bluuebunny/crossref_metadata_2025 huggingface dataset:
Exome sequencing study of 20 patients with high myopia
Authors: Wan Ling , Deng Boling , Wu Zhengzheng , Chen Xiaoming
Published: September 2018

Background

High myopia is a common ocular disease worldwide. To expand our current understanding of the genetic basis of high myopia, we carried out a whole exome sequencing (WES) study to identify potential causal gene mutations.

Methods

A total of 20 individuals with high myopia were exome sequenced. A novel filtering strategy combining phenotypes and functional impact of variants was applied to identify candidate genes by multi-step bioinformatics analyses. Network and enrichment analysis were employed to examine the biological pathways involved in the candidate genes.

Results

In 16 out of 20 patients, we identified 20 potential pathogenic gene variants for high myopia. A total of 18 variants were located in myopia-associated chromosomal regions. In addition to the novel mutations found in five known myopia genes (ADAMTS18, CSMD1, P3H2, RPGR, and SLC39A5), we also identified pathogenic variants in seven ocular disease genes (ABCA4, CEP290, HSPG2, PCDH15, SAG, SEMA4A, and USH2A) as novel candidate genes. The biological processes associated with vision were significantly enriched in our candidate genes, including visual perception, photoreceptor cell maintenance, retinoid metabolic process, and cellular response to zinc ion starvation.

Discussion

Systematic mutation analysis of candidate genes was performed using WES data, functional interaction (FI) network, Gene Ontology and pathway enrichment. FI network analysis revealed important network modules and regulator linker genes (EP300, CTNNB1) potentially related to high myopia development. Our study expanded the list of candidate genes associated with high myopia, which increased the genetic screening performance and provided implications for future studies on the molecular genetics of myopia.
O turismo como um instrumento de proteção florestal na Amazônia: uma análise multivariada
Authors: Gazoni Jefferson Lorencini , Brasileiro Iara Lucia Gomes
Published: September 2018

Propósito do tema: A crescente demanda internacional por bens primários tem gerado oportunidades excepcionais para a mineração e para o agronegócio na Amazônia. Isto está promovendo, em muitos casos, a perda progressiva da cobertura do solo. Muitas são as estratégias propostas para a contenção do desmatamento regional, ente elas, o turismo, apontado como uma atividade econômica alternativa e mais sustentável para a região. Objetivo: A finalidade deste estudo foi estimar a importância relativa do turismo para o ritmo do desmatamento no bioma Amazônia no período 2015/2016. Metodologia e abordagem: Foram utilizadas séries de corte para as 91 microrregiões geográficas do bioma, nas quais foi aplicada a técnica de regressão linear múltipla associada à decomposição das covariâncias pela Medida de Pratt. Resultados: Os resultados sugerem que o desmatamento é uma função da pecuária bovina, da agricultura, da extração de madeira, dos assentamentos rurais, das áreas protegidas e, entre outros, do turismo. Identificou-se uma correlação inversa entre o turismo e as taxas anuais de desmatamento do bioma. Originalidade: Os resultados deste estudo permitem propor o desenvolvimento responsável do turismo como uma estratégia para a proteção da cobertura florestal da Amazônia.
Metformin blocks MYC protein synthesis in colorectal cancer via mTOR‐4EBP‐eIF4E and MNK1‐eIF4G‐eIF4E signaling
Authors: Shen Peng , Reineke Lucas C. , Knutsen Erik , Chen Meng , Pichler Martin , Ling Hui , Calin George A.
Published: September 2018

The antidiabetic drug metformin has been associated with reduced colorectal cancer (CRC) risk and improved prognosis of CRC patients. However, the detailed mechanisms underlying such beneficial effects remain unknown. In this study, we aimed to evaluate metformin activity in CRC models and unveil the underlying molecular mechanisms. We showed that metformin inhibits CRC cell proliferation by arresting cells in the G1 phase of the cell cycle and dramatically reduces colony formation of CRC cells. We discovered that metformin causes a robust reduction of MYC protein level. Through the use of luciferase assay and coincubation with either protein synthesis or proteasome inhibitors, we demonstrated that regulation of MYC by metformin is independent of the proteasome and 3′ UTR‐mediated regulation, but depends on protein synthesis. Data from polysome profiling and ribopuromycylation assays showed that metformin induced widespread inhibition of protein synthesis. Repression of protein synthesis by metformin preferentially affects cell cycle‐associated proteins, by altering signaling through the mTOR‐4EBP‐eIF4E and MNK1‐eIF4G‐eIF4E axes. The inhibition of MYC protein synthesis may underlie metformin's beneficial effects on CRC risk and prognosis.
A Process Controls Approach to Cell Signalling
Authors: McGirr Brooke A , Tubergen Philip J , Hartz Julie L , Myers Paul J , Pitman Mark A , Lazzara Matthew J , Deppmann Christopher D
Published: September 2018

Many biological questions can benefit from the diverse perspectives of multiple disciplines, including engineering. In the last several decades, biological research has been advanced from engineering approaches to delineate processes including stem cell differentiation, optimizing cancer therapies, and building physical and genetic tools to manipulate cell function. The collaboration between fields necessitates a common language to bridge concepts that have historically been developed for engineering and emergent properties of biological systems. By utilizing the expertise of both fields, greater advances can be reached in biological research through the application of large data sets and modelling of biological processes. Parallels between cellular signalling and engineering process controls include feedback and feed‐forward loops, amplification and thresholds; in both fields, these subprocesses contribute widely to the overall function of the cell and engineered system. Feedback and feed‐forward loops, amplification and thresholds, along with their importance in biology and process controls and their contributions to overall function.

