bluuebunny/crossref_metadata_2025 huggingface dataset:
Independent associations of women's age at marriage and first pregnancy with their height in rural lowland Nepal
Authors: Marphatia Akanksha A. , Saville Naomi M. , Manandhar Dharma S. , Cortina‐Borja Mario , Reid Alice M. , Wells Jonathan C. K.
Published: November 2020

Objectives

In many South Asian communities, the majority of women are married during adolescence and reproduce before 20 years. Early reproduction may adversely affect maternal nutrition and linear growth, however whether early marriage has similar effects is unknown. Shorter women might also be preferentially chosen for earlier marriage. We hypothesized that early marriage and early pregnancy may each be associated with women's shorter height, independent of any selection effects.

Materials and Methods

We analyzed cross‐sectional data on 7,146 women aged 20–30 years from rural lowland Nepal. Linear regression models tested associations of early marriage and early reproduction with height, adjusting for women's education and husbands' characteristics (education and wealth) that might index preferential selection of short young women for marriage.

Results

Median ages at marriage and first pregnancy were 15 and 18 years, respectively, with 20% pregnant <16 years. Both early marriage and early pregnancy were independently associated with shorter stature, accounting for a decrement of 1.4 cm, which decreased to 1 cm after adjusting for women's education. Effects of early marriage and reproduction persisted after adjusting for the tendency of poorer and less educated men to marry young and short women, indicating a role for social selection.

Discussion

The decrements in height associated with early marriage and reproduction are indicative of broader adverse effects on maternal metabolism during a “critical period” of growth and maturation in the life‐course of women. Although the magnitudes of effect are relatively small, they affect large numbers of women in this population.
Transparent epoxy resin material with excellent fire retardancy enabled by a P/N/S containing flame retardant
Authors: Dai Shengsong , Yu Xuejun , Chen Rui , Zhou Hong , Pan Zhiquan
Published: November 2020

An epoxy resin (EP) with excellent fire retardancy, good transparency, and satisfactory thermal stability has been obtained by introducing a new N/P/S containing flame retardant (HBD) into EP composites. When the phosphorus content was 0.48 wt%, EP/HBD reached V‐0 rating with the limiting oxygen index of 33.5%. The cone calorimeter test (CC) indicated that the incorporation of HBD resulted in 1.5 times increase in ignition time, a 50% decrease in the maximum of heat release rates, 40% reduction of total heat release, and 50.7% decrease in total smoke production compared with EP. Besides, the fire‐resistant behavior of EP/8% HBD is much better than the EP materials modified by similar P/N/S flame retardants reported in literature. The fire‐retardant mechanism of HBD on EP was also analyzed by Raman, scanning electron microscope, Py‐GC/MS, and Fourier transform infrared spectroscopy. The results show that HBD plays an important role in the formation of a dense intumescent carbon layer and gas phase quenching.
Strengths and Weaknesses of Non‐enhanced and Contrast‐enhanced Cadaver Computed Tomography Scans in the Teaching of Gross Anatomy in an Integrated Curriculum
Authors: Paech Daniel , Klopries Kerstin , Nawrotzki Ralph , Schlemmer Heinz‐Peter , Giesel Frederik L. , Kirsch Joachim , Schultz Jobst‐Hendrik , Kuner Thomas , Doll Sara
Published: November 2020

Cadaver‐specific postmortem computed tomography (PMCT) has become an integral part in anatomy teaching at several universities. Recently, the feasibility of contrast‐enhanced (CE)‐PMCT has been demonstrated. The purpose of this study was to identify particular strengths and weaknesses of both non‐enhanced and contrast‐enhanced PMCT compared to conventional cadaver dissection. First, the students’ perception of the learning effectiveness of the three different modalities have been assessed using a 34‐item survey (five‐point Likert scale) covering all anatomy course modules. Results were compared using the nonparametric Friedman Test. Second, the most frequent artifacts in cadaver CT scans, were systematically analyzed in 122 PMCT and 31 CE‐PMCT data sets to quantify method‐related limitations and characteristics. Perfusion quality was assessed in 57 vascular segments (38 arterial and 19 venous). The survey was answered by n = 257/320 (80.3%) students. Increased learning benefits of PMCT/ CE‐PMCT compared to cadaver dissection were found in osteology (2/3 categories, P < 0.001), head and neck (2/5 categories, P < 0.01), and brain anatomy (3/3 categories, P < 0.01). Contrast‐enhanced‐PMCT was perceived particularly useful in learning vascular anatomy (10/10 categories, P < 0.01). Cadaver dissection received significantly higher scores compared to PMCT and CE‐PMCT in all categories of the abdomen and thorax (7/7 categories, P < 0.001), as well as the majority of muscular anatomy (5/6 categories, P < 0.001). Frequent postmortem artifacts (total n = 28, native‐phase n = 21, contrast injection‐related n = 7) were identified and assessed. The results of this work contribute to the understanding of the value of integrating cadaver‐specific PMCT in anatomy teaching.
Sensors and Analytical Technologies for Air Quality: Particulate Matters and Bioaerosols
Authors: Su Xiaodi , Sutarlie Laura , Loh Xian Jun
Published: November 2020

