bluuebunny/crossref_metadata_2025 huggingface dataset:
HD-eXplosion: visualization of hydrogen–deuterium exchange data as chiclet and volcano plots with statistical filtering
Authors: Zhang Naifu , Yu Xiaohe , Zhang Xinchao , D’Arcy Sheena
Published: October 2020

Hydrogen–Deuterium eXchange coupled to mass spectrometry is a powerful tool for the analysis of protein dynamics and interactions. Bottom-up experiments looking at deuterium uptake differences between various conditions are the most common. These produce multi-dimensional data that can be challenging to depict in a single visual format. Each user must also set significance thresholds to define meaningful differences and make these apparent in data presentation. To assist in this process, we have created HD-eXplosion, an open-source, web-based application for the generation of chiclet and volcano plots with statistical filters. HD-eXplosion fills a void in available software packages and produces customizable plots that are publication quality.

Availability and implementation

The HD-eXplosion application is available at http://hd-explosion.utdallas.edu. The source code can be found at https://github.com/HD-Explosion.
An escape-to-radiate model for explaining the high plant diversity and endemism in campos rupestres
Authors: Rapini Alessandro , Bitencourt Cássia , Luebert Federico , Cardoso Domingos
Published: October 2020

With extraordinary levels of plant diversity and endemism, the Brazilian campos rupestres across the Espinhaço Range have a species/area ratio 40 times higher than the lowland Amazon. Although diversification drivers in campos rupestres remain a matter of debate, the Pleistocene refugium hypothesis (PRH) is often adopted as the most plausible explanation for their high diversity. The PRH has two main postulates: highland interglacial refugia and a species pump mechanism catalysed by climatic changes. We critically assessed studies on campos rupestres diversification at different evolutionary levels and conclude that most of them are affected by sampling biases, unrealistic assumptions or inaccurate results that do not support the PRH. By modelling the palaeo-range of campos rupestres based on the distribution of 1123 species of vascular plants endemic to the Espinhaço Range and using climate and edaphic variables, we projected a virtually constant suitable area for campos rupestres across the last glacial cycle. We challenge the great importance placed on Pleistocene climatic oscillations in campos rupestres plant diversification and offer an alternative explanation named escape-to-radiate model, which emphasizes niche shifts. Under this biogeographic model of diversification, the long-term fragmentation of campos rupestres combined with recurrent extinctions after genetic drift and sporadic events of adaptive radiation may provide an explanation for the current diversity and endemism in the Espinhaço Range. We conclude that long-term diversification dynamics in campos rupestres are mainly driven by selection, while most endemic diversity is ephemeral, extremely fragile and mainly driven by drift.
Can morphological and behavioral traits predict the foraging and feeding dynamics of social arachnids?
Authors: Moura Renan F , Tizo-Pedroso Everton , Del-Claro Kleber
Published: October 2020

Complex social insect species exhibit task specialization mediated by morphological and behavioral traits. However, evidence of such traits is scarce for other social arthropods. We investigated whether the social pseudoscorpion Paratemnoides nidificator exhibits morphologically and behaviorally specialized individuals in prey capture. We measured body and chela sizes of adult pseudoscorpions and analyzed predation processes. Larger individuals spent more time moving through the colony and foraging than smaller pseudoscorpions. Individuals that captured prey had increased body and absolute chelae sizes. Although larger individuals had relatively small chelae size, they showed a higher probability of prey capture. Larger individuals manipulated prey often, although they fed less than smaller pseudoscorpions. Individuals that initiated captures fed more frequently and for more time than the others. Natural selection might be favoring individuals specialized in foraging and colony protection, allowing smaller and less efficient adults to avoid contact with dangerous prey. To our knowledge, there is incipient information regarding specialized individuals in arachnids, and our results might indicate the emergence of a morphologically specialized group in this species.
Abundance and Diversity of Dung Beetles (Coleoptera: Scarabaeoidea) as Affected by Grazing Management in the Nebraska Sandhills Ecosystem
Authors: Wagner Patrick M , Abagandura Gandura Omar , Mamo Martha , Weissling Thomas , Wingeyer Ana , Bradshaw Jeffrey D
Published: October 2020

