bluuebunny/crossref_metadata_2025 huggingface dataset:
Rib Fractures Mimicking Bone Metastases in 18F-PSMA-1007 PET/CT for Prostate Cancer
Authors: Panagiotidis Emmanouil , Paschali Anna , Giannoula Evanthia , Chatzipavlidou Vasiliki
Published: October 2018

Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein that is overexpressed in prostate cancer cells. It is also expressed in other normal tissues and several other malignant and benign diseases. We present a case of a 69-year-old man with history of prostate adenocarcinoma who underwent 18F-PSMA-1007 PET/CT due to suspected biochemical recurrence. PET/CT showed 18F-PSMA-1007 uptake in healing rib fractures with no other pathologic findings. Clinicians reporting 18F-PSMA-1007 PET/CT should be aware of this potential pitfall, especially in nontypical trauma pattern (eg, solitary osseous lesion) mimicking bone metastases.
Increased Muscular MDP Activity in the Lower Extremities Caused by Multiple Arterial Thromboses
Authors: Shao Fuqiang , Li Na , Xie Peng , Li Yiman , Zhang Heng
Published: October 2018

Many reasons could lead to abnormal increased extraosseous tracer uptake on 99mTc-MDP bone scintigraphy. A 75-year-old man was referred a bone scintigraphy to evaluate his chest pain. The images revealed rib fractures. In addition, increased MDP activity in the muscle of the lower extremities was noted. The abnormal increased uptake in the muscles was likely related to the arterial thromboses revealed by vascular ultrasonography. The patient received interventional embolectomy.
Current Evidence in Cardiothoracic Imaging
Authors: Schwartz Fides R. , Koweek Lynne M. , Nørgaard Bjarne L.
Published: October 2018

High-accuracy diagnostic imaging is needed to diagnose and manage coronary artery disease as well as to allow risk stratification for future events. Advancements in multidetector computed tomography and image postprocessing allow for routine computed tomography coronary angiography to provide anatomic luminal assessment similar to invasive coronary angiography, and, similarly, computational fractional flow reserve derived from computed tomography facilitates determination of hemodynamically relevant stenosis comparable to invasive fractional flow reserve. In this review article, we describe the diagnostic performance and the potential impact of fractional flow reserve derived from computed tomography in clinical practice.
Computed Tomography and Magnetic Resonance Imaging of Cardiovascular Anomalies Associated With Turner Syndrome
Authors: Sigakis Christopher J.G. , Browne Lorna P. , Bang Tami , Khanna Amber , Pruente Ryan , Vargas Daniel
Published: October 2018

Cardiovascular imaging plays a central role in the diagnosis, management, and follow-up of congenital and acquired cardiovascular disease in patients with Turner syndrome. Cardiovascular defects in this population may affect a single component of the cardiovascular system or exist in combination with other anomalies, and, they may present early in life or remain occult into adulthood. Careful screening and surveillance imaging are necessary for the early detection and management of cardiovascular defects, especially in cases wherein early intervention may be necessary to prevent a serious cardiovascular outcome. It is critical that these patients are followed-up by specialists aware of their unique cardiovascular risk factors and that imaging examinations are interpreted by cardiovascular imagers familiar with the variety of anomalies that may be present and/or warrant imaging follow-up. Herein, we review common and uncommon cardiovascular anomalies associated with Turner syndrome and provide an image-based approach to analyzing key cardiothoracic findings that should be assessed in this patient population. Current imaging recommendations and guidelines for various anomalies will also be reviewed.
Strategies for Complex Scalp Reconstruction in Patients With Poor Recipient Vessels
Authors: Fodor Lucian , Fodor Marius , Sobec Raluca , Sita Laura , Florian Ioan Stefan
Published: October 2018

Complex scalp defects with poor recipient vessels represent a challenge for plastic surgeons. In these cases, free flaps are the last resort for solving the problem. The authors present 5 difficult cases with complex large scalp and calvarium defects with unsuitable small recipient vessels for anastomoses. For these cases, the lesser saphenous vein was harvested and used as an interposition graft between the external carotid artery, the jugular vein, and the flap. Latissimus Dorsi, Anterolateral Thigh, and serratus anterior were the flaps used for reconstruction. Cranioplasty was simultaneously performed in 4 cases. The scalp defects varied from 83 to 288 cm2. All flaps survived. In 1 case (extended Latissimus Dorsi) there was local infection and wound dehiscence with marginal flap necrosis that required flap readvancement. In conclusion, end-to-end anastomosis to the external carotid artery offers strong outflow through the vein graft and flap. A large vein graft allows good outflow and is more resistant to the pressure of the skin envelope. Anastomosis to large neck vessels (internal or external jugular) facilitates drainage since there is also an aspiration effect due to the venous flow circulation through it.
Examining Occupational Therapists' Awareness of Medical Fitness-to-Drive Legislation Using a Knowledge-to-Action Approach
Authors: Sangrar Ruheena , Griffith Lauren E. , Letts Lori , Vrkljan Brenda
Published: October 2018

One Canadian province now requires occupational therapists (OTs) to report medically at-risk drivers to the transportation authority. This study examined OTs' legal and professional responsibilities with regard to medical fitness to drive. Two knowledge translation models guided the study design. Semi-structured interviews were conducted with 7 OTs, a geriatrician, as well as representatives from professional regulatory organizations and the licensing bureau. Emergent themes highlight gaps in the translation of knowledge specific to professional responsibilities as well as ethical risks to client rapport. Further education on relevant policies is suggested and changes to existing resources that support clinical practice.
Management of Conditions Associated With Aging and Older Adults Using Therapeutic Electromagnetic Energy
Authors: Bridges Michael , Hilliard Jeremy , Chui Kevin
Published: October 2018

Objective:

To assess the effectiveness of therapeutic electromagnetic energy in the management of conditions associated with an aging and older adult population.