Key Concepts

Parallels exist between the structure and function of cellular signal transduction architectures and engineering process control concepts.

Disruptions in signalling pathways and process control systems can have detrimental consequences, including health disorders and manufacturing casualties, respectively.

Understanding cell signalling mechanisms in a process control context can provide a novel perspective for understanding treatments and therapies of diseases stemming from dysregulation of cellular controls.

Similarities between everyday process controls like air conditioning can help unravel apparent complexities in cellular signaling.

Using extended analogy between process controls and cellular signaling may provide insights into mechanisms of manipulation not previously explored.
Structural Chemistry of Hypervalent Iodine Compounds
Authors: Justik Michael W.
Published: September 2018

To quote the modernist architectural mantra: “form follows function.” HVI compounds possess highly unique geometric features, which are highly tunable toward reactivity, making them impressively useful tools in modern synthetic chemistry. This chapter will endeavor to discuss the latest investigations into the structures of λ3‐ and λ5‐iodanes and revisit the past work with fresh insight. A new taxonomy for organizing hypervalent iodine compounds by structure will be introduced. The latest understanding of halogen bonding will be applied to the long‐observed “secondary‐bonding” interactions present in many solid‐state structures. These interactions are now understood to play a key role in the opening stages of reaction mechanisms involving hypervalent iodine reagents, especially in arylation chemistry. The X‐ray crystallographic data from a representative scope of iodanes will be complied in one work, as an easily accessible reference for those new to the field or those cogitating new possible structural motifs to solve synthetic challenges.
Introduction to the Special Issue: An Update on Informal and Incidental Learning Theory
Authors: Marsick Victoria J. , Watkins Karen E.
Published: September 2018

This chapter introduces a constructivist model of informal and incidental learning developed in the 1990s, and various perspectives that authors subsequently use to reexamine and trouble how adult educators conceptualize and practice informal and incidental learning in today's environment.
The Online Alone Together Paradox as a Context for Incidental and Informal Learning
Authors: Cox Alexandra
Published: September 2018

The “alone together” paradox is a phenomenon that occurs when adults make meaning of their learning in the online environment. By way of being “alone together,” the online environment manifests a context for incidental and informal learning.
Concurrent Change in Quadriceps Strength and Physical Function Over Five Years in the Multicenter Osteoarthritis Study
Authors: Bacon Kathryn L. , Segal Neil A. , Øiestad Britt Elin , Lewis Cora E. , Nevitt Michael C. , Brown Carrie , Felson David T.
Published: September 2018

Objective

Quadriceps weakness, associated with functional limitations, is a target of treatment of knee osteoarthritis (OA). Limited data exist on the relationship between modest strength increases and improvements in function. The aim of this study was to evaluate concurrent change in strength and physical function over 5 years.

Methods

Among subjects from the Multicenter Osteoarthritis (MOST) study, we excluded those with knee replacement after baseline. A 3‐category variable defined whether, at 5 years, knee extensor strength increased, decreased, or remained within 15% of baseline, a clinically important cut‐off. The outcomes were the 5‐times sit‐to‐stand test, 20‐meter walk test, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) physical function score, and 3 individual physical functions from WOMAC: arising from a chair, going up stairs, and getting on/off toilet. Linear and logistic models, stratified by sex, evaluated associations between change in strength and change in physical function over 5 years. To compare weaker versus stronger women, we stratified analyses at 56 Nm baseline strength.

Results

Among 1,534 participants (60.6% women), 22% of men and 30% of women increased strength by at least 15% at 5 years. Compared with women whose strength did not change, women whose strength increased had improved chair stand performance (odds ratio 2.27 [95% confidence interval 1.56, 3.30]) but no improvement in other functions. In men, an increase in strength was not associated with significant improvement in physical function. Similar results were observed for a 20% or 30% increase.

Conclusion

Modest improvement in quadriceps strength was associated with improved chair stand performance in women but not in men. Most functions did not improve with an increase in strength, and targeted interventions may be required to improve functional status.
Patient Perspectives on Intravenous Biologics for Rheumatologic Disease
Authors: Grisanti Lucas , Kwiatkowski Alysia , Dyrda Peter , Field Ellen , Grisanti Joseph , Hatem James , Dehoratius Raphael J. , Gaylis Norman
Published: September 2018

Objective

Two surveys were conducted with patients with rheumatologic diseases to evaluate perceptions of different routes of administration (intravenous [IV] or subcutaneous [SC]) for biologic therapy.

Methods

In Survey I, patient preferences toward biologic treatment were evaluated at a rheumatology practice in Buffalo, New York. In Survey II, Canadian patients enrolled in the BioAdvance patient support program and scheduled to receive IV biologic therapy were asked about their opinions of IV treatment.

Results

In Survey I, 243 rheumatology patients participated. Median patient age was 60 years, 76% were female, and 44% were naive to treatment with biologic agents. Among biologic‐naive patients, the majority (56%) were open to either SC or IV treatment; biologic‐naive women were more likely than men to express a preference for the route of administration. In Survey II, 1,598 patients from the BioAdvance program (including 306 rheumatology patients) completed the full survey. Among the rheumatology patients, the median age was 49 years, 58% were female, and 61% had not previously taken biologics before enrolling in the BioAdvance program. The median rating of IV favorability (on a 10‐point scale, with higher numbers indicating increased favorability) recalled by rheumatology patients was 5 prior to their first program infusion, which increased to 9 after multiple treatment infusions.

