral adrenal disease, rare morphologic features, complex DNA microarray findings and novel mutations. Patients often have grim prognoses despite genomic profiling-guided targeted therapy.
Developing an Epidemiologic Study to Investigate Risk Factors for Colorectal Cancer Among Alaska Native People
Authors: Nash Sarah H. , Peters Ulrike , Redwood Diana
Published: April 2019

Alaska Native (AN) people have among the highest rates of colorectal cancer (CRC) recorded globally. Preventing CRC is an important health priority of AN tribal health leaders and communities. Lifestyle and genetic risk and protective factors for CRC among AN people remain understudied. We have been working to establish a tribally led, community-based, comprehensive investigation of lifestyle and genetic risk and protective factors for CRC among AN people. We describe the process of initiating this research study, including conversations with key tribal health system staff. We discuss themes that arose during these conversations and literature review and describe how those themes were used during the study design and protocol development phase. This description is intended to provide guidance to other researchers working to establish community-based studies of cancer risk, particularly among tribal communities.
Recovery From Malnutrition Among Refugee Children Following Participation in the Special Supplemental Nutrition for Women, Infants, and Children (WIC) Program in Massachusetts, 1998-2010
Authors: Smock Laura , Martelon MaryKate , Metallinos-Katsaras Elizabeth , Nguyen Thinh , Cochran Jennifer , Geltman Paul L.
Published: April 2019

Objectives:

(1) To examine patterns of catch-up growth and anemia correction in refugee children younger than 5 years after participation in the Special Supplemental Nutrition for Women, Infants, and Children (WIC) program, and (2) to identify factors associated with recovery from growth abnormalities.

Design:

Records on 1731 refugee children younger than 5 years who arrived in Massachusetts between 1998-2010 were matched to WIC program records and then restricted to 779 children who had at least 2 WIC visits. Kaplan-Meier curves and Cox proportional hazards models were used to examine how sex affected time to recovery from malnutrition and anemia. Factors associated with recovery were analyzed in SAS using multivariate logistic regression.

Setting:

Massachusetts.

Participants:

Refugee children younger than 5 years on arrival, who visited a WIC program at least twice between 1998 and 2010.

Main Outcome Measures:

(1) Proportion of children who recovered from low height-for-age (stunting), low weight-for-age, low weight-for-height (wasting), and anemia; (2) odds ratios for factors associated with recovery; and (3) Kaplan-Meier curves showing recovery over time from low height-for-age, low weight-for-age, and low weight-for-height.

Results:

The number of WIC visits was associated with recovery from stunting, wasting, low weight-for-age, and anemia; results reached statistical significance for stunting (odds ratio [OR] = 8.64; 95% confidence interval [CI], 2.25-33.19), low weight-for-age (OR = 5.28; 95% CI, 1.35-20.73), and anemia (OR = 6.50; 95% CI, 2.69-15.69). Female sex was associated with recovery from stunting, wasting, and low weight-for-age, whereas male sex was associated with recovery from anemia; the associations were statistically significant between female sex and stunting (OR = 9.14; 95% CI, 1.93-43.29), wasting (OR = 14.78; 95% CI, 1.57-138.85), and low weight-for-age (OR = 4.29; 95% CI, 1.09-16.79).

Conclusions:

Children who remained engaged in WIC may recover better from malnutrition than children with fewer WIC visits, although there are limitations to the available data.

These findings suggest that those working with refugee families should prioritize outreach toward initiating and maintaining WIC program enrollment for eligible refugee children.
Identification of American Indians and Alaska Natives in Public Health Data Sets: A Comparison Using Linkage-Corrected Washington State Death Certificates
Authors: Joshi Sujata , Warren-Mears Victoria
Published: April 2019

Context:

Efforts to address disparities experienced by American Indians/Alaska Natives (AI/ANs) have been hampered by a lack of accurate and timely health data. One challenge to obtaining accurate data is determining who “counts” as AI/AN in health and administrative data sets.

Objective:

To compare the effects of definition and misclassification of AI/AN on estimates of all-cause and cause-specific mortality for AI/AN in Washington during 2015-2016.

Design:

Secondary analysis of death certificate data from Washington State. Data were corrected for AI/AN racial misclassification through probabilistic linkage with the Northwest Tribal Registry. Counts and age-adjusted rates were calculated and compared for 6 definitions of AI/AN. Comparisons were made with the non-Hispanic white population to identify disparities.