Particulate matters (PMs), e. g. dusts, fibres, smokes, fumes, mists, liquid droplets and airborne respirable solid or liquid particles, are the major sources of air pollution concerning outdoor and indoor air quality. Among various PMs, bioaerosols are airborne particles that are either living organisms (bacteria, viruses, and fungi) or originate from living organisms (endotoxin, allergen, etc). PMs and/or bioaerosols have adverse health effects of infection, allergy, and irritation. Proper management and source identification of PMs and bioaerosols will reduce their negative health impact. In this review, we will discuss the analytical technologies and sensors for PMs and bioaerosols. We will first introduce four types of PM analysers, namely, filter‐based gravimetric method (GMM), optical method, β‐ray absorption method (BAM), and tapered element oscillating microbalance (TEOM). We will provide examples of how commercial PM analyzers of different principles have been compared and calibrated for specific applications under different climate conditions of specific geographic locations. For bioaerosols, having more complex biological and biochemical identity, we will start from air sampling techniques, followed by a discussion of various detection methods (plate culture, molecular methods, immunoassays and biosensors) in association with compatible sampling technologies. Using Influenza A (H1 N1) virus and SARS‐CoV‐2 (COVID‐19) virus as examples, we have highlighted air sampling and detection challenges for viral aerosols relative to bacterial and fungal aerosols. Finally, we provide a perspective for future trends according to the limitation of current commercial products and the key challenges in this field.
Regional stability analysis of impulsive switched nonlinear systems with multiple equilibrium points
Authors: Wang Zhichuang , Feng Weizhen , Ba Hezhen
Published: November 2020

This paper addresses the regional stability problem for impulsive switched nonlinear systems (ISNSs) whose subsystems have more than one equilibrium point, that is, multiple equilibrium points (MEPs) coexist. Meanwhile, we derive analytical results and sufficient conditions about the regional stability. Through investigating the dynamical behavior of ISNSs with MEPs, the multiple Lyapunov functions (MLFs) method is established for the regional stability. It is shown that main results obtained in this paper not only guarantee the regional stability of ISNSs with MEPs under arbitrary switching signals but also provide a new method to determine the corresponding stable regions for the regional stability. Numerical simulations are given to illustrate and verify advantages of our proposed results.
Houston's Conversion From Groundwater to Surface Water
Authors: Rogers Randy , Kaleyatodi Ravi , Singh Rajinder , Crawford Susan , Lynk Steve
Published: November 2020

Key Takeaways

Houston's Northeast Water Purification Plant expansion project is required to comply with subsidence district rules for conversion from groundwater to surface water supply.

Innovative solutions for the expanded plant include two coagulation recipes to treat water from Lake Houston; treatment with chlorine dioxide, ozone, and biological filtration; and enhanced residuals treatment.

A progressive design–build approach—used for the largest project of this kind presently underway in North America—maximized stakeholder involvement.
Our Water Future Requires Action Now
Authors: Roberson J. Alan , Wilkes Wendi
Published: November 2020

Key Takeaways

Our public health history is strong. The water sector did many of the right things at the right time to effectively protect public health, such as starting chlorination in the early 1900s.

The status quo is not an option. We are collectively losing ground on new and emerging contaminants, funding, and public trust, to name a few of our major challenges.

Water sector leadership at the local, state, and federal levels can change our trajectory and achieve a better future through coordination, collaboration, creativity, and speed.

New regulatory and nonregulatory approaches are needed, such as optimizing the regulatory development process and looking outside of federal mandates for solutions.
The molecular tug of war between immunity and fertility: Emergence of conserved signaling pathways and regulatory mechanisms
Authors: Naim Nikki , Amrit Francis R.G. , McClendon T. Brooke , Yanowitz Judith L. , Ghazi Arjumand
Published: November 2020

Reproduction and immunity are energy intensive, intimately linked processes in most organisms. In women, pregnancy is associated with widespread immunological adaptations that alter immunity to many diseases, whereas, immune dysfunction has emerged as a major cause for infertility in both men and women. Deciphering the molecular bases of this dynamic association is inherently challenging in mammals. This relationship has been traditionally studied in fast‐living, invertebrate species, often in the context of resource allocation between life history traits. More recently, these studies have advanced our understanding of the mechanistic underpinnings of the immunity‐fertility dialogue. Here, we review the molecular connections between reproduction and immunity from the perspective of human pregnancy to mechanistic discoveries in laboratory organisms. We focus particularly on recent invertebrate studies identifying conserved signaling pathways and transcription factors that regulate resource allocation and shape the balance between reproductive status and immune health.
Are endoplasmic reticulum subdomains shaped by asymmetric distribution of phospholipids? Evidence from a C. elegans model system
Authors: Cao Zhe , Wang Xiaowei , Huang Xuhui , Mak Ho Yi
Published: November 2020

Physical contact between organelles are widespread, in part to facilitate the shuttling of protein and lipid cargoes for cellular homeostasis. How do protein‐protein and protein‐lipid interactions shape organelle subdomains that constitute contact sites? The endoplasmic reticulum (ER) forms extensive contacts with multiple organelles, including lipid droplets (LDs) that are central to cellular fat storage and mobilization. Here, we focus on ER‐LD contacts that are highlighted by the conserved protein seipin, which promotes LD biogenesis and expansion. Seipin is enriched in ER tubules that form cage‐like structures around a subset of LDs. Such enrichment is strongly dependent on polyunsaturated and cyclopropane fatty acids. Based on these findings, we speculate on molecular events that lead to the formation of seipin‐positive peri‐LD cages in which protein movement is restricted. We hypothesize that asymmetric distribution of specific phospholipids distinguishes cage membrane tubules from the bulk ER.
Can BCG vaccine protect against COVID‐19 via trained immunity and tolerogenesis?
Authors: Basak Preetam , Sachdeva Naresh , Dayal Devi
Published: November 2020

