bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of annual herb plant community characteristics to increased precipitation and reduced wind velocity in semiarid sandy grassland
Authors: Sun Shan‐Shan , Liu Xin‐Ping , He Yu‐Hui , Wei Shui‐Lian , Zhang La‐Mei , Lv Peng , Bao Chelmeg , Wang Ming‐Ming , Cheng Li
Published: September 2019

Changes in precipitation regimes and wind velocity tend to alter structure and composition of the annual herb plant community, with consequent effects on ecological functioning and biodiversity maintenance. We examined the effects of increased precipitation and reduced wind velocity on annual herb plant community characteristics via a manipulative experiment from the middle of April to middle of August, 2016. There was significant increment in species richness with increased precipitation from June to August, and there were interactive effects between increased precipitation and reduced wind velocity especially in June and the end of July. From June to August, increased precipitation, reduced wind velocity as well as their interaction stimulated sandy plant community development. There was considerable elevation in plant coverage with increased precipitation, and also there was an interactive effect of increased precipitation with 20% reduced wind velocity. However, reduced wind velocity caused more significant stimulation (p < .01) in plant height. Moreover, dominant plants, Salsola collina, Bassia dasyphylla, and Setaria viridis, contributed equally to the elevated community coverage with increased precipitation, whereas S. collina occupied a much larger proportion on the augment of community height compared with the other two species under the increased precipitation and reduced wind velocity. Elevated Shannon–Wiener index was detected with increased precipitation in June and July. Furthermore, increased precipitation and reduced wind velocity enhanced aboveground and belowground biomass, respectively. These species traits‐in structuring and composing plant community were suggested to be conducive to deep understanding the plant functioning and dynamics under global changing precipitation regimes and atmospheric wind velocity scenarios.
Microwave Synthesis of Alkali‐Free Hexaniobate, Decaniobate, and Hexatantalate Polyoxometalate Ions
Authors: Rambaran Mark A. , Pascual‐Borràs Magda , Ohlin C. André
Published: September 2019

Microwave preparation of polyoxoniobates and ‐tantalates afford a more rapid alternative to conventional hydrothermal methods of synthesis, in addition to allowing for the use of anhydrous niobium pentoxide in lieu of niobic acid, albeit with diminished yields. Limitations associated with the pH at which different oxides can be activated and how this affects the accessibility of different products are also discussed.
Synthesis and Catalytic Properties of Cyclopalladated Complexes Bearing a Phosphane‐Sulfonate Ligand
Authors: Dong Jie , Wang Baiquan
Published: September 2019

Reactions of the phosphane‐sulfonate ligand with [Pd(OAc)(8‐Me‐quin‐H)]2 or [Pd(dmba)(µ‐Cl)]2 (dmba = Me2NCH2C6H5) in acetonitrile afforded the corresponding C(sp3),N‐chelated palladacycle Pd1 and C(sp2),N‐chelated palladacycle Pd2 in high yields. Both complexes have been fully characterized by 1H and 13C NMR, high‐resolution mass spectrometry (HRMS), and elemental analysis. The molecular structure of Pd1 was further confirmed by single‐crystal X‐ray diffraction analysis. With Et2AlCl as cocatalyst, these complexes showed moderate catalytic activities for the addition polymerization of norbornene. While with methylaluminoxane (MAO) as cocatalyst, they showed high catalytic activities (up to 5.80 × 107 g of PNB (mol of Pd)–1 h–1) at higher temperatures (above 100 °C). The C(sp3),N‐chelated palladacycle Pd1 exhibited marked higher activities than the C(sp2),N‐chelated palladacycle Pd2, whether Et2AlCl or MAO was used as cocatalyst.
Copper‐Catalyzed A3‐Coupling for the Diversity‐Oriented Synthesis of Proline‐Derived Alkynyl‐Substituted Peptidomimetic Scaffolds
Authors: Innocenti Riccardo , Lenci Elena , Baldini Lorenzo , Faggi Cristina , Menchi Gloria , Trabocchi Andrea
Published: September 2019

The Aldehyde–Amine–Alkyne reaction (A3) proves to be a powerful methodology as a coupling step of the Build/Couple/Pair approach in Diversity Oriented Synthesis (DOS) because it can lead to the formation of polyfunctionalized intermediates suitable for the creation of different molecular entities. In this work we used cyclic α‐amino aldehyde moieties for the microwave‐assisted A3 coupling reaction, resulting in the generation of the corresponding propargylamines and successively exploited in intramolecular pairing reactions to obtain a pool of different alkynyl‐substituted peptidomimetic compounds.
Carbon–Carbon Bond Activation by Group 9 Metal Complexes
Authors: To Ching Tat , Chan Kin Shing
Published: September 2019

Activation of carbon–carbon bond with transition metal complexes in homogeneous conditions is an emerging field in chemical transformation. The numerous reports in last century have aided the understandings and realization of selective cleavage of carbon–carbon bond in organic molecules, from the viewpoints of the choice of metal, ligand design and substrate scopes. Specifically, this review focuses on the oxidative addition of C–C bond with group 9 transition metal complexes including the rational design from stoichiometric to catalytic transformation from the insight of carbon–carbon and metal‐carbon bond strengths.
Synthesis of Porphyrin and Bacteriochlorin Glycoconjugates through CuAAC Reaction Tuning
Authors: Bennion Matthew C. , Burch Morgan A. , Dennis David G. , Lech Melissa E. , Neuhaus Kira , Fendler Nikole L. , Parris Matthew R. , Cuadra Jessica E. , Dixon Charlie F. , Mukosera George T. , Blauch David N. , Hartmann Laura , Snyder Nicole L. , Ruppel Joshua V.
Published: September 2019