Dung beetles (Coleoptera: Scarabaeoidea) serve a significant role in regulating ecosystem services on rangelands. However, the influence of grazing management on dung beetle communities remains largely unknown. The purpose of this study was to investigate dung beetle abundance and diversity throughout the grazing season in the Nebraska Sandhills Ecoregion. Grazing treatments included: continuous grazing (CONT), low-stocking rotational grazing (LSR), high-stocking rotational grazing (HSR), and no grazing (NG). The abundance and diversity of dung beetles were measured in the 2014 and 2015 grazing seasons using dung-baited pitfall traps. Dung beetle abundance for each grazing treatment was characterized through four indices: peak abundance, species richness, Simpson’s diversity index, and Simpson’s evenness. A total of 4,192 dung beetles were collected through both years of trapping in this study. Peak abundance and species richness were greater in grazed treatments when compared to NG in both years. Peak abundance in the HSR was 200% (2014) and 120% (2015) higher than in the LSR. Species richness in the HSR was 70% (2014) and 61% (2015) higher than in the LSR, and 89% (2014) and 133% (2015) higher than in CONT. Simpson’s diversity index was lower in the NG and CONT treatments when compared to the LSR or HSR treatments for both years. We conclude that rotational grazing, regardless of stocking density, promoted dung beetle abundance and diversity within the Nebraska Sandhills Ecoregion.
Efficacy and safety of icosapent ethyl in hypertriglyceridaemia: a recap
Authors: Parhofer Klaus G , Chapman M John , Nordestgaard Børge G
Published: October 2020

Although low-density lipoprotein cholesterol lowering is effective in atherosclerotic cardiovascular disease (ASCVD) prevention, considerable ‘lipid-associated’ residual risk remains, particularly in patients with mild-to-moderate hypertriglyceridaemia (2–10 mmol/L; 176–880 mg/dL). Triglyceride (TG)-rich lipoproteins carry both TGs and cholesterol (remnant-cholesterol). At TG levels >5 mmol/L (440 mg/dL) vs. <1 mmol/L (88 mg/dL) or remnant-cholesterol >2.3 mmol/L (89 mg/dL) vs. <0.5 mmol/L (19 mg/dL), risk is ∼1.5-fold elevated for aortic stenosis, 2-fold for all-cause mortality, 3-fold for ischaemic stroke, 5-fold for myocardial infarction (MI), and 10-fold for acute pancreatitis. Furthermore, Mendelian randomization studies indicate that elevated TG-rich lipoproteins are causally related to increased risk of ASCVD and even all-cause mortality. While genetic and epidemiological data strongly indicate that TG-rich lipoproteins are causally linked to ASCVD, intervention data are ambiguous. Fibrates, niacin and low-dose omega-3 fatty acids have all been used in outcome trials, but have failed to demonstrate clear benefit in combination with statins. Whether the lack of additional benefit relates to methodological issues or true failure is indeterminate. Importantly, a recent intervention trial evaluating a high dose of eicosapentaenoic-acid showed clear benefit. Thus, REDUCE-IT evaluated the effect of icosapent ethyl (4 g/day) on cardiovascular outcomes in 8179 high-risk patients with moderate TG elevation on statin therapy. Over a median duration of 4.9 years, the relative risk for the primary endpoint (composite of cardiovascular death, non-fatal MI, non-fatal stroke, coronary revascularization, or unstable angina) was reduced by 25% (absolute risk 17.2% vs. 22.0%; P < 0.0001; number needed to treat 21). High-dose icosapent ethyl intervention therefore confers substantial cardiovascular benefit in high-risk patients with moderate hypertriglyceridaemia on statin therapy.
Mineral oil: safety and use as placebo in REDUCE-IT and other clinical studies
Authors: Olshansky Brian , Chung Mina K , Budoff Matthew J , Philip Sephy , Jiao Lixia , Doyle, Jr. Ralph T , Copland Christina , Giaquinto Alex , Juliano Rebecca A , Bhatt Deepak L
Published: October 2020

Mineral oil is often used as a clinical trial placebo. Pharmaceutical-grade mineral oil consists of a mixture of saturated hydrocarbons, with a purity and chemical structure that differs substantially from food-grade or technical-/industrial-grade mineral oils. Interest in mineral oil was piqued by suggestions that a portion of the substantially positive results of the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) might be attributable to the theoretical negative effects of mineral oil rather than being due to the clinical benefits of icosapent ethyl. The objective of this review was to explore possible mineral oil safety and efficacy effects and contextualize these findings in light of the REDUCE-IT conclusions. A literature search identified studies employing mineral oil placebos. Eighty studies were identified and relevant data extracted. Adverse events associated with mineral oil were generally gastrointestinal and consistent with use as a lubricant laxative. Changes in triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and other biomarkers were inconsistent and generally not statistically significant, or clinically meaningful with mineral oil, as were changes in blood pressure. There was no consistent evidence that mineral oil in the amounts used in the REDUCE-IT or Effect of Vascepa on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides on Statin Therapy (EVAPORATE) trials affects absorption of essential nutrients or drugs, including statins. These results were then considered alongside publicly available data from REDUCE-IT. Based on available evidence, mineral oil does not appear to impact medication absorption or efficacy, or related clinical outcomes, and, therefore, does not meaningfully affect study conclusions when used as a placebo at the quantities used in clinical trials.
Sinus rhythm voltage fingerprinting in patients with mitral valve disease using a high-density epicardial mapping approach
Authors: van Schie Mathijs S , Starreveld Roeliene , Bogers Ad J J C , de Groot Natasja M S
Published: October 2020

