bluuebunny/crossref_metadata_2025_split huggingface dataset:
Professional Aspirations and Cultural Expectations: A Qualitative Study of Saudi Females in Dentistry
Authors: Sembawa S. , Sabbah W. , Gallagher J.E. 
Published: February 2018

The aim of this study was to explore the perceptions of Saudi female dentists and dental students on their motivation for and expectations of a career in dentistry. Twenty-one semistructured interviews were conducted with a purposive sample of Saudi female dentists (postgraduate students, generalists, specialists, academics, and unemployed), along with final-year female dental students from public and private dental schools. A topic guide, informed by the literature and piloted on a representative group of Saudi dentists, was used to guide the discourse. Interviews were recorded, transcribed verbatim, and then analyzed using framework analysis. We found that highly academic achieving females are interested in a prestigious, financially rewarding career in health care that fulfills their family and community expectations of balancing family life with work. Features of the job that facilitate this balance such as regular hours and no on-call were commonly important. A range of professional interests, most importantly specialization and holding academic positions, often involving studying abroad, emerged. Females’ movement between sectors, location of work, and practice patterns in this study were shaped by their domestic circumstances. The findings suggest that Saudi females in dentistry aspire to fulfill their interest in a successful, professional, highly prestigious, progressive career while recognizing cultural expectations and maintaining a family-work balance and perceive this is possible through a career in dentistry. Knowledge Transfer Statement: This study makes an important contribution to the knowledge on this topic. The findings can inform decisions made by policy makers on dental education and workforce planning, as well as future dentists who plan to join the dental workforce. It gives insight into the motivation and career expectations of Saudi females in dentistry in light of the current economic and cultural changes, as well as their implication for the dental workforce.
Supporting patients self-managing respiratory health: a qualitative study on the impact of the Breathe Easy voluntary group network
Authors: Hashem Ferhana , Merritt Rowena 
Published: February 2018

Self-management strategies are designed to improve lung and respiratory health through structured self-management plans with regular practitioner reviews. Strategies have not, however, focused upon how patient support groups and advocacy networks can help with the management of these conditions; therefore, it is unknown what impact they may have on patient self-management. A qualitative study was designed to help understand what impact the British Lung Foundation's Breathe Easy (BE) groups have on patients managing their lung and respiratory conditions.A semistructured telephone interview schedule was developed to study the network. Topics covered included: perceptions about the BE groups; current referrals systems and integration pathways; benefits of attending the BE groups; and integration of the BE groups into the respiratory pathway.Key themes explored included: shared patient experience and peer support; patient self-management and self-education; attendance of healthcare professionals; and the impact of integrating BE groups into the respiratory pathway.BE networks were shown to support self-care initiatives for people attending the groups, and members expressed a social and educational benefit. BE networks were working with the local National Health Service to become an integral part of the respiratory pathway, yet there was evidence of resistance from the health service in incorporating the networks.
A histogram specification technique for dark image enhancement using a local transformation method
Authors: Hussain Khalid , Rahman Shanto , Rahman Md. Mostafijur , Khaled Shah Mostafa , Abdullah-Al Wadud M. , Hossain Khan Muhammad Asif , Shoyaib Mohammad 
Published: February 2018

Abstract
Traditional image enhancement techniques produce different types of noise such as unnatural effects, over-enhancement, and artifacts, and these drawbacks become more prominent in enhancing dark images. To overcome these drawbacks, we propose a dark image enhancement technique where local transformation of the pixels have been performed. Here, we apply a transformation method of different parts of the histogram of an input image to get a desired histogram. Afterwards, histogram specification technique has been done on the input image using this transformed histogram. The performance of the proposed technique has been evaluated in both qualitative and quantitative manner, which shows that the proposed method improves the quality of the image with minimal unexpected artifacts as compared to the other techniques.
Endogenous Tumor Suppressor microRNA-193b: Therapeutic and Prognostic Value in Acute Myeloid Leukemia
Authors: Bhayadia Raj , Krowiorz Kathrin , Haetscher Nadine , Jammal Razan , Emmrich Stephan , Obulkasim Askar , Fiedler Jan , Schwarzer Adrian , Rouhi Arefeh , Heuser Michael , Wingert Susanne , Bothur Sabrina , Döhner Konstanze , Mätzig Tobias , Ng Michelle , Reinhardt Dirk , Döhner Hartmut , Zwaan C. Michel , van den Heuvel Eibrink Marry , Heckl Dirk , Fornerod Maarten , Thum Thomas , Humphries R. Keith , Rieger Michael A. , Kuchenbauer Florian , Klusmann Jan-Henning 
Published: February 2018