Rapid and reproducible access to a series of unique porphyrin and bacteriochlorin glycoconjugates, including meso‐glycosylated porphyrins and bacteriochlorins, and beta‐glycosylated porphyrins, using copper‐catalyzed azide–alkyne 1,3‐dipolar cycloaddition (CuAAC) is reported for the first time. The work presented highlights the system‐dependent reaction conditions required for CuAAC glycosylation to porphyrins and bacteriochlorins based on the unique electronic properties of each ring system. Optimized reaction conditions were used to synthesize fifteen new glycosylated porphyrin and bacteriochlorin analogs in 74–99 % yield, and were extended to solid support to produce the first oligo(amidoamine)‐based porphyrin glycoconjugate. These compounds hold significant potential as next‐generation water‐soluble catalysts and photodynamic therapy/photodynamic inactivation (PDT/PDI) agents.
Synthesis of 5,9‐Diaza[5]helicenes
Authors: Weiß Aaron , Podlech Joachim
Published: September 2019

A new method for the synthesis of 5,9‐diaza[5]helicenes is presented using 2,3‐bis(acylamino)‐substituted ortho‐terphenyls as precursors. Activation of the amide groups and electrophilic substitution at the ortho positions of the adjacent phenyl groups leads to the 5,9‐diaza[5]helicenes. A stepwise reaction including protection of the first amino group, amide formation at the second amino group with subsequent cyclization, followed by deprotection, amide formation and cyclization at the first amino group ensures that both electrophilic substitutions take place at sufficiently activated arenes and allows for the different substituents at the diaza[5]helicenes brought in with the amide groups. The terphenyl precursors are synthesized by two Suzuki couplings of suitably substituted building blocks. Three different 5,9‐diaza[5]helicenes with aliphatic, alkenyl and methoxycarbonylalkyl substituents were prepared; the latter would allow to attach further functionalities by ester or amide linkage.
Change in fatigue in acceptance and commitment therapy‐based treatment for chronic pain and its association with enhanced psychological flexibility
Authors: Yu Lin , Scott Whitney , McCracken Lance M.
Published: September 2019

Purpose

Fatigue is commonly reported by people with chronic pain. The purpose of the current study was to examine Acceptance and Commitment Therapy (ACT), based on the Psychological Flexibility (PF) model, for fatigue in chronic pain.

Methods

This study included 354 adults attending an interdisciplinary ACT‐oriented treatment for chronic pain. T‐tests and analyses of clinically meaningful change were used to investigate participant improvements in fatigue interference after the treatment. Pearson's correlations and hierarchical regressions were conducted to investigate associations between improvement in fatigue interference and improvements in PF processes. Finally, mixed effects models were used to explore associations between baseline fatigue interference and changes in treatment outcome measures.

Results

Participants improved in fatigue interference (d = 0.37), pain, some PF processes and daily functioning (d = 0.18–1.08). 39.7% of participants demonstrated clinically meaningfully improvements in fatigue interference. Changes in fatigue interference was associated with changes in pain, PF processes and daily functioning, |r| = 0.20–0.46. Change in fatigue interference was associated with change in pain acceptance independent of change in pain, β = −0.36, p < .001. However, baseline fatigue interference did not predict any treatment outcome. Overall, people with fatigue appeared to benefit from the ACT‐oriented interdisciplinary treatment for chronic pain, and relatively higher levels of fatigue did not appear to impede this benefit.

Conclusion

ACT‐based treatments may benefit people with chronic pain and fatigue. Future studies including experimental designs, and studies investigating other PF processes, are needed to better understand the utility of ACT for comorbid fatigue and pain.

Significance

This study investigates the association between fatigue interference and psychological flexibility processes in chronic pain, and the first one investigating fatigue interference as a predictor of functioning in chronic pain following Acceptance and Commitment Therapy (ACT)‐based treatment. Findings of the study provide preliminary evidence for the association between ACT and fatigue in people with chronic pain and support the potential benefit of ACT for people with comorbid chronic pain and fatigue.
Critical materials in PEMFC systems and a LCA analysis for the potential reduction of environmental impacts with EoL strategies
Authors: Stropnik Rok , Lotrič Andrej , Bernad Montenegro Alfonso , Sekavčnik Mihael , Mori Mitja
Published: September 2019