Aims

Unipolar voltage (UV) mapping is increasingly used for guiding ablative therapy of atrial fibrillation (AF) as unipolar electrograms (U-EGMs) are independent of electrode orientation and atrial wavefront direction. This study was aimed at constructing individual, high-resolution sinus rhythm (SR) UV fingerprints to identify low-voltage areas and study the effect of AF episodes in patients with mitral valve disease (MVD).

Methods and results

Intra-operative epicardial mapping (interelectrode distance 2 mm) of the right and left atrium, Bachmann’s bundle (BB), and pulmonary vein area was performed in 67 patients (27 male, 67 ± 11 years) with or without a history of paroxysmal AF (PAF). In all patients, there were considerable regional variations in voltages. UVs at BB were lower in patients with PAF compared with those without [no AF: 4.94 (3.56–5.98) mV, PAF: 3.30 (2.25–4.57) mV, P = 0.006]. A larger number of low-voltage potentials were recorded at BB in the PAF group [no AF: 2.13 (0.52–7.68) %, PAF: 12.86 (3.18–23.59) %, P = 0.001]. In addition, areas with low-voltage potentials were present in all patients, yet we did not find any predilection sites for low-voltage potentials to occur.

Conclusion

Even in SR, advanced atrial remodelling in MVD patients shows marked inter-individual and regional variation. Low UVs are even present during SR in patients without a history of AF indicating that low UVs should carefully be used as target sites for ablative therapy.
Accurate Estimation of Commercial Volume in Tropical Forests
Authors: de Lima Robson Borges , Rutishauser Ervan , da Silva José Antônio Aleixo , Guedes Marcelino Carneiro , Herault Bruno , de Oliveira Cinthia Pereira , da Silva Aparício Perseu , Sotta Eleneide Doff , da Silva Diego Armando Silva , Ferreira Rinaldo Luiz Caraciolo
Published: October 2020

Accurate estimates of commercial volume in tropical forests are key for the implementation of sustainable forest management plans. Because of the lack of local or generic volumetric equations, most forest managers and forestry services are still using traditional expansion factors (i.e., multiplication of the diameter by a given value) to estimate the volume of commercial tree species in the Amazon. Volumetric models were developed through a unique data set of 1,264 fallen trees fully measured in 150 sample plots located across a broad range of forests in Amapá, Brazil. Forest-specific volumetric models were developed and compared with a generic (i.e., across all forests) model and with published equations developed elsewhere in the Amazon. The generic equation performed well in all forest types and allowed precise predictions. The most efficient sampling design to develop volumetric models consists of measuring approximately 50 trees across four different size classes representing the whole population. The form factors (FF) developed locally generated substantial bias but performed better than the traditional FF (0.7). Overall, our results suggest that it is possible to develop accurate generic models to estimate commercial timber volume, and this study can serve as a guideline for forest managers or scientists interested in calibrating volumetric models in a cost-efficient way.
In vitro screening of probiotic properties of Lactobacillus plantarum isolated from fermented milk product
Authors: Nath Soumitra , Sikidar Jibalok , Roy Monisha , Deb Bibhas
Published: October 2020

Objectives

The screening of traditional fermented products is essential for the assessment of safety, security, and further development of functional foods for the well-being of human health. The aim of the present study was to isolate and identify bacteria from fermented raw milk samples that exhibit health benefits upon consumption.

Methods

In order to confirm the isolates as probiotics, several in vitro assays were conducted to assess the probiotic properties of isolated bacteria. The initial screening includes tolerance to acid, bile, pancreatin, and NaCl. The cell surface properties demonstrate their interaction with mucosal epithelium, which includes hydrophobicity and auto-aggregation assay. Safety assessment was done by performing haemolytic test and antibiotic susceptibility test. The antagonistic activity of probiotic strain was further evaluated against some pathogenic bacteria.

