bluuebunny/crossref_metadata_2025 huggingface dataset:
Xinxuekang Regulates Reverse Cholesterol Transport by Improving High-density Lipoprotein Synthesis, Maturation, and Catabolism
Authors: Dong Guang-xin , Li Wen-wen , Wang Ruo-zhu , Zou Wen-jun , Zhong Zhen-dong , Li Bo-gang
Published: April 2017

Di'ao Xinxuekang (XXK) is an herbal product in China and the Netherlands that has been clinically shown to attenuate atherosclerosis; however, the underlying antiatherosclerotic mechanism remains unclear. Because of its role in cholesterol homeostasis, reverse cholesterol transport (RCT) is a potential target for these beneficial effects. This study investigated the effects of XXK on RCT and related proteins. After treating ApoE-deficient mice with XXK for 8 weeks, we observed an increase in the expression level of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1, which in turn stimulated cholesterol efflux and reduced aortic atherosclerotic lesion area. XXK also increased high-density lipoprotein (HDL) synthesis by modulating the peroxisome proliferator–activated receptor γ/liver X receptor α/ATP-binding cassette transporter A1 pathway and promoted HDL maturity by increasing serum lecithin–cholesterol acyltransferase. In addition, XXK improved the selective uptake of HDL-cholesteryl ester by increasing the expression of scavenger receptor class B type I. This is the first study to show that XXK confers a regulation of RCT, at least in part, by improving HDL synthesis, maturation, and catabolism.
Cardiac Outcomes After Perinatal Sertraline Exposure in Mice
Authors: Haskell Sarah E. , Lo Cecilia , Kent Mitchell E. , Eggleston Timothy M. , Volk Kenneth A. , Reinking Benjamin E. , Roghair Robert D.
Published: April 2017

Selective serotonin reuptake inhibitors are prescribed to 6%–10% of pregnant women in the United States. Using an intrauterine plus neonatal exposure model to represent exposure throughout human pregnancy, we hypothesized sertraline exposure would impact intracardiac serotonin signaling and lead to small left heart syndrome in the absence of maternal psychopathology. C57BL/6 adult female mice received sertraline (5 mg·kg−1·d−1IP) or saline throughout pregnancy to time of delivery. Pups maintained exposure on postnatal days 1–14 to encompass the developmental window analogous to human gestation. Sertraline-exposed mice had increased cardiac hydroxyproline content, decreased 5-HT2Breceptor mRNA levels, and increased 5-HT2Areceptor and serotonin transporter mRNA levels on postnatal day 21 (P< 0.05). These changes were associated with diminished exercise capacity at 6 weeks (P< 0.05) and decreased adult shortening fraction and stroke volume at 5 months. Isolated cardiomyocytes from neonatal sertraline-exposed mice had significantly decreased proliferation, cross-sectional area, and phosphorylation of Akt (P< 0.05 vs. neonatal control mice). Perinatal sertraline exposure alters neonatal cardiac development and produces long-standing changes in adult cardiac function and exercise capacity. Further studies are needed to assess whether similar findings are present in the growing population that has been exposed to selective serotonin reuptake inhibitors during development.
Aging and Sexual Differences of the Human Skull
Authors: Toledo Avelar Luiz Eduardo , Cardoso Márcio Alberto , Santos Bordoni Leonardo , de Miranda Avelar Lorena , de Miranda Avelar João Victor
Published: April 2017

Background:

The aging process of the face comprises all layers: skin, subcutaneous fat, muscles, and skeleton, and the signs of aging depend mainly on which layer is mostly affected.

Objective:

To evaluate the aging facial skeleton, as well as establish the sexual differences, areas with a strong predisposition to resorption, and aesthetic repercussion for better treatment approach.

Methods:

Skulls from the Forensic Anthropology Department of the Institute of Forensic Medicine of Belo Horizonte, Brazil, were classified according to gender and age group (i.e., <20 years, 20–50 years, >50 years). Structural changes were classified according to gender and age group.

Results:

Of the 241 skulls included, 192 were male skulls and 49 female. Sexual dimorphism and age-related peculiarities are described herein.

Conclusions:

The knowledge of the anatomy of the aging face, taking into consideration all the layers (skin, fat pads, muscles, and bones), as a whole, for the treatment of folds and shadows is vital for a better and more natural final aesthetic outcome.
Surgical Options for Patellar Stabilization in the Skeletally Immature Patient
Authors: Andrish Jack
Published: April 2017

The surgical management of children and youth with patellar instability can be a challenging exercise. It is possible to identify the various pathoanatomies that coexist with and predispose to patellar instability and in so doing, it is possible to address some, but not all, of these pathoanatomies as part of the surgical management. Although reconstruction of the medial patellofemoral ligament has become a mainstay of treatment, it is not without potential complications. Understanding the importance of surgical technique as it relates to the unique anatomies involved is crucial. Despite the presence of open growth plates, patellar instability in the skeletally immature patient can be effectively and safely performed.
Rehabilitation After Medial Patellofemoral Ligament Reconstruction
Authors: McGee Terrence G. , Cosgarea Andrew J. , McLaughlin Kevin , Tanaka Miho , Johnson Ken
Published: April 2017