Setting:

Washington State.

Participants:

AI/AN and non-Hispanic white residents of Washington State who died in 2015 and 2016.

Main Outcome Measures:

Counts and age-adjusted rates for all-cause mortality and mortality from cardiovascular diseases, cancer, and unintentional injuries.

Results:

The most conservative single-race definition of AI/AN identified 1502 AI/AN deaths in Washington State during 2015-2016. The least conservative multiple-race definition of AI/AN identified 2473 AI/AN deaths, with an age-adjusted mortality rate that was 48% higher than the most conservative definition. Correcting misclassified AI/AN records through probabilistic linkage significantly increased mortality rate estimates by 11%. Regardless of definition used, AI/AN in Washington had significantly higher all-cause mortality rates than non-Hispanic whites in the state.

Conclusions:

Reporting single-race versus multiple-race AI/AN had the most consequential effect on mortality counts and rates. Correction of misclassified AI/AN records resulted in small but statistically significant increases in AI/AN mortality rates. Researchers and practitioners should consult with AI/AN communities on the complex issues surrounding AI/AN identity to obtain the best method for identifying AI/AN in health data sets.
Modulating dream experience: Noninvasive brain stimulation over the sensorimotor cortex reduces dream movement
Authors: Noreika Valdas , Windt Jennifer M. , Kern Markus , Valli Katja , Salonen Tiina , Parkkola Riitta , Revonsuo Antti , Karim Ahmed A. , Ball Tonio , Lenggenhager Bigna
Published: April 2019

Recently, cortical correlates of specific dream contents have been reported, such as the activation of the sensorimotor cortex during dreamed hand clenching. Yet, the causal mechanisms underlying specific dream content remain largely elusive. Here, we investigated how alterations in the excitability of sensorimotor areas through transcranial direct current stimulation (tDCS) might alter dream content. Following bihemispheric tDCS or sham stimulation, participants who were awakened from REM sleep filled out a questionnaire on bodily sensations in dreams. tDCS, compared to sham stimulation, significantly decreased reports of dream movement, especially repetitive actions. Contrary to this, other types of bodily experiences, such as tactile or vestibular sensations, were not affected by tDCS, confirming the specificity of stimulation effects. In addition, tDCS reduced interhemispheric coherence in parietal areas and altered the phasic electromyography correlation between the two arms. These findings reveal that a complex reorganization of the motor network co-occurred with the reduction of dream movement, confirming spatial specificity of the stimulation site. We conclude that tDCS over the sensorimotor cortex causally interferes with dream movement during REM sleep.
The Prevotella copri complex comprises four distinct clades that are underrepresented in Westernised populations
Authors: Tett Adrian , Huang Kun D. , Asnicar Francesco , Fehlner-Peach Hannah , Pasolli Edoardo , Karcher Nicolai , Armanini Federica , Manghi Paolo , Bonham Kevin , Zolfo Moreno , De Filippis Francesca , Magnabosco Cara , Bonneau Richard , Lusingu John , Amuasi John , Reinhard Karl , Rattei Thomas , Boulund Fredrik , Engstrand Lars , Zink Albert , Collado Maria Carmen , Littman Dan R. , Eibach Daniel , Ercolini Danilo , Rota-Stabelli Omar , Huttenhower Curtis , Maixner Frank , Segata Nicola
Published: April 2019

Prevotella copri is a common inhabitant of the human gut. Interest in P. copri has gathered pace due to conflicting reports on whether it is beneficial or detrimental to health. In a cross-continent meta-analysis exploiting >6,500 available metagenomes supported by new isolate sequencing and recovery of high-quality genomes from metagenomes, we obtained >1,000 P. copri genomes. This 100-fold increase over existing isolate genomes allowed the genetic and global population structure of P. copri to be explored at an unprecedented depth. We demonstrate P. copri is not a monotypic species, but encompasses four distinct clades (>10% inter-clade vs. <4% intra-clade average single nucleotide variants) for which we propose the name P. copri complex, comprising clades A, B, C and D. We show the complex is near ubiquitous in non-Westernised populations (95.4% versus 29.6% in Westernised populations), where all four clades are typically co-present within an individual (61.6% of the cases), in contrast to Westernised populations (4.6%). Genomic analysis of the complex reveals substantial and complementary functional diversity, including the potential for utilisation of complex carbohydrates, suggestive that multi-generational dietary modifications may be a driver for the reduced P. copri prevalence in Westernised populations. Analysis of ancient stool microbiomes highlights a similar pattern of P. copri presence consistent with modern non-Westernised populations, allowing us to estimate the time of clade delineation to pre-date human migratory waves out of Africa. Our analysis reveals P. copri to be far more diverse than previously appreciated and this diversity appears to be underrepresented in Western-lifestyle populations.
Ribo-seQC: comprehensive analysis of cytoplasmic and organellar ribosome profiling data
Authors: Calviello Lorenzo , Sydow Dominique , Harnett Dermot , Ohler Uwe
Published: April 2019