Results

Lactobacillus plantarum (L. plantarum) isolated from fermented raw milk was preliminarily identified by biochemical tests and further confirmed using 16S rRNA identification. The isolate designated as L. plantarum strain GCC_19M1 demonstrated significant tolerance to low pH, 0.3% bile, 0.5% pancreatin, and 5% NaCl. In the presence of simulated gastric juice (at pH 3), the isolate exhibited a survival rate of 93.48–96.97%. Furthermore, the development of ecological niches in the human gut and their successful accumulation have been revealed by auto-aggregation and hydrophobicity properties. Absence of haemolytic activity ensures the non-virulent nature of the strain. Lactobacillus plantarum strain GCC_19M1 showed susceptibility towards gentamicin, tetracycline, kanamycin, meropenem, and ceftriaxone and exhibited an antagonistic effect on pathogenic bacteria.

Conclusion

The obtained results conveyed that L. plantarum strain GCC_19M1 has strong probiotic potential, and its presence in the fermented raw milk products may serve as a potent functional probiotic food.
Age-Related Colonic Mucosal Microbiome Community Shifts in Monkeys
Authors: Vemuri Ravichandra , Sherrill Chrissy , Davis Matthew A , Kavanagh Kylie
Published: October 2020

Age-related changes in gut microbiome impact host health. The interactive relationship between the microbiome and physiological systems in an aged body system remains to be clearly defined, particularly in the context of inflammation. Therefore, we aimed to evaluate systemic inflammation, microbial translocation (MT), and differences between fecal and mucosal microbiomes. Ascending colon mucosal biopsies, fecal samples, and blood samples from healthy young and old female vervet monkeys were collected for 16S rRNA gene sequencing, MT, and cytokine analyses, respectively. To demonstrate microbial co-occurrence patterns, we used Kendall’s tau correlation measure of interactions between microbes. We found elevated levels of plasma LBP-1, MCP-1, and CRP in old monkeys, indicative of higher MT and systemic inflammation. Microbiome analysis revealed significant differences specific to age. At the phylum level, abundances of pathobionts such as Proteobacteria were increased in the mucosa of old monkeys. At the family level, Helicobacteriaceae was highly abundant in mucosal samples (old); in contrast, Ruminococcaceae were higher in the fecal samples of old monkeys. We found significantly lower Firmicutes:Bacteroidetes ratio and lower abundance of butyrate-producing microbes in old monkeys, consistent with less healthy profiles. Microbial community co-occurrence analysis on mucosal samples revealed 13 nodes and 41 associations in the young monkeys, but only 12 nodes and 21 associations in the old monkeys. Our findings provide novel insights into systemic inflammation and gut microbial interactions, highlight the importance of the mucosal niche, and facilitate further understanding of the decline in the stability of the microbial community with aging.
A directed acyclic graph for interactions
Authors: Nilsson Anton , Bonander Carl , Strömberg Ulf , Björk Jonas
Published: October 2020

Background

Directed acyclic graphs (DAGs) are of great help when researchers try to understand the nature of causal relationships and the consequences of conditioning on different variables. One fundamental feature of causal relations that has not been incorporated into the standard DAG framework is interaction, i.e. when the effect of one variable (on a chosen scale) depends on the value that another variable is set to. In this paper, we propose a new type of DAG—the interaction DAG (IDAG), which can be used to understand this phenomenon.

Methods

The IDAG works like any DAG but instead of including a node for the outcome, it includes a node for a causal effect. We introduce concepts such as confounded interaction and total, direct and indirect interaction, showing that these can be depicted in ways analogous to how similar concepts are depicted in standard DAGs. This also allows for conclusions on which treatment interactions to account for empirically. Moreover, since generalizability can be compromised in the presence of underlying interactions, the framework can be used to illustrate threats to generalizability and to identify variables to account for in order to make results valid for the target population.

Conclusions

The IDAG allows for a both intuitive and stringent way of illustrating interactions. It helps to distinguish between causal and non-causal mechanisms behind effect variation. Conclusions about how to empirically estimate interactions can be drawn—as well as conclusions about how to achieve generalizability in contexts where interest lies in estimating an overall effect.
Reeb Spaces of Smooth Functions on Manifolds
Authors: Saeki Osamu
Published: October 2020

The Reeb space of a continuous function is the space of connected components of the level sets. In this paper, we first prove that the Reeb space of a smooth function on a closed manifold with finitely many critical values has the structure of a finite graph without loops. We also show that an arbitrary finite graph without loops can be realized as the Reeb space of a certain smooth function on a closed manifold with finitely many critical values, where the corresponding level sets can also be preassigned. Finally, we show that a continuous map of a smooth closed connected manifold to a finite connected graph without loops that induces an epimorphism between the fundamental groups is identified with the natural quotient map to the Reeb space of a certain smooth function with finitely many critical values, up to homotopy.