Purpose Dysregulated microRNAs are implicated in the pathogenesis and aggressiveness of acute myeloid leukemia (AML). We describe the effect of the hematopoietic stem-cell self-renewal regulating miR-193b on progression and prognosis of AML. Methods We profiled miR-193b-5p/3p expression in cytogenetically and clinically characterized de novo pediatric AML (n = 161) via quantitative real-time polymerase chain reaction and validated our findings in an independent cohort of 187 adult patients. We investigated the tumor suppressive function of miR-193b in human AML blasts, patient-derived xenografts, and miR-193b knockout mice in vitro and in vivo. Results miR-193b exerted important, endogenous, tumor-suppressive functions on the hematopoietic system. miR-193b-3p was downregulated in several cytogenetically defined subgroups of pediatric and adult AML, and low expression served as an independent indicator for poor prognosis in pediatric AML (risk ratio ± standard error, −0.56 ± 0.23; P = .016). miR-193b-3p expression improved the prognostic value of the European LeukemiaNet risk-group stratification or a 17-gene leukemic stemness score. In knockout mice, loss of miR-193b cooperated with Hoxa9/Meis1 during leukemogenesis, whereas restoring miR-193b expression impaired leukemic engraftment. Similarly, expression of miR-193b in AML blasts from patients diminished leukemic growth in vitro and in mouse xenografts. Mechanistically, miR-193b induced apoptosis and a G1/S-phase block in various human AML subgroups by targeting multiple factors of the KIT-RAS-RAF-MEK-ERK (MAPK) signaling cascade and the downstream cell cycle regulator CCND1. Conclusion The tumor-suppressive function is independent of patient age or genetics; therefore, restoring miR-193b would assure high antileukemic efficacy by blocking the entire MAPK signaling cascade while preventing the emergence of resistance mechanisms.
Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma
Authors: Lang Frederick F. , Conrad Charles , Gomez-Manzano Candelaria , Yung W.K. Alfred , Sawaya Raymond , Weinberg Jeffrey S. , Prabhu Sujit S. , Rao Ganesh , Fuller Gregory N. , Aldape Kenneth D. , Gumin Joy , Vence Luis M. , Wistuba Ignacio , Rodriguez-Canales Jaime , Villalobos Pamela A. , Dirven Clemens M.F. , Tejada Sonia , Valle Ricardo D. , Alonso Marta M. , Ewald Brett , Peterkin Joanna J. , Tufaro Frank , Fueyo Juan 
Published: February 2018