Methods:

A systematic review of literature from 2008 to 2018 was completed in PubMed, CINAHL, and Science Direct. We also reviewed sources to identify additional relevant studies. Studies in this review were limited to randomized controlled trials that evaluated the effects of shortwave diathermy or pulsed electromagnetic energy units in treating conditions commonly experienced by adults older than 50 years. Study quality was determined using the Physiotherapy Evidence Database (PEDro) classification scale.

Results:

Fifteen randomized controlled trials met our search criteria. Multiple pathologies were evaluated with the studies examining treatment effects of knee osteoarthritis (n = 12), frozen shoulder (n = 1), postoperative rotator cuff repair (n = 1), and postmenopausal osteoporosis (n = 1). Of the 12 studies that examined knee osteoarthritis, 2 compared pulsed electromagnetic field to placebo or sham, 2 compared the addition of shortwave diathermy to strengthening activities alone, 3 evaluated shortwave diathermy dosage, 3 compared shortwave diathermy to other modalities, and 2 reviewed the benefits of adding pulsed electromagnetic field to other modalities and exercise. Due to the high degree of variability in protocols and outcome measures among studies, meta-analysis was not appropriate. Studies on knee osteoarthritis reported that the use of pulsed electromagnetic field and shortwave diathermy provides statistically significant improvement in pain and function compared with placebo, sham, or control, although there appears to be no benefit in using either form of electromagnetic radiation in addition to or in place of another modality. It also appears that dosage does not significantly change short-term outcomes. These findings are similar to those identified in other recently published systematic reviews that focused exclusively on knee osteoarthritis. Subjects with shoulder pathologies showed improvements in pain, mobility (range of motion), function, activities of daily living, and pain medication usage with pulsed electromagnetic field or shortwave diathermy. Changes in postmenopausal bone density were similar when pulsed electromagnetic field was compared with medication.

Conclusion:

Shortwave diathermy and pulsed electromagnetic frequency demonstrate similar clinical benefits as other modalities for improving pain, function, and quality of life in the short-term. Further research is needed to better evaluate the parameters of electromagnetic energy and effects for other conditions commonly affecting aging and older adults and at other treatment sites on the body.
Medical Nutrition Therapy for Symptom Management in Adults With Gastroparesis
Authors: Fisher Kelly , Touger-Decker Riva , Ziegler Jane
Published: October 2018

Gastroparesis is a complex, difficult-to-manage condition of delayed gastric emptying that can result in a debilitating set of symptoms. Diagnosis involves objective measurement of gastric emptying delay. Treatment success is typically based on subjective improvement in patient-reported symptoms. Medical nutrition therapy is recommended as a primary management strategy, but patient compliance is an issue. Medical nutrition therapy recommendations are largely based on empirical evidence extrapolated from the physiological effect of food on gastric emptying in the absence of interventional trials. The purpose of this article is to present and assess available evidence on MNT strategies for symptom relief in adult patients with gastroparesis and provide an application to practice.
Mechanisms of Injury in APOL1-associated Kidney Disease
Authors: Ma Lijun , Divers Jasmin , Freedman Barry I.
Published: October 2018

Background.

An improved understanding of the pathogenesis in apolipoprotein L1 (APOL1) gene–associated chronic kidney disease (CKD) arose from observations in kidney transplantation. APOL1 genotyping could soon improve the safety of living kidney donation in individuals with recent African ancestry and alter the allocation of deceased donor kidneys.

Methods.

This article reviews the potential mechanisms that underlie development of APOL1-associated nephropathy. Roles for circulating APOL1 protein versus intrinsic renal expression of APOL1 are discussed, as well as the requirement for modifying genetic and/or environmental factors.

Results.

Abundant evidence supports local kidney production of APOL1 renal-risk variant protein in the development of nephropathy; this is true in both native kidney disease and after renal transplantation. Only a minority of kidneys from individuals with APOL1 high-risk genotypes will develop CKD or manifest shorter renal allograft survival after transplantation. Therefore, modifying factors that explain why only a subset of kidneys develops nephropathy remain critical to identify. It appears likely that environmental exposures, as opposed to major APOL1-second gene interactions, will prove to be stronger modifiers of the risk for nephropathy.

Conclusions.

The evolving understanding of the pathogenesis in APOL1-associated nephropathy will identify biomarkers predicting nephropathy in individuals at high genetic risk and lead to novel therapies to prevent or slow native CKD progression and prolong survival of transplanted kidneys. In the interim, the National Institutes of Health–sponsored “APOL1 Long-term Kidney Transplantation Outcomes” Network will determine whether APOL1 genotyping in individuals with recent African ancestry improves outcomes and safety in kidney transplantation.
Mild, moderate and severe: terminology implications for clinical and experimental traumatic brain injury
Authors: Yamamoto Satoshi , Levin Harvey S. , Prough Donald S.
Published: October 2018

Purpose of review

When describing clinical or experimental traumatic brain injury (TBI), the adjectives ‘mild,’ ‘moderate’ and ‘severe’ are misleading. ‘Mild’ clinical TBI frequently results in long-term disability. ‘Severe’ rodent TBI actually resembles mild or complicated mild clinical TBI.

