bluuebunny/crossref_metadata_2025 huggingface dataset:
Incident chronic obstructive pulmonary disease associated with occupation, industry, and workplace exposures in the Health and Retirement Study
Authors: Silver Sharon R. , Alarcon Walter A. , Li Jia
Published: October 2020

Background

Chronic health effects from accumulated occupational exposures manifest as the workforce ages. The Health and Retirement Study (HRS), a panel survey of U.S. adults nearing/in retirement, allows assessment of associations among industry and occupation (I/O), workplace exposures, and incident chronic obstructive pulmonary disease (COPD).

Methods

The study population comprised respondents from the 1992 HRS cohort employed in 1972 or later and not diagnosed with COPD as of initial interview. We examined associations with incident COPD through 2016 and: (1) broad and selected detailed I/O, (2) workplace exposures, and (3) exposures within I/O. Given the cohort's baseline age (50–62), we calculated subhazard ratios (SHRs) for COPD accounting for competing risk of death.

Results

SHRs for COPD were significantly elevated for several industries: mining; blast furnaces, steelworks, rolling and finishing mills; groceries and related products; and automotive repair shops. Occupations with significantly elevated SHRs were maids and housemen; farmworkers; vehicle/mobile equipment mechanics and repair workers; material moving equipment operators; and nonconstruction laborers. Significantly elevated COPD SHRs were observed for specific I/O‐exposure pairs: blast furnace/steelworks/rolling/finishing mills and asbestos; automotive repair shops and aerosol paints; farmworkers and pesticide exposures; and both material moving equipment operators and nonconstruction laborers exposed to dust and ash.

Conclusions

Certain jobs and occupational exposures are associated with increased risk for developing COPD in late preretirement and during retirement. Given the disability and economic costs of COPD, these findings support focusing exposure prevention and medical monitoring resources on groups of workers at increased risk.
The occurrence of the red‐handed howler monkey (Alouatta belzebul) in amazonian savannas is related to forest patch area and density of flooded area palms
Authors: Silvestre Saulo M. , Setchell Joanna M. , Calle‐Rendón Bayron R. , de Toledo José J. , Hilário Renato R.
Published: October 2020

All Neotropical primates are arboreal and thus depend on forests for their survival. Arboreality puts many Neotropical primates at risk of extinction due to the high rates of deforestation in the tropics. We assessed the influence of vegetation structure and forest patch attributes on the occurrence of the threatened red‐handed howler monkey (Alouatta belzebul) in an Amazonian savanna. Using a sample of 38 forest patches in a region of approximately 2000 km2in the state of Amapá, northern Brazil, we used logistic regression to find the best predictors of the occurrence ofA. belzebul. We assessed patch area, patch isolation, the proportion of seasonally flooded forest in the patch, the density of flooded area palms, forest height, canopy cover, and diameter at breast height of trees. Patch area and palm density were the best predictors of the occurrence ofA. belzebulin forest patches, both having a positive effect on the probability of occurrence. Our results indicate that areas of flooded forest in forest patches may be keystone habitats forA. belzebulliving in Amazonian savannas. The observed effect of palm density onA. belzebulsuggests that this variable is useful for planning conservation actions, including the selection of areas for protection and management strategies for areas inhabited by this primate.
Pristine Hollow Metal–Organic Frameworks: Design, Synthesis and Application
Authors: Qiu Tianjie , Gao Song , Liang Zibin , Wang De‐Gao , Tabassum Hassina , Zhong Ruiqin , Zou Ruqiang
Published: October 2020

Metal–organic frameworks (MOFs), featuring porous crystalline structures with coordinated metal nodes and organic linkers, have recently found increasing interest in diverse applications. By virtue of their versatile and highly tunable compositions and structures, constructing hollow architectures will further endow MOFs with enhanced properties and designability, exceeding the molecular scale. MOFs could be considered as promising building units to fabricate complex hollow nanocomposites with faster mass transport, multiple active components, more exposed active sites, and better compatibility than bulk MOFs. To construct a promising blueprint for hollow pristine MOFs, this review provides a comprehensive overview for structural design strategies and applications of hollow pristine MOFs. We will highlight the merits, challenges and future potential by structuring and applying MOFs in sensing, separation, storage, catalysis, environmental remediation, photochemical and electrochemical energy conversion. This review might pave a new avenue for future development of novel pristine hollow MOFs.
Synthesis of a Pentasaccharide Repeating Unit of Lipopolysaccharide Derived from Virulent E. coli O1 and Identification of a Glycotope Candidate of Avian Pathogenic E. coli O1
Authors: Nishi Nobuya , Seki Katsunori , Takahashi Daisuke , Toshima Kazunobu
Published: October 2020

Avian pathogenic Escherichia coli (APEC) is a common bacterial pathogen infecting chickens, resulting in economic losses to the poultry industry worldwide. In particular, APEC O1, one of the most common serotypes of APEC, is considered problematic due to its zoonotic potential. Therefore, many attempts have been made to develop an effective vaccine against APEC O1. In fact, the lipopolysaccharide (LPS) O‐antigen of APEC O1 has been shown to be a potent antigen for inducing specific protective immune responses. However, the detailed structure of the O‐antigen of APEC O1 is not clear. The present study demonstrates the first synthesis of a pentasaccharide repeating unit of LPS derived from virulent E. coli O1 and its conjugate with BSA. ELISA tests using the semi‐synthetic glycoconjugate and the APEC O1 immune chicken serum revealed that the pentasaccharide is a glycotope candidate of APEC O1, with great potential as an antigen for vaccine development.
Bunsen the Geochemist: Icelandic Volcanism, Geyser Theory, and Gas, Rock and Mineral Analyses
Authors: Wentrup Curt
Published: October 2020