As the number of infections and mortalities from the SARS‐CoV‐2 pandemic continues to rise, the development of an effective therapy against COVID‐19 becomes ever more urgent. A few reports showing a positive correlation between BCG vaccination and reduced COVID‐19 mortality have ushered in some hope. BCG has been suggested to confer a broad level of nonspecific protection against several pathogens, mainly via eliciting “trained immunity” in innate immune cells. Secondly, BCG has also been proven to provide benefits in autoimmune diseases by inducing tolerogenicity. Being an acute inflammatory disease, COVID‐19 requires a therapy that induces early priming of anti‐viral immune responses and regulates aberrant hyperactivity of innate‐immune cells. Here, we hypothesize that BCG can offer reliable spatiotemporal protection from COVID‐19 by triggering trained immunity and tolerogenesis, through multiple cellular pathways. We propose further research on BCG‐mediated immunoprotection, especially in vulnerable individuals, as a strategy to halt the progress of the SARS‐CoV‐2 pandemic. Also see the video abstract here https://youtu.be/P2D2RXfq6Vg.
The exploration of neuraminidase inhibitory activity on Fallopia denticulata, an ethnic herb in China
Authors: Zheng Yan , Zhang Xiang , Cao Yu , Huang Linfang
Published: November 2020

This study was designed to explore the bioactive ingredients in the extracts of Fallopia denticulata (C.C. Huang) Holub, a medicinal plant grown in China, which exhibits the best neuraminidase (NA) inhibition activity. Three fractions of ethyl acetate, ethanol, and water were tested on NA inhibition assay, and the best one was conducted by ultra‐performance liquid chromatography–time‐of‐flight mass spectrometry in the negative and positive modes to analyze the metabolic components. The results revealed the identification of the following 21 compounds: 3 organic acids, 11 flavonoids, 1 coumarin, and 6 others, such as β‐daucosterol, gallic acid, and syringic acid, of which 12 compounds were discovered for the first time in F. denticulata. In addition, we used the molecular docking technique to support the anti‐NA activity of each compound in the best extract. The results confirmed that the two better bioactive compounds were (−)‐epicatechin gallate and (+)‐catechin. Therefore, F. denticulata could be used as a potential material for new anti‐influenza drugs.
Semicontinuous system for the production of recombinant mCherry protein in Chlamydomonas reinhardtii
Authors: Arias Cesar Andres Diaz , Matsudo Marcelo Chuei , Ferreira‐Camargo Livia Seno , Molino João Vitor Dutra , Mayfield Stephen Patrick , de Carvalho João Carlos Monteiro
Published: November 2020

Biotechnology advances have allowed bacteria, yeasts, plants, mammalian and insect cells to function as heterologous protein expression systems. Recently, microalgae have gained attention as an innovative platform for recombinant protein production, due to low culture media cost, compared to traditional systems, as well as the fact that microalgae such as Chlamydomonas reinhardtii are considered safe (GRAS) by the Food and Drug Administration (FDA). Previous studies showed that recombinant protein production in traditional platforms by semicontinuous process increased biomass and bio product productivity, when compared to batch process. As there is a lack of studies on semicontinuous process for recombinant protein production in microalgae, the production of recombinant mCherry fluorescent protein was evaluated by semicontinuous cultivation of Chlamydomonas reinhardtii in bubble column photobioreactor. This semicontinuous cultivation process was evaluated in the following conditions: 20%, 40%, and 60% culture portion withdrawal. The highest culture withdrawal percentage (60%) provided the best results, as an up to 161% increase in mCherry productivity (454.5 RFU h−1 – Relative Fluorescence Unit h−1), in comparison to batch cultivation (174.0 RFU h−1) of the same strain. All cultivations were carried out for 13 days, at pH 7, temperature 25°C and, by semicontinuous process, two culture withdrawals were taken during the cultivations. Throughout the production cycles, it was possible to obtain biomass concentration up to 1.36 g L−1.
Real‐world experience of carfilzomib‐associated cardiovascular adverse events: SEER‐Medicare data set analysis
Authors: Bishnoi Rohit , Xie Zhigang , Shah Chintan , Bian Jiang , Murthy Hemant S. , Wingard John R. , Farhadfar Nosha
Published: November 2020