Ribosome profiling enables genome-wide analysis of translation with unprecedented resolution. We present Ribo-seQC, a versatile tool for the comprehensive analysis of Ribo-seq data, providing in-depth insights on data quality and translational profiles for cytoplasmic and organelle ribosomes. Ribo-seQC automatically generates platform-independent HTML reports, offering a detailed and easy-to-share basis for collaborative Ribo-seq projects.

Availability

Ribo-seQC is available at https://github.com/ohlerlab/RiboseQC and submitted to Bioconductor.

Contact

uwe.ohler@mdc-berlin.de
Myelin Basic Protein dynamics from out-of-equilibrium functional state to degraded state in myelin
Authors: Di Gioacchino M. , Bianconi A. , Burghammer M. , Ciasca G. , Bruni F. , Campi G.
Published: April 2019

Living matter is a quasi-stationary out-of-equilibrium system; in this physical condition, structural fluctuations at nano- and meso-scales are needed to understand the physics behind its biological functionality. Myelin has a simple ultrastructure whose fluctuations show correlated disorder in its functional out-of-equilibrium state. However, there is no information on the relationship between this correlated disorder and the dynamics of the intrinsically disordered Myelin Basic Protein (MBP) which is expected to influence the membrane structure and overall functionality. In this work, we have investigated the role of this protein structural dynamics in the myelin ultrastructure fluctuations in and out-of-equilibrium conditions, by using synchrotron Scanning micro X Ray Diffraction and Small Angle X ray Scattering. We have induced the crossover from out-of-equilibrium functional state to in-equilibrium degeneration changing the pH far away from physiological condition. While the observed compression of the cytosolic layer thickness probes the unfolding of the P2 protein and of the cytoplasmic P0 domain (P0cyt), the intrinsic large MBP fluctuations preserve the cytosol structure also in the degraded state. Thus, the transition of myelin ultrastructure from correlated to uncorrelated disordered state, is significantly affected by the unfolding of the P2 and P0 proteins, which in this latter state do not act in synergistic manner with MBP to determine the membrane functionality.

STATEMENT OF SIGNIFICANCE

A better comprehension of myelin degenerative process and the role of protein dynamics in this biological membrane is a topic issue in today’s scientific community. The myelin ultrastructural fluctuations exhibit correlated disorder in its functional state, that becomes uncorrelated as it degenerates. In this work we elucidate the interplay of protein structural dynamics and myelin ultrastructure in the transition from its functional state to the degraded state. The results highlight that the intrinsically disordered Myelin Basic Protein (MBP) allows to preserve the myelin structure following both the small correlated fluctuations in physiological state and the large disordered fluctuations in degraded conditions, where the myelin functionality is close to being lost and the MBP remains the single active protein.
Citizen scientists highlight conservation value of a small subtropical reef, Flinders Reef, southeast Queensland, Australia
Authors: Grol Monique G.G. , Vercelloni Julie , Kenyon Tania M. , Bayraktarov Elisa , van den Berg Cedric P. , Haris Daniel , Loder Jennifer A. , Mihaljević Morana , Rowland Phebe I. , Roelfsema Chris M.
Published: April 2019

