bluuebunny/crossref_metadata_2025 huggingface dataset:
EpCAM Intracellular Domain Promotes Porcine Cell Reprogramming by Upregulation of Pluripotent Gene Expression via Beta-catenin Signaling
Authors: Yu Tong , Ma Yangyang , Wang Huayan
Published: April 2017

Previous study showed that expression of epithelial cell adhesion molecule (EpCAM) was significantly upregulated in porcine induced pluripotent stem cells (piPSCs). However, the regulatory mechanism and the downstream target genes of EpCAM were not well investigated. In this study, we found that EpCAM was undetectable in fibroblasts, but highly expressed in piPSCs. Promoter of EpCAM was upregulated by zygotic activated factors LIN28, and ESRRB, but repressed by maternal factors OCT4 and SOX2. Knocking down EpCAM by shRNA significantly reduced the pluripotent gene expression. Conversely, overexpression of EpCAM significantly increased the number of alkaline phosphatase positive colonies and elevated the expression of endogenous pluripotent genes. As a key surface-to-nucleus factor, EpCAM releases its intercellular domain (EpICD) by a two-step proteolytic processing sequentially. Blocking the proteolytic processing by inhibitors TAPI-1 and DAPT could reduce the intracellular level of EpICD and lower expressions of OCT4, SOX2, LIN28, and ESRRB. We noticed that increasing intracellular EpICD only was unable to improve activity of EpCAM targeted genes, but by blocking GSK-3 signaling and stabilizing beta-catenin signaling, EpICD could then significantly stimulate the promoter activity. These results showed that EpCAM intracellular domain required beta-catenin signaling to enhance porcine cell reprogramming.
Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles
Authors: Pesarrodona Mireia , Crosas Eva , Cubarsi Rafael , Sánchez-Chardi Alejandro , Saccardo Paolo , Unzueta Ugutz , Rueda Fabian , Sanchez-García Laura , Serna Naroa , Mangues Ramón , Ferrer-Miralles Neus , Vázquez Esther , Villaverde Antonio
Published: April 2017

Self-assembling proteins are gaining attention as building blocks for application-tailored nanoscale materials.
A diarylethene-based “on–off–on” fluorescence sensor for the sequential recognition of mercury and cysteine
Authors: Li Gang , Ma Lele , Liu Gang , Fan Congbin , Pu Shouzhi
Published: April 2017

A novel photochromic diarylethene with a quinoline unit was synthesized with multi-controllable fluorescence switching properties, which could be induced by light, mercury (Hg2+) and cysteine (Cys).
Synthesis and biological evaluation of novel technetium-99m-labeled phenylquinoxaline derivatives as single photon emission computed tomography imaging probes targeting β-amyloid plaques in Alzheimer's disease
Authors: Iikuni Shimpei , Ono Masahiro , Tanimura Keiichi , Watanabe Hiroyuki , Yoshimura Masashi , Saji Hideo
Published: April 2017

The development of an imaging probe targeting β-amyloid (Aβ) plaques in Alzheimer's disease labeled with technetium-99m, the most commonly used radioisotope for clinical diagnoses, has been strongly anticipated.
Screening and design of high-performance indoline-based dyes for DSSCs
Authors: Li Yuanzuo , Li Yuanchao , Song Peng , Ma Fengcai , Liang Jianping , Sun Mengtao
Published: April 2017

The photophysical properties of three D–A–π–A dyes (WS-2, WS-92 and WS-95) were calculated based on DFT and TDDFT.
Viable approach toward efficient p-type conductivity in Al-doped anatase TiO2via strain engineering
Authors: Zhou Wei , Umezawa Naoto
Published: April 2017

The tensile strain in the (001) plane can effectively delocalized the trapped holes in anatase TiO2, which gives a viable way to realize the effective p-type conductivity.
Carbon-embedded Ni nanocatalysts derived from MOFs by a sacrificial template method for efficient hydrogenation of furfural to tetrahydrofurfuryl alcohol
Authors: Su Yanping , Chen Chun , Zhu Xiaoguang , Zhang Yong , Gong Wanbing , Zhang Haimin , Zhao Huijun , Wang Guozhong
Published: April 2017

A Ni/C catalyst prepared by the pyrolysis of Ni-MOFs, synthesized by a facile oil-bath method, showed high activity of hydrogenation of FAL.
Sulfated polysaccharides from Enteromorpha prolifera suppress SREBP-2 and HMG-CoA reductase expression and attenuate non-alcoholic fatty liver disease induced by a high-fat diet
Authors: Ren Rendong , Gong Junjie , Zhao Yanyan , Zhuang Xinyun , Ye Yin , Lin Wenting
Published: April 2017

Enteromorpha prolifera polysaccharides (EP) suppressed SREBP-2 and regulates expression of HMG-CoA reductase. Therefore, EP may be a functional food that can prevent nonalcoholic fatty liver disease.
Selective biomolecular separation system inspired by the nuclear pore complex and nuclear transport
Authors: Kim Minkyu , Chen Wesley G. , Souza Bruno S. , Olsen Bradley D.
Published: April 2017