Carfilzomib was approved for the treatment of multiple myeloma in 2012 and since then there have been concerns for cardiovascular toxicity from its use. With this study, we aim to further study the hazards and underlying risk factors for cardiovascular adverse events associated with carfilzomib. This study was conducted using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data set of multiple myeloma from 2001 to 2015. Data were analyzed for hazards ratio of cardiovascular adverse events between carfilzomib users and nonusers. We identified 7330 patients with multiple myeloma of whom 815 were carfilzomib users. Carfilzomib users had a statistically significant hazard ratio of 1.41 with p < 0.0001 for all cardiovascular adverse events as compared to nonusers. Carfilzomib use was significantly associated with increased risk of heart failure (HR 1.47, p = 0.0002), ischemic heart disease (HR 1.45, p = 0.0002), and hypertension (HR 3.33, p < 0.0001), whereas there was no association between carfilzomib use and cardiac conduction disorders (arrhythmia and heart blocks). Carfilzomib users were at higher risk of new‐onset edema (HR 5.09, p < 0.0001), syncope (HR 4.27, p < 0.0001), dyspnea (HR 1.33, p < 0.0001), and chest pain (HR 1.18, p < 0.0001) as compared to carfilzomib nonusers. Age above 75 years, preexisting cardiovascular disease, obesity, and twice a week carfilzomib schedule were significant risk factors associated with cardiovascular adverse events in carfilzomib users. The median time of the onset for all cardiovascular adverse events was 3.1 months. This study has identified a significantly higher likelihood of cardiovascular adverse events in elderly Medicare patients receiving carfilzomib.
Chemical Composition Analysis, Antioxidant, and Antibacterial Activities of Eggplant Leaves
Authors: Bouhajeb Rim , Selmi Salima , Nakbi Amel , Jlassi Ibrahim , Montevecchi Giuseppe , Flamini Guido , Zarrad Imen , Dabbou Samia
Published: November 2020

Agricultural by‐products represent one of the biggest pollutants for the environment, therefore, investigating new sources for the extraction of bioactive compounds is a topic of great interest for the entire scientific community. This work is aimed at studying the chemical composition (pigments, phenolics, volatile compounds) and biological activities (antioxidant and antimicrobial properties) of young and mature leaves of five eggplant cultivars (Solanum melongena L.) grown in Tunisia (Tizona, A1014, Nawel, A336, and Mirval).

Pigment analysis showed no statistical variations between the two types of leaves, whereas higher levels of anthocyanins were recorded in young leaves of three out of five cultivars (24.7–52.8 mg 100 g−1). Total phenolic compounds (966.5–2072.6 mg 100 g−1) and o‐diphenols (343.9–741.2 mg 100 g−1) contents varied significantly according to leaf age and cultivar. However, no statistically significant variation between young and mature leaves was found in flavonols and tannins content. As for volatile profiles, 62 constituents were characterized with non‐terpene derivatives (52.0–61.6 %) and apocarotenes (19.9–35.6 %) as major chemical classes.

Regarding the antioxidant activity, methanol extracts of Tizona cultivar mature leaves displayed important antiradical properties using DPPH, ABTS, and phosphomolybdenum assays (IC50 0.1, 0.2 and 0.01 mg mL−1, respectively). With regards to reducing power determination, the most active extract was obtained from mature A1014 leaves. Further, young Mirval leaves proved to be significantly active from a bactericidal point of view against Candida albicans and Staphylococcus aureus of 3.1 mg mL−1 and 0.2 mg mL−1 MBC, respectively.

In conclusion, eggplant leaves are a noteworthy source of antioxidant and antimicrobial compounds with potential use in the pharmaceutical, the cosmetics and the food industries.
The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase
Authors: O'Loughlin Jennie , Napolitano Silvia , Alkhathami Fahad , O'Beirne Cillian , Marhöfer Daniel , O'Shaughnessy Megan , Howe Orla , Tacke Matthias , Rubini Marina
Published: November 2020

Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver‐related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3‐dibenzyl‐4,5‐diphenyl‐imidazol‐2‐ylidene silver(I) acetate/NHC*‐Ag‐OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; Ki=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR.
Silicosis in a paint‐production worker: Study of a lung histological specimen with scanning electron microscopy—Energy dispersive X‐ray spectrometer
Authors: De Maria Luigi , Caputi Antonio , Luisi Vito , Delfino Maria Celeste , Cavone Domenica , Acquafredda Pasquale , Pallara Mauro , Lovreglio Piero , Vimercati Luigi
Published: November 2020

The occupational risks in silica‐exposed workers have been greatly reduced over the last decades; however, only few studies investigated uncommon forms of exposure to crystalline silica as shown by this case of silicosis in a paint‐production worker.
Microtubular Gas Diffusion Electrode Based on Ruthenium‐Carbon Nanotubes for Ambient Electrochemical Nitrogen Reduction to Ammonia
Authors: Wei Xin , Vogel Dominik , Keller Laura , Kriescher Stefanie , Wessling Matthias
Published: November 2020

The drawback of the energy‐intensive Haber‐Bosch process promotes the research and development of alternative ammonia (NH3) synthesis approaches. The electrochemical nitrogen (N2) reduction reaction (eNRR) may offer a promising method to produce NH3 independent of fossil‐fuel‐based hydrogen production. However, the low solubility and the low‐efficiency mass transport of N2 in aqueous electrolytes are still among the challenges facing the feasibility of eNRR. Herein, we demonstrate a microtubular ruthenium‐carbon nanotube gas diffusion electrode (Ru−CNT GDE), for the first time, applying it to electrochemical NH3 synthesis in an H‐type cell under ambient conditions. The highest reported Ru‐catalyzed NH3 yield rate of 2.1×10−9 mol/cm2 s and high faradaic efficiency of 13.5 % were achieved, showing the superior effect of Ru−CNT GDEs on the eNRR performance. This work provides a new approach for the design and fabrication of self‐standing catalyst‐loaded GDEs for eNRR.
Indol‐2‐ylidene (IdY): Ambiphilic N‐Heterocyclic Carbene Derived from Indole**
Authors: Kim Hyunho , Kim Minseop , Song Hayoung , Lee Eunsung
Published: November 2020