Conclusion

These survey results indicate that patients with rheumatoid arthritis are generally open to IV treatment and express high satisfaction with IV therapy. Additional patient and provider education may improve shared decision‐making regarding biologic therapy administration options.
Repetitive Knee Bending and Synovitis in Individuals at Risk of and With Knee Osteoarthritis: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium
Authors: Van Ginckel Ans , Wittoek Ruth , De Mits Sophie , Calders Patrick
Published: September 2018

Objective

To investigate associations between engagement in knee bending (stair climbing, kneeling, squatting, heavy lifting, getting in/out of a squatting position) and synovitis prevalence on noncontrast magnetic resonance imaging (MRI) in individuals at risk of and with knee osteoarthritis.

Methods

We included baseline data from 594 participants (mean ± SD age 61.5 ± 8.9 years, 61% had Kellgren/Lawrence grade ≥2; 59% were female; mean ± SD body mass index was 30.7 ± 4.8 kg/m2) of the Osteoarthritis Biomarker Consortium Foundation for the National Institutes of Health project. Knee bending activities were queried by a standard questionnaire, and the severity of Hoffa synovitis and effusion synovitis (surrogate outcomes of synovitis) were graded using the MRI OsteoArthritis Knee Scoring system. Logistic regression was used, unadjusted and adjusted, for metabolic syndrome, physical activity level, and sex. A grade ≥1 defined synovitis prevalence, with a grade ≥2 cutoff implemented in sensitivity analyses.

Results

The prevalence of grade ≥1 Hoffa synovitis and effusion synovitis equaled 59% (n = 353) and 62% (n = 366), respectively. Adjusted for confounders, kneeling for ≥30 minutes during a single day was associated with grade ≥1 Hoffa synovitis prevalence (odds ratio [OR] 1.65 [95% confidence interval (95% CI) 1.11–2.47]). Participants engaging in this activity ≤1 day per week had greater odds for prevalent Hoffa synovitis than those who did not perform the activity (OR 1.88 [95% CI 1.11–3.18]). No other significant associations were found. Sensitivity analyses yielded similar findings.

Conclusion

In this selected sample with a preponderance of grade ≥1 Hoffa and/or effusion synovitis on noncontrast MRI, only prolonged kneeling was associated with Hoffa synovitis prevalence. Replication in other samples is warranted.
Carbon‐Based Photocathode Materials for Solar Hydrogen Production
Authors: Bellani Sebastiano , Antognazza Maria Rosa , Bonaccorso Francesco
Published: September 2018

Hydrogen is considered a promising environmentally friendly energy carrier for replacing traditional fossil fuels. In this context, photoelectrochemical cells effectively convert solar energy directly to H2 fuel by water photoelectrolysis, thereby monolitically combining the functions of both light harvesting and electrolysis. In such devices, photocathodes and photoanodes carry out the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), respectively. Here, the focus is on photocathodes for HER, traditionally based on metal oxides, III–V group and II–VI group semiconductors, silicon, and copper‐based chalcogenides as photoactive material. Recently, carbon‐based materials have emerged as reliable alternatives to the aforementioned materials. A perspective on carbon‐based photocathodes is provided here, critically analyzing recent research progress and outlining the major guidelines for the development of efficient and stable photocathode architectures. In particular, the functional role of charge‐selective and protective layers, which enhance both the efficiency and the durability of the photocathodes, is discussed. An in‐depth evaluation of the state‐of‐the‐art fabrication of photocathodes through scalable, high‐troughput, cost‐effective methods is presented. The major aspects on the development of light‐trapping nanostructured architectures are also addressed. Finally, the key challenges on future research directions in terms of potential performance and manufacturability of photocathodes are analyzed.
Visible‐Light‐Responsive 2D Cadmium–Organic Framework Single Crystals with Dual Functions of Water Reduction and Oxidation
Authors: Xiao Yejun , Qi Yu , Wang Xiuli , Wang Xiaoyu , Zhang Fuxiang , Li Can
Published: September 2018

The development of new metal–organic frameworks (MOFs) with dual functions of both water reduction and oxidation under visible‐light irradiation is highly desirable for promising solar water splitting, but is not yet reported. Herein, a cadmium‐based MOF (denoted as “Cd‐TBAPy”) single crystal with a 2D layered framework by employing 1,3,6,8‐tetrakis(p‐benzoic acid)pyrene (H4TBAPy) as an organic linker is reported, which exhibits good visible‐light absorption with edge of ≈600 nm. The Mott–Schottky (M–S) measurement and UV–vis analysis integrally reveal that the Cd‐TBAPy is an n‐type semiconductor with a bandgap of ≈2.15 eV whose conduction and valence band are estimated to be −0.05 and 2.10 eV, respectively. Together with loading of Pt or CoPi cocatalyst, the Cd‐TBAPy is active for both water reduction and oxidation in the presence of scavengers under visible‐light irradiation. Especially, the optimized apparent quantum efficiency for O2 evolution reaches 5.6% at 420 nm, much higher than that of previous MOF‐based photocatalysts reported so far. This is thought to be the first MOF that functions as a photocatalyst for both water reduction and oxidation under visible light, demonstrating the intriguing future of MOF materials in solar‐to‐chemical energy conversion.
An In Situ Reversible Heterodimeric Nanoswitch Controlled by Metal‐Ion–Ligand Coordination Regulates the Mechanosensing and Differentiation of Stem Cells
Authors: Kang Heemin , Zhang Kunyu , Jung Hee Joon , Yang Boguang , Chen Xiaoyu , Pan Qi , Li Rui , Xu Xiayi , Li Gang , Dravid Vinayak P. , Bian Liming
Published: September 2018