Patellar instability resulting from subluxation or dislocation is a painful and commonly recurring condition. Retinacular restraints control patellar tracking, limiting the movement of the patella in the trochlear groove. The medial patellofemoral ligament (MPFL) is considered the main soft tissue stabilizer against lateral displacement. Few studies of patellar instability discuss rehabilitation after MPFL reconstruction. In this review, we discuss the phases of rehabilitation after MPFL reconstruction, typical interventions by rehabilitation specialists, and patient-specific guidelines for return to prior level of function. The Musculoskeletal Institute at The Johns Hopkins Hospital (a collaboration of orthopedic surgeons, primary care sports medicine physicians, and clinicians from the Department of Physical Medicine and Rehabilitation) presents its rehabilitation protocol with phase-specific guidelines for progression after MPFL reconstruction. This evidence-based protocol is a generalized approach that is customized for each patient’s needs.
Diagnosis and Characterization of Patellofemoral Instability: Review of Available Imaging Modalities
Authors: Haj-Mirzaian Arya , Thawait Gaurav K. , Tanaka Miho J. , Demehri Shadpour
Published: April 2017

Patellofemoral instability (PI) is defined as single or multiple episodes of patellar dislocation. Imaging modalities are useful for characterization of patellar malalignment, maltracking, underlying morphologic abnormalities, and stabilizing soft-tissue injuries. Using these findings, orthopedic surgeons can decide when to operate, determine the best operation, and measure degree of correction postoperatively in PI patients. Also, these methods assist with PI diagnosis in some suspicious cases. Magnetic resonance imaging is the preferred method especially in the setting of acute dislocations. Multidetector computed tomography allows a more accurate assessment for malalignment such as patellar tilt and lateral subluxation and secondary osteoarthritis. Dynamic magnetic resonance imaging and 4-dimensional computed tomography have been introduced for better kinematic assessment of the patellofemoral maltracking during extension-flexion motions. In this review article, we will discuss the currently available evidence regarding both the conventional and the novel imaging modalities that can be used for diagnosis and characterization of PI.
Administration of Dexrazoxane Improves Cardiac Indices in Children and Young Adults With Acute Myeloid Leukemia (AML) While Maintaining Survival Outcomes
Authors: Schloemer Nathan J. , Brickler Molly , Hoffmann Raymond , Pan Amy , Simpson Pippa , McFadden Vanessa , Block Joseph , Tower Richard L. , Burke Michael J.
Published: April 2017

Anthracycline-induced cardiotoxicity remains a significant contributor to late morbidity/mortality in children and young adults with acute myeloid leukemia (AML). The cardioprotectant dexrazoxane can be used as prophylaxis to diminish risk for cardiomyopathy but whether it affects risk of relapse in pediatric AML is unclear. Our institution adopted the use of dexrazoxane before anthracyclines administration for all oncology patients in 2011. We compared patients with AML (ages, 0 to 21 y) who received or did not receive dexrazoxane during the years 2008 to 2013. In total, 44 patients with AML (ages, 4.5 mo to 21.7 y) were included. We identified no statistical difference in 2-year event rate (62% vs. 50%, P=0.41) or 2-year overall survival (69% vs. 69%, P=0.53) between patients receiving (n=28) or not receiving (n=16) dexrazoxane. Ejection fraction (P=0.0262) and shortening fraction (P=0.0381) trended significantly higher in patients that received dexrazoxane compared with those that did not receive dexrazoxane. Utilization of the cardioprotectant dexrazoxane before anthracycline chemotherapy in pediatric patients with AML demonstrated no significant difference in either event rate or overall survival relative to institutional controls and seems to improve cardiac function indices. Further studies in this patient population are needed to confirm these findings.
TERT-mediated and ATRX-mediated Telomere Maintenance and Neuroblastoma
Authors: Duan Xiao-Feng , Zhao Qiang
Published: April 2017

Neuroblastomas (NB) are one of the most common extracranial solid tumors in children, and they frequently display high heterogeneity in the disease course. With ongoing research, more information regarding the genetic etiology and molecular mechanisms underlying these contrasting phenotypes is being uncovered. The proto-oncogene MYCN is amplified in approximately 20% of NB cases and is considered a indicator of poor prognosis and an indicator of high-risk NB. The poor prognosis of high risk NB is incompletely explained by MYCN amplification. Recently, massive parallel sequencing studies reported several relatively common gene alterations, such as ATRX mutation and TERT rearrangement that are involved in telomere maintenance through telomerase activity and alternative lengthening of telomeres. Thus, these are important for understanding the etiology and molecular pathogenesis of NB, and hence, for identifying diagnostic and treatment markers. Development of telomerase inhibitors and identification of alternative lengthening of telomeres related targets will contribute to the individualized treatment for high-risk NB. In this mini-review, we will discuss the research progress of TERT-mediated and ATRX-mediated telomere maintenance and NB, especially high-risk tumors.
Joint Impact of Early Life Adversity and COMT Val158Met (rs4680) Genotypes on the Adult Cortisol Response to Psychological Stress
Authors: Lovallo William R. , Enoch Mary-Anne , Sorocco Kristen H. , Vincent Andrea S. , Acheson Ashley , Cohoon Andrew J. , Hodgkinson Colin A. , Goldman David
Published: April 2017

Objective

Exposure to stress during critical periods of development can diminish stress reactivity by the hypothalamic-pituitary-adrenocortical axis. Genetic characteristics may further modify this effect of early adversity, leading to a gene by environment (G × E) interaction on stress reactivity in adulthood. Val-allele carriers of a common polymorphism of the COMT gene (Val158Met, rs4680) have rapid removal of catecholamines in the prefrontal cortex, limbic system, and reward centers. Carriers of the Val and Met alleles may therefore respond differently to the environment and differ in the long-term impact of exposure to early life adversity (ELA).