Following the eruption of Hekla in 1845–1846 Bunsen was invited by King Christian VIII of Denmark and Iceland to participate in a geochemical expedition to Iceland together with the geologist Sartorius von Waltershausen and the physiologist Carl Bergmann from Göttingen. The French mineralogist Des Cloizeaux went to Iceland separately and joined the expedition. The eudiometer invented by Bunsen was crucial for his accurate characterization of volcanic gases and determination of the composition of mixtures. His analyses of the chemical compositions of numerous rocks and minerals led him to the classification of two fundamental rock types, the more silica rich (nowadays called felsic) and the less silica rich, more basic (mafic) in agreement with Des Cloizeaux and the Danish scientist J. C. Schythe. Bunsen also formulated the correct mechanism of geyser action and helped disband the theory of connections between geysers, volcanoes and the sea. He disagreed vehemently with Waltershausen over the mechanisms of formation of sal ammoniac and of volcanic rocks and their chemical compositions. He revealed himself as an ardent experimentalist vigorously opposed to hypotheses of any kind, which also made him dismiss the new chemical theories, for example, those of Dumas and Kekulé.
Antimicrobial and antiprotozoal activities of silver coordination polymers derived from the asymmetric halogenated Schiff base ligands
Authors: Kordestani Nazanin , Rudbari Hadi Amiri , Fateminia Zohreh , Caljon Guy , Maes Louis , Mineo Placido G. , Cordaro Annalaura , Mazzaglia Antonino , Scala Angela , Micale Nicola
Published: October 2020

A series of polymeric silver(I) complexes with Schiff base ligands containing pyridine and 3,5‐halogen substituted phenol moieties were synthesized and characterized by spectroscopic methods and in the case of Ag6 also by X‐ray crystallography. All silver(I) complexes (Ag1–Ag8) were evaluated for their biological activity against a panel of pathogens including the protozoa Trypanosoma cruzi, T. brucei, T. rhodesiense and Leishmania infantum; the bacteria Staphylococcus aureus, Escherichia coli, Mycobacterium tuberculosis H37Ra and the yeast Candida albicans. Cytotoxicity evaluation was carried out on human lung fibroblasts (MRC‐5) and on primary peritoneal mouse macrophages. The most relevant result reveals antileishmanial activity potential with all complexes demonstrating higher potency than the reference drug miltefosine. Complexes with the best antiprotozoal profile (i.e., Ag2 and Ag7) were selected for incorporation into poly (lactic acid) nanoparticles (PLA NPs) with the aim to enhance selectivity. PLA/Ag2 NPs and PLA/Ag7 NPs exhibited adequate physicochemical properties, that is, average size of 263 ± 60 nm and 225 ± 6 nm, respectively, good entrapment efficiency (69% and 63%), loading content (6.2% and 5.7%) and stability. The cytotoxicity of PLA/Ag2 NPs and PLA/Ag7 NPs on MRC‐5 cells was reduced with respect to the “free” metal complexes by ~2‐fold and ~6‐fold, respectively.
3D printing‐assistedcombinatorial approach for designing mechanically‐tunable and vascular supportive nanofibrous membranes to repair perforated eardrum
Authors: Liu Suihong , Huo Zirong , Zhang Haiguang , Hu Qingxi , Ramalingam Murugan
Published: October 2020

Perforation of eardrum or tympanic membrane (TM) is a common clinical condition, which occurs due to infection or injury of the eardrum, and could results in varying degrees of conductive hearing loss among all ages. In this study, the authors report the combinatorial approach of designing mechanically‐tunable and vascular supportive nanofibrous membranes by 3D printing‐assisted electrospinning (e‐spin) using polycaprolactone (PCL) and gelatin with different mass ratios suitable to repair a perforated eardrum. The physicochemical, mechanical, and biological properties of the membranes were characterized. The results show that the membrane has nanofibrous morphology with fibers are of varying size (400–600 nm in diameter) depending on processing conditions. The wettability and mechanical properties of the membrane can be tuned by regulating the gelatin content. Moreover, a biomimetic repair strategy inspired by chicken eggshell membrane, often used in wound dressings, was also presented for study and results show that the suture retention strength of the fabricated membrane can meet clinical translational requirements to promote TM healing. The vascular cell responsiveness of PCL/gelatin nanofibrous membrane was evaluated using human umbilical vein endothelial cells (HUVECs) and the results showed satisfactory biocompatibility, vascular cell responsiveness, and cell proliferation. The findings of this study demonstrate that the combinatorically engineered PCL/gelatin nanofibrous membrane has great potential for repairing perforated eardrum.
An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus
Authors: Chen Bei‐di , Jia Xin‐miao , Xu Jia‐yue , Zhao Li‐dan , Ji Jun‐yi , Wu Bing‐xuan , Ma Yue , Li Hao , Zuo Xiao‐xia , Pan Wen‐you , Wang Xiao‐han , Ye Shuang , Tsokos George C. , Wang Jun , Zhang Xuan
Published: October 2020

Objective

Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in‐depth understanding of the contribution of gut microbiota to the immunopathogenesis of SLE.