In situ and cytocompatible nanoswitching by external stimuli is highly appealing for reversibly regulating cellular adhesion and functions in vivo. Here, a heterodimeric nanoswitch is designed to facilitate in situ switchable and combinatorial presentation of integrin‐binding cell‐adhesive moieties, such as Mg2+ and Arg‐Gly‐Asp (RGD) ligand in nanostructures. In situ reversible nanoswitching is controlled by convertible coordination between bioactive Mg2+ and bisphosphonate (BP) ligand. A BP‐coated gold‐nanoparticle monomer (BP‐AuNP) on a substrate is prepared to allow in situ assembly of cell‐adhesive Mg2+‐active Mg‐BP nanoparticles (NPs) on a BP‐AuNP surface via Mg2+‐BP coordination, yielding heterodimeric nanostructures (switching “ON”). Ethylenediaminetetraacetic acid (EDTA)‐based Mg2+ chelation allows in situ disassembly of Mg2+‐BP NP, reverting to Mg2+‐free monomer (switching “OFF”). This in situ reversible nanoswitching on and off of cell‐adhesive Mg2+ presentation allows reversible cell adhesion and release in vivo, respectively, and spatiotemporally controls cyclic cell adhesion. In situ heterodimeric assembly of dual RGD ligand‐ and Mg2+‐active RGD‐BP‐Mg2+ NP (switching “Dual ON”) further tunes and promotes focal adhesion, spreading, and differentiation of stem cells. The modular nature of this in situ nanoswitch can accommodate various bioactive nanostructures via metal‐ion–ligand coordination to regulate diverse cellular functions in vivo in reversible and compatible manner.
Photophysical Pathways in Highly Sensitive Cs2AgBiBr6 Double‐Perovskite Single‐Crystal X‐Ray Detectors
Authors: Steele Julian A. , Pan Weicheng , Martin Cristina , Keshavarz Masoumeh , Debroye Elke , Yuan Haifeng , Banerjee Subhasree , Fron Eduard , Jonckheere Dries , Kim Cheol Woong , Baekelant Wouter , Niu Guangda , Tang Jiang , Vanacken Johan , Van der Auweraer Mark , Hofkens Johan , Roeffaers Maarten B. J.
Published: September 2018

The sensitive detection of X‐rays embodies an important research area, being motivated by a common desire to minimize the radiation doses required for detection. Among metal halide perovskites, the double‐perovskite Cs2AgBiBr6 system has emerged as a promising candidate for the detection of X‐rays, capable of high X‐ray stability and sensitivity (105 μC Gy−1 cm−2). Herein, the important photophysical pathways in single‐crystal Cs2AgBiBr6 are detailed at both room (RT) and liquid‐nitrogen (LN2T) temperatures, with emphasis made toward understanding the carrier dynamics that influence X‐ray sensitivity. This study draws upon several optical probes and an RT excitation model is developed which is far from optimal, being plagued by a large trap density and fast free‐carrier recombination pathways. Substantially improved operating conditions are revealed at 77 K, with a long fundamental carrier lifetime (>1.5 µs) and a marked depopulation of parasitic recombination pathways. The temperature dependence of a single‐crystal Cs2AgBiBr6 X‐ray detecting device is characterized and a strong and monotonic enhancement to the X‐ray sensitivity upon cooling is demonstrated, moving from 316 μC Gy−1 cm−2 at RT to 988 μC Gy−1 cm−2 near LN2T. It is concluded that even modest cooling—via a Peltier device—will facilitate a substantial enhancement in device performance, ultimately lowering the radiation doses required.
Motion Control of Piezoelectric Tripod Platform via Feedforward Hysteresis Compensation
Authors: Kim Hyeong‐Geon , Kim Jong‐Nam , Na Tae‐Won , Park Kwang‐Chun , Oh Il‐Kwon
Published: September 2018

In this study, a precise motion control strategy for a piezoelectric tripod manipulator integrated with compliant mechanisms based on feedforward hysteresis compensation and feedback control is reported. The piezoelectric tripod platform is designed with three piezoelectric legs to produce large transverse stroke and angular motions with three degrees‐of‐freedom (3‐DOF). The piezoelectric actuation legs, which are made with four piezoelectric stack actuators and reverse‐type compliant mechanisms, have highly nonlinear inherent hysteresis, resulting in critical difficulties of accurate motion control. To properly compensate inherent hysteresis of the present 3‐DOF tripod manipulator stemming from interaction between piezoelectric stack actuators and compliant amplification mechanisms, a feedforward hysteresis control is successfully implemented with a third‐order rate‐dependent polynomial fit. Present results reveal that the feedforward compensator based on the rate‐dependent hysteresis model and feedback control integrated with rate‐independent compensator can be successfully applied to the motion control of the piezoelectric 3‐DOF tripod manipulator with severe inherent hysteresis.
When Memristance Crosses the Path with Humidity Sensing—About the Importance of Protons and Its Opportunities in Valence Change Memristors
Authors: Messerschmitt Felix , Jansen Maximilian , Rupp Jennifer L. M.
Published: September 2018