Inspired by selectively filtering system of the nucleus, we developed biosynthetic system that can selectively “catch-trap” biotoxins from aqueous environment.
Pyrene-fused bisphenazinothiadiazoles with red to NIR electroluminescence
Authors: Cortizo-Lacalle Diego , Pertegás Antonio , Melle-Franco Manuel , Bolink Henk J. , Mateo-Alonso Aurelio
Published: April 2017

Deep red and NIR electroluminescence from pyrene-fused bisphenazinothiadiazoles.
Anaerobic lipopeptide biosurfactant production by an engineered bacterial strain for in situ microbial enhanced oil recovery
Authors: Liang Xiaolong , Shi Rongjiu , Radosevich Mark , Zhao Feng , Zhang Yingyue , Han Siqin , Zhang Ying
Published: April 2017

Anaerobic lipopeptide biosurfactant production by engineered bacterial strain FA-2 was fulfilled forin situMEOR potential application.
Towards highly efficient thermally activated delayed fluorescence devices through a trap-assisted recombination mechanism and reduced interfacial exciton annihilation
Authors: Zhang Wenzhi , Jin Jiangjiang , Huang Zhi , Lv Xialei , Zhuang Shaoqing , Wang Lei
Published: April 2017

Highly efficient TADF OLEDs were realized by facilitating trap-assisted recombination and reducing interfacial triplet–polaron annihilation.
RNA-binding proteins with prion-like domains in health and disease
Authors: Harrison Alice Ford , Shorter James
Published: April 2017

Approximately 70 human RNA-binding proteins (RBPs) contain a prion-like domain (PrLD). PrLDs are low-complexity domains that possess a similar amino acid composition to prion domains in yeast, which enable several proteins, including Sup35 and Rnq1, to form infectious conformers, termed prions. In humans, PrLDs contribute to RBP function and enable RBPs to undergo liquid–liquid phase transitions that underlie the biogenesis of various membraneless organelles. However, this activity appears to render RBPs prone to misfolding and aggregation connected to neurodegenerative disease. Indeed, numerous RBPs with PrLDs, including TDP-43 (transactivation response element DNA-binding protein 43), FUS (fused in sarcoma), TAF15 (TATA-binding protein-associated factor 15), EWSR1 (Ewing sarcoma breakpoint region 1), and heterogeneous nuclear ribonucleoproteins A1 and A2 (hnRNPA1 and hnRNPA2), have now been connected via pathology and genetics to the etiology of several neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal dementia, and multisystem proteinopathy. Here, we review the physiological and pathological roles of the most prominent RBPs with PrLDs. We also highlight the potential of protein disaggregases, including Hsp104, as a therapeutic strategy to combat the aberrant phase transitions of RBPs with PrLDs that likely underpin neurodegeneration.
Longitudinal Impacts of Print-Focused Read-Alouds for Children With Language Impairment
Authors: Justice Laura M. , Logan Jessica , Kaderavek Joan N.
Published: April 2017

Purpose

Preschoolers with language impairment (LI) are prime candidates for early-literacy interventions, given their susceptibility for future reading difficulties. To date, most studies of early-literacy interventions for this population has assessed short-term impacts, with limited attention to whether initial effects are sustained over time. This study was designed to evaluate longitudinal impacts of print-focused read-alouds implemented by early childhood special education teachers for a clinic sample of children with LI.

Method

Assessment data available for 172 children with LI were analyzed to examine their print knowledge 1-year postintervention. Measures examined children's alphabet knowledge, print concepts, and name-writing skills, which were used to derive a print-knowledge composite.

Results

Results of hierarchical linear models examining children's print knowledge at 1-year postintervention showed that the effect size (
d
= 0.20) favoring the treatment group was similar to that observed one year prior (
d
= 0.21) at the end of intervention, suggesting that results did not fade over time. Results also showed that children with LI and comorbid low nonverbal cognition benefited the most from the intervention delivered 1 year earlier.

Conclusion

The maintenance of short-term effects to 1-year postintervention supports the value of early childhood teachers using print-focused read-alouds to improve the early-literacy skills of children with LI in their classrooms.
Efficacy of Visual–Acoustic Biofeedback Intervention for Residual Rhotic Errors: A Single-Subject Randomization Study
Authors: McAllister Byun Tara
Published: April 2017

Purpose

This study documented the efficacy of visual–acoustic biofeedback intervention for residual rhotic errors, relative to a comparison condition involving traditional articulatory treatment. All participants received both treatments in a single-subject experimental design featuring alternating treatments with blocked randomization of sessions to treatment conditions.

Method

Seven child and adolescent participants received 20 half-hour sessions of individual treatment over 10 weeks. Within each week, sessions were randomly assigned to feature traditional or biofeedback intervention. Perceptual accuracy of rhotic production was assessed in a blinded, randomized fashion. Each participant's response to the combined treatment package was evaluated by using effect sizes and visual inspection. Differences in the magnitude of response to traditional versus biofeedback intervention were measured with individual randomization tests.

Results

Four of 7 participants demonstrated a clinically meaningful response to the combined treatment package. Three of 7 participants showed a statistically significant difference between treatment conditions. In all 3 cases, the magnitude of within-session gains associated with biofeedback exceeded the gains associated with traditional treatment.