Methods

Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole‐genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single‐nucleotide polymorphism–based strain‐level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides.

Results

Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA‐442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE‐enriched species.

Conclusion

This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen‐mimicking peptides. Our data demonstrate that microbiome‐altering approaches may offer valuable adjuvant therapies in SLE.
Correlating Spatial Ability With Anatomy Assessment Performance: A Meta‐Analysis
Authors: Roach Victoria A. , Mi Misa , Mussell Jason , Van Nuland Sonya E. , Lufler Rebecca S. , DeVeau Kathryn M. , Dunham Stacey M. , Husmann Polly , Herriott Hannah L. , Edwards Danielle N. , Doubleday Alison F. , Wilson Brittany M. , Wilson Adam B.
Published: October 2020

Interest in spatial ability has grown over the past few decades following the emergence of correlational evidence associating spatial aptitude with educational performance in the fields of science, technology, engineering, and mathematics. The research field at large and the anatomy education literature on this topic are mixed. In an attempt to generate consensus, a meta‐analysis was performed to objectively summarize the effects of spatial ability on anatomy assessment performance across multiple studies and populations. Relevant studies published within the past 50 years (1969–2019) were retrieved from eight databases. Study eligibility screening was followed by a full‐text review and data extraction. Use of the Mental Rotations Test (MRT) was required for study inclusion. Out of 2,450 screened records, 15 studies were meta‐analyzed. Seventy‐three percent of studies (11 of 15) were from the United States and Canada, and the majority (9 of 15) studied professional students. Across 15 studies and 1,245 participants, spatial ability was weakly associated with anatomy performance (rpooled = 0.240; CI at 95% = 0.09, 0.38; P = 0.002). Performance on spatial and relationship‐based assessments (i.e., practical assessments and drawing tasks) was correlated with spatial ability, while performance on assessments utilizing non‐spatial multiple‐choice items was not correlated with spatial ability. A significant sex difference was also observed, wherein males outperformed females on spatial ability tasks. Given the role of spatial reasoning in learning anatomy, educators are encouraged to consider curriculum delivery modifications and a comprehensive assessment strategy so as not to disadvantage individuals with low spatial ability.
Stabilization bound of singularly perturbed switched nonlinear systems subject to actuator saturation using the Takagi–Sugeno fuzzy model
Authors: Wang Qianjin , Ma Lei , Wang Dongyang , Ma Xiaoping
Published: October 2020

This paper addresses the measurement problem of stability bound for saturated singularly perturbed switched nonlinear systems (SPSNSs) through the Takagi–Sugeno (T‐S) fuzzy model method. The common Lyapunov function method is applied to construct a state‐feedback stabilization controller that incorporates ε (the singular perturbation parameter) such that the asymptotic stability can be achieved for the switched closed‐loop system under arbitrary switching. Additionally, a basin of attraction is determined by solving a convex optimization problem. Finally, a numerical example and a practical engineering problem are presented to verify the usefulness and feasibility of the proposed results.
A MIF‐Derived Cyclopeptide that Inhibits MIF Binding and Atherogenic Signaling via the Chemokine Receptor CXCR2
Authors: Krammer Christine , Kontos Christos , Dewor Manfred , Hille Kathleen , Dalla Volta Beatrice , El Bounkari Omar , Taş Karin , Sinitski Dzmitry , Brandhofer Markus , Megens Remco T. A. , Weber Christian , Schultz Joshua R. , Bernhagen Jürgen , Kapurniotu Aphrodite
Published: October 2020

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine and atypical chemokine with a key role in inflammatory diseases including atherosclerosis. Key atherogenic functions of MIF are mediated by noncognate interaction with the chemokine receptor CXCR2. The MIF N‐like loop comprising the sequence 47–56 is an important structural determinant of the MIF/CXCR2 interface and MIF(47–56) blocks atherogenic MIF activities. However, the mechanism and critical structure–activity information within this sequence have remained elusive. Here, we show that MIF(47–56) directly binds to CXCR2 to compete with MIF receptor activation. By using alanine scanning, essential and dispensable residues were identified. Moreover, MIF(cyclo10), a designed cyclized variant of MIF(47–56), inhibited key inflammatory and atherogenic MIF activities in vitro and in vivo/ex vivo, and exhibited strongly improved resistance to proteolytic degradation in human plasma in vitro, thus suggesting that it could serve as a promising basis for MIF‐derived anti‐atherosclerotic peptides.
An Animal Able To Tolerate D2O
Authors: de Carli Gabriel José , Contiliani Danyel Fernandes , Giuliatti Silvana , Pereira Tiago Campos
Published: October 2020