Commonly used materials constituting the core components of polymer electrolyte membrane fuel cells (PEMFCs), including the balance‐of‐plant, were classified according to the EU criticality methodology with an additional assessment of hazardousness and price. A life‐cycle assessment (LCA) of the materials potentially present in PEMFC systems was performed for 1 g of each material. To demonstrate the importance of appropriate actions at the end of life (EoL) for critical materials, a LCA study of the whole life cycle for a 1‐kW PEMFC system and 20,000 operating hours was performed. In addition to the manufacturing phase, four different scenarios of hydrogen production were analyzed. In the EoL phase, recycling was used as a primary strategy, with energy extraction and landfill as the second and third. The environmental impacts for 1 g of material show that platinum group metals and precious metals have by far the largest environmental impact; therefore, it is necessary to pay special attention to these materials in the EoL phase. The LCA results for the 1‐kW PEMFC system show that in the manufacturing phase the major environmental impacts come from the fuel cell stack, where the majority of the critical materials are used. Analysis shows that only 0.75 g of platinum in the manufacturing phase contributes, on average, 60% of the total environmental impacts of the manufacturing phase. In the operating phase, environmentally sounder scenarios are the hydrogen production with water electrolysis using hydroelectricity and natural gas reforming. These two scenarios have lower absolute values for the environmental impact indicators, on average, compared with the manufacturing phase of the 1‐kW PEMFC system. With proper recycling strategies in the EoL phase for each material, and by paying a lot of attention to the critical materials, the environmental impacts could be reduced, on average, by 37.3% for the manufacturing phase and 23.7% for the entire life cycle of the 1‐kW PEMFC system.
A comparative study of the nanopore structure characteristics of coals and Longmaxi shales in China
Authors: Zhou Shangwen , Liu Honglin , Chen Hao , Wang Hongyan , Guo Wei , Liu Dexun , Zhang Qin , Wu Jin , Shen Weijun
Published: September 2019

Both of the coalbed methane (CBM) and shale gas reservoirs are dominated by nanometer‐scale pores with their nanopore structures controlling the occurrence, enrichment, and accumulation of natural gas. Low‐pressure nitrogen gas adsorption (LP‐N2GA), low‐pressure carbon dioxide gas adsorption (LP‐CO2GA), high‐pressure methane adsorption (HPMA), and field emission scanning electron microscope (FE‐SEM) experiments were conducted on 14 different‐rank coal samples and nine Longmaxi shale samples collected from various basins in China to compare their nanopore characteristics. The FE‐SEM results indicate that the pore structures of both the coal and shale samples consist of nanometer‐sized pores that primarily developed in the organic matter. The types of their isothermal adsorption curves are similar. However, the coal and shale samples possess various hysteresis loops, which suggest that the nanopores in shale are open‐plated, whereas those in coal are semi‐open. Furthermore, the specific surface area (SSA) and pore volume (PV) of the micropores in coal are much larger than those of the mesopores, with the micropore SSAs accounting for 99% of the total SSA in the coal samples. However, the micropore SSAs in the shale samples only account 42.24% of the total SSA. These different nanopore structures reflect their different methane adsorption mechanisms. The methane adsorption of coal is primarily controlled by the micropore SSA, whereas that of shale is primarily controlled by the mesopore SSA. If we use mesopore SSA to analyze its impact on methane adsorption capacity of coal and shale, it will be mismatched. However, no mismatching relationship exists between the total SSAs and adsorption capacities of coal and shale. This study highlights the controlling effect of total SSA on methane adsorption capacity.
A new test methodology for studying the response of walls to real fire environments
Authors: Ellingham Jennifer , DiDomizio Matthew J. , Weckman Elizabeth J.
Published: September 2019

A new test methodology was developed to investigate the response of walls, partitions, and in‐wall systems exposed to real fires. The apparatus includes a 3.5 m long, 2.3 m wide, and 2.3 m high fire compartment within a standard sea container. A wall specimen measuring up to 1.8 m wide, 1.8 m tall, and 0.3 m deep is mounted in a steel frame at one end of the fire compartment. Fire exposures to the wall specimen evolve over time depending on the fuel load and ventilation configuration. Gas temperatures and heat flux were characterized for five different fuel and ventilation configurations. Peak exposures ranged from 30 to 75 kW/m2 for about 20 minutes. Five additional tests were conducted using a single fuel and ventilation configuration to assess the repeatability of the test methodology. It was found that a 19.3 minute growth period occurred plateauing at a ceiling temperature of 708°C for 8.4 minutes, on average. Compartment gas temperatures were found to be repeatable, having a sample standard deviation less than 32°C for symmetric data. Repeatability improved when account was taken for the rapid fire growth inflection point. The utility of the approach for studying fire performance of building elements was demonstrated.
Diet‐induced DNA methylation within the hypothalamic arcuate nucleus and dysregulated leptin and insulin signaling in the pathophysiology of obesity
Authors: Samodien Ebrahim , Pheiffer Carmen , Erasmus Melisse , Mabasa Lawrence , Louw Johan , Johnson Rabia
Published: September 2019

Obesity rates continue to rise in an unprecedented manner in what could be the most rapid population‐scale shift in human phenotype ever to occur. Increased consumption of unhealthy, calorie‐dense foods, coupled with sedentary lifestyles, is the main factor contributing to a positive energy balance and the development of obesity. Leptin and insulin are key hormones implicated in pathogenesis of this disorder and are crucial for controlling whole‐body energy homeostasis. Their respective function is mediated by the counterbalance of anorexigenic and orexigenic neurons located within the hypothalamic arcuate nucleus. Dysregulation of leptin and insulin signaling pathways within this brain region may contribute not only to the development of obesity, but also systemically affect the peripheral organs, thereby manifesting as metabolic diseases. Although the exact mechanisms detailing how these hypothalamic nuclei contribute to disease pathology are still unclear, increasing evidence suggests that altered DNA methylation may be involved. This review evaluates animal studies that have demonstrated diet‐induced DNA methylation changes in genes that regulate energy homeostasis within the arcuate nucleus, and elucidates possible mechanisms causing hypothalamic leptin and insulin resistance leading to the development of obesity and metabolic diseases.
Assessment of the physicochemical characteristics, chemical and microbiological safety of two types of kilichi, a grilled meat produced in Niger
Authors: Boubacar Seydou Ramatou , Harouna AbdoulKader , Kpoclou Yénoukounmè Euloge , Douny Caroline , Brose François , Hamani Marichatou , Mahillon Jacques , Anihouvi Victor Bienvenu , Scippo Marie‐Louise , Hounhouigan Djidjoho Joseph
Published: September 2019