Dedicated to Professor Toshizumi Fukui on the occasion of his 60th birthday.
Reuse of process-based models: automatic transformation into many programming languages and simulation platforms
Authors: Midingoyi Cyrille Ahmed , Pradal Christophe , Athanasiadis Ioannis N , Donatelli Marcello , Enders Andreas , Fumagalli Davide , Garcia Frédérick , Holzworth Dean , Hoogenboom Gerrit , Porter Cheryl , Raynal Hélène , Thorburn Peter , Martre Pierre
Published: October 2020

The diversity of plant and crop process-based modelling platforms in terms of implementation language, software design and architectural constraints limits the reusability of the model components outside the platform in which they were originally developed, making model reuse a persistent issue. To facilitate the intercomparison and improvement of process-based models and the exchange of model components, several groups in the field joined to create the Agricultural Model Exchange Initiative (AMEI). Agricultural Model Exchange Initiative proposes a centralized framework for exchanging and reusing model components. It provides a modular and declarative approach to describe the specification of unit models and their composition. A model algorithm is associated with each model specification, which implements its mathematical behaviour. This paper focuses on the expression of the model algorithm independently of the platform specificities, and how the model algorithm can be seamlessly integrated into different platforms. We define CyML, a Cython-derived language with minimum specifications to implement model component algorithms. We also propose CyMLT, an extensible source-to-source transformation system that transforms CyML source code into different target languages such as Fortran, C#, C++, Java and Python, and into different programming paradigms. CyMLT is also able to generate model components to target modelling platforms such as DSSAT, BioMA, Record, SIMPLACE and OpenAlea. We demonstrate our reuse approach with a simple unit model and the capacity to extend CyMLT with other languages and platforms. The approach we present here will help to improve the reproducibility, exchange and reuse of process-based models.
Evaluation of clinical practice guideline quality: comparison of two appraisal tools
Authors: Koc Esra Meltem , Aksoy Hilal , Ayhan Baser Duygu , Baydar Artantas Aylin , Kahveci Rabia , Cihan Fatma Goksin
Published: October 2020

Objective

The tools used for critically appraising the quality of clinical practice guidelines are complex and not suitable for the busy end users. So rapid, effective and simple instruments are more preferred. The aim of this study is to compare two critical appraisal tools: iCAHE as a rapid instrument and AGREE II as a complex instrument on guideline quality assessment.

Material and Methods

The diabetes mellitus guidelines of the Scottish Intercollegiate Guidelines Network (SIGN), the National Institute for Health and Clinical Excellence (NICE), the International Diabetes Federation (IDF) and the Society of Endocrinology and Metabolism of Turkey (SEMT) were assessed separately by four appraisers using the iCAHE and AGREE II instruments. The mean iCAHE criteria scores and the total and domain AGREE II scores given by the four appraisers are presented for each guideline.

Results

No statistically significant difference was detected between the iCAHE scale scores of the guidelines evaluated (P = 0.063). The rank of the guidelines according to their average total iCAHE and AGREE II instrument scores was similar. The iCAHE mean scores of the guidelines were as follows: NICE, 92.85%; SIGN, 92.85%; IDF, 66.07% and SEMT, 73.21%. The AGREE II mean scores of the guidelines were as follows: NICE, 87.13%; SIGN, 78.25%; IDF, 53.44% and SEMT, 53.22%.

Conclusions

In addition to being a quality scale, the iCAHE checklist is easy, practical and short to implement. It also helps the users to understand the quality of the guideline in a shorter time. To increase the use of guidelines, it is important that users with little experience and time use the iCAHE scale as a rapid appraisal tool, but more studies are needed to decide the best appraisal tool.
Safety and efficacy of fumagillin for the treatment of intestinal microsporidiosis. A French prospective cohort study
Authors: Maillard Alexis , Scemla Anne , Laffy Benjamin , Mahloul Nadir , Molina Jean-Michel
Published: October 2020

Background

Intestinal microsporidiosis due to Enterocytozoon bieneusi is a cause of chronic diarrhoea in immunocompromised patients. Fumagillin has been approved in France for its treatment.