It is possible to gain a deeper insight into the role of water in biology by using physicochemical variant molecules, such as deuterium oxide (D2O); however, D2O is toxic to multicellular organisms in high concentrations. By using a unique desiccation‐rehydration process, we demonstrate that the anhydrobiotic nematode Panagrolaimus superbus is able to tolerate and proliferate in 99 % D2O. Moreover, we analysed P. superbus’ water‐channel protein (aquaporin; AQP), which is associated with dehydration/rehydration, by comparing its primary structure and modelling its tertiary structure in silico. Our data evidence that P. superbus’ AQP is an aquaglyceroporin, a class of water channel known to display a wider pore; this helps to explain the rapid and successful organismal influx of D2O into this species. This is the first demonstration of an animal able to withstand high D2O levels, thus paving a way for the investigation of the effects D2O on higher levels of biological organization.
A Light‐Harvesting/Charge‐Separation Model with Energy Gradient Made of Assemblies of meta‐Pyridyl Zinc Porphyrins
Authors: Otsuki Joe , Okumura Takumi , Sugawa Kosuke , Kawano Shin‐ichiro , Tanaka Kentaro , Hirao Takehiro , Haino Takeharu , Lee Yu Jin , Kang Seongsoo , Kim Dongho
Published: October 2020

Self‐assembly of porphyrins is a fascinating topic, not only for mimicking chlorophyll assemblies in photosynthetic organisms, but also for the potential of creating molecular‐level devices. Herein, zinc porphyrin derivatives bearing a meta‐pyridyl group at the meso position were prepared and their assemblies studied in chloroform. Among the porphyrins studied, one with a carbamoylpyridyl moiety gave a distinct 1H NMR spectrum in CDCl3, which allowed the supramolecular structure in solution to be probed in detail. Ring‐current‐induced chemical‐shift changes in the 1H NMR spectrum, together with vapor‐pressure osmometry and diffusion‐ordered NMR spectroscopy, among other evidence, suggested that the porphyrin molecules form a trimer with a triangular cone structure. Incorporation of a directly linked porphyrin–ferrocene dyad with the same assembling properties in the assemblies led to a rare example of a light‐harvesting/charge‐separation system in which an energy gradient is incorporated and reductive quenching occurs.
Applications of Low‐Melting‐Point Metals in Rechargeable Metal Batteries
Authors: Li Qingwen , He Guang , Ding Yi
Published: October 2020

Low‐melting‐point (LMP) metals represent an interesting family of electrode materials owing to their high ionic conductivity, good ductility or fluidity, low hardness and/or superior alloying capability, all of which are crucial characteristics to address battery challenges such as interfacial incompatibility, electrode pulverization, and dendrite growth. This minireview summarizes recent research progress of typical LMP metals including In, Ga, Hg, and their alloys in rechargeable metal batteries. Emphasis is placed on mainstream electrochemical storage devices of Li, Na, and K batteries as well as the representative multi‐valent metal batteries. The fundamental correlations between unique physiochemical properties of LMP metals and the battery performance are highlighted. In addition, this article also provides insights into future development and potential directions of LMP metals/alloys for practical applications.
Isoindolinone Synthesis via One‐Pot Type Transition Metal Catalyzed C−C Bond Forming Reactions
Authors: Savela Risto , Méndez‐Gálvez Carolina
Published: October 2020

Isoindolinone structure is an important privileged scaffold found in a large variety of naturally occurring as well as synthetic, biologically and pharmaceutically active compounds. Owing to its crucial role in a number of applications, the synthetic methodologies for accessing this heterocyclic skeleton have received significant attention during the past decade. In general, the synthetic strategies can be divided into two categories: First, direct utilization of phthalimides or phthalimidines as starting materials for the synthesis of isoindolinones; and second, construction of the lactam and/or aromatic rings by different catalytic methods, including C−H activation, cross‐coupling, carbonylation, condensation, addition and formal cycloaddition reactions. Especially in the last mentioned, utilization of transition metal catalysts provides access to a broad range of substituted isoindolinones. Herein, the recent advances (2010–2020) in transition metal catalyzed synthetic methodologies via formation of new C−C bonds for isoindolinones are reviewed.
Activation of Molecular Oxygen by a Cobalt(II) Tetra‐NHC Complex**
Authors: Schlagintweit Jonas F. , Altmann Philipp J. , Böth Alexander D. , Hofmann Benjamin J. , Jandl Christian , Kaußler Clemens , Nguyen Linda , Reich Robert M. , Pöthig Alexander , Kühn Fritz E.
Published: October 2020

The first dicobalt(III) μ2‐peroxo N‐heterocyclic carbene (NHC) complex is reported. It can be quantitatively generated from a cobalt(II) compound bearing a 16‐membered macrocyclic tetra‐NHC ligand via facile activation of dioxygen from air at ambient conditions. The reaction proceeds via an end‐on superoxo intermediate as demonstrated by EPR studies and DFT. The peroxo moiety can be cleaved upon addition of acetic acid, yielding the corresponding CoIII acetate complex going along with H2O2 formation. In contrast, both CoII and CoIII complexes are also studied as catalysts to utilize air for olefin and alkane oxidation reactions; however, not resulting in product formation. The observations are rationalized by DFT‐calculations, suggesting a nucleophilic nature of the dicobalt(III) μ2‐peroxo complex. All isolated compounds are characterized by NMR, ESI‐MS, elemental analysis, EPR and SC‐XRD.
Lässt ein Gewitter Milch wirklich sauer werden?
Authors: Filianina Mariia
Published: October 2020