Recent findings

Many mild TBI patients appear to have recovered completely but have postconcussive symptoms, deficits in cognitive and executive function and reduced cerebral blood flow. After moderate TBI, 31.8% of patients died or were discharged to skilled nursing or hospice. Among survivors of moderate and severe TBI, 44% were unable to return to work. On MRI, 88% of mild TBI patients have evidence of white matter damage, based on measurements of fractional anisotropy and mean diffusivity/apparent diffusion coefficient. After sports concussion, clinically recovered patients have abnormalities in functional connectivity on functional MRI. Methylphenidate improved fatigue and cognitive impairment and, combined with cognitive rehabilitation, improved memory and executive functioning. In comparison to clinical TB, because the entire spectrum of experimental rodent TBI, although defined as moderate or severe, more closely resembles mild or complicated mild clinical TBI.

Many patients after mild or moderate TBI suffer long-term sequelae and should be considered a major target for translational research. Treatments that improve outcome in rodent TBI, even when the experimental injuries are defined as severe, might be most applicable to mild or moderate TBI.
Oliver Heaviside: an accidental time traveller
Authors: Nahin Paul J.
Published: October 2018

A little discussed aspect of Heaviside's work in electromagnetics concerned faster-than-light (FTL) charged particles, precursors to the hypothetical tachyon and his discovery that such motion should produce a characteristic radiation signature (now calledCherenkov radiation). When Heaviside wrote, the time travel implications of FTL were not known (Einstein was still a teenager), and in this paper some speculations are offered on what Heaviside would have thought of FTL time travel, and of the associated (now classic) time travel paradoxes, including the possibility (or not) of sending information into the past.

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
Magnetoelectric multipoles in metals
Authors: Thöle Florian , Spaldin Nicola A.
Published: October 2018

In this paper, we demonstrate computationally the existence of magnetoelectric multipoles, arising from the second-order term in the multipole expansion of a magnetization density in a magnetic field, in non-centrosymmetric magnetic metals. While magnetoelectric multipoles have long been discussed in the context of the magnetoelectric effect in non-centrosymmetric magnetic
insulators
, they have not previously been identified in metallic systems, in which the mobile carriers screen any electrical polarization. Using first-principles density functional calculations, we explore three specific systems: first, a conventional centrosymmetric magnetic metal, Fe, in which we break inversion symmetry by introducing a surface, which both generates magnetoelectric monopoles and allows a perpendicular magnetoelectric response. Next, the hypothetical cation-ordered perovskite, SrCaRu
2
O
6
, in which we study the interplay between the magnitude of the polar symmetry breaking and that of the magnetic dipoles and multipoles, finding that both scale proportionally to the structural distortion. Finally, we identify a hidden
antiferromultipolar
order in the non-centrosymmetric, antiferromagnetic metal Ca
3
Ru
2
O
7
, and show that, while its competing magnetic phases have similar magnetic dipolar structures, their magnetoelectric multipolar structures are distinctly different, reflecting the strong differences in transport properties.

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
The Noether current in Maxwell's equations and radiation under symmetry breaking
Authors: Sinha Dhiraj , Amaratunga Gehan
Published: October 2018

Symmetries in physical systems are defined in terms of conserved Noether Currents of the associated Lagrangian. In electrodynamic systems, global symmetry is defined through conservation of charges, which is reflected in gauge symmetry; however, loss of charges from a radiating system can be interpreted as localized loss of the Noether current which implies that electrodynamic symmetry has been locally broken. Thus, we propose that global symmetries and localized symmetry breaking are interwoven into the framework of Maxwell's equations which appear as globally conserved and locally non-conserved charges in an electrodynamic system and define the geometric topology of the electromagnetic field. We apply the ideas in the context of explaining radiation from dielectric materials with low physical dimensions. We also briefly look at the nature of reversibility in electromagnetic wave generation which was initially proposed by Planck, but opposed by Einstein and in recent years by Zoh.

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
Measuring the shielding properties of flexible or rigid enclosures for portable electronics
Authors: Duffy A. P. , Arihilam E. , Sasse Hugh , Parker Sarah , Armstrong R. , Wainwright N. , Steggles S. , Thomas T.
Published: October 2018

Heaviside, in volume 1 of
Electromagnetic theory
, considered shielding of conducting materials in the form of attenuation. This treatment is still significant in the understanding of shielding effectiveness. He also considered propagation of electromagnetic waves in free-space. What Heaviside (1850–1925) could never have imagined is that 125 years later, there would be devices we know as mobile phones (or cell phones, handies, etc.) with capabilities beyond the dreams of the great science fiction writers of the day like H. G. Wells (1866–1949) or Jules Verne (1828–1905). More than this, that there would be a need for law enforcement agencies, among others, to use electromagnetically shielded enclosures to protect electronic equipment from communicating with the ‘outside world’. Nevertheless, Heaviside's work is still fundamental to the developments discussed here. This paper provides a review of Heaviside's view of shielding and propagation provided in volume 1 of
Electromagnetic theory
and develops that to the design of new experiments to test the shielding of these portable enclosures in a mode-stirred reverberation chamber, a test environment that relies entirely on reflections from conducting surfaces for its operation.