Subtropical reefs are unique ecosystems that require effective management – informed by regular ecological monitoring – to foster resilience to environmental changes. Resources to conduct monitoring are limited, and citizen science can complement data from local management agencies. Here, citizen science efforts document the ecological status of a subtropical reef, Flinders Reef, Moreton Bay Marine Park, Australia. Ecological surveys, following Reef Check Australia and CoralWatch protocols, were conducted by 44 trained volunteers. Ten sites at Flinders Reef were surveyed at 5-10 m depth in autumn and spring. Additionally, underwater photos and depth surveys were integrated with satellite imagery to create a detailed habitat map. Coral cover across sites ranged between 14% and 67%. Branching corals dominated the site with 67% cover and showed 89% dissimilarity in coral community composition compared to other sites. Coral community composition was mostly explained by spatial variation, of which 16% was influenced by wave exposure. Observed reef impacts including physical damage, unknown scars and coral disease were three times lower than studies on more accessible reefs in Moreton Bay Marine Park. Invertebrate abundance was relatively low (6.65 individuals per 100 m2), with the most abundant groups observed being sea urchins (Diademaspp.), gastropods (Drupellaspp.) and anemones. Butterflyfish were recorded at every site and were the most abundant fish group surveyed. Findings highlight the healthy condition of Flinders Reef, likely influenced by its offshore location and protection status as a ‘no-take’ zone. This study demonstrates that increasing the current 500m radius protection zone by a further 500m could double the protected area of coral, offering potential further conservation benefits. The findings resulting from the ecological data analysis and created benthic habitat map, provide an example of how citizen science based projects can assist marine park authorities and the public in ongoing conservation efforts.
Intestinal peroxisomal fatty acid β-oxidation regulates neural serotonin signaling through a feedback mechanism
Authors: Bouagnon Aude , Srivastava Shubhi , Panda Oishika , Schroeder Frank C. , Srinivasan Supriya , Ashrafi Kaveh
Published: April 2019

The ability to coordinate behavioral responses with metabolic status is fundamental to the maintenance of energy homeostasis. In numerous species includingC. elegansand mammals, neural serotonin signaling regulates a range of food-related behaviors. However, the mechanisms that integrate metabolic information with serotonergic circuits are poorly characterized. Here, we identify metabolic, molecular, and cellular components of a circuit that links peripheral metabolic state to serotonin-regulated behaviors inC. elegans. We find that blocking the entry of fatty acyl-CoAs into peroxisomal β-oxidation in the intestine results in blunting of the effects of neural serotonin signaling on feeding and egg-laying behaviors. Comparative genomics and metabolomics revealed that interfering with intestinal peroxisomal β-oxidation results in a modest global transcriptional change but significant changes to the metabolome, including a large number of changes in ascaroside and phospholipid species, some of which affect feeding behavior. We also identify body cavity neurons and an ether-a-go-go related (EAG) potassium channel that functions in these neurons as key cellular components of the circuitry linking peripheral metabolic signals to regulation of neural serotonin signaling. These data raise the possibility that the effects of serotonin on satiety may have their origins in feedback, homeostatic metabolic responses from the periphery.
In Search of Consciousness: Examining the Temporal Dynamics of Conscious Visual Perception using MEG time-series data
Authors: Mai Anh-Thu , Grootswagers Tijl , Carlson Thomas A.
Published: April 2019

The mere presence of information in the brain does not always mean that this information is available to consciousness (de-Wit, Alexander, Ekroll, & Wagemans, 2016). Experiments using paradigms such as binocular rivalry, visual masking, and the attentional blink have shown that visual information can be processed and represented by the visual system without reaching consciousness. Using multivariate pattern analysis (MVPA) and magneto-encephalography (MEG), we investigated the temporal dynamics of information processing for unconscious and conscious stimuli. We decoded stimulus information from the brain recordings while manipulating visual consciousness by presenting stimuli at threshold contrast in a backward masking paradigm. Participants’ consciousness was measured using both a forced-choice categorisation task and self-report. We show that brain activity during both conscious and non-conscious trials contained stimulus information, and that this information was enhanced in conscious trials. Overall, our results indicate that visual consciousness is characterised by enhanced neural activity representing the visual stimulus, and that this effect arises as early as 180 ms post-stimulus onset.
RhoG and Cdc42 can contribute to Rac-dependent lamellipodia formation through WAVE Regulatory Complex-binding
Authors: Schaks Matthias , Döring Hermann , Kage Frieda , Steffen Anika , Klünemann Thomas , Blankenfeldt Wulf , Stradal Theresia , Rottner Klemens
Published: April 2019