Aberglaube hat es vergleichsweise schwer in unserer modernen, ständig fortschreitenden Welt. Es ist nicht mehr leicht, jemanden mit einem Mythos oder einer schönen Legende aus der Kindheit zu täuschen. Aber wie ist es damit: Haben Sie jemals gehört, dass ein Gewitter Milch sauer werden ließe?
Stable Lithium Storage at Subzero Temperatures for High‐capacity Co3O4@graphene Composite Anodes
Authors: Tan Liang , Lan Xuexia , Hu Renzong , Liu Jun , Yuan Bin , Zhu Min
Published: October 2020

Achieving high energy density and long‐term stability at subzero temperatures remains one of the main challenges for the development of lithium‐ion batteries. Shortcomings in energy density and stability mainly highlight on the increase in internal resistance and electrode polarization at subzero temperatures, which greatly affect the reversible capacities of lithium‐ion batteries. In this work, a conversion type Co3O4@graphene (Co3O4@G) composite is prepared via a simple hydrothermal method and first evaluated at subzero temperatures. Benefitting from the especially suitable lithiation/delithiation potentials of Co3O4, ingenious nanostructure and high conductivity of graphene, the Co3O4@G anode exhibits much higher capacity retentions than intercalation‐ and alloying‐type anodes at subzero temperatures, with 58.4% of room‐temperature capacity retention at −30 °C for initial cycle and a highly stable reversible capacity of 605.0 mAh g−1 (0.5 A g−1) for 600 cycles at −10 °C. Furthermore, very high capacities of ∼920.4 mAh g−1 (0.2 A g−1) can be maintained at 30 °C, and ∼450.2 mAh g−1 (0.5 A g−1) can be remained at −20 °C during alternating cycling. This work demonstrates that conversion‐type Co3O4@G composites have superior extreme temperature lithium storage capabilities and can be viable Li‐ion anode materials with fast and highly efficient ion/electron transport capacity at subzero operating temperatures.
Effects of NT5C2 Germline Variants on 6‐Mecaptopurine Metabolism in Children With Acute Lymphoblastic Leukemia
Authors: Jiang Chuang , Yang Wenjian , Moriyama Takaya , Liu Chengcheng , Smith Colton , Yang Wentao , Qian Maoxiang , Li Ziping , Tulstrup Morten , Schmiegelow Kjeld , Crews Kristine R. , Zhang Hui , Pui Ching‐Hon , Evans William , Relling Mary , Bhatia Smita , Yang Jun J.
Published: October 2020

6‐mercaptopurine (6‐MP) is widely used in the treatment of acute lymphoblastic leukemia (ALL), and its cytotoxicity is primarily mediated by thioguanine nucleotide (TGN) metabolites. A recent genomewide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6‐MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6‐MP drug activation has not been comprehensively examined. To this end, we performed targeted sequencing of NT5C2 in 588 children with ALL and identified 121 single nucleotide polymorphisms nominally associated with erythrocyte TGN during 6‐MP treatment (P < 0.05). Of these, 61 variants were validated in a replication cohort of 372 children with ALL. After considering linkage disequilibrium and multivariate analysis, we confirmed two clusters of variants, represented by rs72846714 and rs58700372, that independently affected 6‐MP metabolism. Functional studies showed that rs58700372 directly altered the activity of an intronic enhancer, with the variant allele linked to higher transcription activity and reduced 6‐MP metabolism (lower TGN). By contrast, rs72846714 was not located in a regulatory element and instead its association signal was explained by linkage disequilibrium with a proximal functional variant rs12256506 that activated NT5C2 transcription in‐cis. Our results indicated that NT5C2 germline variation significantly contributes to interpatient variability in thiopurine drug disposition.
Preliminary data on the potential for unintentional antidoping rule violations by permitted cannabidiol (CBD) use
Authors: Mareck Ute , Fusshöller Gregor , Geyer Hans , Huestis Marilyn A. , Scheiff Anja B. , Thevis Mario
Published: October 2020

According to the World Anti‐Doping Agency (WADA) regulations, cannabinoids use is prohibited in competition except for cannabidiol (CBD) use. For an adverse analytical finding (AAF) in doping control, cannabinoid misuse is based on identification of the pharmacologically inactive metabolite 11‐nor‐delta‐9‐carboxy‐tetrahydrocannabinol‐9‐carboxylic acid (carboxy‐THC) in urine at a concentration greater than 180 ng/ml. All other (minor) cannabinoids are reported as AAF when identified, except for CBD that has been explicitly excluded from the class of cannabinoids on WADA's Prohibited List since 2018. However, due to the fact that CBD isolated from cannabis plants may contain additional minor cannabinoids, the permissible use of CBD can lead to unintentional violations of antidoping regulations. An assay for the detection of 16 cannabinoids in human urine was established. The sample preparation consisted of enzymatic hydrolysis of glucuronide conjugates, liquid–liquid extraction, trimethylsilylation, and analysis by gas chromatography/tandem mass spectrometry (GC–MS/MS). Spot urine samples from CBD users, as well as specimens obtained from CBD administration studies conducted with 15 commercially available CBD products, were analyzed, and assay characteristics such as selectivity, reproducibility of detection at the minimum required performance level, limit of detection, and limit of identification were determined. An ethical committee approved controlled single dose commercially available CBD products administration study was conducted to identify 16 cannabinoids in urine samples collected after ingestion or application of the CBD products as well as their presence in spot urine samples of habitual CBD users. Variable patterns of cannabinoids or their metabolites were observed in the urine samples, especially when full spectrum CBD products were consumed. The presence of minor cannabinoids or their metabolites in an athlete's in‐competition urine sample represents a substantial risk of an antidoping rule violation.
Landscape‐dependent effects of varietal mixtures on insect pest control and implications for farmer profits
Authors: Snyder Lauren D. , Gómez Miguel I. , Mudrak Erika L. , Power Alison G.
Published: October 2020