Production of kilichi, a grilled meat of West Africa, is a common method of meat preservation in Niger. Thirty samples of condiments‐coated kilichi and uncoated kilichi collected in Niger, were analyzed for microbiological contamination, as well as NaCl, protein and lipid contents, using standard methods. Contamination with Polycyclic Aromatic Hydrocarbons (PAHs) was also assessed using a HPLC–FLD technique. Highly significant differences (p < .001) were observed between coated kilichi and uncoated kilichi, for NaCl content (2.56% and 1.40%), for proteins (51% and 72%) and lipids (18% and 13%), respectively. Water activity was low in both kilichi, showing a potential microbial stability. Among the 15 European Union (EU) priority PAHs, 12 were detected in the samples. About 56.3% of coated kilichi samples exceeded the EU maximal limit for BaP, and 75% exceeded the EU maximal limit for the sum of 4 PAHs (PAH4). For uncoated kilichi, 28.6% of samples did not meet the standards for BaP and PAH4. About 6% of coated kilichi samples were not compliant with standards related to Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, and 31%, 50% for yeasts and fungi, respectively. Escherichia coli and Enterobacteria were below the detection limit in both kilichi, but Salmonella and Bacillus cereus were detected only in one coated kilichi. The noncompliant samples of uncoated kilichi were in the proportions varying between 7% –86% for S. aureus, C. perfringens, yeasts, and fungi. This study showed potential risks associated with the consumption of traditionally produced kilichi in Niger due to both PAHs and pathogen bacteria contamination.
Effect of Pretreatment on Microstructure and Mechanical Properties of Nafion™ XL Composite Membrane
Authors: Lin Q. , Sun X. , Chen X. , Shi S.
Published: September 2019

As an ion‐conductive polymer electrolyte, Nafion™ XL composite membrane is used to meet the requirement for cost reduction, performance and durability improvement in polymer electrolyte fuel cells. While significant durability is observed for Nafion™ XL membrane, the mechanisms of improved mechanical durability, especially the impact induced by pretreatment, is still left unexplored. In this paper, ex situ mechanical tests of pretreated membranes are carried out, including tensile, fracture and fatigue crack propagation tests, to unravel the complex interplay between strength, fracture toughness and cyclic hygrothermal stress that controls the mechanical durability. Pretreatment increases strain‐hardening modulus at the expense of reduced ductility, while the break stress is not affected. Results from in situ SEM tensile tests reveal that pretreatment increases the orientation resistance during tension, leading to increased stress responses. In addition, the fracture resistance and fatigue crack propagation resistance increase after pretreatment, which is ascribed to increased membrane stiffness and reinforcement fiber reorientation, respectively. From a microscopic point of view, fibers along the cross‐sectional reinforcement layer collapse, corresponding to fiber reorientation at a smaller size scale and accounting for the above increased resistance. The findings reported here will provide more insights into the mechanical durability of composite ion‐conductive membranes.
Multifocal perineural invasion is a better prognosticator than depth of invasion in oral squamous cell carcinoma
Authors: Hasmat Shaheen , Ebrahimi Ardalan , Gao Kan , Low Tsu‐Hui (Hubert) , Palme Carsten , Gupta Ruta , Clark Jonathan
Published: September 2019

Objectives

Prognostic significance of perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) characterized as unifocal and multifocal was compared to depth of invasion (DOI) and extranodal extension (ENE).

Materials and Methods

Univariable and multivariable analyses of 861 consecutive patients with OSCC undergoing treatment between 1995 and 2018 were performed, with local failure (LF) and disease‐specific mortality (DSS) as the primary endpoints.

Results

After adjusting for other adverse histopathological factors and adjuvant therapy, multifocal PNI was associated with a greater risk of LF (P = .01) and DSS (P = 0.02) compared to DOI. The effect of multifocal PNI was comparable to the effect of nodal metastases without ENE (P = 0.02). LF and DSS were not improved by the administration of adjuvant radiotherapy within unifocal or multifocal PNI groups.

Conclusion

Multifocal PNI is associated with a greater risk of death in OSCC than DOI. Its effect is comparable to that of nodal metastases (without ENE).
How job satisfaction can influence air traffic controllers' backup‐providing behavior in parallel runway operation
Authors: Kuang Ying , E Xiaotian , Li Yazhe , Zhang Jingyu
Published: September 2019

Team members can request and provide backup from one to other members, which can help teams with high workload achieve dynamic workload optimization at the group level. However, studies on this issue are limited, especially on real‐world high‐risk operations. This study explored how to approach air traffic controllers make backup decisions in the dependent parallel approach operation. In this study, we focused on how individual difference factors can influence the controller's backup willingness and decision. Forty licensed controllers performed 32 simulated scenarios varied in their own task load, the backup recipients' task load, and shorter taxing possibility. We also measured their job satisfaction and work experience. Multilevel regression analyses showed that controllers with a higher level of job satisfaction were more likely to provide help to their colleagues. Moreover, when their job satisfaction was high, they were less sensitive to the seemingly inappropriate request, but they only used their additional resources to help others. The findings were discussed in the literature of teamwork and aviation safety.
Whole‐body magnetic resonance imaging (WB‐MRI) in lymphoma: State of the art
Authors: Albano Domenico , Bruno Alberto , Patti Caterina , Micci Giuseppe , Midiri Massimo , Tarella Corrado , Galia Massimo
Published: September 2019