Resistive switching devices based on oxides have outstanding properties, making them a promising candidate to replace today's transistor‐based computer memories as non‐volatile valence change memories, and can even find future application in neuromorphic computing. To date, the scientific discussion is so far mainly restricted to oxygen vacancy contributions disregarding the role of protonic defects on resistive switching. In this work, the effect of moisture and protonic contributions on resistive switching by changes in the surface to bulk ratio and oxide surface exposure of the oxide SrTiO3 is studied. Here, a linear to exponential SET current density dependency, when changing the film thickness by a factor of four, is found, whereby the surface‐to‐bulk ratio of the oxide is significantly changed. This behavior is discussed in terms of differences in total concentration of oxygen vacancies and their interplay with moisture. For classic memristor applications, this study demonstrates that protonic defects need to be accounted for memristor characteristics, as they crucially influence the switching characteristics, and give new opportunities as an additional handle to actively tune the switching performance. This memristive dependency on protonic defects opens a whole plethora of new modulatable sensor characteristics like creating humidity sensors using the property of memristance.
Solution‐Grown Serpentine Silver Nanofiber Meshes for Stretchable Transparent Conductors
Authors: Li Peng , Zhang Wei , Ma Jiangang , Wang Xiao , Xu Haiyang , Cong Lujia , Liu Yichun
Published: September 2018

Metal fiber nanomeshes, fabricated by depositing metals on the electrospun nanofiber templates, have come into the spotlight as promising stretchable transparent conductors. However, most currently stretchable metal fibers are produced via expensive vacuum deposition methods. This work reports a low‐cost approach to prepare transparent, conducting, and serpentine silver nanofiber mesh elastomers (SNME). The key of forming SNME is buckling the electrospun polymer nanofiber templates into wavy structure and subsequently electrolessly depositing silver on the templates. Optoelectronic performance of the SNME is elaborately optimized by tuning the number of Ag nanoseeds and the electroless deposition time. The resulting SNME exhibit a high visible light transmittance of 81%, a low sheet resistance of 9.2 Ω sq−1, and an excellent stretchability with 2.4‐times of resistance increases after repeated stretching to 70% for 1000 cycles. In situ observations indicate that the SNME are capable of straightening and rearranging to adapt to the tensile deformation. Its application potential as an ideal platform for fabricating intelligent interfaces is demonstrated by using the SNME as a wearable resistance sensor which can monitor finger joint motions.
Pediatric Case Exposure During Emergency Medicine Residency
Authors: Li Joyce , Roosevelt Genie , McCabe Kerry , Preotle Jane , Pereira Faria , Takayesu James K. , Monuteaux Michael , Bachur Richard G.
Published: September 2018

Objective

While emergency medicine (EM) physicians treat the majority of pediatric EM (PEM) patients in the United States, little is known about their PEM experience during training. The primary objective was to characterize the pediatric case exposure and compare to established EM residency training curricula among EM residents across five U.S. residency programs.

Methods

We performed a multicenter medical record review of all pediatric patients (aged < 18 years) seen by the 2015 graduating resident physicians at five U.S. EM training programs. Resident‐level counts of pediatric patients were measured and specific counts were classified by the 2016 Model of Clinical Practice of Emergency Medicine (MCP) and Pediatric Emergency Care Applied Research Network (PECARN) diagnostic categories. We assessed variability between residents and between programs.

Results

A total of 36,845 children were managed by 68 residents across all programs. The median age was 6 years. The median number of patients per resident was 660 with an interquartile range of 336. The most common PECARN diagnostic categories were trauma, gastrointestinal, and respiratory disease. Thirty‐two core MCP diagnoses (43% of MCP list) were not seen by at least 50% of the residents. We found statistically significant variability between programs in both PECARN diagnostic categories (p < 0.01) and MCP diagnoses (p < 0.01).

Conclusion

There is considerable variation in the number of pediatric patients and the diagnostic case volume seen by EM residents. The relationship between this case variability and competence upon graduation is unknown; further investigation is warranted to better inform program‐specific curricula and to guide training requirements in EM.
Trajectories of Posttraumatic Stress and Depression in Police and Community Members Following the Violence during Civil Unrest in Ferguson, Missouri
Authors: Galovski Tara E. , Peterson Zoe D. , Fox‐Galalis Annie
Published: September 2018

Longitudinal research following discreet traumatic events reveals distinct symptom trajectories in untreated survivors of trauma. Trajectories within communities exposed to shared, prolonged violence involving subgroups differing in perspectives, and roles during the event have not been studied. This study examined trajectories of posttraumatic stress (PTS) and depressive symptoms secondary to exposure to violence during civil unrest in citizens (n = 311) and law enforcement (n = 255) over 1.5 years following exposure. Latent class growth modeling was used to examine trajectories of PTS and depressive symptoms. Four‐class quadratic solutions for both PTS and depressive symptoms demonstrated best fit. Similar patterns emerged for such that most participants were classified as resistant (57% and 67%, respectively), followed by resilience (23.8% and 17.2%), chronic (12.6% and 12.0%), and worsening (6.1% and 4.4%). When all predictors were entered in a single model, race, and membership in citizen or law enforcement groups did not distinguish trajectories of recovery. Higher income and social support emerged as consistent protective factors against PTS and depressive symptoms, while trauma history emerged as a risk factor for PTS. Women were more at risk for depressive symptoms only. Implications for improving police/civilian relations in Ferguson, Missouri, and other communities are discussed.
The presence of females induces elevated cortisol levels in an alpha male: Experimental evidence in chimpanzees
Authors: Kutsukake Nobuyuki , Teramoto Migaku , Honma Seijiro , Mori Yusuke , Ikeda Koki , Yamamoto Rain , Ishida Takafumi , Hasegawa Toshikazu
Published: September 2018

Objectives

In group‐living primates, it has been reported that the alpha male exhibits high concentrations of cortisol and testosterone in the context of mating competition. We investigated how the presence of females affected salivary cortisol and testosterone levels in males from a small captive group of chimpanzees (Pan troglodytes). Specifically, we assessed whether the presence of females resulted in a rapid increase in salivary cortisol and testosterone levels in the alpha male.