Cell migration frequently involves the formation of lamellipodial protrusions, the initiation of which requires Rac GTPases signalling to heteropentameric WAVE regulatory complex (WRC). While Rac-related RhoG and Cdc42 can potently stimulate lamellipodium formation, so far presumed to occur by upstream signalling to Rac activation, we show here that the latter can be bypassed by RhoG and Cdc42 given that WRC has been artificially activated. This evidence arises from generation of B16-F1 cells simultaneously lacking both Rac GTPases and WRC, followed by reconstitution of lamellipodia formation with specific Rho-GTPase and differentially active WRC variant combinations. We conclude that formation of canonical lamellipodia requires WRC activation through Rac, but can possibly be tuned, in addition, by WRC interactions with RhoG and Cdc42.
Nanopore sequencing and comparative genome analysis confirm lager-brewing yeasts originated from a single hybridization
Authors: Salazar Alex N. , Gorter de Vries Arthur R. , van den Broek Marcel , Brouwers Nick , de la Torre Cortès Pilar , Kuijpers Niels G. A , Daran Jean-Marc G. , Abeel Thomas
Published: April 2019

Background

The lager brewing yeast,S. pastorianus, is a hybrid betweenS. cerevisiaeandS. eubayanuswith extensive chromosome aneuploidy.S. pastorianusis subdivided into Group 1 and Group 2 strains, where Group 2 strains have higher copy number and a larger degree of heterozygosity forS. cerevisiaechromosomes. As a result, Group 2 strains were hypothesized to have emerged from a hybridization event distinct from Group 1 strains. Current genome assemblies ofS. pastorianusstrains are incomplete and highly fragmented, limiting our ability to investigate their evolutionary history.

Results

To fill this gap, we generated a chromosome-level genome assembly of theS. pastorianusstrain CBS 1483 using MinION sequencing and analysed the newly assembled subtelomeric regions and chromosome heterozygosity. To analyse the evolutionary history ofS. pastorianusstrains, we developed Alpaca: a method to compute sequence similarity between genomes without assuming linear evolution. Alpaca revealed high similarities between theS. cerevisiaesubgenomes of Group 1 and 2 strains, and marked differences from sequencedS. cerevisiae strains.

Conclusions

Our findings suggest that Group 1 and Group 2 strains originated from a single hybridization involving a heterozygousS. cerevisiaestrain, followed by different evolutionary trajectories. The clear differences between both groups may originate from a severe population bottleneck caused by the isolation of the first pure cultures. Alpaca provides a computationally inexpensive method to analyse evolutionary relationships while considering non-linear evolution such as horizontal gene transfer and sexual reproduction, providing a complementary viewpoint beyond traditional phylogenetic approaches.
Subcellular compartments interplay for carbon and nitrogen allocation in Chromera velia and Vitrella brassicaformis
Authors: Füssy Zoltán , Faitová Tereza , Oborník Miroslav
Published: April 2019

Endosymbioses necessitate functional cooperation of cellular compartments to avoid pathway redundancy and streamline the control of biological processes. To gain insight into the metabolic compartmentation in chromerids, phototrophic relatives to apicomplexan parasites, we prepared a reference set of proteins probably localized to mitochondria, cytosol and the plastid, taking advantage of available genomic and transcriptomic data. Training of prediction algorithms with the reference set now allows a genome-wide analysis of protein localization in C. velia and V. brassicaformis. We confirm that the chromerid plastids house enzymatic pathways needed for their maintenance and photosynthetic activity, but for carbon and nitrogen allocation, metabolite exchange is necessary with the cytosol and mitochondria. This indeed suggests that the regulatory mechanisms operate in the cytosol to control carbon metabolism based on the availability of both light and nutrients. We discuss that this arrangement is largely shared with apicomplexans and dinoflagellates, possibly stemming from a common ancestral metabolic architecture, and supports the mixotrophy of the chromerid algae.
Unexpected phase transition sequence in the ferroelectric Bi4Ti3O12
Authors: Guo Yuan-Yuan , Gibbs Alexandra S. , Perez-Mato J. Manuel , Lightfoot Philip
Published: April 2019

The high-temperature phase behaviour of the ferroelectric layered perovskite Bi4Ti3O12 has been re-examined by high-resolution powder neutron diffraction. Previous studies, both experimental and theoretical, had suggested conflicting structural models and phase transition sequences, exacerbated by the complex interplay of several competing structural instabilities. This study confirms that Bi4Ti3O12 undergoes two separate structural transitions from the aristotype tetragonal phase (space group I4/mmm) to the ambient-temperature ferroelectric phase (confirmed as monoclinic, B1a1). An unusual, and previously unconsidered, intermediate paraelectric phase is suggested to exist above T
C with tetragonal symmetry, space group P4/mbm. This phase is peculiar in displaying a unique type of octahedral tilting, in which the triple perovskite blocks of the layered structure alternate between tilted and untilted. This is rationalized in terms of the bonding requirements of the Bi3+ cations within the perovskite blocks.
Crystal structure of N-{N-[N-(tert-butoxycarbonyl)-L-α-aspartyl]-L-α-aspartyl}-L-α-aspartic acid 14,24,34-trimethyl ester 31-2-oxo-2-phenylethyl ester {Boc-[Asp(OMe)]3-OPac}
Authors: Kato Takuma , Kishimoto Saki , Asano Akiko , Doi Mitsunobu
Published: April 2019