This article is part of the theme issue ‘Celebrating 125 years of Oliver Heaviside's ‘Electromagnetic Theory’’.
Everybody hands-on to avoid ESKAPE: effect of sustained hand hygiene compliance on healthcare-associated infections and multidrug resistance in a paediatric hospital
Authors: De la Rosa-Zamboni Daniela , Ochoa Sara A. , Laris-González Almudena , Cruz-Córdova Ariadnna , Escalona-Venegas Gerardo , Pérez-Avendaño Georgina , Torres-García Margarita , Suaréz-Mora Roselia , Castellanos-Cruz Carmen , Sánchrez-Flores Yadhira V. , Vázquez-Flores Adalberto , Águila-Torres Rosalinda , Parra-Ortega Israel , Klünder-Klünder Miguel , Arellano-Galindo José , Hernández-Castro Rigoberto , Xicohtencatl-Cortes Juan
Published: October 2018

Purpose. Hand hygiene is the most important strategy for preventing healthcare-associated infections (HCAIs); however, the impact of hand hygiene in middle-income countries has been poorly described. In this work, we describe the impact of the programme ‘Let’s Go for 100’ on hand hygiene adherence, HCAIs rates and multidrug-resistant (MDR) bacteria, including the molecular typing of methicillin-resistant Staphylococcus aureus (MRSA) strains.

Methodology. A multimodal, hospital-wide hand hygiene programme was implemented from 2013. ‘Let’s Go for 100’ involved all healthcare workers and encompassed education, awareness, visual reminders, feedback and innovative strategies. Monthly hand hygiene monitoring and active HCAI surveillance were performed in every ward. Molecular typing of MRSA was analysed by pulsed-field gel electrophoresis (PFGE).

Results/Key findings. Hand hygiene adherence increased from 34.9 % during the baseline period to 80.6 % in the last 3 months of this study. The HCAI rate decreased from 7.54 to 6.46/1000 patient-days (P=0.004). The central line-associated bloodstream infection (CLABSIs) rate fell from 4.84 to 3.66/1000 central line-days (P=0.05). Negative correlations between hand hygiene and HCAIs rates were identified. The attack rate of MDR-ESKAPE group bloodstream infections decreased from 0.54 to 0.20/100 discharges (P=0.024). MRSA pulsotypes that were prevalent during the baseline period were no longer detected after the 5th quarter, although new strains were identified.

Conclusions. A multimodal hand hygiene programme in a paediatric hospital in a middle-income country was effective in improving adherence and reducing HCAIs, CLABSIs and MDR-ESKAPE bloodstream infections. Sustaining hand hygiene adherence at a level of >60 % for one year limited MRSA clonal transmission.
Species limits in butterflies (Lepidoptera: Nymphalidae): Reconciling classical taxonomy with the multispecies coalescent
Authors: Matos-Maraví Pável , Wahlberg Niklas , Antonelli Alexandre , Penz Carla M.
Published: October 2018

Species delimitation is at the core of biological sciences. During the last decade, molecular-based approaches have advanced the field by providing additional sources of evidence to classical, morphology-based taxonomy. However, taxonomy has not yet fully embraced molecular species delimitation beyond threshold-based, single-gene approaches, and taxonomic knowledge is not commonly integrated to multi-locus species delimitation models. Here we aim to bridge empirical data (taxonomic and genetic) with recently developed coalescent-based species delimitation approaches. We use the multispecies coalescent model as implemented in two Bayesian methods (DISSECT/STACEY and BP&P) to infer species hypotheses. In both cases, we account for phylogenetic uncertainty (by not using any guide tree) and taxonomic uncertainty (by measuring the impact of using or not a priori taxonomic assignment to specimens). We focus on an entire Neotropical tribe of butterflies, the Haeterini (Nymphalidae: Satyrinae). We contrast divergent taxonomic opinion—splitting, lumping and misclassifying species—in the light of different phenotypic classifications proposed to date. Our results provide a solid background for the recognition of 22 species. The synergistic approach presented here overcomes limitations in both traditional taxonomy (e.g. by recognizing cryptic species) and molecular-based methods (e.g. by recognizing structured populations, and not raise them to species). Our framework provides a step forward towards standardization and increasing reproducibility of species delimitations.
Genome-wide association and functional studies identify 46 novel loci for alcohol consumption and suggest common genetic mechanisms with neuropsychiatric disorders
Authors: Evangelou Evangelos , Gao He , Chu Congying , Ntritsos Georgios , Blakeley Paul , Butts Andrew R. , Pazoki Raha , Suzuki Hideaki , Koskeridis Fotios , Yiorkas Andrianos M. , Karaman Ibrahim , Elliott Joshua , Aeschbacher Stefanie , Bartz Traci M. , Baumeister Sebastian E. , Braund Peter S. , Brown Michael R. , Brody Jennifer A. , Clarke Toni-Kim , Dimou Niki , Faul Jessica D. , Homuth Georg , Jackson Anne U. , Kentistou Katherine A. , Joshi Peter K. , Lemaitre Rozenn N. , Lind Penelope A. , Lyytikäinen Leo-Pekka , Mangino Massimo , Milaneschi Yuri , Nelson Christopher P. , Nolte Ilja M. , Perälä Mia-Maria , Polasek Ozren , Porteous David , Ratliff Scott M. , Smith Jennifer A. , Stančáková Alena , Teumer Alexander , Tuominen Samuli , Thériault Sébastien , Vangipurapu Jagadish , Whitfield John B. , Wood Alexis , Yao Jie , Yu Bing , Zhao Wei , Arking Dan E. , Auvinen Juha , Liu Chunyu , Männikkö Minna , Risch Lorenz , Rotter Jerome I. , Snieder Harold , Veijola Juha , Blakemore Alexandra I. , Boehnke Michael , Campbell Harry , Conen David , Eriksson Johan G. , Grabe Hans J. , Guo Xiuqing , Harst Pim van der , Hartman Catharina A. , Hayward Caroline , Heath Andrew C. , Jarvelin Marjo-Riitta , Kähönen Mika , Kardia Sharon LR , Kühne Michael , Kuusisto Johanna , Laakso Markku , Lahti Jari , Lehtimäki Terho , McIntosh Andrew M. , Mohlke Karen L. , Morrison Alanna C. , Martin Nicholas G. , Oldehinkel Albertine J. , Penninx Brenda WJH , Psaty Bruce M. , Raitakari Olli T. , Rudan Igor , Samani Nilesh J. , Scott Laura J. , Spector Tim D. , Verweij Niek , Weir David R. , Wilson James F. , Levy Daniel , Tzoulaki Ioanna , Bell Jimmy D. , Matthews Paul , Rothenfluh Adrian , Desrivières Sylvane , Schumann Gunter , Elliott Paul
Published: October 2018