Materials and methods

We compared the social behavior and salivary hormone concentrations of four males before and after the presentation of receptive females. Three times a day, we collected saliva samples, a useful matrix for investigating short‐term hormonal changes, and measured cortisol and testosterone concentration by liquid chromatography–tandem mass spectrometry (LC–MS/MS).

Results

The frequency of inter‐male aggression increased in the presence of females, indicating intense competition among males. Salivary cortisol levels increased in all males in the presence of females; however, the increase was significantly more pronounced in the alpha male. We found a complex three‐way interaction among the presence of females, sampling timings, and male dominance rank in the analysis of salivary testosterone. Contrary to our prediction, a post hoc analysis revealed that salivary testosterone levels decreased after female introduction and that the alpha male did not show a higher level of salivary testosterone.

Conclusions

Our study provides experimental evidence suggesting that the presence of females plays a significant role in the rank‐related variation in the cortisol levels in male chimpanzees. Furthermore, our findings demonstrate the usefulness of salivary hormones for detecting short‐term physiological changes in studies of socioendocrinology.
The Crystal Structure of a Class of Cyclases that Catalyze the Cope Rearrangement
Authors: Chen Chun‐Chi , Hu Xiangying , Tang Xueke , Yang Yunyun , Ko Tzu‐Ping , Gao Jian , Zheng Yingying , Huang Jian‐Wen , Yu Zhengsen , Li Liping , Han Shuai , Cai Ningning , Zhang Yonghui , Liu Weidong , Guo Rey‐Ting
Published: September 2018

Found recently in stignomatales, the Stig cyclases catalyze the Cope rearrangement and intramolecular cyclization to produce complex indole alkaloids. Five crystal structures were solved of subfamily 1 and 2 Stig cyclases, which adopt a β‐sandwich fold like the non‐catalytic carbohydrate‐binding motif. Several complex structures were also determined of indole‐based compounds, which are bound to the hydrophobic terminal cavity, where a conserved Asp residue makes an H‐bond to the indole N and triggers the acid‐catalyzed Cope rearrangement. Through analyzing the enzyme–ligand interactions and mutagenesis experiments, several aromatic residues were found important in catalysis. Apart from a common substrate binding mode and catalytic mechanism, potential subfamily variations that may attribute to the different product specificity are implicated. These results shall expand our scope of enzymology, in particular for further investigation of the biosynthetic Cope rearrangement.
Adenine‐Driven Structural Switch from a Two‐ to Three‐Quartet DNA G‐Quadruplex
Authors: Lenarčič Živković Martina , Rozman Jan , Plavec Janez
Published: September 2018

A G‐rich sequence found in the regulatory region of the RANKL gene, which is associated with homeostasis of bone metabolism, folds into a two‐quartet basket‐type G‐quadruplex stabilized by A⋅G⋅A and G⋅G⋅G base‐triads. Perusal of local structural features together with G/A‐to‐T modifications uncovered the critical role of A5 for the formation of a distinct antiparallel two‐quartet topology and not the three‐quartet topology that would be expected based on the sequence with four GGG‐tracts alone. The structural changes induced by the A5‐to‐T5 modification include a switch in orientation and relative positions of G‐strands that together with anti to syn reorientation of G12 provide insights into the complexity of the interactions that influence the folding of G‐rich DNA. Understanding the impact of loop residues on the stability and formation of G‐quadruplexes advances our knowledge and ability to predict structures adopted by G‐rich sequences, which are involved in regulatory mechanisms in the cell, and may also facilitate drug design.
Platinum(II)‐Based Supramolecular Scaffold‐Templated Side‐by‐Side Assembly of Gold Nanorods through Pt⋅⋅⋅Pt and π–π Interactions
Authors: Wong Yip‐Sang , Leung Frankie Chi‐Ming , Ng Maggie , Cheng Heung‐Kiu , Yam Vivian Wing‐Wah
Published: September 2018

The side‐by‐side assembly of gold nanorods (GNRs) was shown to be directed by the supramolecular scaffolds formed by sulfonate‐containing alkynylplatium(II) terpyridine complexes. Driven by Pt⋅⋅⋅Pt and π–π stacking interactions, the PtII complex has a high propensity to assemble in water with the head‐to‐tail stacking arrangement to construct supramolecular scaffolds, in which the sulfonate groups on the terpyridine ligand at the peripheral position preferentially bind to the sides of the GNRs. The extent of the assembly of the GNRs into ladder rung‐like nanostructures can be modulated by the concentration of the PtII complex. The Pt⋅⋅⋅Pt interaction‐assisted formation of the scaffolds and its directed assembly of GNRs were characterized by UV/Vis spectroscopy, quantum‐chemical modeling, electron microscopy, energy dispersed X‐ray (EDX) analysis, and SERS. This work provides insights for the construction of higher‐ordered nano‐assemblies using both Pt⋅⋅⋅Pt interactions and template‐directed approaches.
Redistricting without gerrymandering, utilizing the convexity ratio, and other applications to business and industry
Authors: Bozeman James R. , Davey Matt , Hutchins Sam , Mori Jillian , Nicholson Timothy , Salvadore Abigail , St. Germain Kayla
Published: September 2018