Conclusions

These results suggest that the inclusion of visual–acoustic biofeedback can enhance the efficacy of intervention for some individuals with residual rhotic errors. Further research is needed to understand which participants represent better or poorer candidates for biofeedback treatment.
Comprehending Comprehension: Selected Possibilities for Clinical Practice Within a Multidimensional Model
Authors: Wallach Geraldine P. , Ocampo Alaine
Published: April 2017

Purpose

In this discussion as part of a response to Catts and Kamhi's “Prologue: Reading Comprehension Is Not a Single Activity” (2017), the authors provide selected examples from 4th-, 5th-, and 6th-grade texts to demonstrate, in agreement with Catts and Kamhi, that reading comprehension is a multifaceted and complex ability. The authors were asked to provide readers with evidence-based practices that lend support to applications of a multidimensional model of comprehension.

Method

We present examples from the reading comprehension literature that support the notion that reading is a complex set of abilities that include a reader's ability, especially background knowledge; the type of text the reader is being asked to comprehend; and the task or technique used in assessment or intervention paradigms. An intervention session from 6th grade serves to demonstrate how background knowledge, a text's demands, and tasks may come together in the real world as clinicians and educators aim to help students comprehend complex material.

Conclusions

The authors agree with the conceptual framework proposed by Catts and Kamhi that clinicians and educators should consider the multidimensional nature of reading comprehension (an interaction of reader, text, and task) when creating assessment and intervention programs. The authors might depart slightly by considering, more closely, those reading comprehension strategies that might facilitate comprehension across texts and tasks with an understanding of students' individual needs at different points in time.
Cytokine regulation of experimental intestinal inflammation in genetically engineered and T‐lymphocyte reconstituted rodents.
Authors: Sartor RB
Published: April 2017

Phenotypically similar intestinal inflammation and systemic wasting develops following overexpression or targeted deletion of several key immunoregulatory molecules and transfer of lymphocyte subsets into immunodeficient recipients. Although many of these recently described models of intestinal inflammation have not been thoroughly investigated, several consistent features are present which provide important insights into the role of cytokines in the pathogenesis of intestinal inflammation: (i) entirely distinct genetic alterations of cytokine expression and T‐lymphocyte activity can lead to phenotypically similar intestinal inflammation, suggesting that human inflammatory bowel disease could have marked genetic heterogeneity; (ii) dysregulation of any of a number to immunoregulatory molecules can result in intestinal inflammation, illustrating the complexity of the mucosal immune response; (iii) active immunosuppression is critical to maintaining mucosal homeostasis; (iv) interferon‐gamma and CD4+ lymphocytes, probably of the TH1 phenotype, are required for progression of chronic intestinal inflammation; (v) monokines are consistently upregulated, but tumour necrosis factor blockade is only partially protective. These models represent powerful new tools to understand better the basic mechanisms of mucosal immunoregulation and to develop novel therapeutic approaches of enhancing endogenous immunosuppressive pathways and blocking key regulatory cytokines and cells.
Cytokine assays and their limitations.
Authors: Tsang ML , Weatherbee JA
Published: April 2017

With the increasing popularity of the use of cytokine immunoassays in basic and clinical research, there is an urgent need for cytokine immunoassay reference preparations and standards in order that results published by various investigators can be directly compared. Until such standards are available, it is recommended that results obtained using immunoassays from different sources be compared with caution. Additionally, users of immunoassays should clearly understand the biology of the systems they are studying and the characteristics of their immunoassays with respect to cross‐reactivities with cytokine isoforms, interferences by soluble receptors, and matrix effects on samples of interest. It is also recommended that immunoassay developers take special precautions in the selection of antibodies and only use antibodies that are not biased against one or the other of the recombinant forms.
Exact and asymptotic BER analysis of 2 × 2 FRLR‐STBC with BPSK modulation
Authors: Lee Hoojin
Published: April 2017

The bit error rate (BER) performance of 2 × 2 full‐rate linear‐receiver space–time block code (FRLR‐STBC) is evaluated. By using the Appell and Gauss hypergeometric functions, the novel exact and asymptotic closed‐form BER formulas of FRLR‐STBC with BPSK modulation, along with the corresponding coding gain and diversity order, are derived over Rayleigh fading channels. Some numerical results are presented to demonstrate the validity of the derived analytical results.
DC‐link capacitor voltage offset suppression with no filters for three‐phase four‐switch inverter fed PMSM drives
Authors: Yuan Qingwei , Zhao Rongxiang
Published: April 2017

The adjustable speed range for three‐phase four‐switch inverter (TPFSI) fed permanent magnet synchronous motor (PMSM) drives is seriously limited by the DC‐link capacitor voltage offset in TPFSI. For the traditional offset suppression schemes, the low‐pass filters or notch filters are necessary to extract the capacitor voltage offset, which will deteriorate the control performance of the offset suppression schemes severely, especially for the low‐speed range. Thus, a novel offset suppression scheme with no filters is proposed to improve the situation. For the proposed scheme, to extract the offset with no filters, a new static coordinate is defined, the relationships between the fundamental/offset components of capacitor voltages and the load currents are revealed, based on which a simple algorithm is developed. Then, the desired compensatory current is obtained by a closed‐loop control and injected into the stator current control loop. Experimental results have validated the proposed scheme.
Circularly polarised filtering monopole antenna based on miniaturised coupled filter
Authors: Cheng Wenbin , Li Dagang
Published: April 2017