The synthesis of ambiphilic N‐heterocyclic carbene ligand, indol‐2‐ylidene (IdY, A), is described. A series of indolenium precursors (2 a–f) were prepared on a gram scale in good yields. Trapping experiments with elemental selenium, [RhCl(cod)]2 and CuCl provided the expected carbene adducts. Further computational and spectroscopic studies supported the ambiphilicity of IdY, which lies between cyclic (alkyl)(amino)carbenes (CAAC‐5) and cyclic (amino)(aryl)carbene (CAArC). The copper complexes (6) show high percent buried volume (% Vbur = 58.1) and allow for carboboration of terminal alkynes within 30 minutes in a demonstration of synthetic utility with good yields and high regioselectivity.
Whose autonomy support is more effective? Managers' or Co‐Workers’? An experimental comparison of source and occupational context on intrinsic motivation
Authors: Jungert Tomas , Schattke Kaspar , Proulx Félix Alexandre , Taylor Geneviève , Koestner Richard
Published: November 2020

The purpose of this paper was to experimentally test whether support from different sources would lead to increased intrinsic work motivation and to examine whether occupational context moderated this effect. In Study 1, we manipulated autonomy support, source of behaviour, and occupational context. In Study 2, we allocated participants to a conventional or social work context depending on their real occupation to increase ecological validity. Altogether, 495 workers participated. We found a main effect for autonomy support, and that managers' autonomy support was more effective in a conventional occupational context, whereas co‐workers’ autonomy support was more effective in the social occupational context. Findings highlight the importance of having both autonomy‐supportive managers and co‐workers for workers' intrinsic motivation.
Less harmful and less toxic sparklers: a well‐known school experiment in a new light
Authors: Scheid Michael , Pohl Laura , Rusan Magdalena , Klapötke Thomas M. , Schwarzer Stefan
Published: November 2020

Wunderkerzen bieten für den Chemieunterricht vielfältige Anknüpfungspunkte. Nicht nur Lehrplaninhalte der Redoxchemie und Oxidationsmittel können vertieft, sondern auch Umweltaspekte aufgezeigt und mit den hier vorgestellten neu entwickelten und umweltfreundlicheren Wunderkerzen ein Einblick in aktuelle Forschungsthemen aus dem Bereich der Pyrotechnik gegeben werden. Im Fokus der Unterrichtseinheit steht die Herstellung von Wunderkerzen als Schülerexperiment. Ergänzend wird in einem Modellexperiment die Auswirkung auf lebende Organismen dieser neu entwickelten Wunderkerzenrezeptur sowie der herkömmlichen Wunderkerzenzusammensetzung verglichen. Abschließend werden im Artikel ausführlich die rechtlichen Rahmenbedingungen der Wunderkerzenherstellung als Schülerexperiment im Hinblick auf die Sicherheit thematisiert. Mit Hilfe von Sensitivitätstests konnte nachgewiesen werden, dass die hier vorgestellten Wunderkerzenmischungen keine explosiven Gemische sind. Somit dürfen diese Mischungen im Einklang mit der aktuellen Fassung der RiSU 2019 erstmals auch von Schülerinnen und Schülern hergestellt werden.
A multi‐institutional phase 2 trial of stereotactic body radiotherapy in the treatment of bone metastases in pediatric and young adult patients with sarcoma
Authors: Elledge Christen R. , Krasin Matthew J. , Ladra Matthew M. , Alcorn Sara R. , Han Peijin , Gibbs Iris C. , Hiniker Susan M. , Laack Nadia N. , Terezakis Stephanie A.
Published: November 2020

Background

Metastasectomy is standard of care for pediatric patients with metastatic sarcoma with limited disease. For patients with unresectable disease, stereotactic body radiotherapy (SBRT) may serve as an alternative. Herein, the authors report the results of a prospective, multi‐institutional phase 2 trial of SBRT in children and young adults with metastatic sarcoma.

Methods

Patients aged >3 years and ≤40 years with unresected, osseous metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone were eligible. Patients received SBRT to a dose of 40 Gray (Gy) in 5 fractions. Local control (LC), progression‐free survival (PFS), and overall survival (OS) were calculated using the Kaplan‐Meier method.

Results

Fourteen patients with a median age of 17 years (range, 4‐25 years) were treated to 37 distinct metastatic lesions. With a median follow‐up of 6.8 months (30.5 months in surviving patients), the Kaplan‐Meier patient‐specific and lesion‐specific LC rates at 6 months were 89% and 95%, respectively. The median PFS was 6 months and the median OS was 24 months. In a post hoc analysis, PFS (median, 9.3 months vs 3.7 months; log‐rank P = .03) and OS (median not reached vs 12.7 months; log‐rank P = .02) were improved when all known sites of metastatic disease were consolidated with SBRT compared with partial consolidation. SBRT was well tolerated, with 2 patients experiencing grade 3 toxicities.