Methods

We measured saliva cortisol reactivity to public speaking and mental arithmetic stress in 252 healthy young adults exposed to low, medium, and high levels of ELA and who were genotyped for the Val158Met polymorphism.

Results

Cortisol responses showed a G × E interaction (F(4,243) = 2.78, p = .028); simple effects tests showed that Met/Met carriers had progressively smaller cortisol responses with greater levels of ELA. In comparison, Val/Val homozygotes had blunted responses that did not vary with ELA exposure.

Conclusions

Met/Met homozygotes seem sensitive to stressful events in childhood and adolescence, leading to environmental programming of the stress axis. Glucocorticoid responsivity may represent a common pathway revealing targeted genetic vulnerabilities to the long-term effects of early life stress. The results suggest that further G × E studies of ELA are warranted in relation to health behaviors and health outcomes in adulthood.
Improving Patient Safety in Handover From Intensive Care Unit to General Ward: A Systematic Review
Authors: Wibrandt Ida , Lippert Anne
Published: April 2017

Objectives

Despite of the increasing knowledge about patient safety improvements in the handover process in hospitals, we still lack knowledge about what magnitude of patient safety gains can be expected from improvements in handover between the intensive care unit (ICU) and the general ward. The aim of this systematic review was to investigate which handover tools are devised and evaluated with the aim of improving patient safety in the handover process from ICU to ward and whether the described handover tools fulfill their purpose.

Methods

A systematic literature search of 6 databases was performed to answer the review question, developed by using the “Patient Population, Intervention, Comparison, Outcome” format. Two authors independently performed the selection process, as well as the data extraction and quality assessment. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement were followed.

Results

Eight studies were finally included in the qualitative analysis. One study investigated a written information tool, 1 study investigated improved verbal information, 1 study investigated the effect of an additional safety check, and 5 studies investigated a Liaison Nurse as handover tool. Because of heterogeneity among the included studies, the study results could not be pooled.

Conclusions

Not many well-conducted studies can shed light on this important topic. Giving patients and their families a supplementary written or verbal status report before transfer might improve patient safety. The introduction of a Liaison Nurse may be effective in improving communication between ICU and ward staff, which might reduce risks in patient safety. However, there is no evidence of improved mortality and/or readmission rates after introducing handover tools in the transfer from ICU to ward.
Cost-Benefit Analysis of a Support Program for Nursing Staff
Authors: Moran Dane , Wu Albert W. , Connors Cheryl , Chappidi Meera R. , Sreedhara Sushama K. , Selter Jessica H. , Padula William V.
Published: April 2017

Objectives

A peer-support program called Resilience In Stressful Events (RISE) was designed to help hospital staff cope with stressful patient-related events. The aim of this study was to evaluate the impact of the RISE program by conducting an economic evaluation of its cost benefit.

Methods

A Markov model with a 1-year time horizon was developed to compare the cost benefit with and without the RISE program from a provider (hospital) perspective. Nursing staff who used the RISE program between 2015 and 2016 at a 1000-bed, private hospital in the United States were included in the analysis. The cost of running the RISE program, nurse turnover, and nurse time off were modeled. Data on costs were obtained from literature review and hospital data. Probabilities of quitting or taking time off with or without the RISE program were estimated using survey data. Net monetary benefit (NMB) and budget impact of having the RISE program were computed to determine cost benefit to the hospital.

Results

Expected model results of the RISE program found a net monetary benefit savings of US $22,576.05 per nurse who initiated a RISE call. These savings were determined to be 99.9% consistent on the basis of a probabilistic sensitivity analysis. The budget impact analysis revealed that a hospital could save US $1.81 million each year because of the RISE program.

Conclusions

The RISE program resulted in substantial cost savings to the hospital. Hospitals should be encouraged by these findings to implement institution-wide support programs for medical staff, based on a high demand for this type of service and the potential for cost savings.
Quality of Handoffs in Community Pharmacies
Authors: Abebe Ephrem , Stone Jamie A. , Lester Corey A. , Chui Michelle A.
Published: April 2017

Objectives

The aims of the study were to characterize handoffs in community pharmacies and to examine factors that contribute to perceived handoff quality.

Methods

A cross-sectional study of community pharmacists in a Midwest State of the United States. Self-administered questionnaires were used to collect information on participant and practice setting characteristics. Data were analyzed using descriptive statistics and multivariate logistic regression.