Purpose DNX-2401 (Delta-24-RGD; tasadenoturev) is a tumor-selective, replication-competent oncolytic adenovirus. Preclinical studies demonstrated antiglioma efficacy, but the effects and mechanisms of action have not been evaluated in patients. Methods A phase I, dose-escalation, biologic-end-point clinical trial of DNX-2401 was conducted in 37 patients with recurrent malignant glioma. Patients received a single intratumoral injection of DNX-2401 into biopsy-confirmed recurrent tumor to evaluate safety and response across eight dose levels (group A). To investigate the mechanism of action, a second group of patients (group B) underwent intratumoral injection through a permanently implanted catheter, followed 14 days later by en bloc resection to acquire post-treatment specimens. Results In group A (n = 25), 20% of patients survived > 3 years from treatment, and three patients had a ≥ 95% reduction in the enhancing tumor (12%), with all three of these dramatic responses resulting in > 3 years of progression-free survival from the time of treatment. Analyses of post-treatment surgical specimens (group B, n = 12) showed that DNX-2401 replicates and spreads within the tumor, documenting direct virus-induced oncolysis in patients. In addition to radiographic signs of inflammation, histopathologic examination of immune markers in post-treatment specimens showed tumor infiltration by CD8+ and T-bet+ cells, and transmembrane immunoglobulin mucin-3 downregulation after treatment. Analyses of patient-derived cell lines for damage-associated molecular patterns revealed induction of immunogenic cell death in tumor cells after DNX-2401 administration. Conclusion Treatment with DNX-2401 resulted in dramatic responses with long-term survival in recurrent high-grade gliomas that are probably due to direct oncolytic effects of the virus followed by elicitation of an immune-mediated antiglioma response.
Self-organizing periodicity in development: organ positioning in plants
Authors: Bhatia Neha , Heisler Marcus G. 
Published: February 2018

ABSTRACTPeriodic patterns during development often occur spontaneously through a process of self-organization. While reaction-diffusion mechanisms are often invoked, other types of mechanisms that involve cell-cell interactions and mechanical buckling have also been identified. Phyllotaxis, or the positioning of plant organs, has emerged as an excellent model system to study the self-organization of periodic patterns. At the macro scale, the regular spacing of organs on the growing plant shoot gives rise to the typical spiral and whorled arrangements of plant organs found in nature. In turn, this spacing relies on complex patterns of cell polarity that involve feedback between a signaling molecule – the plant hormone auxin – and its polar, cell-to-cell transport. Here, we review recent progress in understanding phyllotaxis and plant cell polarity and highlight the development of new tools that can help address the remaining gaps in our understanding.
Mapping human development at single-cell resolution
Authors: Behjati Sam , Lindsay Susan , Teichmann Sarah A. , Haniffa Muzlifah 
Published: February 2018

ABSTRACT
Human development is regulated by spatiotemporally restricted molecular programmes and is pertinent to many areas of basic biology and human medicine, such as stem cell biology, reproductive medicine and childhood cancer. Mapping human development has presented significant technological, logistical and ethical challenges. The availability of established human developmental biorepositories and the advent of cutting-edge single-cell technologies provide new opportunities to study human development. Here, we present a working framework for the establishment of a human developmental cell atlas exploiting single-cell genomics and spatial analysis. We discuss how the development atlas will benefit the scientific and clinical communities to advance our understanding of basic biology, health and disease.
A ‘molecular guillotine’ reveals the interphase function of Kinesin-5
Authors: Lv Zhiyi , Rosenbaum Jan , Aspelmeier Timo , Großhans Jörg 
Published: February 2018

ABSTRACT
Motor proteins are important for transport and force generation in a variety of cellular processes and in morphogenesis. Here, we describe a general strategy for conditional motor mutants by inserting a protease cleavage site into the ‘neck’ between the head domain and the stalk of the motor protein, making the protein susceptible to proteolytic cleavage at the neck by the corresponding protease. To demonstrate the feasibility of this approach, we inserted the cleavage site of the tobacco etch virus (TEV) protease into the neck of the tetrameric motor Kinesin-5. Application of TEV protease led to a specific depletion and functional loss of Kinesin-5 in Drosophila embryos. With our approach, we revealed that Kinesin-5 stabilizes the microtubule network during interphase in syncytial embryos. The ‘molecular guillotine’ can potentially be applied to many motor proteins because Kinesins and myosins have conserved structures with accessible neck regions.
This article has an associated First Person interview with the first author of the paper.
The Golgi ribbon in mammalian cells negatively regulates autophagy by modulating mTOR activity
Authors: Gosavi Prajakta , Houghton Fiona J. , McMillan Paul J. , Hanssen Eric , Gleeson Paul A. 
Published: February 2018