The improvements in magnetic resonance imaging (MRI) technology and the concern related to the increased cancer risk in patients with lymphoma, also due to radiation exposure associated with imaging examinations, have led to the introduction of whole‐body MRI (WB‐MRI) as a radiation‐free alternative to standard imaging procedures. WB‐MRI seems a less histology‐dependent functional imaging test than 18F‐fluorodeoxyglucose‐positron emission tomography/CT (18F‐FDG‐PET/CT). In patients with FDG‐avid lymphomas, such as diffuse large B‐cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), 18F‐FDG‐PET/CT remains the imaging reference standard for staging, with WB‐MRI potentially being a complementary modality that could replace CT, especially in young patients. On the other hand, WB‐MRI is a valuable imaging procedure for lymphoma surveillance and in lymphomas with variable/low FDG avidity and nonfollicular indolent lymphomas. The aim of this paper is to discuss the current state of the art of WB‐MRI in lymphoma by evaluating its diagnostic performance in different lymphoma subtypes: Hodgkin, aggressive, and indolent lymphomas.
Recent snow cover changes over central European low mountain ranges
Authors: Dong Chunyu , Menzel Lucas
Published: September 2019

In this study, we simulated the snow water equivalent (SWE), rain‐on‐snow (ROS) events, evapotranspiration, and run‐off for the period 1961–2016 in a central European region covered by low mountain ranges (<820 m a.s.l.) using a distributed hydrological model TRAnspiration and INterception evaporation model (TRAIN). We utilized improved cloud‐free Moderate Resolution Imaging Spectroradiometer (MODIS) snow cover products to evaluate the modelled snow‐covered area, indicating a good performance of the snow modelling. We analysed the intra‐ and inter‐annual variations of the simulated hydrological variables and the synchronous climate variables (air temperature and precipitation). Trend detection indicates a significant SWE decline throughout the snow season, but principally at the high elevations; the most severe warming occurred in early spring (March), whereas precipitation showed a slight increase in January and February. The snowpack in February has displayed the most striking reduction during the past 56 years, which is likely related to both the highest susceptibility of snow to warming and the increased ROS occurrence in February since the early 1990s. The increased combination of high temperatures and extreme rainfalls, as well as the earlier snowmelt, has resulted in a run‐off increase during the earlier winter but a decrease in March. The expected changing climate towards warmer and wetter winters will probably exacerbate winter flooding in the future.
Establishing a valid approach for estimating familial risk of cancer explained by common genetic variants
Authors: Weigl Korbinian , Chang‐Claude Jenny , Hsu Li , Hoffmeister Michael , Brenner Hermann
Published: September 2019

We critically examined existing approaches for the estimation of the excess familial risk of cancer that can be attributed to identified common genetic risk variants and propose an alternative, more straightforward approach for calculating this proportion using well‐established epidemiological methodology. We applied the underlying equations of the traditional approaches and the new epidemiological approach for colorectal cancer (CRC) in a large population‐based case–control study in Germany with 4,447 cases and 3,480 controls, who were recruited from 2003 to 2016 and for whom interview, medical and genomic data were available. Having a family history of CRC (FH) was associated with a 1.77‐fold risk increase in our study population (95% CI 1.52–2.07). Traditional approaches yielded estimates of the FH‐associated risk explained by 97 common genetics variants from 9.6% to 23.1%, depending on various assumptions. Our alternative approach resulted in smaller and more consistent estimates of this proportion, ranging from 5.4% to 14.3%. Commonly employed methods may lead to strongly divergent and possibly exaggerated estimates of excess familial risk of cancer explained by associated known common genetic variants. Our results suggest that familial risk and risk associated with known common genetic variants might reflect two complementary major sources of risk.
Guiding principles for evaluating tertiary health care resources: The A2C2QUIRE framework
Authors: Phillips Jennifer A. , Hanrahan Conor T. , Brown Jamie N. , May Dianne , Britnell Sara R. , Ficzere Cathy H.
Published: September 2019

Introduction

Drug information, medical, and other resources, in the form of textbooks, online databases, and mobile applications (apps), are commonly consulted by health care professionals when providing answers to drug information questions or researching information prior to making recommendations for patient care. Thus, there is a need to train health care professionals on how to identify high‐quality resources to ensure patient safety and improve patient care. Given the variety of different resource types available in contemporary health care settings, a framework that can be universally applied to a variety of different resources is needed.

Objective

The primary objective of this paper is to introduce health care professionals to a unified framework for evaluating all types of tertiary health care resources that takes into account practical and contemporary considerations. The A2C2QUIRE framework centers around three main tenets: quality, functionality, and practical considerations, and specifically addresses the following components: Authorship and publisher, Accessibility, Currency of information, Cost and value of materials, Quality of content, Usability and resource design, Intent of the resource, Review process, and Endorsements.