Results

A total of 445 completed surveys were returned (response rate, 82%). In almost half of the time, handoffs that occur in a community pharmacy setting were inaccurate or incomplete. Nearly half of the time handoffs occur in environments full of interruptions and distractions. More than 90% of the respondents indicated that they have undergone no formal training on proper ways of handing off information. Nearly 40% of respondents reported that their pharmacy dispensing technology does not have adequate functionality to support handing off information and that at least 50% of the time, poor handoffs result in additional work to the pharmacist because of the need for complete information before providing patient care. Multivariate analysis showed that being very familiar with patients, lower daily prescription volume, not having a 24-hour operation, and larger percentage of handoffs occurring in a synchronous fashion are all associated with better handoff quality.

Conclusions

Handoffs occur frequently and are problematic in community pharmacies. Current pharmacy environments offer limited support to conduct good handoffs, and as a result, pharmacists report loss of information. This could present as a significant patient safety hazard. Future interventions should target facilitating better communication during shift changes.
Biphasic Renal Sympathetic Response to Hemorrhagic Hypotension in Mice
Authors: Zhang Tao , Tanida Mamoru , Uchida Kunitoshi , Suzuki Yoshiro , Yang Wei , Kuda Yuhichi , Kurata Yasutaka , Tominaga Makoto , Shibamoto Toshishige
Published: April 2017

Aim:

The inhibitory responses of renal sympathetic nerve activity (RSNA) and heart rate (HR) to sustained hemorrhagic shock occurred in anesthetized rats, but have not yet been determined in mice. Here, we investigated the responses of RSNA and HR to hemorrhagic hypotension in anesthetized mice, with an emphasis on the molecule-based mechanism for roles of afferent vagal nerves.

Methods:

RSNA, HR, and mean systemic arterial pressure were continuously measured in male pentobarbital-anesthetized C57BL/6N mice. Hemorrhagic hypotension of 50 mmHg was evoked and maintained for 10 min.

Results:

During hemorrhagic hypotension, RSNA initially increased and then sustainedly decreased, while HR progressively decreased. Vagotomy eliminated the second-phase sympathoinhibition and bradycardia, and carotid sinus denervation with vagotomy abolished the initial renal sympathoexcitation. The renal sympathoinihibition during hemorrhagic hypotension of 50 mmHg was eliminated in mice pretreated with a transient receptor potential vanilloid type 1 channel (TRPV1) inhibitor, capsazepine, and in TRPV1 knockout (TRPV1−/−) mice, but not in TRPV4 knockout mice. The bradycardia response to hemorrhagic hypotension was also absent in TRPV1−/− mice and mice pretreated with capsazepine.

Conclusion:

Hemorrhagic hypotension in anesthetized mice causes biphasic responses of RSNA with an initial increase, followed by a sustained decrease, and a progressive decrease in HR. The initial sympathoexcitation is mediated by carotid sinus baroreceptors, while the later sympathoinhibition and bradycardia are mediated via the TRPV1 signals of vagal afferents.
ICTV Virus Taxonomy Profile: Secoviridae
Authors: Thompson Jeremy R , Dasgupta Indranil , Fuchs Marc , Iwanami Toru , Karasev Alexander V , Petrzik Karel , Sanfaçon Hélène , Tzanetakis Ioannis , van der Vlugt René , Wetzel Thierry , Yoshikawa Nobuyuki ,   ICTV Report Consortium
Published: April 2017

Members of the family Secoviridae are non-enveloped viruses with mono- or bipartite (RNA-1 and RNA-2) linear positive-sense ssRNA genomes with the size of the RNAs combined ranging from 9 to 13.7 kb. They are related to picornaviruses and are classified in the order Picornavirales. The majority of known members infect dicotyledonous plants and many are important plant pathogens (e.g. grapevine fanleaf virus and rice tungro spherical virus). This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) report on the taxonomy of the family Secoviridae available at www.ictv.global/report/secoviridae.
Cadmium-associated differential methylation throughout the placental genome: epigenome-wide association study of two US birth cohorts
Authors: Everson Todd M. , Punshon Tracy , Jackson Brian P. , Hao Ke , Lambertini Luca , Chen Jia , Karagas Margaret R. , Marsit Carmen J.
Published: April 2017

Background

Cadmium (Cd) is a ubiquitous toxicant that during pregnancy can impair fetal development. Cd sequesters in the placenta where it can impair placental function, impacting fetal development. We aimed to investigate Cd-associated variations in placental DNA methylation (DNAM), associations with gene expression, and identify novel pathways involved in Cd-associated reproductive toxicity.

Methods

Using placental DNAM and Cd concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the Rhode Island Child Health Study (RICHS, n=141), we performed an EWAS between Cd and DNAM, adjusting for tissue heterogeneity using a reference-free method. Cohort-specific results were aggregated via inverse variance weighted fixed effects meta-analysis, and variably methylated CpGs were associated with gene expression. We then performed functional enrichment analysis and tests for associations between gene expression and birth metrics.

Results

We identified 17 Cd-associated differentially methylated CpG sites with meta-analysis p-values < 1e-05, two of which were within a 5% false discovery rate (FDR). Methylation levels at 9 of the 17 loci were associated with increased expression of 6 genes (5% FDR):TNFAIP2,EXOC3L4,GAS7,SREBF1,ACOT7, andRORA. Higher placental expression ofTNFAIP2andACOT7, and lower expression ofRORA, were associated with lower birth weight z-scores (p-values < 0.05).