In the title homotripeptide {Boc-[Asp(OMe)]3-OPac}, C28H37N3O13, all peptide bonds adopt an s-trans conformation with respect to the N—H and C=O groups. In the crystal, N—H...O hydrogen bonds result in an infinite parallel β-sheet structure running along the b-axis direction. The Boc protecting group at the N-terminus of the peptide is disordered over two sites with occupancy factors of 0.504 (5) and 0.496 (5).
Inflation shocks and income inequality
Authors: Gonzales Rolando , Rojas-Hosse Andrea
Published: April 2019

Purpose

The purpose of this paper is to analyze the effects of inflationary shocks on inequality, using data of selected countries of the Middle East and North Africa (MENA).

Design/methodology/approach

Inflationary shocks were measured as deviations from core inflation, based on a genetic algorithm. Bayesian quantile regression was used to estimate the impact of inflationary shocks in different levels of inequality.

Findings

The results showed that inflationary shocks substantially affect countries with higher levels of inequality, thus suggesting that the detrimental impact of inflation is exacerbated by the high division of classes in a country.

Originality/value

The study contributes to the literature about the relationship between inflation and inequality by proposing that not only the sustained increase in prices but also the inflationary shocks – the deviations from core inflation – contribute to the generation of inequality. Also, to the best of the authors knowledge, the relationship between inflation shocks and inequality in the MENA region has never been analyzed before, thus creating a research gap to provide additional empirical evidence about the sources of inequality. Additionally, the authors contribute with a methodological approach to measure inflationary shocks, based on a semelparous genetic algorithm.
Innovations in intellectual property rights management
Authors: Modic Dolores , Hafner Ana , Damij Nadja , Cehovin Zajc Luka
Published: April 2019

Purpose

The purpose of this paper is to evaluate innovations in intellectual property rights (IPR) databases, techniques and software tools, with an emphasis on selected new developments and their contribution towards achieving advantages for IPR management (IPRM) and wider social benefits. Several industry buzzwords are addressed, such as IPR-linked open data (IPR LOD) databases, blockchain and IPR-related techniques, acknowledged for their contribution in moving towards artificial intelligence (AI) in IPRM.

Design/methodology/approach

The evaluation, following an original framework developed by the authors, is based on a literature review, web analysis and interviews carried out with some of the top experts from IPR-savvy multinational companies.

Findings

The paper presents the patent databases landscape, classifying patent offices according to the format of data provided and depicting the state-of-art in the IPR LOD. An examination of existing IPR tools shows that they are not yet fully developed, with limited usability for IPRM. After reviewing the techniques, it is clear that the current state-of-the-art is insufficient to fully address AI in IPR. Uses of blockchain in IPR show that they are yet to be fully exploited on a larger scale.

Originality/value

A critical analysis of IPR tools, techniques and blockchain allows for the state-of-art to be assessed, and for their current and potential value with regard to the development of the economy and wider society to be considered. The paper also provides a novel classification of patent offices and an original IPR-linked open data landscape.
Urban tourism hypertrophy: who should deal with it? The case of Krakow (Poland)
Authors: Zmyślony Piotr , Kowalczyk-Anioł Joanna
Published: April 2019

Purpose

The purpose of this paper is twofold: first, to analyze the phenomenon of urban tourism hypertrophy (UTH) in the context of the process of tourism-related social conflicts formation; and second, to discuss the extent to which destination management organizations (DMOs) are prepared to take responsibilities and actions undertaken in this process.

Design/methodology/approach

The paper adopts conflict management (CM) theory as a framework for discussing UTH within the city context. The paper then analyzes the empirical example of social conflict in Kraków (Poland) to assess the predispositions of key institutions engaged in destination governance to lead CM process triggered by UTH. The Circle of Conflict approach proposed by C. Moore (The Mediation Process: Practical Strategies for Resolving Conflict, Jossey Bass, San Francisco, CA, 2014) is utilized as the main application method.