Conclusion

The foundational concepts reviewed in this paper provide health care professionals with a unified framework for assessing the quality of various types of resources, while also incorporating practical and contemporary considerations.
Personality, Motivation, and Internet Gaming Disorder: Conceptualizing the Gamer
Authors: Carlisle Kristy L. , Neukrug Edward , Pribesh Shana , Krahwinkel Jill
Published: September 2019

Using a group correlational design and path analysis, the authors examined the relationships among personality, motivation, and internet gaming disorder (IGD). Findings showed that significant predictors of IGD included male gender, neurotic and introverted personality traits, and motivation related to achievement.
Fracture Risk in Trans Women and Trans Men Using Long-Term Gender-Affirming Hormonal Treatment: A Nationwide Cohort Study
Authors: Wiepjes Chantal M , de Blok Christel JM , Staphorsius Annemieke S , Nota Nienke M , Vlot Mariska C , de Jongh Renate T , den Heijer Martin
Published: September 2019

Concerns about bone health in transgender people using gender-affirming hormonal treatment (HT) exist, but the fracture risk is not known. In this nationwide cohort study, we aimed to compare the fracture incidence in transgender people using long-term HT with an age-matched reference population. All adult transgender people who started HT before 2016 at our gender-identity clinic were included and were linked to a random population-based sample of 5 age-matched reference men and 5 age-matched reference women per person. Fracture incidence was determined using diagnoses from visits to hospital emergency rooms nationwide between 2013 and 2015. A total of 1089 trans women aged <50 years (mean 38 ± 9 years) and 934 trans women aged ≥50 years (mean 60 ± 8 years) using HT for median 8 (interquartile range [IQR] 3–16) and 19 (IQR 11–29) years, respectively, were included. A total of 2.4% of the trans women aged <50 years had a fracture, whereas 3.0% of the age-matched reference men (odds ratio [OR] = 0.78, 95% confidence interval [CI] 0.51–1.19) and 1.6% of the age-matched reference women (OR = 1.49, 95% CI 0.96–2.32) experienced a fracture. In trans women aged ≥50 years, 4.4% experienced a fracture compared with 2.4% of the age-matched reference men (OR = 1.90, 95% CI 1.32–2.74) and 4.2% of the age-matched reference women (OR = 1.05, 95% CI 0.75–1.49). A total of 1036 trans men (40 ± 14 years) using HT for median 9 (IQR 2–22) years were included. Fractures occurred in 1.7% of the trans men, 3.0% of the age-matched reference men (OR = 0.57, 95% CI 0.35–0.94), and 2.2% of the age-matched reference women (OR = 0.79, 95% CI 0.48–1.30). In conclusion, fracture risk was higher in older trans women compared with age-matched reference men. In young trans women, fracture risk tended to be increased compared with age-matched reference women. Fracture risk was not increased in young trans men. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
EZH2 Supports Osteoclast Differentiation and Bone Resorption Via Epigenetic and Cytoplasmic Targets
Authors: Adamik Juraj , Pulugulla Sree H , Zhang Peng , Sun Quanhong , Lontos Konstantinos , Macar David A , Auron Philip E , Galson Deborah L
Published: September 2019

Key osteoclast (OCL) regulatory gene promoters in bone marrow–derived monocytes harbor bivalent histone modifications that combine activating Histone 3 lysine 4 tri-methyl (H3K4me3) and repressive H3K27me3 marks, which upon RANKL stimulation resolve into repressive or activating architecture. Enhancer of zeste homologue 2 (EZH2) is the histone methyltransferase component of the polycomb repressive complex 2, which catalyzes H3K27me3 modifications. Immunofluorescence microscopy reveals that EZH2 localization during murine osteoclastogenesis is dynamically regulated. Using EZH2 knockdown and small molecule EZH2 inhibitor GSK126, we show that EZH2 plays a critical epigenetic role in OCL precursors (OCLp) during the first 24 hours of RANKL activation. RANKL triggers EZH2 translocation into the nucleus where it represses OCL-negative regulators MafB, Irf8, and Arg1. Consistent with its cytoplasmic localization in OCLp, EZH2 methyltransferase activity is required during early RANKL signaling for phosphorylation of AKT, resulting in downstream activation of the mTOR complex, which is essential for induction of OCL differentiation. Inhibition of RANKL-induced pmTOR-pS6RP signaling by GSK126 altered the translation ratio of the C/EBPβ-LAP and C/EBPβ-LIP isoforms and reduced nuclear translocation of the inhibitory C/EBPβ-LIP, which is necessary for transcriptional repression of the OCL negative-regulatory transcription factor MafB. EZH2 in multinucleated OCL is primarily cytoplasmic and mature OCL cultured on bone segments in the presence of GSK126 exhibit defective cytoskeletal architecture and reduced resorptive activity. Here we present new evidence that EZH2 plays epigenetic and cytoplasmic roles during OCL differentiation by suppressing MafB transcription and regulating early phases of PI3K-AKT–mTOR-mediated RANKL signaling, respectively. Consistent with its cytoplasmic localization, EZH2 is required for cytoskeletal dynamics during resorption by mature OCL. Thus, EZH2 exhibits complex roles in supporting osteoclast differentiation and function. © 2019 American Society for Bone and Mineral Research.
High-Dose TGF-β1 Impairs Mesenchymal Stem Cell–Mediated Bone Regeneration via Bmp2 Inhibition
Authors: Xu Jiajia , Liu Jinlong , Gan Yaokai , Dai Kerong , Zhao Jingyu , Huang Mingjian , Huang Yan , Zhuang Yifu , Zhang Xiaoling
Published: September 2019