Conclusions

SBRT achieved high rates of LC in pediatric patients with inoperable metastatic nonrhabdomyosarcoma sarcomas of soft tissue and bone. These results suggest that the ability to achieve total consolidation of metastatic disease with SBRT is associated with improved PFS and OS.
Preparation of Few‐Layer Porous Graphene by a Soft Mechanical Method with a Short Rolling Transfer Process
Authors: Huang Jialiang , Zhao Xuewen , Ma Chuansheng , Cheng Yonghong , Zhang Jinying
Published: November 2020

Few‐layer porous graphene is a promising material for a variety of fields. However, the synthesis of few‐layer porous graphene is a great challenge. Here we report a feasible green path to produce few‐layer porous graphene, which was exfoliated from high‐pressure graphite balls onto microspheres with rough surfaces by a mild rolling transfer process. Ordinary ball milling equipment was adopted for the low‐speed (100 rpm) ball–microsphere rolling transfer process. The rolling time (<10 min) was controlled to obtain porous graphene instead of graphene. The porous graphene on the exfoliating microspheres was then easily dispersed in solution by bath sonication. The product contains very few impure functional groups. The hole size and layer distribution of the few‐layer porous graphene have been demonstrated to be 2.37±1.17 nm and 2.4±0.7 layers, respectively, and can be adjusted by redesigning the surface of the microspheres.
Perennial ryegrass phytotoxicity increases with mesotrione rate and growth‐promoting environmental conditions
Authors: Gonçalves Clebson G. , Ricker Daniel B. , Askew Shawn D.
Published: November 2020

Bleaching of young leaf tissue is a common response to the herbicide mesotrione and varies from one application to another. To better elucidate factors that may contribute to perennial ryegrass (Lolium perenne L.) phytotoxicity from mesotrione, studies were conducted at Blacksburg, VA. Continuous field monitoring of temperature, humidity, solar radiation, soil moisture, and leaf wetness was used to elucidate environmental conditions that led to perennial ryegrass injury by mesotrione applied at 0.14 kg a.i. ha−1. The study found that 2 of 17 weekly treatments caused unacceptable perennial ryegrass injury at two field sites. Ten‐day temporal trends prior to mesotrione treatment showed that temperature, for one injury event, and volumetric soil water content, for the other injury event, were exclusively correlated to visually and digitally assessed perennial ryegrass injury. Both instances suggest that alleviation of suboptimal temperature or moisture with more optimal growing conditions influenced the turf injury response. Additional studies in growth chambers showed that carotenoid levels and turf phytotoxicity were strongly temperature dependent and followed a quadratic response with peak injury occurring at perennial ryegrass growth optima. Carotenoid levels decreased and perennial ryegrass injury increased in response to increased mesotrione rate. These data suggest that mesotrione is more likely to injure perennial ryegrass turf when used at higher rates and under conditions of rapid turfgrass growth.
A new approach to interspecific synchrony in population ecology using tail association
Authors: Ghosh Shyamolina , Sheppard Lawrence W. , Reid Philip C. , Reuman Daniel
Published: November 2020

Standard methods for studying the association between two ecologically important variables provide only a small slice of the information content of the association, but statistical approaches are available that provide comprehensive information. In particular, available approaches can reveal tail associations, that is, accentuated or reduced associations between the more extreme values of variables. We here study the nature and causes of tail associations between phenological or population‐density variables of co‐located species, and their ecological importance. We employ a simple method of measuring tail associations which we call the partial Spearman correlation. Using multidecadal, multi‐species spatiotemporal datasets on aphid first flights and marine phytoplankton population densities, we assess the potential for tail association to illuminate two major topics of study in community ecology: the stability or instability of aggregate community measures such as total community biomass and its relationship with the synchronous or compensatory dynamics of the community's constituent species; and the potential for fluctuations and trends in species phenology to result in trophic mismatches. We find that positively associated fluctuations in the population densities of co‐located species commonly show asymmetric tail associations; that is, it is common for two species’ densities to be more correlated when large than when small, or vice versa. Ordinary measures of association such as correlation do not take this asymmetry into account. Likewise, positively associated fluctuations in the phenology of co‐located species also commonly show asymmetric tail associations. We provide evidence that tail associations between two or more species’ population‐density or phenology time series can be inherited from mutual tail associations of these quantities with an environmental driver. We argue that our understanding of community dynamics and stability, and of phenologies of interacting species, can be meaningfully improved in future work by taking into account tail associations.
Ecological and morphological determinants of evolutionary diversification in Darwin's finches and their relatives
Authors: Reaney Ashley M. , Bouchenak‐Khelladi Yanis , Tobias Joseph A. , Abzhanov Arkhat
Published: November 2020

Darwin's finches are a classic example of adaptive radiation, a process by which multiple ecologically distinct species rapidly evolve from a single ancestor. Such evolutionary diversification is typically explained by adaptation to new ecological opportunities. However, the ecological diversification of Darwin's finches following their dispersal to Galápagos was not matched on the same archipelago by other lineages of colonizing land birds, which diversified very little in terms of both species number and morphology. To better understand the causes underlying the extraordinary variation in Darwin's finches, we analyze the evolutionary dynamics of speciation and trait diversification in Thraupidae, including Coerebinae (Darwin's finches and relatives) and, their closely related clade, Sporophilinae. For all traits, we observe an early pulse of speciation and morphological diversification followed by prolonged periods of slower steady‐state rates of change. The primary exception is the apparent recent increase in diversification rate in Darwin's finches coupled with highly variable beak morphology, a potential key factor explaining this adaptive radiation. Our observations illustrate how the exploitation of ecological opportunity by contrasting means can produce clades with similarly high diversification rate yet strikingly different degrees of ecological and morphological differentiation.
Impacts of climate change on multiple use management of Bureau of Land Management land in the Intermountain West, USA
Authors: Brice Elaine M. , Miller Brett A. , Zhang Hongchao , Goldstein Kirsten , Zimmer Scott N. , Grosklos Guenchik J. , Belmont Patrick , Flint Courtney G. , Givens Jennifer E. , Adler Peter B. , Brunson Mark W. , Smith Jordan W.
Published: November 2020