This Letter proposes a circularly polarised (CP) monopole antenna with filtering function, which is achieved by integrating a miniaturised coupled filter based on the bent‐loop resonators. The circular‐polarisation is obtained by using the falcate‐shaped patch as the radiation part, and the existence of the coupled filter in the feeding line would not affect the CP radiation performances. Both numerical simulation and experimental demonstration are performed for the designed CP filtering antenna, and good agreements are obtained. The designed antenna with dimension of 70 × 75 mm2 exhibits good frequency selective performances for the return loss, gain and axial ratio at 2.45 GHz with measured impedance matching bandwidth (|S11| < 10 dB) of 0.23 GHz. Such CP filtering antenna is a good candidate for the emerging application area, e.g. wearable biotelemetric devices.
Natural Products as Lead Compounds for Sodium Glucose Cotransporter (SGLT) Inhibitors
Authors: Blaschek Wolfgang
Published: April 2017

Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs). The intestinal glucose absorption by endothelial cells is managed by SGLT1, the transfer from them to the blood by GLUT2. In the kidney SGLT2 and SGLT1 are responsible for reabsorption of filtered glucose from the primary urine, and GLUT2 and GLUT1 enable the transport of glucose from epithelial cells back into the blood stream.

The flavonoid phlorizin was isolated from the bark of apple trees and shown to cause glucosuria. Phlorizin is an inhibitor of SGLT1 and SGLT2. With phlorizin as lead compound, specific inhibitors of SGLT2 were developed in the last decade and some of them have been approved for treatment mainly of type 2 diabetes. Inhibition of SGLT2 eliminates excess glucose via the urine. In recent times, the dual SGLT1/SGLT2 inhibitory activity of phlorizin has served as a model for the development and testing of new drugs exhibiting both activities.

Besides phlorizin, also some other flavonoids and especially flavonoid enriched plant extracts have been investigated for their potency to reduce postprandial blood glucose levels which can be helpful in the prevention and supplementary treatment especially of type 2 diabetes.
Morpho-physiological responses to dehydration stress of perennial ryegrass and tall fescue genotypes
Authors: Shahidi Reihaneh , Yoshida Junko , Cougnon Mathias , Reheul Dirk , Van Labeke Marie-Christine
Published: April 2017

Worldwide drought stress is the most important restriction factor on food and fodder productivity. In this study, morpho-physiological adaptations to dehydration stress were investigated in two tall fescue (Festuca arundinacea Schreb.) genotypes (Fa13 and Fa19 with a high and low sheep grazing preference respectively) and Lolium perenne L. Drought stress as evaluated by decreasing stomatal conductance and chlorophyll content, chlorophyll fluorescence parameters and fructan concentration were first observed in L. perenne (16 days after the start of the drought stress). Furthermore, after 20 days of drought stress the activities of ascorbate peroxide (APX), catalase (CAT), and superoxide dismutase (SOD) were reduced in stressed plants indicating that the capacity to scavenge ROS diminished under severe stress though no differences between genotypes were observed. Osmotic adjustment by carbohydrates did also not differ between the genotypes. Proline, however, reached its highest level in drought-stressed L. perenne followed by Fa13 and Fa19 respectively. The studied species showed a similar degree in response in the traits assessed when plants were exposed to dehydration stress; however changes were first observed in L. perenne.
Die Eifler Regel
Authors: Ternes Elmar
Published: April 2017

Der Artikel behandelt die sog. “Eifler Regel”, eine satzphonetische Erscheinung in westdeutschen Dialekten und im Luxemburgischen. Ein wortauslautendes -n wird unter bestimmten Bedingungen getilgt oder bleibt erhalten. Die Bedingungen, welche phonetischer, grammatischer und lexikalischer Natur sind, werden zum ersten Mal in ihrer vollen Komplexität beschrieben. Die Beispiele entstammen zum größten Teil dem Dialekt der Stadt Trier. Es wird aber auch auf einige geographisch bedingte Abweichungen eingegangen. Zum Schluß wird die Erscheinung in einen typologischen Zusammenhang im weiteren deutschsprachigen und germanischen Rahmen gestellt.
The Gospel according to Borges
Authors: Van Wyke Ben
Published: April 2017

Borges’s “Gospel According to Mark,” written 1,900 years after the first biblical Gospel by the same name, provides a compelling illustration of how translators always play a visible, creative role in the work they perform (even when they do not realize it or want this role). The characters’ interaction with the Bible is an ideal platform to explore some complex notions that stem from postmodern conceptions of translation, such as the complicated relationship established between translators, their translations and audience. Furthermore, it is worth noting that Mark had a considerable impact on two of the three other Gospel authors, and that the Bible has had immeasurable impact on the general interpretation and translation of texts around the world. Borges’s story may seem to portray an absurd misreading of the Mark, but I propose that this radical misreading is not altogether different from the millions of interactions with the texts that have been responsible for creating and disseminating the Bible. Through brief histories of both Mark and the Vulgate in tandem with Borges’s text, we can understand that millions of nameless translators, interpreters and scribes have been responsible for actually creating what is now, in a fragmented nature, the Bible.
A halo substructure in Gaia Data Release 1
Authors: Myeong G. C. , Evans N. W. , Belokurov V. , Koposov S. E. , Sanders J. L.
Published: April 2017