Transforming growth factor-β1 (TGF-β1) is a key factor in bone reconstruction. However, its pathophysiological role in non-union and bone repair remains unclear. Here we demonstrated that TGF-β1 was highly expressed in both C57BL/6 mice where new bone formation was impaired after autologous bone marrow mesenchymal stem cell (BMMSC) implantation in non-union patients. High doses of TGF-β1 inhibited BMMSC osteogenesis and attenuated bone regeneration in vivo. Furthermore, different TGF-β1 levels exhibited opposite effects on osteogenic differentiation and bone healing. Mechanistically, low TGF-β1 doses activated smad3, promoted their binding to bone morphogenetic protein 2 (Bmp2) promoter, and upregulated Bmp2 expression in BMMSCs. By contrast, Bmp2 transcription was inhibited by changing smad3 binding sites on its promoter at high TGF-β1 levels. In addition, high TGF-β1 doses increased tomoregulin-1 (Tmeff1) levels, resulting in the repression of Bmp2 and bone formation in mice. Treatment with the TGF-β1 inhibitor SB431542 significantly rescued BMMSC osteogenesis and accelerated bone regeneration. Our study suggests that high-dose TGF-β1 dampens BMMSC-mediated bone regeneration by activating canonical TGF-β/smad3 signaling and inhibiting Bmp2 via direct and indirect mechanisms. These data collectively show a previously unrecognized mechanism of TGF-β1 in bone repair, and TGF-β1 is an effective therapeutic target for treating bone regeneration disability. © 2019 American Society for Bone and Mineral Research.
Construction of a circular RNA‐microRNA‐messengerRNA regulatory network in stomach adenocarcinoma
Authors: Liu Qincheng , Zhang Wei , Wu Zhenqian , Liu Haijun , Hu Huiqiong , Shi Huisen , Li Shaohua , Zhang Xueli
Published: September 2019

Objectives

Circular RNAs (circRNAs) can interact with microRNAs (miRNAs) to regulate gene expression in cancer cells. However, the roles of competitive endogenous RNA (ceRNA) networks consisting of differentially expressed circRNAs (DECs), miRNAs, and messenger RNAs (mRNAs) in stomach adenocarcinoma (STAD) remain unclear. This study was performed to explore novel regulatory networks in STAD.

Methods

The circRNA expression profiles, as well as miRNA and mRNA sequence data of STAD, were retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), respectively. Candidates were identified to construct a network through a comprehensive bioinformatics strategy. The expression of hub‐genes identified by protein‐protein interactions (PPI) was validated by quantitative reverse transcription (RT) polymerase chain reaction.

Results

A total of 51 DECs were identified in the GSE83521 and GSE89143 datasets of GEO. A total of 11 448 differentially expressed mRNAs (DEMs) and 458 differentially expressed miRNAs (DEMIs) were obtained by RNA sequencing of TCGA‐STAD. Prediction by using five online databases (Cancer‐Specific CircRNA, CircInteractome, miRTarBase, miRDB, and TargetScan) resulted in the selection of 6 DECs, 6 DEMIs, and 36 DEMs to establish a circRNA‐miRNA‐mRNA regulatory network based on the interactions of circRNA‐miRNA and miRNA‐mRNA. Through PPI analysis, four hub‐genes (COL10A1, COL5A2, COL4A1, and COL3A1) were discovered. Moreover, overexpressions of COL10A1, COL5A1, and COL4A1 were associated with a poor overall survival rate of patients with STAD. On the basis of TNM staging, we found that the expressions of COL10A1, COL5A2, and COL3A1 in T2, T3, and T4 was significantly higher than in T1. Hub‐genes expressions were validated in STAD tissues and cell lines.

Conclusions

Our study provides a novel perspective on the regulatory mechanism of STAD involving ceRNAs including DECs, DEMIs, and DEMs.
Janus kinase inhibitors role in bone remodeling
Authors: Maruotti Nicola , Corrado Addolorata , Rotondo Cinzia , Cantatore Francesco Paolo
Published: September 2019

Janus kinases (JAKs) play a pleiotropic role in several important physiological processes, such as cell maturation, cell proliferation, and cell death, via providing transmission signals from several molecules, such as cytokines, interferons, hormones, and growth factors, to the nucleus. Bone physiology and remodeling are markedly influenced by proinflammatory cytokines. Among them, interleukin‐1 (IL‐1) and IL‐6 are considered potent stimulator of bone resorption. Several cytokine receptors, such as IL‐6 receptors, are characterized by tyrosine kinases of the JAK family associated with their intracellular domains. There is an emerging interest in the effects of JAKs inhibition on the cells involved in bone remodeling. JAK inhibitors represent a new class of molecules involved in the therapy of numerous immune‐mediated inflammatory diseases. In this review, we want to focus on the role of JAKs inhibitors on bone remodeling and on RANKL‐RANK‐OPG signal and inflammatory cytokines which are involved in the regulation of bone cells, such as osteoblasts and osteoclasts.
CARD14/CARMA2sh and TANK differentially regulate poly(I:C)–induced inflammatory reaction in keratinocytes
Authors: Voccola Serena , Polvere Immacolata , Madera Jessica R. , Paolucci Marina , Varricchio Ettore , Telesio Gianluca , Porcaro Piero , Vito Pasquale , Stilo Romania , Zotti Tiziana
Published: September 2019