Conclusion

Cd associated differential DNAM and corresponding DNAM-expression associations at these loci are involved in inflammatory signaling and cell growth. The expression levels of genes involved in inflammatory signaling (TNFAIP2,ACOT7, andRORA), were also associated with birth metrics, suggesting a role for inflammatory processes in Cd-associated reproductive toxicity.

Significance

Cadmium is a toxic environmental pollutant that can impair fetal development. The mechanisms underlying this toxicity are unclear, though disrupted placental functions could play an important role. In this study we examined associations between cadmium concentrations and DNA methylation throughout the placental genome, across two US birth cohorts. We observed cadmium-associated differential methylation, and corresponding methylation-expression associations at genes involved in cellular growth processes and/or immune and inflammatory signaling. This study provides supporting evidence that disrupted placental epigenetic regulation of cellular growth and immune/inflammatory signaling could play a role in cadmium associated reproductive toxicity in human pregnancies.
Inference of the Human Polyadenylation Code
Authors: Leung Michael K. K. , Delong Andrew , Frey Brendan J.
Published: April 2017

Processing of transcripts at the 3’-end involves cleavage at a polyadenylation site followed by the addition of a poly(A)-tail. By selecting which polyadenylation site is cleaved, alternative polyadenylation enables genes to produce transcript isoforms with different 3’-ends. To facilitate the identification and treatment of disease-causing mutations that affect polyadenylation and to understand the underlying regulatory processes, a computational model that can accurately predict polyadenylation patterns based on genomic features is desirable. Previous works have focused on identifying candidate polyadenylation sites and classifying sites which may be tissue-specific. What is lacking is a predictive model of the underlying mechanism of site selection, competition, and processing efficiency in a tissue-specific manner. We develop a deep learning model that trains on 3’-end sequencing data and predicts tissue-specific site selection among competing polyadenylation sites in the 3’ untranslated region of the human genome.

Two neural network architectures are evaluated: one built on hand-engineered features, and another that directly learns from the genomic sequence. The hand-engineered features include polyadenylation signals, cis-regulatory elements, n-mer counts, nucleosome occupancy, and RNA-binding protein motifs. The direct-from-sequence model is inferred without prior knowledge on polyadenylation, based on a convolutional neural network trained with genomic sequences surrounding each polyadenylation site as input. Both models are trained using the TensorFlow library.

The proposed polyadenylation code can predict site selection among competing polyadenylation sites in different tissues. Importantly, it does so without relying on evolutionary conservation. The model can distinguish pathogenic from benign variants that appear near annotated polyadenylation sites in ClinVar and inspect the genome to find candidate polyadenylation sites. We also provide an analysis on how different features affect the model’s performance.
Heterogeneous Contribution of Microdeletions in the Development of Common Generalized and Focal epilepsies
Authors: Pérez-Palma Eduardo , Helbig Ingo , Klein Karl Martin , Anttila Verneri , Horn Heiko , Reinthaler Eva Maria , Gormley Padhraig , Ganna Andrea , Byrnes Andrea , Pernhorst Katharina , Toliat Mohammad R. ,   EuroEPINOMICS-RE consortium,   Italian League against Epilepsy Consortium, Saarentaus Elmo , Howrigan Daniel P. , Hoffman Per , Miquel Juan Francisco , Ferrari Giancarlo De , Nürnberg Peter , Lerche Holger , Zimprich Fritz , Neubauer Bern A. , Becker Albert J. , Rosenow Felix , Perucca Emilio , Zara Federico , Weber Yvonne G. , Lal Dennis
Published: April 2017

Background

Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement “hotspot” loci. However, deciphering their role outside hotspots and risk assessment by epilepsy sub-type has not been conducted.

Methods

We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1,366 patients with Genetic Generalized Epilepsy (GGE) plus two sets of additional unpublished genome-wide microdeletions found in 281 Rolandic Epilepsy (RE) and 807 Adult Focal Epilepsy (AFE) patients, totaling 2,454 cases. These microdeletion sets were assessed in a combined analysis and in sub-type specific approaches against 6,746 ethnically matched controls.

Results

When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted-P= 2.00×10-7; OR = 1.89; 95%-CI: 1.51-2.35), where the implicated microdeletions overlapped with rarely deleted genes and those involved in neurodevelopmental processes. Sub-type specific analyses showed that hotspot deletions in the GGE subgroup contribute most of the signal (adjusted-P = 1.22×10-12; OR = 7.45; 95%-CI = 4.20-11.97). Outside hotspot loci, microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted-P = 4.78×10-3; OR = 2.30; 95%-CI = 1.42-3.70), whereas no additional signal was observed for RE and AFE. Still, gene content analysis was able to identify known (NRXN1,RBFOX1andPCDH7) and novel (LOC102723362) candidate genes affected in more than one epilepsy sub-type but not in controls.