We identify a halo substructure in the Tycho Gaia Astrometric Solution (TGAS) data set, cross-matched with the Radial Velocity Experiment (RAVE-on) data release. After quality cuts, the stars with large radial action (JR > 800 km s−1 kpc) are extracted. A subset of these stars is clustered in longitude and velocity and can be selected with further cuts. The 14 stars are centred on (X, Y, Z) ≈ (9.0, −1.0, −0.6) kpc and form a coherently moving structure in the halo with median (vR, vϕ, vz) = (167.33, 0.86, −94.85) km s−1. They are all metal-poor giants with median [Fe/H] = −0.83. To guard against the effects of distance errors, we compute spectrophotometric distances for 8 out of the 14 stars where this is possible. We find that six of the stars are still comoving. These six stars also have a much tighter [Fe/H] distribution ∼−0.7 with one exception ([Fe/H] = −2.12). We conclude that the existence of the comoving cluster is stable against changes in distance estimation and conjecture that this is the dissolving remnant of a globular cluster accreted long ago.
Cervical Spine Muscle-Tendon Unit Length Differences Between Neutral and Forward Head Postures: Biomechanical Study Using Human Cadaveric Specimens
Authors: Khayatzadeh Saeed , Kalmanson Olivia A. , Schuit Dale , Havey Robert M. , Voronov Leonard I. , Ghanayem Alexander J. , Patwardhan Avinash G.
Published: April 2017

Background. Forward head posture (FHP) may be associated with neck pain and poor health-related quality of life. Literature describes only qualitative muscle length changes associated with FHP.

Objective. The purpose of this study was to quantify how muscle-tendon unit lengths are altered when human cadaveric specimens are placed in alignments representing different severities of FHP.

Design. This biomechanical study used 13 fresh-frozen cadaveric cervical spine specimens (Occiput-T1, 54±15 y).

Methods. Specimens’ postural changes simulating increasing FHP severity while maintaining horizontal gaze were assessed. Specimen-specific anatomic models derived from computed tomography–based anatomic data were combined with postural data and specimen-specific anatomy of muscle attachment points to estimate the muscle length changes associated with FHP.

Results. Forward head posture was associated with flexion of the mid-lower cervical spine and extension of the upper cervical (sub-occipital) spine. Muscles that insert on the cervical spine and function as flexors (termed “cervical flexors”) as well as muscles that insert on the cranium and function as extensors (“occipital extensors”) shortened in FHP when compared to neutral posture. In contrast, muscles that insert on the cervical spine and function as extensors (“cervical extensors”) as well as muscles that insert on the cranium and function as flexors (“occipital flexors”) lengthened. The greatest shortening was seen in the major and minor rectus capitis posterior muscles. These muscles cross the Occiput-C2 segments, which exhibited extension to maintain horizontal gaze. The greatest lengthening was seen in posterior muscles crossing the C4-C6 segments, which exhibited the most flexion.

Limitations. This cadaver study did not incorporate the biomechanical influence of active musculature.

Conclusions. This study offers a novel way to quantify postural alignment and muscle length changes associated with FHP. Model predictions are consistent with qualitative descriptions in the literature.
Translating Research to Practice
Authors: Nelson Harriett , Mott Sandra
Published: April 2017

Background:

A freestanding quaternary pediatric hospital in New England has been facilitating parents’ requests to take their child home or to a hospice facility from an Intensive Care Unit at end of life for the withdrawal of life sustaining measures for the past 16 years. However, knowledge of the aftermath of this decision was very limited. Before responding to a growing interest in making this service more available, an exploratory study was done to learn about the parents’ perceptions of the experience over time. We learned that the parents were very positive and highly recommending that pediatric palliative transports be made more available.

Objective:

The aim of this study was to describe the steps and rationale used to create a structured platform for pediatric palliative transports, drawing on findings from a previous study.

Outcomes:

To standardize the process, describe distinct responsibilities, and ensure quality and safety, an algorithm was created. The development of a checklist followed to enable the coordinator to follow the status of preparation for the transport. Empowered by parents’ requests and positive reflections, these transports are now offered more frequently to parents of children requiring care in an intensive care unit at end of life.
Evolution and revolution in cardiopulmonary resuscitation
Authors: Fowler Ray , Chang Mary P. , Idris Ahamed H.
Published: April 2017

Purpose of review

To discuss the evolution of the technique of cardiopulmonary resuscitation (CPR), including presenting important research that has made substantial improvements in patient outcome.

Recent findings

The last half century has seen the arising of guidelines for performing CPR increasingly based on good scientific evidence. Improvements in the technique, including teaching citizens ‘compressions only CPR’, have simplified the process of rescue while improving survival.