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. We conducted a genome-wide association study (GWAS) of alcohol use in ~480,000 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 novel, common loci, and investigated their potential functional significance using magnetic resonance imaging data, gene expression and behavioral studies inDrosophila. Our results identify new genetic pathways associated with alcohol consumption and suggest common genetic mechanisms with several neuropsychiatric disorders including schizophrenia.
GRIPT: A novel case-control analysis method for Mendelian disease gene discovery
Authors: Wang Jun , Zhao Li , Wang Xia , Chen Yong , Xu Mingchu , Soens Zachry T. , Ge Zhongqi , Wang Peter Ronghan , Wang Fei , Chen Rui
Published: October 2018

Despite rapid progress of next-generation sequencing (NGS) technologies, the disease-causing genes underpinning about 50% of Mendelian diseases remain elusive. One main challenge is the high genetic heterogeneity of Mendelian diseases in which similar phenotypes are caused by different genes and each gene only accounts for a small proportion of the patients. To overcome this gap, we developed a novel method, the Gene Ranking, Identification and Prediction Tool (GRIPT), for performing case-control analysis of NGS data. Analyses of simulated and real datasets show that GRIPT is well-powered for disease gene discovery, especially for diseases with high locus heterogeneity.
Countering Cross-Individual Variance in Event Related Potentials with Functional Profiling
Authors: Alsufyani Abdulmajeed , Zoumpoulaki Alexia , Filetti Marco , Janssen Dirk P. , Bowman Howard
Published: October 2018

In this study, a simple method called the Weight Template (WT) is proposed for classifying brain responses of individuals into deceiving and non-deceiving. The performance of our method was evaluated on a number of identity deception data sets and on artificial EEG data sets. A comparison was made with a standard method used to measure P3 presence, called Peak-to-Peak. In the real experimental data, the WT showed higher performance in terms of sensitivity and specificity. In the artificial EEG data, in ERPs with low Signal-to-Noise Ratio (SNR), the WT was more resistant to noise and provided more accurate measures.

Highlights

We propose a method for classifying ERPs of the P3 Concealed Information Tests.

The new method is based on computing a weighted template (WT) for each individual.

The WT is used to characterize the shape of each individual’s P3.

The performance of the WT was compared with the standard Peak-to-Peak method.

The WT showed higher performance in terms of sensitivity and specificity.
Fusion of DARPin to aldolase enables visualization of small protein by cryoEM
Authors: Yao Qing , Weaver Sara J. , Mock Jee-Young , Jensen Grant J.
Published: October 2018

In recent years, solving protein structures by single particle cryogenic electron microscopy (cryoEM) has become a crucial tool in structural biology. While exciting progress is being made towards the visualization of smaller and smaller macromolecules, the median protein size in both eukaryotes and bacteria is still beyond the reach of single particle cryoEM. To overcome this problem, we implemented a platform strategy in which a small protein target was rigidly attached to a large, symmetric base via a selectable adapter. Seven designs were tested. In the best construct, a designed ankyrin repeat protein (DARPin) was rigidly fused to tetrameric rabbit muscle aldolase through a helical linker. The DARPin retained its ability to bind its target, the 27 kDa green fluorescent protein (GFP). We solved the structure of this complex to 3.0 Å resolution overall, with 5 to 8 Å resolution in the GFP region. As flexibility in the DARPin limited the overall resolution of the target, we describe strategies to rigidify this element.