Conclusions

Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor to negligible contribution in the etiology of RE and AFE.
Quantifying the efficacy of first aid treatments for burn injuries using mathematical modelling and in vivo porcine experiments
Authors: Simpson Matthew J , McInerney Sean , Carr Elliot J , Cuttle Leila
Published: April 2017

First aid treatment of burn injuries reduces scarring and improves healing. Here, we quantify the efficacy of various first aid treatments by using a mathematical model to describe a suite of experimental data from a series of in vivo porcine experiments. We study a series of consistent burn injuries that are subject to first aid treatments that vary in both the temperature and duration of the first aid treatment. Calibrating the mathematical model to the experimental data provides estimates of the in vivo thermal diffusivity, the rate at which thermal energy is lost to the blood (perfusion), and the heat transfer coefficient controlling the loss of thermal energy at the interface of the fat and muscle layers. A limitation of working with in vivo animal experiments is the difficulty of resolving spatial variations in temperature across the tissues. Here, we use the solution of the calibrated mathematical model to predict and visualise the temperature distribution across the thickness of the tissue during the creation of the burn injury and the application of various first aid treatments. Using this information we propose, and report values for, a novel measure of the potential for tissue damage. This measure quantifies two important aspects that are thought to be related to thermal injury: (i) the volume of tissue that rises above the threshold temperature associated with the accumulation of tissue damage; and, (ii) the duration of time that the tissue remains above this threshold temperature. We conclude by discussing the clinical relevance of our findings.
Leaf rolling as indicator of water stress inCistus incanusfrom different provenances
Authors: Puglielli Giacomo , Gratani Loretta , Varone Laura
Published: April 2017

The relationship between leaf rolling and physiological traits under imposed water stress conditions was analyzed inC. incanusrepresentative saplings collected at different altitudes (i.e. Castelporziano, 41°45′N, 12°26′E, 0 m a.s.l. and Natural Park of Monti Lucretili, 42°33′N, 12°54′E, 750 m a.s.l) and grownex-situ.The hypothesis that leaf rolling reflected physiological changes occurring during water stress irrespective to the different acclimation to cope with water stress was tested.

On the whole, the results show that leaf rolling is associated to an increased sub-stomatal CO2concentration (Ci) and a decreased carboxylation efficiency (Ce). Moreover, leaf rolling inC. incanusleaves might be involved in protecting the PSII complex under water stress during the progressive inhibition of photosynthetic metabolism.
The Ndc80 complex targets Bod1 to human mitotic kinetochores
Authors: Schleicher Katharina , Have Sara ten , Porter Iain M. , Swedlow Jason R.
Published: April 2017

Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of PP2A-B56. This phosphatase controls the amount of phosphorylation of mitotic kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis. The PP2A-B56 regulatory protein Bod1 directly localises to mitotic kinetochores and is required for correct segregation of mitotic chromosomes. In this report, we have probed the spatio-temporal regulation of Bod1 during mitotic progression. Kinetochore localisation of Bod1 increases from nuclear envelope breakdown until metaphase. Phosphorylation of Bod1 at threonine 95 (T95), which increases Bod1’s binding and inhibition of PP2A-B56, peaks in prometaphase, when PP2A-B56 localisation to kinetochores is highest. Kinetochore targeting of Bod1 depends on the outer kinetochore protein Ndc80 and not PP2A-B56. Additionally, Bod1 depletion leads to a defect in the phosphorylation kinetics of Ndc80 at serine 55 (S55) within its N-terminus. Therefore, Ndc80 recruits a phosphatase inhibitor to kinetochores which directly feeds forward to regulate Ndc80 phosphorylation and the stability of the attachments of microtubules to kinetochores.
Metastatic triple-negative breast cancer patient with TP53 tumor mutation experienced 11 months progression-free survival on bortezomib monotherapy without adverse events after ending standard treatments with grade 3 adverse events
Authors: Meißner Tobias , Mark Adam , Williams Casey , Berdel Wolfgang E. , Wiebe Stephanie , Kerkhoff Andrea , Wardelmann Eva , Gaiser Timo , Müller-Tidow Carsten , Rosenstiel Philip , Arnold Norbert , Leyland-Jones Brian , Franke Andre , Stanulla Martin , Forster Michael
Published: April 2017

A triple-negative breast cancer patient had no hereditary BRCA1, BRCA2, or TP53 risk variants. After exhaustion of standard treatments, she underwent experimental treatments and whole-exome sequencing of tumor, blood, and a metastasis. Well-tolerated experimental bortezomib monotherapy was administered for a progression-free period of 11 mo. After progression, treatments were changed and the exome data were evaluated, expanded with RNA and exome sequencing of a late-stage metastasis. In the final stage, eribulin alone and in combination with anthracyclines were administered. While suffering from grade 3 adverse events, skin metastases progressed. She lived 51 mo after initial diagnosis.

Toxicity from anthracyclines and cisplatin may have been due to associated germline variants CBR3 C4Y and V224M and GSTP1 I105V, respectively. Somatic mutations predicted or reported as pathogenic were detected in 38 genes in tumor tissues. All tumor samples harbored the heterozygous TP53 Y220C variant, known to destabilize p53 and down-regulate p53-mediated apoptosis. The success of bortezomib may be explained by the previously reported up-regulation of caspase-mediated apoptosis, which is p53-independent. Phylogenetic analysis of blood, primary tumor, and two metastases inferred an ancestral tumor cell with 12 expressed tumor mutations from which all three tumors may have evolved.