Numerous scientific studies and the better understanding of physiology have contributed to enhanced outcomes while creating community-based systems of care.
Molecular Typing of Syphilis-Causing Strains Among Human Immunodeficiency Virus-Positive Patients in Antwerp, Belgium
Authors: Mikalová Lenka , Grillová Linda , Osbak Kara , Strouhal Michal , Kenyon Chris , Crucitti Tania , Šmajs David
Published: April 2017

Centers for Disease Control and Prevention and sequencing-based treponeme typing was used to analyze 72 blood samples, collected from human immunodeficiency virus and syphilis co-infected patients during 2014 to 2015 in Antwerp, Belgium. Twenty-nine (40.3%) isolates were polymerase chain reaction positive for Treponema pallidum, and all tested were macrolide-resistant. Four genotypes were identified by sequencing-based typing including two new genotypes, U4NR8 and SU9R8, whereas enhanced Centers for Disease Control and Prevention typing revealed 7 subtypes.
Assortativity and Mixing by Sexual Behaviors and Sociodemographic Characteristics in Young Adult Heterosexual Dating Partnerships
Authors: Malagón Talía , Burchell Ann , El-Zein Mariam , Tellier Pierre-Paul , Coutlée François , Franco Eduardo L.
Published: April 2017

Background

Assortative sexual mixing, the tendency for individuals to choose partners with similar characteristics to themselves, may be an important contributor to the unequal distribution of sexually transmitted infections in populations. We analyzed the tendency for assortative mixing on demographic and sexual behaviors characteristics in newly formed young adults dating partnerships.

Methods

Women aged 18 to 24 years and their male sexual partners of no more than 6 months were recruited during 2005 to 2010 at universities in Montreal, Canada. New dating partners were also prospectively recruited during the 2-year follow-up. We used Spearman and Newman coefficients to examine correlations between partners' demographic characteristics and sexual behaviors, and multivariable logistic modeling to determine which characteristics were assortative.

Results

Participants in 502 recruited partnerships were assortative on age (Spearman P = 0.60), smoking behavior (P = 0.43), ethnicity (Newman coefficient=0.39), lifetime number of sexual partners (P = 0.36), sex partner acquisition rates (P = 0.22), gap length between partnerships (P = 0.20), and on whether they had concurrent partners (P = 0.33). Partners were assortative on number of lifetime partners, sexual partner acquisition rates, concurrency, and gap length between partnerships even after adjustment for demographic characteristics. Reported condom use was correlated between initial and subsequently recruited partners (P = 0.35). There was little correlation between the frequencies of vaginal/oral/digital/anal sex between subsequent partnerships.

Conclusions

Dating partnerships were substantially assortative on various sexual behaviors as well as demographic characteristics. Though not a representative population sample, our recruitment of relatively new partnerships reduces survivor bias inherent to cross-sectional surveys where stable long-term partnerships are more likely to be sampled.
Keeping an Eye on Chlamydia and Gonorrhea Conjunctivitis in Infants in the United States, 2010–2015
Authors: Kreisel Kristen , Weston Emily , Braxton Jim , Llata Eloisa , Torrone Elizabeth
Published: April 2017

Perinatal transmission of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) can result in conjunctivitis in infants. We examined national rates of reported CT/GC conjunctivitis among infants. Surveillance of these infections is heavily affected by the completeness of reported data on specimen source and age. Alternative data sources should be evaluated.
Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma
Authors: Kuraoka Masatsugu , Amatya Vishwa J. , Kushitani Kei , Mawas Amany S. , Miyata Yoshihiro , Okada Morihito , Kishimoto Takumi , Inai Kouki , Nishisaka Takashi , Sueda Taijiro , Takeshima Yukio
Published: April 2017

As there are currently no absolute immunohistochemical positive markers for the definite diagnosis of malignant epithelioid mesothelioma, the identification of additional “positive” markers that may facilitate this diagnosis becomes of clinical importance. Therefore, the aim of this study was to identify novel positive markers of malignant mesothelioma. Whole genome gene expression analysis was performed using RNA extracted from formalin-fixed paraffin-embedded tissue sections of epithelioid mesothelioma and pulmonary adenocarcinoma. Gene expression analysis revealed that disabled homolog 2 (DAB2) and Intelectin-1 had significantly higher expression in epithelioid mesothelioma compared with that in pulmonary adenocarcinoma. The increased mRNA expression of DAB2 and Intelectin-1 was validated by reverse transcriptase polymerase chain reaction of RNA from tumor tissue and protein expression was validated by Western blotting of 5 mesothelioma cell lines. The utility of DAB2 and Intelectin-1 in the differential diagnosis of epithelioid mesothelioma and pulmonary adenocarcinoma was examined by an immunohistochemical study of 75 cases of epithelioid mesothelioma and 67 cases of pulmonary adenocarcinoma. The positive rates of DAB2 and Intelectin-1 expression in epithelioid mesothelioma were 80.0% and 76.0%, respectively, and 3.0% and 0%, respectively, in pulmonary adenocarcinoma. Immunohistochemically, the sensitivity and specificity of DAB2 was 80% and 97% and those of Intelectin-1 were 76% and 100% for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma. In conclusion, DAB2 and Intelectin-1 are newly identified positive markers of mesothelioma and have potential to be included in future immunohistochemical marker panels for differentiation of epithelioid mesothelioma from pulmonary adenocarcinoma.
Evaluating the Effectiveness of Concurrent Review: Does It Improve Stroke Measure Results?
Authors: McGillivray Celia Gomes , Silver Brian
Published: April 2017

Background:

Concurrent review is a quality improvement strategy in which patients are tracked from admission to discharge, and messages are communicated to the responsible physician when quality stroke measures have not been met. There is little research regarding interventions that might influence clinical practice patterns and improvement in compliance with core quality measures. This study sought to evaluate whether concurrent review implementation was associated with change in performance on stroke measure outcome data.