ABSTRACT
In vertebrates, individual Golgi stacks are joined into a compact ribbon structure; however, the relevance of a ribbon structure has been elusive. Here, we exploit the finding that the membrane tether of the trans-Golgi network, GCC88 (encoded by GCC1), regulates the balance between Golgi mini-stacks and the Golgi ribbon. Loss of Golgi ribbons in stable cells overexpressing GCC88 resulted in compromised mechanistic target of rapamycin (mTOR) signaling and a dramatic increase in LC3-II-positive autophagosomes, whereas RNAi-mediated depletion of GCC88 restored the Golgi ribbon and reduced autophagy. mTOR was absent from dispersed Golgi mini-stacks whereas recruitment of mTOR to lysosomes was unaffected. We show that the Golgi ribbon is a site for localization and activation of mTOR, a process dependent on the ribbon structure. We demonstrate a strict temporal sequence of fragmentation of Golgi ribbon, loss of Golgi mTOR and subsequent increased autophagy. Golgi ribbon fragmentation has been reported in various neurodegenerative diseases and we demonstrate the potential relevance of our findings in neuronal cells using a model of neurodegeneration. Overall, this study highlights a role for the Golgi ribbon in pathways central to cellular homeostasis.
This article has an associated First Person interview with the first author of the paper.
New techniques, applications and perspectives in neuropeptide research
Authors: DeLaney Kellen , Buchberger Amanda R. , Atkinson Louise , Gründer Stefan , Mousley Angela , Li Lingjun 
Published: February 2018

ABSTRACT
Neuropeptides are one of the most diverse classes of signaling molecules and have attracted great interest over the years owing to their roles in regulation of a wide range of physiological processes. However, there are unique challenges associated with neuropeptide studies stemming from the highly variable molecular sizes of the peptides, low in vivo concentrations, high degree of structural diversity and large number of isoforms. As a result, much effort has been focused on developing new techniques for studying neuropeptides, as well as novel applications directed towards learning more about these endogenous peptides. The areas of importance for neuropeptide studies include structure, localization within tissues, interaction with their receptors, including ion channels, and physiological function. Here, we discuss these aspects and the associated techniques, focusing on technologies that have demonstrated potential in advancing the field in recent years. Most identification and structural information has been gained by mass spectrometry, either alone or with confirmations from other techniques, such as nuclear magnetic resonance spectroscopy and other spectroscopic tools. While mass spectrometry and bioinformatic tools have proven to be the most powerful for large-scale analyses, they still rely heavily on complementary methods for confirmation. Localization within tissues, for example, can be probed by mass spectrometry imaging, immunohistochemistry and radioimmunoassays. Functional information has been gained primarily from behavioral studies coupled with tissue-specific assays, electrophysiology, mass spectrometry and optogenetic tools. Concerning the receptors for neuropeptides, the discovery of ion channels that are directly gated by neuropeptides opens up the possibility of developing a new generation of tools for neuroscience, which could be used to monitor neuropeptide release or to specifically change the membrane potential of neurons. It is expected that future neuropeptide research will involve the integration of complementary bioanalytical technologies and functional assays.
Machine learning from fetal flow waveforms to predict adverse perinatal outcomes: a study protocol
Authors: Hoodbhoy Zahra , Hasan Babar , Jehan Fyezah , Bijnens Bart , Chowdhury Devyani 
Published: February 2018

Background: In Pakistan, stillbirth rates and early neonatal mortality rates are amongst the highest in the world. The aim of this study is to provide proof of concept for using a computational model of fetal haemodynamics, combined with machine learning. This model will be based on Doppler patterns of the fetal cardiovascular, cerebral and placental flows with the goal to identify those fetuses at increased risk of adverse perinatal outcomes such as stillbirth, perinatal mortality and other neonatal morbidities. Methods: This will be prospective one group cohort study which will be conducted in Ibrahim Hyderi, a peri-urban settlement in south east of Karachi. The eligibility criteria include pregnant women between 22-34 weeks who reside in the study area. Once enrolled, in addition to the performing fetal ultrasound to obtain Dopplers, data on socio-demographic, maternal anthropometry, haemoglobin and cardiotocography will be obtained on the pregnant women. Discussion: The machine learning approach for predicting adverse perinatal outcomes obtained from the current study will be validated in a larger population at the next stage. The data will allow for early interventions to improve perinatal outcomes.
Stage 1 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: protocol for a test of the double hit hypothesis
Authors: Newbury Dianne F. , Simpson Nuala H. , Thompson Paul A. , Bishop Dorothy V. M. 
Published: February 2018