We exhibit the convexity ratio of voting districts in many states of the USA, which have had their plans challenged. The convexity ratio confirms that these states have likely been gerrymandered. We then redistrict the largest of these states, Texas, avoiding gerrymandering by starting with counties and their populations and only adding or deleting municipalities as necessary. The voting districts themselves are made as nicely shaped as possible, using the convexity ratio as a guide. Those districts with immovable boundaries that cause a poorly shaped designation, a topic of much current research, are dealt with appropriately in the context of the convexity ratio. Algorithms for finding the convexity ratio and designing non‐gerrymandered districts are shown. Other more probabilistic convexity measures are discussed. Finally, we comment on how the convexity ratio can be used in other countries, both politically and in other contexts, for example, in territory design for geomarketing and on the electrical or police districting problem.
Dynamic clinical prediction models for discrete time‐to‐event data with competing risks—A case study on the OUTCOMEREA database
Authors: Heyard Rachel , Timsit Jean‐François , Essaied Wafa Ibn , Held Leonhard ,             on behalf of the COMBACTE‐MAGNET consortium
Published: September 2018

The development of clinical prediction models requires the selection of suitable predictor variables. Techniques to perform objective Bayesian variable selection in the linear model are well developed and have been extended to the generalized linear model setting as well as to the Cox proportional hazards model. Here, we consider discrete time‐to‐event data with competing risks and propose methodology to develop a clinical prediction model for the daily risk of acquiring a ventilator‐associated pneumonia (VAP) attributed to P. aeruginosa (PA) in intensive care units. The competing events for a PA VAP are extubation, death, and VAP due to other bacteria. Baseline variables are potentially important to predict the outcome at the start of ventilation, but may lose some of their predictive power after a certain time. Therefore, we use a landmark approach for dynamic Bayesian variable selection where the set of relevant predictors depends on the time already spent at risk. We finally determine the direct impact of a variable on each competing event through cause‐specific variable selection.
Advances and Future Perspectives in 4D Bioprinting
Authors: Ashammakhi Nureddin , Ahadian Samad , Zengjie Fan , Suthiwanich Kasinan , Lorestani Farnaz , Orive Gorka , Ostrovidov Serge , Khademhosseini Ali
Published: September 2018

Three‐dimensionally printed constructs are static and do not recapitulate the dynamic nature of tissues. Four‐dimensional (4D) bioprinting has emerged to include conformational changes in printed structures in a predetermined fashion using stimuli‐responsive biomaterials and/or cells. The ability to make such dynamic constructs would enable an individual to fabricate tissue structures that can undergo morphological changes. Furthermore, other fields (bioactuation, biorobotics, and biosensing) will benefit from developments in 4D bioprinting. Here, the authors discuss stimuli‐responsive biomaterials as potential bioinks for 4D bioprinting. Natural cell forces can also be incorporated into 4D bioprinted structures. The authors introduce mathematical modeling to predict the transition and final state of 4D printed constructs. Different potential applications of 4D bioprinting are also described. Finally, the authors highlight future perspectives for this emerging technology in biomedicine.
Trials and tribulations of neoadjuvant therapy in pancreatic cancer
Authors: Del Chiaro M , Søreide K
Published: September 2018

Difficult to prove benefit
Oral Infection Involving Nocardia and Actinomyces: A Case Report
Authors: Arora Kirandeep K. , Gruwell Scott F. , Cobb Charles M.
Published: September 2018

Introduction

Both Actinomyces and Nocardia are Gram‐positive microbes characterized by a filamentous morphology. Both can be causative agents in slowly progressive, localized, or disseminated infections that are rare and typically occur in immunocompromised patients. Oral infections involving both microorganisms are very rare.

Case Presentation

A black male with a history of Type 2 diabetes was referred with a chief complaint of a persistent 3 mm × 3 mm swelling facial to the mandibular central incisors. The swelling was asymptomatic except for occasional discharge of purulent exudate. Examination revealed 5‐ to 6‐mm mesio‐lingual and mid‐lingual probing depths. Radiographs revealed a well‐defined radiolucency between the roots of teeth #24 and #25. A full‐thickness gingival flap was reflected exposing an oval‐shaped bony defect, which was debrided and the contents submitted for microscopic examination. The resulting defect was filled with demineralized freeze‐dried bone allograft (DFDBA) and capped with calcium sulfate. The patient was prescribed amoxicillin and 0.12% chlorhexidine gluconate mouthrinse. Examination of the biopsied tissue revealed both Actinomyces and Nocardia microorganisms. The patient was followed for 24 months and remains symptom‐free with noted radiographic evidence of bone fill in the lesion area.