Methods:

Randomly selected charts from 2 hospitals (A and B) during 3 time periods were reviewed. In period 1, neither hospital had a process for concurrent review. In period 2, hospital A, where concurrent review was implemented, was compared with hospital B without this process. In period 3, both hospitals had the process of concurrent review. Information on baseline demographics, insurance status, and length of stay was collected, as well as stroke performance measures.

Results:

A total of 620 medical records were reviewed during the 3 time periods. Although the number of beds and annual stroke volume were higher at hospital B, patient characteristics were similar. During period 2, when hospital A implemented concurrent review and hospital B had not, a statistically significant higher compliance with performance in 7 stroke measures occurred in hospital A than in hospital B. In period 3, when both hospitals utilized concurrent review, no statistical significant differences occurred in 7 of the 10 stroke measures.

Conclusion:

Concurrent review is a quality improvement intervention that increases performance with stroke performance measures.
The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide
Authors: Williams Robert C. , Opelz Gerhard , Weil E. Jennifer , McGarvey Chelsea J. , Chakkera Harini A.
Published: April 2017

Background

Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years.

Methods

Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets.

Results

There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation.

Conclusions

These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible.
Addressing the digital divide in contemporary biology: Lessons from teaching UNIX
Authors: Mangul Serghei , Martin Lana S. , Hoffmann Alexander , Pellegrini Matteo , Eskin Eleazar
Published: April 2017

Researchers in the biomedical sciences increasingly rely on applications that lack a graphical interface and require inputting code that, such as UNIX. Scientists who are not trained in computer science face an enormous challenge in analyzing the high-throughput data their research groups generate. We present a training model for use of command-line tools when the learner has little to no prior knowledge of UNIX.
The odd one out:Arabidopsisreticulon20 has a role in lipid biosynthesis
Authors: Kriechbaumer Verena , Maneta-Peyret Lilly , Botchway Stanley W , Upson Jessica , Hughes Louise , Richardson Jake , Kittelmann Maike , Moreau Patrick , Hawes Chris
Published: April 2017

The family of reticulon proteins has been shown to be involved in a variety of functions in eukaryotic cells including tubulation of the endoplasmic reticulum (ER), formation of cell plates and primary plasmodesmata. Reticulons are integral ER membrane proteins characterised by a reticulon homology domain comprising four transmembrane domains which results in the reticulons sitting in the membrane in a W-topology. Here we report on a subgroup of reticulons with an extended N-terminal domain and in particular on arabidopsis reticulon 20. We show that reticulon 20 is located in a unique punctate pattern on the ER membrane. Its closest homologue reticulon 19 labels the whole ER. We show that mutants in RTN20 or RTN19, respectively, display a significant change in sterol composition in the roots indicating a role in lipid biosynthesis or regulation. A third homologue in this family - 3BETAHSD/D1- is localised to ER exit sites resulting in an intriguing location difference for the three proteins.
Assessing inhibitors of mutant isocitrate dehydrogenase using a suite of pre-clinical discovery assays
Authors: Urban Daniel J. , Martinez Natalia J. , Davis Mindy I. , Brimacombe Kyle R. , Cheff Dorian M. , Lee Tobie D. , Henderson Mark J. , Titus Steven A. , Pragani Rajan , Rohde Jason M. , Wang Yuhong , Karavadhi Surendra , Shah Pranav , Lee Olivia W. , Wang Amy , McIver Andrew , Zheng Hongchao , Wang Xiaodong , Xu Xin , Jadhav Ajit , Simeonov Anton , Shen Min , Boxer Matthew B. , Hall Matthew D.
Published: April 2017

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that are mutated in a variety of cancers to confer a gain-of-function activity resulting in the accumulation and secretion of an oncometabolite, D-2-hydroxyglutarate (2-HG). Accumulation of 2-HG can result in epigenetic dysregulation and a block in cellular differentiation, suggesting these mutations play a role in neoplasia. Based on its potential as a cancer target, a number of small molecule inhibitors have been developed to specifically inhibit mutant forms of IDH (mIDH1 and mIDH2). Here, a panel of mIDH inhibitors were systematically profiled using biochemical, cell-based, and tier-one ADME techniques. We quantified the biochemical effect of each inhibitor on mIDH1 (R132H and R132C) and mIDH2 (R172Q). The effect of these inhibitors on 2-HG concentrations in seven cell lines representing five different IDH1 mutations in both 2D and 3D cell cultures was assessed. Target engagement of these inhibitors was analyzed utilizing cellular thermal shift assays (CETSA), the effects of inhibitors on reversing 2-HG-induced block on leukemic cellular differentiation. We conclude from our mIDH1 assay panel that AG-120 and a Novartis inhibitor exhibited excellent activity in all biochemical and most cellular assays. While AG-120 has superior DMPK properties, it lacks efficacy a leukemic differentiation model. In conclusion, we present a comprehensive suite ofin vitropreclinical drug development assays that can be used as a tool-box to identify lead compounds for mIDH drug discovery programs, as well as what we believe is the most comprehensive publically available dataset on the top mIDH inhibitors.
Testing the principles of Mendelian randomization: Opportunities and complications on a genomewide scale
Authors: Taylor M , Tansey KE , Lawlor DA , Bowden J , Evans DM , Davey Smith G , Timpson NJ
Published: April 2017