Author summary

Single particle cryogenic electron microscopy (cryoEM) is a technique that uses images of purified proteins to determine their atomic structure. Unfortunately, the majority of proteins in the human and bacterial proteomes are too small to be analyzed by cryoEM. Over the years, several groups have suggested the use of a platform to increase the size of small protein targets. The platform is composed of a large protein base and a selectable adapter that binds the target protein. Here we report a platform based on tetrameric rabbit muscle aldolase that is fused to a Designed Ankyrin Repeat Protein (DARPin). Phage display libraries can be used to generate DARPins against target proteins. The residues mutated in a phage display library to generate a DARPin against a new target do not overlap with the DARPin-base fusion in the platform, thus changing the DARPin identity will not disrupt the platform design. The DARPin adapter used here is capable of binding Green Fluorescent Protein (GFP). We report the structure of GFP to 5 to 8 Å local resolution by single particle cryoEM. Our analysis demonstrates that flexibility in the DARPin-aldolase platform prevents us from achieving higher resolution in the GFP region. We suggest changes to the DARPin design to rigidify the DARPin-aldolase platform. This work expands on current platforms and paves a generally applicable way toward structure determination of small proteins by cryoEM.
Comparative transcriptome analysis reveals higher expression of stress and defense responsive genes in dwarf soybeans obtained from the crossing of G. max and G. soja
Authors: Ban Yong-Wook , Roy Neha Samir , Yang Heejung , Choi Hong-Kyu , Kim Jin-Hyun , babu Prakash , Ha Keon-Soo , Ham Jin-Kwan , Park Kyong Cheul , Choi Ik-Young
Published: October 2018

Plant height is an important component of plant architecture and significantly affects crop breeding practices and yield. We obtained a few segregated dwarf soybeans in the populations derived from the crossing of Glycine max var. Peking and Glycine soja var. IT182936 in an F5 RIL population. These dwarf soybeans may be useful genetic resources for plant breeders, geneticists and biologists. We attempted to find differentially expressed genes to classify and understand the regulation of genes related to plant growth in mutant dwarf soybeans, which appeared in the F5 generation. Using the Illumina high-throughput platform, transcriptomes were generated and compared among normal and dwarf soybeans in triplicate. We found complex relationship of the expressed genes to plant growth. There are highly significantly up-/downregulated genes according to the comparison of gene expression in normal and dwarf soybeans. The genes related to disease and stress responses were found to be upregulated in dwarf soybeans. Such over-expression of disease resistance and other immune response genes was targeted to understand how the immune genes regulate the response of plant growth. In addition, photosynthesis-related genes showed very low expression in dwarf lines. The transcriptome expression and genes classified as related to plant growth may be useful resources to researchers studying plant growth.
Umbelliprenin isolated from Ferula sinkiangensis inhibits tumor growth and migration through the disturbance of Wnt signaling pathway in gastric cancer
Authors: Zhang Lijing , Sun Xiaobo , Si Jianyong , Li Guangzhi , Cao Li
Published: October 2018

The traditional herb medicine Ferula sinkiangensis K. M. Shen (F. sinkiangensis) has been used to treat stomach disorders in Xinjiang District for centuries. Umbelliprenin is the effective component isolated from F. sinkiangensis which is particularly found in plants of the family Ferula. We previously reported the promising effects of Umbelliprenin against gastric cancer cells, but its anti-migration effect remained unknown. Here we investigated the anti-migration effect and mechanism of Umbelliprenin in human gastric cancer cells. In SRB assay, Umbelliprenin showed cytotoxic activities in the gastric cancer cell lines AGS and BGC-823 in a dose-and-time-dependent manner, while it showed lower cytotoxic activity in the normal gastric epithelium cell line GES-1. During transwell, scratch and colony assays, the migration of tumor cells was inhibited by Umbelliprenin treatment. The expression levels of the Wnt-associated signaling pathway proteins were analyzed with western blots, and the results showed that Umbelliprenin decreased the expression levels of proteins of the Wnt signalling pathway, such as Wnt-2, β-catenin, GSK-3β, p-GSK-3β, Survivin and c-myc. The translocation of β-catenin to the nucleus was also inhibited by Umbelliprenin treatment. In TCF reporter assay, the transcriptional activity of T-cell factor/lymphoid enhancer factor (TCF/LEF) was decreased after Umbelliprenin treatment. Thein vivo results suggested that Umbelliprenin induced little to no harm in the lung, heart and kidney. Overall, these data provided evidence that Umbelliprenin may inhibit the growth, invasion and migration of gastric cancer cells by disturbing the Wnt signaling pathway.
One of the gang: social group dynamics in a juvenile passerine bird
Authors: Franks Victoria R. , Ewen John G. , McCready Mhairi , Marcus Rowcliffe J. , Smith Donal , Thorogood Rose
Published: October 2018

Living in groups comes with many potential benefits, especially for juveniles. Naïve individuals may learn how to forage, or avoid predators through group vigilance. Understanding these benefits, however, requires an appreciation of the opportunities juveniles have to associate with (and learn from) others. Here we describe social groups in terms of residency, movement, relatedness, and social associations from the perspective of juvenile hihi, a threatened New Zealand passerine bird. Over three years, we identified individuals in groups, their relatedness, and behavioural interactions. Using multistate analysis, we compared movement and residency of adults and juveniles and found that groups were composed predominately of juveniles which remained at group sites for longer than more transient adults. Movement of juveniles between groups did occur but was generally low. There was no evidence that siblings and parents were likely to be seen in groups together. With an initial understanding of group structure, we next asked what characteristics predicted assortment in social network associations. By identifying groups of co-occurring juveniles from time-stamped observations of individual hihi and building a social network, we found that juveniles were most likely to associate with other juveniles. Associations were also predominantly based on locations where hihi spent the most time, reflecting limited movement among separate groups. We suggest groups are best described as “gangs” where young hihi have little interaction with adults. These spatially-separated groups of juveniles may have consequences for social information use during the first few months of independence in young birds.
Accumulating computational resource usage of genomic data analysis workflow to optimize cloud computing instance selection
Authors: Ohta Tazro , Tanjo Tomoya , Ogasawara Osamu
Published: October 2018