Although our first urgent analysis could only include 40 genes, postmortem analysis uncovered the aggressiveness and suggested experimental therapies including 16 actionable targets, partly validated by immunohistochemistry. Exome and transcriptome analyses yielded comprehensive therapy-relevant information and should be considered for patients at first diagnosis.
Crystallization and biochemical characterization of an archaeal lectin fromMethanococcus voltaeA3
Authors: Sivaji N. , Abhinav K. V. , Vijayan M.
Published: April 2017

A lectin fromMethanococcus voltaeA3 has been cloned, expressed, purified and characterized. The lectin appears to be specific for complex sugars. The protein crystallized in a tetragonal space group, with around 16 subunits in the asymmetric unit. Sequence comparisons indicate the lectin to have a β-prism I fold, with poor homology to lectins of known three-dimensional structure.
Crystal structure of N-hydroxyquinoline-2-carboxamide monohydrate
Authors: Safyanova Inna S. , Ohui Kateryna A. , Omelchenko Iryna V. , Shyshkina Svitlana V.
Published: April 2017

The title compound, C10H8N2O2·H2O, consists of an N-hydroxyquinoline-2-carboxamide molecule in the keto tautomeric form and a water molecule connected through an O—H...O hydrogen bond. The N-hydroxyquinoline-2-carboxamide molecule has a nearly planar structure [maximum deviation = 0.062 (1) Å] and only the hydroxy H atom deviates significantly from the molecule plane. In the crystal, π–π stacking between the aromatic rings [intercentroid distance = 3.887 (1) Å] and intermolecular O—H...O hydrogen bonds organize the crystal components into columns extending along the b-axis direction.
Crystal structures of two alkaline earth (M = Ba and Sr) dimanganese(II) iron(III) tris(orthophosphates)
Authors: Alhakmi Ghaleb , Assani Abderrazzak , Saadi Mohamed , El Ammari Lahcen
Published: April 2017

Two new orthophosphates, BaMn2Fe(PO4)3 [barium dimanganese(II) iron(III) tris(orthophosphate)] and SrMn2Fe(PO4)3 [strontium dimanganese(II) iron(III) tris(orthophosphate)], were synthesized by solid-state reactions. They are isotypic and crystallize in the orthorhombic system with space group type Pbcn. Their crystal structures comprise infinite zigzag chains of edge-sharing FeO6 octahedra (point group symmetry .2.) and Mn2O10 double octahedra running parallel to [001], linked by two types of PO4 tetrahedra. The so-formed three-dimensional framework delineates channels running along [001], in which the alkaline earth cations (site symmetry .2.) are located within a neighbourhood of eight O atoms.
Digital competences of the workforce – a research topic?
Authors: Murawski Matthias , Bick Markus
Published: April 2017

Purpose

Considering working in the digital age, questions on the consequences for the individual workers are, so far, often neglected. The purpose of this paper is to deal with the question of whether the digital competences of the workforce is a research topic. The authors argue for the thesis that it is indeed a research topic.

Design/methodology/approach

In addition to a literature analysis of the top IS, HR, and learning publications, non-scientific sources, as well as the opinions of the authors, are included. The authors’ thesis is challenged through a debate of corresponding pros and cons.

Findings

The definition of digital competences lacks scientific depth. Focussing on the workforce is valid, as a “lifelong” perspective is not mandatory for research. Digital competence research is a multidisciplinary task to which the IS field can make a valuable contribution.

Research limitations/implications

Although relevant references are included, some aspects are mainly driven by the opinions of the authors. The theoretical implications encompass a call for a scientific definition of digital competences. Furthermore, scholars should focus on the competences of the workforce, including occupations, roles, or industries. The authors conclude by providing a first proposal of a research agenda.

Practical implications

The practical implications include the alignment of multiple stakeholders for the design of “digital” curricula and the integration by HR departments of the construct of digital competences, e.g. for compensation matters and job requirements.

Originality/value

This paper is one of very few contributions in the area of the digital competences of the workforce, and it presents a starting point for future research activities.
A big data framework for facilitating product innovation processes
Authors: Zhan Yuanzhu , Tan Kim Hua , Ji Guojun , Chung Leanne , Tseng Minglang
Published: April 2017

Purpose

The purpose of this paper is to suggest how firms could use big data to facilitate product innovation processes, by shortening the time to market, improving customers’ product adoption and reducing costs.

Design/methodology/approach

The research is based on a two-step approach. First, this research identifies four potential key success factors for organisations to integrate big data in accelerating their product innovation processes. The proposed factors are further examined and developed by conducting interviews with different organisation experts and academic researchers. Then a framework is developed based on the interview outputs. The framework sets out the key success factors involved in leveraging big data to reduce lead times and costs in product innovation processes.

Findings

The three determined key success factors are: accelerated innovation process; customer connection; and an ecosystem of innovation. The authors believe that the developed framework based on big data represents a paradigm shift. It can help firms to make new product development dramatically faster and less costly.

Research limitations/implications

The proposed accelerated innovation processes demand a shift in traditional organisational culture and practices. It is, though, meaningful only for products and services with short life cycles. Moreover, the framework has not yet been widely tested.