Although natural resource managers are concerned about climate change, many are unable to adequately incorporate climate change science into their adaptation strategies or management plans, and are not always aware of or do not always employ the most current scientific knowledge. One of the most prominent natural resource management agencies in the United States is the Bureau of Land Management (BLM), which is tasked with managing over 248 million acres (>1 million km2) of public lands for multiple, often conflicting, uses. Climate change will affect the sustainability of many of these land uses and could further increase conflicts between them. As such, the purpose of our study was to determine the extent to which climate change will affect public land uses, and whether the BLM is managing for such predicted effects. To do so, we first conducted a systematic review of peer‐reviewed literature that discussed potential impacts of climate change on the multiple land uses the BLM manages in the Intermountain West, USA, and then expanded these results with a synthesis of projected vegetation changes. Finally, we conducted a content analysis of BLM Resource Management Plans in order to determine how climate change is explicitly addressed by BLM managers, and whether such plans reflect changes predicted by the scientific literature. We found that active resource use generally threatens intrinsic values such as conservation and ecosystem services on BLM land, and climate change is expected to exacerbate these threats in numerous ways. Additionally, our synthesis of vegetation modeling suggests substantial changes in vegetation due to climate change. However, BLM plans rarely referred to climate change explicitly and did not reflect the results of the literature review or vegetation model synthesis. Our results suggest there is a disconnect between management of BLM lands and the best available science on climate change. We recommend that the BLM actively integrates such research into on‐the‐ground management plans and activities, and that researchers studying the effects of climate change make a more robust effort to understand the practices and policies of public land management in order to effectively communicate the management significance of their findings.
Stirring up the relationship between quantified environmental DNA concentrations and exoskeleton‐shedding invertebrate densities
Authors: Trimbos Krijn B. , Cieraad Ellen , Schrama Maarten , Saarloos Aagje I. , Musters Kees. J. M. , Bertola Laura D. , van Bodegom Peter M.
Published: November 2020

The application of eDNA techniques for the detection, monitoring, and conservation of biodiversity holds great promise. While many studies apply eDNA techniques in aquatic systems to determine the presence or absence of a given species, using eDNA for the purpose of species density or biomass predictions remains a challenge, especially for freshwater invertebrates that shed exoskeletons. Here, we aimed to determine whether and how eDNA concentrations relate to exoskeleton‐shedding invertebrate densities. We used microcosms holding different densities of a common invertebrate freshwater species, Daphnia magna. During 2 weeks, we monitored temporal dynamics of eDNA and the eDNA/density relationship by taking water samples and quantifying eDNA concentrations with the droplet digital PCR. The setup included one treatment without and one with homogenization before sampling, to test the effects of admixture on the relation between eDNA concentration and density. Daphnia magna individuals were removed after 1.5 weeks to track DNA degradation rates. In the stagnant water setup, hardly any DNA was detected before D. magna removal. Within days after removal, eDNA concentrations became undetectable. No significant correlation between D. magna density and eDNA concentrations was observed. In the homogenization treatment, a significant positive correlation between eDNA concentration and densities was demonstrated for the days around D. magna removal, albeit with some within‐treatment variability. Our results show that, given adequate time for eDNA production and degradation to stabilize, positive correlations between eDNA and organism densities in water with sufficient homogenization are detectable for exoskeleton‐shedding invertebrates. Therefore, our study indicates that—although difficult—using eDNA to quantify freshwater exoskeleton‐shedding invertebrate densities may be possible under field conditions if circumstances result in frequent homogenization of the water column.
Heterogeneity of health status treatment response with sacubitril/valsartan: insights from the CHAMP‐HF registry
Authors: Khariton Yevgeniy , Fonarow Gregg C. , Hellkamp Ann , Thomas Laine , Nassif Michael E. , Butler Javed , Duffy Carol I. , Albert Nancy M. , Spertus John A.
Published: November 2020

Aims

The aim of our study was to investigate heterogeneity of health status treatment response of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF).

Methods and results

We leveraged data from CHAMP‐HF, an observational registry of 140 US clinics and 5026 outpatients with chronic HFrEF, where health status was serially assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ)‐12 Overall Summary Scale (range from 0 to 100; ≥20‐point improvement is a very large improvement). In 334 patients newly initiated on sacubitril/valsartan, we used hierarchical multivariable logistic regression (13 patient‐level characteristics as well as baseline KCCQ‐12 score) to calculate the odds ratio (OR) of any characteristic being associated with a very large health status improvement. A total of 104/334 (31.1%) of patients achieved the primary endpoint, where only worse baseline health status [KCCQ‐12 score of 0–60 points had an OR = 0.86/5‐point higher score (CI 0.79, 0.93)], and those with a KCCQ‐12 score of 60–80 points had an OR = 0.61/5‐point higher score (0.45–0.82), which was associated with a very large benefit. No other patient characteristic was associated with a very large health status improvement (P > 0.05).