Conclusions

This may be the first published report of an oral infection featuring both Actinomyces and Nocardia. The case reinforces the importance of microscopic examination of biopsy material removed from unusual and persistent pathologic lesions that are destructive of bone.
Ligand Migration from Cluster to Support: A Crucial Factor for Catalysis by Thiolate‐protected Gold Clusters
Authors: Zhang Bei , Sels Annelies , Salassa Giovanni , Pollitt Stephan , Truttmann Vera , Rameshan Christoph , Llorca Jordi , Olszewski Wojciech , Rupprechter Günther , Bürgi Thomas , Barrabés Noelia
Published: September 2018

Thiolate protected metal clusters are valuable precursors for the design of tailored nanosized catalysts. Their performance can be tuned precisely at atomic level, e. g. by the configuration/type of ligands or by partial/complete removal of the ligand shell through controlled pre‐treatment steps. However, the interaction between the ligand shell and the oxide support, as well as ligand removal by oxidative pre‐treatment, are still poorly understood. Typically, it was assumed that the thiolate ligands are simply converted into SO2, CO2 and H2O. Herein, we report the first detailed observation of sulfur ligand migration from Au to the oxide support upon deposition and oxidative pre‐treatment, employing mainly S K‐edge XANES. Consequently, thiolate ligand migration not only produces clean Au cluster surfaces but also the surrounding oxide support is modified by sulfur‐containing species, with pronounced effects on catalytic properties.
Directional Self‐Assembly and Photoinduced Polymerization of Diacetylene‐Containing Platinum(II) Terpyridine Complexes
Authors: Fang Shishi , Leung Sammual Yu‐Lut , Li Yongguang , Yam Vivian Wing‐Wah
Published: September 2018

A series of newly designed and synthesized diacetylene‐containing platinum(II) terpyridine complexes exhibited intriguing self‐assembly properties. Facilitated by Pt⋅⋅⋅Pt, π–π stacking, hydrogen‐bonding and hydrophobic–hydrophobic interactions, these complexes are preorganized to readily undergo topochemical polymerization reactions upon photoirradiation. The in situ polymerization of the diacetylene units to form polydiacetylene, indicated by the UV/Vis spectral changes, gel permeation chromatography and dynamic light scattering, was found to alter their assembly behaviours, as revealed by TEM images.
Metallacarboranes on the Road to Anticancer Therapies: Cellular Uptake, DNA Interaction, and Biological Evaluation of Cobaltabisdicarbollide [COSAN]−
Authors: Fuentes Isabel , García‐Mendiola Tania , Sato Shinichi , Pita Marcos , Nakamura Hiroyuki , Lorenzo Encarnación , Teixidor Francesc , Marques Fernanda , Viñas Clara
Published: September 2018

After uptake by U87 MG and A375 cancer cells, cobaltabisdicarbollide [COSAN]− distributes between membrane and nucleus and presents no relevant cytotoxicity against both cell lines even for long incubation times. The cytotoxicity of Na[COSAN] was also tested towards one normal cell line, the V79 fibroblasts, in order to ascertain the noncytotoxic profile of the compound. As the cell's nucleus contains DNA, the interaction between [COSAN]− and double‐stranded calf thymus DNA (CT‐dsDNA) has been investigated. There is a strong interaction between both molecules forming a nanohybrid CT‐dsDNA‐[COSAN] biomaterial, which was fully characterized. Moreover, Na[COSAN] shows characteristic redox peaks ascribed to the oxidation/reduction of Co3+/2+ at a formal potential of −1.444 V and it can be accumulated at a surface‐immobilized DNA layer of glassy carbon electrodes. The equilibrium surface‐binding constants (Kox/Kred), which confirm that [COSAN]− interacts with DNA by an intercalative or electrostatic mode, depending on the ionic strength of the solution, were estimated. In addition, high binding affinity of Na[COSAN] to proteins was observed by 11B{1H} NMR and confirmed in vivo. Finally, biodistribution studies of [COSAN]− in normal mice were run. After administration, Na[COSAN] was distributed into many organs but mainly accumulated in the reticuloendothelial system (RES), including liver and spleen. After 1 h, the formation of aggregates by plasma protein interaction plays a role in the biodistribution profile; the aggregates accumulate mostly in the lungs. Na[COSAN], which displays low toxicity and high uptake by relevant cancer cells accumulating boron within the nucleus, could act as a suitable compound for further developments as boron neutron capture therapy (BNCT) agents.
Low‐Temperature Cross‐Linkable Small Molecules for Fully Solution‐Processed OLEDs
Authors: Lee Sungkoo , Seo Min Hye
Published: September 2018

Cross‐linkable hole‐transporting, host, and electron‐transporting materials with a new cross‐linking group, uracil, are designed and synthesized. These compounds exhibited good solubility in common organic solvents and excellent solvent resistance after cross‐linking at a low temperature of 120 °C. The OLED was fabricated by all‐solution processing using cross‐linkable synthetic compounds, except for the electrodes. This device exhibited a current efficiency of 39.2 cd A−1 and a power efficiency of 15.3 lm W−1.
Bifunctional Molecular Probes for Activity‐Based Visualization of Quinone‐Dependent Amine Oxidases
Authors: Burke Ashley A. , Barrows Luke , Solares Maria J. , Wall Alexander D. , Jakobsche Charles E.
Published: September 2018

The design, synthesis, and evaluation of two bifunctional molecular probes that can be used to visualize quinone‐dependent amine oxidase enzymes in an activity‐dependent manner are described. These probes use alkylhydrazines to irreversibly bind the target enzymes, which can then be visualized with either Western blotting or in‐gel fluorescence. The results show that the Western blotting readout, which utilizes commercially available anti‐nitrophenyl antibodies to detect a simple dinitrophenyl antigen, provides a stronger readout than the fluorescein‐based fluorescence readout. This visualization strategy can be used to measure the potency of enzyme inhibitors by selectively visualizing the active enzyme that remains after treatment with an inhibitor. Looking forward, this probe molecule and visualization strategy will enable activity‐based protein‐profiling experiments, such as determining inhibitor selectivity values within full proteome mixtures, for this family of amine oxidase enzymes.