Intraspecific plant diversity can significantly impact insect herbivore populations in natural systems. Yet, its role as an insect pest control strategy in agriculture has received less attention, and little is known about which crop traits are important to herbivores in different landscape contexts. Moreover, empirical economic analyses on the cost‐effectiveness of varietal mixtures are lacking. We used varietal mixtures ofBrassica oleraceacrops on working farms to examine how two metrics of intraspecific crop diversity, varietal richness and number of plant colors (color richness), affect crop damage and the incidence and abundance of two insect pest species:Pieris rapaeandPhyllotretaspp. We evaluated the context‐dependency of varietal mixtures by sampling early‐ and late‐season plantings ofB. oleraceacrops in farms across a gradient of landscape composition. We developed crop budgets and used a net present value analysis to assess the impact of varietal mixtures on input and labor costs, crop revenues, and profit. We found context‐dependent effects of varietal mixtures on both pests. In early‐season plantings, color richness did not affectPhyllotretaspp. populations. However, increasing varietal richness reducedPhyllotretaspp. incidence in simple landscapes dominated by cropland, but this trend was reversed in complex landscapes dominated by natural habitats. In late‐season plantings, color richness reduced the incidence and abundance ofP. rapaelarvae, but only in complex landscapes where their populations were highest. Varietal richness had the same effect onP. rapaelarvae as color richness. Unexpectedly, we consistently found lower pest pressure and reduced crop damage in simple landscapes. Although varietal mixtures did not affect crop damage, increasing color richness corresponded with increased profits, due to increased revenue and a marginal reduction in labor and input costs. We demonstrate varietal mixtures can significantly impact pest populations, and this effect can be mediated by intraspecific variation in crop color. However, the strength and direction of these effects vary by season, landscape composition, and pest species. The association between varietal color richness and profitability indicates farmers could design mixtures to enhance economic returns. We recommend additional research on the benefits of intraspecific trait variation for farmers.
Comparative patterns in taxonomic and functional spider diversities between tropical vs. temperate forests
Authors: Privet Kaïna , Pétillon Julien
Published: October 2020

High diversity in tropical compared to temperate regions has long intrigued ecologists, especially for highly speciose taxa like terrestrial arthropods in tropical rainforests. Previous studies showed that arthropod herbivores account for much tropical diversity, yet differences in the diversity of predatory arthropods between tropical and temperate systems have not been properly quantified. Here, we present the first standardized tropical–temperate forest quantification of spider diversities, a dominant and mega‐diverse taxon of generalist predators. Spider assemblages were collected using a spatially replicated protocol including two standardized sampling methods (vegetation sweep netting and beating). Fieldwork took place between 2010 and 2015 in metropolitan (Brittany) and overseas (French Guiana) French territories. We found no significant difference in functional diversity based on hunting guilds between temperate and tropical forests, while species richness was 13–82 times higher in tropical versus temperate forests. Evenness was also higher, with tropical assemblages up to 55 times more even than assemblages in temperate forests. These differences in diversity far surpass previous estimates and exceed tropical–temperate ratios for herbivorous taxa.
Tricky partners: native plants show stronger interaction preferences than their exotic counterparts
Authors: Coux Camille , Donoso Isabel , Tylianakis Jason M. , García Daniel , Martínez Daniel , Dehling D. Matthias , Stouffer Daniel B.
Published: October 2020

In ecological networks, neutral predictions suggest that species’ interaction frequencies are proportional to their relative abundances. Deviations from neutral predictions thus correspond to interaction preferences (when positive) or avoidances (when negative), driven by nonneutral (e.g., niche‐based) processes. Exotic species interact with many partners with which they have not coevolved, and it remains unclear whether this systematically influences the strength of neutral processes on interactions, and how these interaction‐level differences scale up to entire networks. To fill this gap, we compared interactions between plants and frugivorous birds at nine forest sites in New Zealand varying in the relative abundance and composition of native and exotic species, with independently sampled data on bird and plant abundances from the same sites. We tested if the strength and direction of interaction preferences differed between native and exotic species. We further evaluated whether the performance of neutral predictions at the site level was predicted by the proportion of exotic interactions in each network from both bird and plant perspectives, and the species composition in each site. We found that interactions involving native plants deviated more strongly from neutral predictions than did interactions involving exotics. This “pickiness” of native plants could be detrimental in a context of global biotic homogenization where they could be increasingly exposed to novel interactions with neutrally interacting mutualists. However, the realization of only a subset of interactions in different sites compensated for the neutrality of interactions involving exotics, so that neutral predictions for whole networks did not change systematically with the proportion of exotic species or species composition. Therefore, the neutral and niche processes that underpin individual interactions may not scale up to entire networks. This shows that seemingly simplistic neutral assumptions entail complex processes and can provide valuable understanding of community assembly or invasion dynamics.
Iodine‐Catalyzed Aerobic Oxidative Cleavage of C–C δ‐Bonds: Difunctionalization of Dienones
Authors: Feng Kai‐Xiang , Shen Qiao‐Yu , Xia Ai‐Bao , Zhang Xing , Huang Li‐Sha , Xu Zhong‐Yang , Zhou Zhan‐Yu , Xu Dan‐Qian , Du Xiao‐Hua
Published: October 2020