Findings

The study shows that DMO is the most appropriate entity to deal with UTH as a conflict manager; however, it has insufficient resources to fulfill all requirements relating to that role. Therefore, the range of responsibilities and roles of the contemporary DMOs should be completed with CM as the permanent task during UTH crisis.

Research limitations/implications

The example study was based on interviews carried out with a limited number of informants. Also, the contextual nature of the research as well as specific destination governance structure in Kraków blurred the picture of DMOs predispositions to leading the CM process.

Practical implications

The study supports urban DMO managers by suggesting a tool of diagnosis and intervention in UTH-induced conflicts. Thus, it makes fulfilling the mediator role a destination governance task.

Social implications

CM brings agreement among parties as to the understanding of the nature of conflict, which forms the basis for quick and mutually agreed actions, according to sustainable development principles.

Originality/value

The paper proposes an alternative approach to mitigate UTH-related problems in cities by adopting the CM framework which emphasizes the universal nature of conflict causes and proposes adequate tools for undertaking actions by DMOs.
Goal programming optimization model under uncertainty and the critical areas characterization in humanitarian logistics management
Authors: Chong Mario , Lazo Lazo Juan G. , Pereda Maria Cristina , Machuca De Pina Juan Manuel
Published: April 2019

Purpose

The purpose of this paper is to improve disaster management models, have an optimal distribution of assets, reduce human suffering in a crisis and find a good solution for warehouse locations, distribution points, inventory levels and costs, considering the uncertainty of a wide range of variables, to serve as a support model for decision making in real situations.

Design/methodology/approach

A model is developed based on the recent models. It includes structured and non-structured data (historical knowledge) from a humanitarian perspective. This model considers the uncertainty in a landslide and flood area and it is applied in a representative Peruvian city.

Findings

The proposed model can be used to determine humanitarian aid supply and its distribution with uncertainty, regarding the affected population and its resilience. This model presents a different point of view from the efficiency of the logistics perspective, to identify the level of trust between all the stakeholders (public, private and academic). The finding provides a new insight in disaster management to cover the gap between applied research and human behavior in crisis.

Research limitations/implications

In this study the access of reliable information is limited.

Practical implications

This paper provides an operation model with uncertainty in a humanitarian crisis and a decision-making tool with some recommendation for further public policies.

Originality/value

This study presents a model for decision makers in a low-income zone and highlights the importance of preparedness in the humanitarian system. This paper expands the discussion of how the mathematical models and human behaviors interact with different perspectives in a humanitarian crisis.
Positions in the N‐methyl‐D‐aspartate Receptor GluN2C Subunit M3 and M4 Domains Regulate Alcohol Sensitivity and Receptor Kinetics
Authors: Wu Man , Katti Priya , Zhao Yulin , Peoples Robert W.
Published: April 2019

Background

Alcohol alters synaptic transmission in the brain. The N‐methyl‐D‐aspartate (NMDA) receptor (NMDAR), a subtype of glutamate‐gated ion channel, is an important synaptic target of alcohol in the brain. We and others have previously identified 4 alcohol‐sensitive positions in the third and fourth membrane‐associated (M) domains, designated M31‐2 and M41‐2, of the GluN1, GluN2A, and GluN2B NMDAR subunits. In the present study, we tested whether the corresponding positions in the GluN2C subunit also regulate alcohol sensitivity and ion channel gating.

Methods

We performed alanine‐ and tryptophan‐scanning mutagenesis in the GluN2C subunit followed by expression in HEK 293 cells and electrophysiological patch‐clamp recording.

Results

Alanine substitution at the M31 (F634) and M41‐2 (M821 and M823) positions did not alter ethanol (EtOH) sensitivity, whereas substitution of alanine at the M32 position (F635) yielded nonfunctional receptors. Tryptophan substitution at the M31‐2 positions did not change EtOH sensitivity, whereas tryptophan substitution at the M41 position increased, and at the M42 position decreased, EtOH sensitivity. The increased EtOH sensitivity of the tryptophan mutant at M41 is in marked contrast to previous results observed in the GluN2A and GluN2B subunits. In addition, this mutant exhibited increased desensitization, but to a much lesser extent compared to the corresponding mutations in GluN2A and GluN2B. A series of mutations at M41 altered EtOH sensitivity, glutamate potency, and desensitization. Seven amino acid substitutions (of 15 tested) at this position yielded nonfunctional receptors. Among the remaining mutants at M41, EtOH sensitivity was not significantly correlated with hydrophobicity, molecular volume, or polarity of the substituent, or with glutamate EC50 values, but was correlated with maximal steady‐state‐to‐peak current ratio, a measure of desensitization.