Background

Container virtualization technologies such as Docker became popular in the bioinformatics domain as they improve portability and reproducibility of software deployment. Along with software packaged in containers, the workflow description standards Common Workflow Language also enabled to perform data analysis on multiple different computing environments with ease. These technologies accelerate the use of on-demand cloud computing platform which can scale out according to the amount of data. However, to optimize the time and the budget on a use of cloud, users need to select a suitable instance type corresponding to the resource requirements of their workflows.

Results

We developed CWL-metrics, a system to collect runtime metrics of Docker containers and workflow metadata to analyze resource requirement of workflows. We demonstrated the analysis by using seven transcriptome quantification workflows on six instance types. The result showed instance type options of lower financial cost and faster execution time with required amount of computational resources.

Conclusions

The summary of resource requirements of workflow executions provided by CWL-metrics can help users to optimize the selection of cloud computing instance. The runtime metrics data also accelerate to share workflows among different workflow management frameworks.
A diagnostic multiplex PCR scheme for identification of plant-associated bacteria of the genusPantoea
Authors: Kini Kossi , Agnimonhan Raoul , Dossa Rachelle , Silué Drissa , Koebnik Ralf
Published: October 2018

Background

The genusPantoeaforms a complex of more than 25 species, among which several cause diseases of several crop plants, including rice. Notably, strains ofPantoea ananatisandPantoea stewartiihave been found to cause bacterial leaf blight of rice in Togo and Benin, while other authors have observed thatPantoea agglomeranscan also cause bacterial leaf blight of rice. The contribution of these and perhaps other species ofPantoeato plant diseases and yield losses of crop plants is currently not well documented, partly due to the lack of efficient diagnostic tools.

Result

Using 34 whole genome sequences of the three-major plant-pathogenicPantoeaspecies, a set of PCR primers that specifically detect each of the three species,P. agglomerans,P. ananatis, andP. stewartii, was designed. A multiplex PCR protocol which can distinguish these three species and also detects members of otherPantoeaspecies was further developed. Upon validation on a set of reference strains, 609 suspectedPantoeastrains that were isolated from rice leaves or seeds originating from 11 African countries were screened. In total, 41P. agglomeransstrains from eight countries, 79P. ananatisstrains from nine countries, 269P. stewartiistrains from nine countries and 220 unsolvedPantoeastrains from ten countries were identified. The PCR protocol allowed detectingPantoeabacteria grown in vitro, in planta and in rice seeds. The detection threshold was estimated at 5 ng/mL of total genomic DNA and 1 × 105CFU/mL of heated cells.

Conclusion

This new molecular diagnostic tool will help accurately diagnose major plant-pathogenic species ofPantoea. Due to its robustness, specificity, sensitivity, and cost efficiency it will be very useful for plant protection services and for the epidemiological surveillance of these important crop-threatening bacteria.
Transcriptional profiling of isogenic Friedreich ataxia induced pluripotent stem cell-derived neurons
Authors: Lai Jiun-I , Nachun Daniel , Petrosyan Lina , Throesch Benjamin , Campau Erica , Gao Fuying , Baldwin Kristin K. , Coppola Giovanni , Gottesfeld Joel M. , Soragni Elisabetta
Published: October 2018

Friedreich ataxia (FRDA) is a rare childhood neurodegenerative disorder with no effective treatment. FRDA is caused by transcriptional silencing of the FXN gene and consequent loss of the essential mitochondrial protein frataxin. Based on the knowledge that a GAA•TTC repeat expansion in the first intron of FXN leads to heterochromatin formation and gene silencing, we have shown that members of the 2-aminobenzamide family of histone deacetylase inhibitors (HDACi) reproducibly increase FXN mRNA levels in induced pluripotent stem cell (iPSC)-derived FRDA neuronal cells and in peripheral blood mononuclear cells from patients treated with the drug in a phase I clinical trial. How the reduced expression of frataxin leads to neurological and other systemic symptoms in FRDA patients remains unclear. Similarly to other triplet repeat disorders, it is not known why only specific cells types are affected in the disease, primarily the large sensory neurons of the dorsal root ganglia and cardiomyocytes. The combination of iPSC technology and genome editing techniques offers the unique possibility of addressing these questions in a relevant cell model of the disease, without the confounding effect of different genetic backgrounds. We derived a set of isogenic iPSC lines that differ only in the length of the GAA•TTC repeats, using “scarless” gene-editing methods (helper-dependent adenovirus-mediated homologous recombination). To uncover the gene expression signature due to GAA•TTC repeat expansion in FRDA neuronal cells and the effect of HDACi on these changes, we performed transcriptomic analysis of iPSC-derived central nervous system (CNS) and isogenic sensory neurons by RNA sequencing. We find that multiple cellular pathways are commonly affected by the loss of frataxin in CNS and peripheral nervous system neurons and these changes are partially restored by HDACi treatment.
Attenuation of chronic antiviral T cell responses through constitutive COX2-dependent prostanoid synthesis by lymph node fibroblasts
Authors: Schaeuble Karin , Cannelle Hélène , Favre Stéphanie , Huang Hsin-Ying , Oberle Susanne G. , Zehn Dietmar , Luther Sanjiv A.
Published: October 2018