A new and efficient catalytic strategy that combines organocatalysis and iodine catalysis was first developed for the difunctionalization of dienone. The reaction proceeds under metal‐free conditions and employs dioxygen from air as the mild oxidant. The approach results in 1,5‐diketo epoxides in moderate to high yields.
Voltammetric and Impedimetric Detection of Norfloxacin at Co Nanoparticle Modified Polymer Composite Electrodes
Authors: J. Louw Clementine , Hamnca Siyabulela , G. L. Baker Priscilla
Published: October 2020

The measurement of antibiotics in environmental water systems is increasingly becoming a top priority for global environmental watchdog organisations, as the looming threat of emerging contaminants moves to centre stage. A novel chemical sensor based on polyamic acid (PAA) semiconducting polymer and cobalt nanoparticles (CoNP) was developed and used to demonstrate proof of concept evidence for measurement of norfloxacin at trace concentrations in aqueous systems. Polyamic acid and cobalt nanoparticles were both chemically synthesised and characterised using Fourier transform infrared spectroscopy, transmission electron microscopy, cyclic voltammetry and small angle x‐ray scattering. The polyamic acid and cobalt nanoparticles were electrodeposited onto screen printed carbon electrodes to produce novel composite sensors (SPCE/PAA/CoNP). The polymer composite chemical sensors were applied to the detection of norfloxacin in the micromolar concentration using square wave voltammetry, with a sensitivity of 18.0±6.59 μA/mM, calculated from the slope of the calibration curve and a limit of detection (LOD) of 0.979 ±0.419 mM, with LOD=3.3(Sy/S). The SPCE/PAA/CoNP sensor response to norfloxacin as measured by electrochemical impedance spectroscopy, yielded a sensitivity of 17.6±8.72 Ω/mM as and a limit of detection (LOD) of 0.228±0.0935 mM.
Validation of (not‐historical) large‐event near‐fault ground‐motion simulations for use in civil engineering applications
Authors: Petrone Floriana , Abrahamson Norman , McCallen David , Miah Mamun
Published: October 2020

Ground‐motion simulations generated from physics‐based wave propagation models are gaining increasing interest in the engineering community for their potential to inform the performance‐based design and assessment of infrastructure residing in active seismic areas. A key prerequisite before the ground‐motion simulations can be used with confidence for application in engineering domains is their comprehensive and rigorous investigation and validation. This article provides a four‐step methodology and acceptance criteria to assess the reliability of simulated ground motions of not historical events, which includes (1) the selection of a population of real records consistent with the simulated scenarios, (2) the comparison of the distribution of Intensity Measures (IMs) from the simulated records, real records, and Ground‐Motion Prediction Equations (GMPEs), (3) the comparison of the distribution of simple proxies for building response, and (4) the comparison of the distribution of Engineering Demand Parameters (EDPs) for a realistic model of a structure. Specific focus is laid on near‐field ground motions (<10km) from large earthquakes (Mw7), for which the database of real records for potential use in engineering applications is severely limited. The methodology is demonstrated through comparison of (2490) near‐field synthetic records with 5 Hz resolution generated from the Pitarka et al (2019) kinematic rupture model with a population of (38) pulse‐like near‐field real records from multiple events and, when applicable, with NGA‐W2 GMPEs. The proposed procedure provides an effective method for informing and advancing the science needed to generate realistic ground‐motion simulations, and for building confidence in their use in engineering domains.
Earthquake ground motion modeling of induced seismicity in the Groningen gas field
Authors: Paolucci R. , Mazzieri I. , Piunno G. , Smerzini C. , Vanini M. , Özcebe A.G.
Published: October 2020

A physics‐based numerical approach is used to characterize earthquake ground motion due to induced seismicity in the Groningen gas field and to improve empirical ground motion models for seismic hazard and risk assessment. To this end, a large‐scale (20 km × 20 km) heterogeneous 3D seismic wave propagation model for the Groningen area is constructed, based on the significant bulk of available geological, geophysical, geotechnical, and seismological data. Results of physics‐based numerical simulations are validated against the ground motion recordings of the January 8, 2018, ML 3.4 Zeerijp earthquake. Taking advantage of suitable models of slip time functions at the seismic source and of the detailed geophysical model, the numerical simulations are found to reproduce accurately the observed features of ground motions at epicentral distances less than 10 km, in a broad frequency range, up to about 8 Hz. A sensitivity analysis is also addressed to discuss the impact of 3D underground geological features, the stochastic variability of seismic velocities and the frequency dependence of the quality factor. Amongst others, results point out some key features related to 3D seismic wave propagation, such as the magnitude and distance dependence of site amplification functions, that may be relevant to the improvement of the empirical models for earthquake ground motion prediction.
Research status and analysis of stabilization mechanisms and demulsification methods of heavy oil emulsions
Authors: Fajun Zhao , Zhexi Tian , Zhongqi Yu , Hongzhi Shang , Yanping Wu , Yufei Zhang
Published: October 2020