CARD14/CARMA2sh (CARMA2sh) is a scaffold protein whose mutations are associated with the onset of human genetic psoriasis and other inflammatory skin disorders. Here we show that the immunomodulatory adapter protein TRAF family member‐associated NF‐κB activator (TANK) forms a complex with CARMA2sh and MALT1 in a human keratinocytic cell line. We also show that CARMA2 and TANK are individually required to activate the nuclear factor κB (NF‐κB) response following exposure to polyinosinic‐polycytidylic (poly [I:C]), an agonist of toll‐like receptor 3. Finally, we present data indicating that TANK is essential for activation of the TBK1/IRF3 pathway following poly (I:C) stimulation, whereas CARMA2sh functions as a repressor of it. More important, we report that two CARMA2sh mutants associated with psoriasis bind less efficiently to TANK and are therefore less effective in suppressing the TBK1/IRF3 pathway. Overall, our data indicate that TANK and CARMA2sh regulate TLR3 signaling in human keratinocytes, which could play a role in the pathophysiology of psoriasis.
Estimating Private School Effects for School Children in Peru: Evidence from Individual‐level Panel Data
Authors: Eigbiremolen Godstime Osekhebhen , Ogbuabor Jonathan Emenike , Nwambe Chioma Sylvia
Published: September 2019

This paper presents the first value‐added model of private school effects in Peru, using the unique Young Lives longitudinal data. Raw differences in test scores show that children in private schools have higher test scores in both maths and Peabody Picture Vocabulary Test for the most part. Estimates from ordinary least squares regression also indicate the existence of private school premium in maths. However, when we controlled for prior achievement, we find no private school effects in learning. These results hold true for both low‐ability and high‐ability children and are robust to sorting on unobserved ability, grouping on lag structures and transfer between private and public schools. © 2019 John Wiley & Sons, Ltd.
Functional evolution of the colony-stimulating factor 1 receptor (CSF1R) and its ligands in birds
Authors: Hume David A. , Gutowska-Ding Maria W. , Garcia-Morales Carla , Kebede Adebabay , Bamidele Oladeji , Trujillo Adriana Vallejo , Gheyas Almas A. , Smith Jacqueline
Published: September 2019

Macrophage colony-stimulating factor (CSF1 or M-CSF) and interleukin 34 (IL34) are secreted cytokines that control macrophage survival and differentiation. Both act through the CSF1 receptor (CSF1R), a type III transmembrane receptor tyrosine kinase. The functions of CSF1R and both ligands are conserved in birds. We have analyzed protein-coding sequence divergence among avian species. The intracellular tyrosine kinase domain of CSF1R was highly conserved in bird species as in mammals but the extracellular domain of avian CSF1R was more divergent in birds with multiple positively selected amino acids. Based upon crystal structures of the mammalian CSF1/IL34 receptor-ligand interfaces and structure-based alignments, we identified amino acids involved in avian receptor-ligand interactions. The contact amino acids in both CSF1 and CSF1R diverged among avian species. Ligand-binding domain swaps between chicken and zebra finch CSF1 confirmed the function of variants that confer species specificity on the interaction of CSF1 with CSF1R. Based upon genomic sequence analysis, we identified prevalent amino acid changes in the extracellular domain of CSF1R even within the chicken species that distinguished commercial broilers and layers and tropically adapted breeds. The rapid evolution in the extracellular domain of avian CSF1R suggests that at least in birds this ligand-receptor interaction is subjected to pathogen selection. We discuss this finding in the context of expression of CSF1R in antigen-sampling and antigen-presenting cells.
Developmental architecture of the nervous system in Themiste lageniformis (Sipuncula): New evidence from confocal laser scanning microscopy and gene expression
Authors: Carrillo‐Baltodano Allan M. , Boyle Michael J. , Rice Mary E. , Meyer Néva P.
Published: September 2019

Sipuncula is a clade of unsegmented marine worms that are currently placed among the basal radiation of conspicuously segmented Annelida. Their new location provides a unique opportunity to reinvestigate the evolution and development of segmented body plans. Neural segmentation is clearly evident during ganglionic ventral nerve cord (VNC) formation across Sedentaria and Errantia, which includes the majority of annelids. However, recent studies show that some annelid taxa outside of Sedentaria and Errantia have a medullary cord, without ganglia, as adults. Importantly, neural development in these taxa is understudied and interpretation can vary widely. For example, reports in sipunculans range from no evidence of segmentation to vestigial segmentation as inferred from a few pairs of serially repeated neuronal cell bodies along the VNC. We investigated patterns of pan‐neuronal, neuronal subtype, and axonal markers using immunohistochemistry and whole mount in situ hybridization (WMISH) during neural development in an indirect‐developing sipunculan, Themiste lageniformis. Confocal imaging revealed two clusters of 5HT+ neurons, two pairs of FMRF+ neurons, and Tubulin+ peripheral neurites that appear to be serially positioned along the VNC, similar to other sipunculans, to other annelids, and to spiralian taxa outside of Annelida. WMISH of a synaptotagmin1 ortholog in T. lageniformis (Tl‐syt1) showed expression throughout the centralized nervous system (CNS), including the VNC where it appears to correlate with mature 5HT+ and FMRF+ neurons. An ortholog of elav1 (Tl‐elav1) showed expression in differentiated neurons of the CNS with continuous expression in the VNC, supporting evidence of a medullary cord, and refuting evidence of ontogenetic segmentation during formation of the nervous system. Thus, we conclude that sipunculans do not exhibit any signs of morphological segmentation during development.