Fibroblastic reticular cells (FRC) of lymphoid T zones actively promote T cell trafficking, homeostasis and expansion, but can also attenuate excessive T cell responses via inducible nitric oxide and constitutive prostanoid release. It has remained unclear under which conditions these FRC-derived mediators can dampen T cell responses and whether this occurs in vivo. Here we confirm that murine lymph node FRC produce prostaglandin E2 (PGE2) in a cyclooxygenase-2 (COX2)-dependent and inflammation-independent fashion. We show that this COX2/PGE2 pathway is active during both strong and weak T cell responses, in contrast to nitric oxide which only comes into play during strong T cell responses. In chronic infections in vivo, PGE2-receptor signaling in virus-specific CD8 T cells was shown by others to suppress T cell survival and function. Using CCL19cre x COX2flox/flox mice we now identify CCL19cre+ FRC as the critical source of this COX2-dependent suppressive factor, suggesting PGE2-expressing FRC within lymphoid tissues are an interesting therapeutic target to improve T cell mediated pathogen control during chronic infection.
Spatial signature of white matter hyperintensities in stroke patients
Authors: Schirmer Markus D. , Giese Anne-Katrin , Fotiadis Panagiotis , Etherton Mark R. , Cloonan Lisa , Viswanathan Anand , Greenberg Steven M. , Wu Ona , Rost Natalia S.
Published: October 2018

Purpose

White matter hyperintensity (WMH) is a common phenotype across a variety of neurological diseases, particularly prevalent in stroke patients; however, vascular territory dependent variation in WMH burden has not yet been identified. Here, we sought to investigate the spatial specificity of WMH burden in patients with acute ischemic stroke (AIS).

Materials and Methods

We created a novel age-appropriate high-resolution brain template and anatomically delineated the cerebral vascular territories. We used WMH masks derived from the clinical T2 FLAIR MRI scans and spatial normalization of the template to discriminate between WMH volume within each subject’s anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) territories. Linear regression modeling including age, sex, common vascular risk factors, and TOAST stroke subtypes was used to assess for spatial specificity of WMH volume (WMHv) in a cohort of 882 AIS patients.

Results

Mean age of this cohort was 65.23±14.79 years, 61.7% were male, 63.6% were hypertensive, 35.8% never smoked. Mean WMHv was 11.58c +/-13.49 cc. There were significant differences in territory-specific, relative to global, WMH burden. In contrast to PCA territory, age (0.018±0.002, p<0.001) and small-vessel stroke subtype (0.212±0.098, p<0.001) were associated with relative increase of WMH burden within the anterior (ACA and MCA) territories, whereas male sex (−0.275±0.067, p<0.001) was associated with a relative decrease in WMHv.

Conclusions

Our data establish the spatial specificity of WMH distribution in relation to vascular territory and risk factor exposure in AIS patients and offer new insights into the underlying pathology.
Structures of two fimbrial adhesins, AtfE and UcaD, from the uropathogenProteus mirabilis
Authors: Jiang Wangshu , Ubhayasekera Wimal , Pearson Melanie M. , Knight Stefan D.
Published: October 2018

The important uropathogenProteus mirabilisencodes a record number of chaperone/usher-pathway adhesive fimbriae. Such fimbriae, which are used for adhesion to cell surfaces/tissues and for biofilm formation, are typically important virulence factors in bacterial pathogenesis. Here, the structures of the receptor-binding domains of the tip-located two-domain adhesins UcaD (1.5 Å resolution) and AtfE (1.58 Å resolution) from twoP. mirabilisfimbriae (UCA/NAF and ATF) are presented. The structures of UcaD and AtfE are both similar to the F17G type of tip-located fimbrial receptor-binding domains, and the structures are very similar despite having only limited sequence similarity. These structures represent an important step towards a molecular-level understanding ofP. mirabilisfimbrial adhesins and their roles in the complex pathogenesis of urinary-tract infections.
An approach for the protection of users’ book browsing preference privacy in a digital library
Authors: Wu Zongda , Zheng Chengren , Xiejian Jian , Zhou Zhifeng , Xu Guandong , Chen Enhong
Published: October 2018

Purpose

The problem of privacy protection in digital libraries is causing people to have increasingly extensive concerns. This study aims to design an approach to protect the preference privacy behind users’ book browsing behaviors in a digital library.

Design/methodology/approach

This paper proposes a client-based approach, whose basic idea is to construct a group of plausible book browsing dummy behaviors, and submit them together with users’ true behaviors to the untrusted server, to cover up users’ sensitive preferences.

Findings

Both security analysis and evaluation experiment demonstrate the effectiveness of the approach, which can ensure the privacy security of users’ book browsing preferences on the untrusted digital library server, without compromising the usability, accuracy and efficiency of book services.

Originality/value

To the best of the authors’ knowledge, this paper provides the first attempt to the protection of users’ behavior privacy in digital libraries, which will have a positive influence on the development of privacy-preserving libraries in the new network era.