Conclusions

The identity and characteristics of alcohol‐sensitive positions in the GluN2C subunit differ from those previously reported for GluN2A and GluN2B subunits, despite the high homology among these subunits.
Short duration of untreated psychosis enhances negative symptom remission in extended early intervention service for psychosis
Authors: Dama M. , Shah J. , Norman R. , Iyer S. , Joober R. , Schmitz N. , Abdel‐Baki A. , Malla A.
Published: April 2019

Objective

To test whether duration of untreated psychosis (DUP) < 3 months, recommended by the World Health Organization/International Early Psychosis Association, enhances the effects of an extended early intervention service (EEIS) on symptom remission.

Method

We examined data from a randomized controlled trial in which patients who received 2 years of treatment in EIS for psychosis were subsequently randomized to either 3 years of EEIS or 3 years of regular care (RC). Using a DUP cut‐off ≤ 12 weeks (approximately < 3 months), patients were split into two groups. Length of positive, negative and total symptom remission were the outcomes.

Results

Patients (N = 217) were mostly male (68%) with schizophrenia spectrum disorder (65%); 108 (50%) received EEIS (58 had DUP ≤12 weeks; 50 had DUP >12 weeks). Interaction between treatment condition (EEIS vs. RC) and DUP cut‐off ≤ 12 weeks was only significant in multiple linear regression model examining length of negative symptom remission as the outcome (adjusted β = 36.88 [SE = 15.88], t = 2.32, P = 0.02). EEIS patients with DUP ≤12 weeks achieved 25 more weeks of negative symptom remission than EEIS patients with DUP >12 weeks.

Conclusion

Having a short DUP may be critical in deriving long‐term benefits from EIS for psychosis, including EEIS settings. This work empirically supports policy recommendations of reducing DUP <3 months.
Video games to measure outcome for children with neuromuscular disorders
Authors: Servais Laurent
Published: April 2019

This commentary is on the original article by Alfano et al. on pages 303–309 of this issue.
First sighting of a tropical benthic reef shark species at Rapa Nui: chance dispersal or a sign of things to come?
Authors: Morales Naiti , Coghlan Amy Rose , Hayden Gonzalo , Guajardo Paula
Published: April 2019

On 20 December 2017, a mature Triaenodon obesus was observed at Hanga Roa Bay, Rapa Nui (Easter Island) at c.18 m depth. This observation increases both the range of T. obesus in the Pacific Ocean and the number of elasmobranch species at Rapa Nui. In combination with other recent sightings further extending the southern range of this species during the Austral summer, sea surface temperature is suggested as key to southern dispersal.
End‐of‐life product management as a resilience driver for developing countries: A policy experiment for used tires in Ecuador
Authors: Cecchin Andrea , Lamour Mathieu , Joseph Maks Davis Michael , Jácome Polit David
Published: April 2019

Over the last decades, a number of new environmental policies have been designed to improve waste management. Among them, extended producer responsibility (EPR) has introduced a mechanism to shift the environmental and financial burden of end‐of‐life products from public management to producers. Recently, EPR has been adopted by a growing number of developing countries, but this policy often struggles in being effectively implemented in such contexts, missing the opportunity of using waste management as a sustainability driver. By discussing the EPR for end‐of‐life tires (ELTs) in Ecuador, this paper proposes a different approach in designing and implementing EPR schemes in developing countries: it recommends consideration of social sustainability, rather than merely copying foreign management frameworks. To address this point, two case studies on socially directed ELT applications were designed and carried out. The case studies aimed at improving resilience of vulnerable populations to natural disasters by increasing the resistance of housing and settlements against catastrophic events using civil engineering applications. The analysis of the case studies’ outcomes brings to light possible policy adjustments, in which social sustainability goals are taken into account within the national EPR scheme. The Ecuadorian case also highlights the benefit of employing an adaptive governance approach when dealing with challenging urban management topics, such as informality (a widespread phenomenon in developing countries) and resilience.