Background: The presence of an extra sex chromosome is associated with an increased rate of neurodevelopmental difficulties involving language. Group averages, however, obscure a wide range of outcomes. Hypothesis: The 'double hit' hypothesis proposes that the adverse impact of the extra sex chromosome is amplified when genes that are expressed from the sex chromosomes interact with autosomal variants that usually have only mild effects. Neuroligin-4 genes are expressed from X and Y chromosomes; they play an important role in synaptic development and have been implicated in neurodevelopment. We predict that the impact of an additional sex chromosome on neurodevelopment will be correlated with common autosomal variants involved in related synaptic functions. We describe here an analysis plan for testing this hypothesis using existing data. The analysis of genotype-phenotype associations will be conducted after this plan is published and peer-reviewed Methods: Neurodevelopmental data and DNA are available for 130 children with sex chromosome trisomies (SCTs: 42 girls with trisomy X, 43 boys with Klinefelter syndrome, and 45 boys with XYY). Children from a twin study using the same phenotype measures will form two comparison groups (Ns = 184 and 186). Three indicators of a neurodevelopment disorder phenotype will be used: (i) Standard score on a test of nonword repetition; (ii). A language factor score derived from a test battery; (iii) A general scale of neurodevelopmental challenges based on all available information. Autosomal genes were identified by literature search on the basis of prior association with (a) speech/language/reading phenotypes and (b) synaptic function. Preselected regions of two genes scoring high on both criteria, CNTNAP2 and NRXN1, will be tested for association with neurodevelopmental outcomes using Generalised Structural Component Analysis. We predict the association with one or both genes will be detectable in children with SCTs and stronger than in the comparison samples.
Customizable pre-printed consent forms: a solution in light of the Montgomery ruling
Authors: Owen Deborah , Aresti Nick , Mulligan Alex , Kosuge Dennis 
Published: February 2018

Introduction: This article presents an audit cycle supported quality improvement project addressing best practice in the consent process for lower limb arthroplasty which takes into account the new standard in surgical consent and the importance of material risks. Methods: 50 consecutive total hip and total knee replacement consent forms over a 3-month period were reviewed for legibility and completeness. Following the introduction of a new, pre-printed but customizable consent form the review process was repeated. Results: The introduction of a customizable, pre-printed consent form that can be adjusted to reflect the individualized material risks of each patient increased legibility, reduced inappropriate human error variation and abolished the use of abbreviations and medical jargon. Conclusions: When used as part of an extended consent process, the authors feel that the use of pre-printed but customizable consent forms improves legibility, completeness and consistency and also provides the ability to highlight those complications that are of particular importance for that patient to satisfy the new accepted standard in surgical consent.
On Hyers–Ulam stability of fractional differential equations with Prabhakar derivatives
Authors: Derakhshan Mohammad Hossein , Ansari Alireza 
Published: February 2018

Abstract
In this article, we study the Hyers–Ulam stability of the linear and nonlinear fractional differential equations with the Prabhakar derivative. By using the Laplace transform, we show that the introduced fractional differential equations with the Prabhakar fractional derivative is Hyers–Ulam stable. The results generalize the stability of ordinary and fractional differential equations in the Riemann–Liouville sense.
Sustainability of Riga 21st Century Apartment Complexes
Authors: Freimane Santa 
Published: February 2018

Abstract
The research focuses on the sustainability of Riga 21st century apartment complexes, including the context of Riga, as well as sustainability assessment, results of the survey and SWOT analysis. Theoretical studies as well as empiric research methods were used. Research results show that there are some weaknesses, which do not allow achieving the best results, and should be improved in order to increase sustainability of residential environment and the city.