One major challenge often encountered during the production and transportation of crude oil in petroleum industries is the formation of extremely stable emulsions. This problem is particularly present during the production of heavy oils where steam is used to reduce the viscosity of heavy oil or where submersible pumps are used to artificially lift the produced fluids. This review elaborates on the mechanism of the formation and stability of heavy oil emulsions, discusses the effect of natural surfactants (resins, asphaltenes, solid particles, etc) on the stability of heavy oil emulsions, and summarizes the prominent and sustainable technological and methodological developments in the demulsification of heavy oil emulsions from an economical and environmental perspective. Ionic liquids have been reported as efficient and environmental demulsifiers, and the latest research results on this topic are discussed. Microwave and ultrasonic demulsification methods have been reported to be effective in treating heavy oil emulsions and are also recommended as substitutes in the further development of demulsification technology for treating heavy oil emulsions.
A novel hybrid scale for the assessment of cognitive and executive function: The Free‐Cog
Authors: Burns Alistair , Harrison Judith R. , Symonds Catherine , Morris Julie
Published: October 2020

Background

Scales measuring cognitive and executive functions are integral to the assessment and management of patients with suspected cognitive impairment. Some of the most commonly used cognitive tests are now subject to copyright restrictions. Furthermore, no existing scale assesses both executive and cognitive abilities.

Aims

We aimed to develop and validate a novel hybrid scale for use in clinical practice which integrate measures of cognition and executive abilities (‘Free‐Cog’).

Methods

The instrument was devised through a national collaboration including health professionals, those with lived experience of dementia and researchers. Following ethics committee approval, the Free‐Cog was assessed in 25 real‐world clinical settings across England, Wales and Scotland. It was compared to three other cognitive tests routinely administered in clinical practice: the Mini‐Mental State Examination (MMSE), the Montreal Cognitive Assessment (MOCA), and the Addenbrooke's Cognitive Examination (ACE).

Results

The Free‐Cog was tested in 960 patients with clinical diagnoses of dementia, Mild Cognitive Impairment (MCI), and normal controls. Similar to the MMSE, MOCA and ACE, it discriminated well between the three groups (p < 0.001). It correlated well with the other instruments. Using a receiver operating characteristic curve analysis, Free‐Cog achieved an Area Under Curve of 0.94 for dementia versus controls, 0.80 for MCI versus controls and 0.77 for dementia versus MCI. A version of the tool adapted for telephone consultation, the Tele Free‐Cog, also discriminated well between patient groups.

Conclusions

Free‐Cog is a non‐proprietary, empirically derived, concise assessment. Uniquely, it combines cognitive and executive function questions in the one instrument. It could be used to inform the assessment of people presenting with cognitive impairment and is available to anyone interested in trialling it.
Hepatic Fibrosis Associates With Multiple Cardiometabolic Disease Risk Factors: The Framingham Heart Study
Authors: Long Michelle T. , Zhang Xiaoyu , Xu Hanfei , Liu Ching‐Ti , Corey Kathleen E. , Chung Raymond T. , Loomba Rohit , Benjamin Emelia J.
Published: October 2020

Background and Aims

NAFLD is increasing in prevalence and will soon be the most common chronic liver disease. Liver stiffness, as assessed by vibration‐controlled transient elastography (VCTE), correlates with hepatic fibrosis, an important predictor of liver‐related and all‐cause mortality. Although liver fat is associated with cardiovascular risk factors, the association between hepatic fibrosis and cardiovascular risk factors is less clear.

Approach and Results

We performed VCTE, assessing controlled attenuation parameter (CAP; measure of steatosis) and liver stiffness measurement (LSM) in 3,276 Framingham Heart Study adult participants (53.9% women, mean age 54.3 ± 9.1 years) presenting for a routine study visit. We performed multivariable‐adjusted logistic regression models to determine the association between LSM and obesity‐related, vascular‐related, glucose‐related, and cholesterol‐related cardiovascular risk factors. The prevalence of hepatic steatosis (CAP ≥ 290 dB/m) was 28.8%, and 8.8% had hepatic fibrosis (LSM ≥ 8.2 kPa). Hepatic fibrosis was associated with multiple cardiovascular risk factors, including increased odds of obesity (OR, 1.82; 95% CI, 1.35‐2.47), metabolic syndrome (OR, 1.49; 95% CI 1.10‐2.01), diabetes (OR, 2.67; 95% CI, 1.21‐3.75), hypertension (OR, 1.52; 95% CI, 1.15‐1.99), and low high‐density lipoprotein cholesterol (OR, 1.47; 95% CI, 1.09‐1.98), after adjustment for age, sex, smoking status, alcohol drinks/week, physical activity index, aminotransferases, and CAP.

Conclusions

In our community‐based cohort, VCTE‐defined hepatic fibrosis was associated with multiple cardiovascular risk factors, including obesity, metabolic syndrome, diabetes, hypertension, and high‐density lipoprotein cholesterol, even after accounting for covariates and CAP. Additional longitudinal studies are needed to determine if hepatic fibrosis contributes to incident cardiovascular disease risk factors or events.