Background

Mendelian randomization (MR) uses genetic variants as instrumental variables to assess whether observational associations between exposures and disease reflect causal relationships. MR requires genetic variants to be independent of factors that confound observational associations.

Methods

Using data from the Avon Longitudinal Study of Parents and Children, associations within and between 121 phenotypes and 13,720 genetic variants (from the NHGRI-EBI GWAS catalog) were examined to assess the validity of MR assumptions.

Results

Amongst 7,260 pairwise comparisons between the 121 phenotypes, 2,188 (30%) provided evidence of association, where 363 were expected at the 5% level (observed:expected ratio=6.03; 95% CI: 5.42, 6.70; χ2=9682.29; d.f. =1, P≤1x10-50). Amongst 1,660,120 pairwise associations between phenotypes and genotypes, 86,748 (5.2%) gave evidence of association at the same threshold, where 83,006 were expected (observed:expected ratio=1.05; 95% CI: 1.04, 1.05; χ2=117.57; d.f. =1, P=2.15x10-27). Amongst 1,171,764 pairwise associations between the phenotypes and LD pruned independent genetic variants, 60,136 (5.1%) gave evidence of association, where 58,588 were expected (observed:expected ratio=1.03; 95% CI: 1.03, 1.08; χ2= 43.05; d.f. = 1, P=5.33x10-11).

Conclusion

These results confirm previously observed patterns of phenotypic correlation. They also provide evidence of a substantially lower level of association between genetic variants and phenotypes, with residual inflation the likely product of indistinguishable real genetic association, multiple variables measuring the same biological phenomena, or pleiotropy. These results reflect the favorable properties of genetic instruments for estimating causal relationships, but confirm the need for functional information or analytical methods to account for pleiotropic events.
Genetic control of age-related gene expression and complex traits in the human brain
Authors: Martin Trevor , Fraser Hunter B.
Published: April 2017

Age is the primary risk factor for many of the most common human diseases—particularly neurodegenerative diseases—yet we currently have a very limited understanding of how each individual’s genome affects the aging process. Here we introduce a method to map genetic variants associated with age-related gene expression patterns, which we call temporal expression quantitative trait loci (teQTL). We found that these loci are markedly enriched in the human brain and are associated with neurodegenerative diseases such as Alzheimer’s disease and Creutzfeldt-Jakob disease. Examining potential molecular mechanisms, we found that age-related changes in DNA methylation can explain some cis-acting teQTLs, and that trans-acting teQTLs can be mediated by microRNAs. Our results suggest that genetic variants modifying age-related patterns of gene expression, acting through both cis- and trans-acting molecular mechanisms, could play a role in the pathogenesis of diverse neurological diseases.
Lethal Haplotypes and Candidate Causal Mutations in Angus Cattle
Authors: Hoff Jesse L. , Decker Jared E. , Schnabel Robert D. , Taylor Jeremy F.
Published: April 2017

Background

If unmanaged, high rates of inbreeding in livestock populations adversely impact their reproductive fitness. In beef cattle, historical selection strategies have increased the frequency of several segregating fatal autosomal recessive polymorphisms. Selective breeding has also decreased the extent of haplotypic diversity genome-wide. By identifying haplotypes for which homozygotes are not observed but would be expected based on their frequency, developmentally lethal recessive loci can be localized. This analysis comes without the need for observation of the loss-associated phenotype (e.g., failure to implant, first trimester abortion, deformity at birth). In this study, haplotypes were estimated for 3,961 registered Angus individuals using 52,545 SNP loci using findhap v2, which exploited the complex pedigree among the individuals in this population.

Results

Seven loci were detected to possess haplotypes that were not observed in homozygous form despite a sufficiently high frequency and pedigree-based expectation of homozygote occurrence. These haplotypes were identified as candidates for harboring autosomal recessive lethal alleles. Of the genotyped individuals, 109 were resequenced to an average 27X depth of coverage to identify putative loss-of-function alleles genome-wide and had variants called using a custom in-house developed pipeline. For the candidate lethal-harboring haplotypes present in these bulls, sequence-called genotypes were used to identify concordant variants. In addition, whole-genome sequence imputation of variants was performed into the set of 3,961 genotyped animals using the 109 resequenced animals to identify candidate lethal recessive variants at the seven loci.

Conclusions

Selective breeding programs could utilize the predicted lethal haplotypes associated with SNP genotypes. Sequencing and other methods for identifying the causal variants underlying these haplotypes can allow for more efficient methods of management such as gene editing. These two methods in total will reduce the negative impacts of inbreeding on fertility and maximize overall genetic gains.