Conclusions

We found that, after initiation of sacubitril/valsartan, only worse baseline health status was associated with very large health status improvement. Accordingly, a trial of therapy—particularly in those with worse symptoms, function, and quality of life—and assessing treatment response are likely to be the best prospective strategy.
Conditioned pain modulation affects the N2/P2 complex but not the N1 wave: A pilot study with laser‐evoked potentials
Authors: Squintani Giovanna , Rasera Andrea , Segatti Alessia , Concon Elisa , Bonetti Bruno , Valeriani Massimiliano , Tinazzi Michele
Published: November 2020

Background

The ‘pain‐inhibits‐pain’ effect stems from neurophysiological mechanisms involving endogenous modulatory systems termed diffuse noxious inhibitory controls (DNIC) or conditioned pain modulation (CPM). Laser‐evoked potentials (LEPs) components, the N2/P2 complex, and the N1 wave, reflect the medial and lateral pain pathway, respectively: anatomically, the lateral thalamic nuclei (LT) project mainly to the somatosensory cortex (N1 generator), while the medial thalamic nuclei (MT) are bound to the limbic cortices (N2/P2 generators).

Methods

We applied a CPM protocol in which the test stimulus was laser stimulation and the conditioning stimulus was a cold pressor test. LEPs recordings were obtained from 15 healthy subjects in three different conditions: baseline, during heterotopic noxious conditioning stimulation (HNCS) and post‐HNCS.

Results

We observed a significant reduction in N2/P2 amplitude during HNCS and a return to pre‐test amplitude post‐HNCS, whereas the N1 wave remained unchanged during and post‐HNCS.

Conclusions

Our results indicate that CPM affects only the medial pain system. The spinothalamic tract (STT) transmits to both the LT and the MT, while the spinoreticulothalamic (SRT) projects only to the MT. The reduction in the amplitude of the N2/P2 complex and the absence of change in the N1 wave suggest that DNIC inhibition on the dorsal horn neurons affects only pain transmission via the SRT, while the neurons that give rise to the STT are not involved. The N1 wave can be a reliable neurophysiological parameter for assessment of STT function in clinical practice, as it does not seem to be influenced by CPM.

Significance

No reports have described the effect of DNIC on lateral and medial pain pathways. We studied the N1 wave and the N2/P2 complex to detect changes during a CPM protocol. We found a reduction in the amplitude of the N2/P2 complex and no change in the N1 wave. This suggests that the DNIC inhibitory effect on dorsal horns neurons affects only pain transmission via the SRT, whereas the neurons that give rise to the STT are not involved.
The serotonin receptor 2A (HTR2A) rs6313 variant is associated with higher ongoing pain and signs of central sensitization in neuropathic pain patients
Authors: Sachau Juliane , Bruckmueller Henrike , Gierthmühlen Janne , Magerl Walter , May Denisa , Binder Andreas , Forstenpointner Julia , Koetting Judith , Maier Christoph , Tölle Thomas R. , Treede Rolf‐Detlef , Berthele Achim , Caliebe Amke , Diesch Carolin , Flor Herta , Huge Volker , Maihöfner Christian , Rehm Stefanie , Kersebaum Dilara , Fabig Sophie‐Charlotte , Vollert Jan , Rolke Roman , Stemmler Susanne , Sommer Claudia , Westermann Andrea , Cascorbi Ingolf , Baron Ralf
Published: November 2020

Background

The serotonin receptor 2A (HTR2A) has been described as an important facilitation mediator of spinal nociceptive processing leading to central sensitization (CS) in animal models of chronic pain. However, whether HTR2A single nucleotide variants (SNVs) modulate neuropathic pain states in patients has not been investigated so far. The aim of this study was to elucidate the potential association of HTR2A variants with sensory abnormalities or ongoing pain in neuropathic pain patients.

Methods

At total of 240 neuropathic pain patients and 253 healthy volunteers were included. Patients were phenotypically characterized using standardized quantitative sensory testing (QST). Patients and controls were genotyped for HTR2A g.‐1438G > A (rs6311) and c.102C > T (rs6313). Genotype‐related differences in QST parameters were assessed considering QST profile clusters, principal somatosensory components and sex.

Results

There was an equal distribution of rs6313 and linked rs6311 between patients and controls. However, the rs6313 variant was significantly associated with a principal component of pinprick hyperalgesia and dynamic mechanical allodynia, indicating enhanced CS in patients with sensory loss (−0.34 ± 0.15 vs. +0.31 ± 0.11 vs., p < .001). In this cluster, the variant allele was also associated with single QST parameters of pinprick hyperalgesia (MPT, +0.64 ± 0.18 vs. −0.34 ± 0.23 p = .002; MPS, +0.66 ± 0.17 vs. −0.09 ± 0.23, p = .009) and ongoing pain was increased by 30%.

Conclusions

The specific association of the rs6313 variant with pinprick hyperalgesia and increased levels of ongoing pain suggests that the HTR2A receptor might be an important modulator in the development of CS in neuropathic pain.

Significance

This article presents new insights into serotonin receptor 2A‐mediating mechanisms of central sensitization in neuropathic pain patients. The rs6313 variant allele was associated with increased mechanical pinprick sensitivity and increased levels of ongoing pain supporting a contribution of central sensitization in the genesis of ongoing pain providing a possible route for mechanism‐based therapies.