Practical implications

This paper points to the vital role of big data in helping firms to accelerate product innovation processes. First of all, it allows organisations to launch new products to market as quickly as possible. Second, it helps organisations to determine the weaknesses of the product earlier in the development cycle. Third, it allows functionalities to be added to a product that customers are willing to pay a premium for, while eliminating features they do not want. Last, but not least, it identifies and then prioritises customer needs for specific markets.

Originality/value

The research shows that firms could harvest external knowledge and import ideas across organisational boundaries. An accelerated innovation process based on big data is characterised by a multidimensional process involving intelligence efforts, relentless data collection and flexible working relationships with team members.
Employees’ reactions to IT-enabled process innovations in the age of data analytics in healthcare
Authors: Bala Hillol , Venkatesh Viswanath
Published: April 2017

Purpose

Interorganizational business process standards (IBPS) are IT-enabled process specifications that standardize, streamline, and improve business processes related to interorganizational relationships. There has been much interest in IBPS as organizations from different industries implement these process standards that lead to successful organizational outcomes by integrating and standardizing intra- and inter-organizational business processes. These process standards enable data analytics capabilities by facilitating new sources of interorganizational process data. The purpose of this paper is to unearth employees’ reactions to a new type of supply chain process innovations that involved an implementation of new IBPS, a supply chain management (SCM) system, and associated analytics capabilities.

Design/methodology/approach

The authors gathered and analyzed qualitative data for a year from the employees of a healthcare supplier, a high-tech manufacturing organization, during the implementation of a SCM system and RosettaNet-based IBPS.

Findings

In what the authors termed the initiation stage, there was quite a bit of confusion and unrest among employees regarding the relevance of the new process standards and associated analytics capabilities. With the passage of time, in the institutionalization stage, although the situation improved slightly, employees found workarounds that allowed them to appropriate just part of specific processes and the analytics capabilities. Finally, once routinized, employees felt comfortable in the situation but still did not appropriate the new supply chain processes faithfully. Overall, employees’ reactions toward the SCM system and associated analytics capabilities were different from their reactions toward the new business processes.

Originality/value

The paper contributes to the literature by offering novel insights on how employees react to and appropriate process innovations that change their work processes.
Influence of organizational culture and leadership style on employee satisfaction, commitment and motivation in the educational sector in Qatar
Authors: Al-Sada Maryam , Al-Esmael Bader , Faisal Mohd. Nishat
Published: April 2017

Purpose

The purpose of this paper is to explore the influence of organizational culture and leadership style on employees’ job satisfaction, organizational commitment and work motivation in the educational sector in the state of Qatar.

Design/methodology/approach

The study was conducted using a questionnaire with a sample size of 364 employees in the educational sector in Qatar. Data were analyzed using factor analysis, Pearson correlation and multiple linear regression, were employed to examine the relationships between the variables under investigation.

Findings

Significant positive relationships were observed between supportive culture and job satisfaction; supportive culture and organizational commitment; participative-supportive leadership and job satisfaction; directive leadership and job satisfaction; job satisfaction and work motivation; job satisfaction and organizational commitment.

Practical implications

This paper would help managers and policy-makers in the education sector to develop a better understanding of organizational culture and leadership styles and their influence on employee satisfaction, commitment and motivation.

Originality/value

The education sector is experiencing a fast growth in Qatar due to significant outlays by the government. This study is among the first in the country to understand the variables affecting employees’ performance in education sector.
Leader narcissism and subordinate embeddedness
Authors: Erkutlu Hakan Vahit , Chafra Jamel
Published: April 2017

Purpose

The purpose of this paper is to examine the relationship between leader narcissism (LN) and subordinate embeddedness as well as to test the moderating roles of moral attentiveness (MA) and behavioral integrity (BI) on that very relationship.

Design/methodology/approach

Data were collected from 19 five-star hotels in Turkey. The sample included 1,613 employees along with their first-line managers. The moderating roles of MA and BI on the LN and subordinate embeddedness relationship were tested using the moderated hierarchical regression analysis.

Findings

The moderated hierarchical regression analysis results revealed that there was a significant negative relationship between LN and subordinate embeddedness. In addition, this very relation was weaker when both MA and BI were higher than when they were lower.

Practical implications

This study showed that employee perception of LN decreased employee’s job embeddedness (JE). The study findings point out the importance of reinforcing an ethical context as well as the importance of leader selection. Specifically, in order to ensure that narcissistic leaders do not thrive in organizations, it is significant to maintain an ethical context. Whether the context is ethical, unethical, or interpersonally ineffective, behaviors will likely be more salient and evaluated more negatively by coworkers. On the other hand, when narcissistic leaders are inserted in organizations with unethical contexts, the result is a perfect storm that reinforces narcissists’ unethical behaviors and potentially promotes narcissistic leaders. Still, it is likely that narcissists exhibit unethical and ineffective behaviors regardless of the ethical context, meaning that an ethical context does not necessarily prevent narcissistic leaders from behaving ineffectively and unethically. Thus, the implementation of management selection geared toward targeting precursors of unethical behaviors is an equally vital strategy to prevent unethical behaviors on the part of organizational leaders.

Originality/value

The study provides new insights into the influence that LN may have on subordinate JE and the moderating roles of MA and BI in the link between LN and JE. The paper also offers a practical assistance to employees in the hospitality industry and their leaders interested in building trust and increasing leader-subordinate relationship and JE.