Objectives

To investigate the efficacy and safety of fumagillin in a real-life setting.

Methods

As required by the French Medicine Agency, all patients receiving fumagillin were enrolled in a prospective study to evaluate its efficacy and safety. Stool examination with identification of E. bieneusi by PCR was performed at baseline, end of treatment and monthly thereafter for 6 months. Safety was monitored up to 6 months and full blood counts were monitored up to 42 days after treatment initiation. The primary endpoint was safety. Parasite clearance and relapses were secondary endpoints.

Results

From 2007 to 2018, 166 patients received fumagillin, including 6 children. Patients were transplant recipients (84%), HIV-infected patients (13%) or had another cause of immunosuppression (5%). Serious adverse events were reported in 41 patients (25%), mainly thrombocytopenia (15%) and neutropenia (5%), with two haemorrhagic events leading to one death. Severe thrombocytopenia (<50 G/L) developed in 50 patients (29.6%), neutropenia (<1 G/L) in 20 patients (11.8%) and severe anaemia (<8 g/dL) in 21 patients (12.4%). At the end of treatment, 94% of patients with available stool examination (n = 132) had no spores detected. Among 99 patients with available follow-up after the end of treatment, three parasite relapses were documented.

Conclusions

E. bieneusi microsporidiosis was mainly diagnosed in transplant recipients. Fumagillin was associated with haematological toxicity but showed high efficacy with a low relapse rate.
Knowledge gaps in candidaemia/invasive candidiasis in haematological cancer patients
Authors: Colombo Arnaldo Lopes , Agnelli Caroline , Kontoyiannis Dimitrios P
Published: October 2020

As neutropenic patients with haematological cancer are not typically included in randomized controlled trials (RCTs) of candidaemia, there is low quality of evidence regarding the management of this common opportunistic mycosis in this patient population, which is at high risk for poor outcomes. Herein we identify the gaps in knowledge that are not addressed by the modern RCTs and candidaemia guidelines, and outline some considerations for the future clinical research agenda in candidaemia/invasive candidiasis in haematological patients.
HPLC-UV-Based Simultaneous Determination of Canthin-6-One Alkaloids, Quassinoids, and Scopoletin: The Active Ingredients in Eurycoma Longifolia Jack and Eurycoma Harmandiana Pierre, and Their Anti-Inflammatory Activities
Authors: Chaingam Jiranan , Juengwatanatrakul Thaweesak , Yusakul Gorawit , Kanchanapoom Tripetch , Putalun Waraporn
Published: October 2020

Background

Quassinoids and canthin-6-one alkaloids are bioactive markers of Eurycoma longifolia (EL) and E. harmandiana (EH) and have been commercially utilized to treat inflammation and male infertility.

Objectives

This study aims to reveal the contents of bioactive compounds and compare anti-inflammatory activities of these two species.

Methods

HPLC methods coupled with UV-Vis detection were developed and validated for the simultaneous analysis of the chemical profiles and their contents in EL and EH. The anti-inflammatory activities of both species were investigated using RAW 264.7 cell line.

Results

The HPLC methods provided a sensitivity (LOD) of 0.02–0.05 µg/mL for the eight bioactive compounds (canthin-6-one alkaloids, quassinoids, and scopoletin) with high precision (% relative standard deviation (RSD) ≤6.48) and recoveries between 80.0 and 120%. The chaparrinone: eurycomanone ratio was high in EH, whereas EL had a higher ratio of eurycomanone: chaparrinone than EH. The contents of total canthin-6-one alkaloids, quassinoids, and scopoletin were 0.01–0.75, 0.19–1.54, and 0.01–0.28 mg/g, respectively, in EL roots and 0.12–1.80, 7.05–9.26, and 0.02 mg/g, respectively, in EH roots. The anti-inflammatory effects of EL and EH extracts varied among the samples due to the variation in their chemical constituents.

Conclusions

In summary, our study indicated that chaparrinone was the major compound in EH. EH exhibited anti-inflammatory activity to the same extent as EL.

Highlights

EH and EL extracts were analyzed using developed HPLC-UV methods, revealing a high concentration of chaparrinone in EH, and an anti-inflammatory assay indicated that EH had a potency comparable to that of EL.
Cannabinoids Determination in Brain: A Supplemental Helpful in Postmortem Evaluation
Authors: Palazzoli F , Santunione A L , Marchesi F , Verri P , Vandelli D , Licata M , Silingardi E
Published: October 2020

The scientific interest in cannabis has been documented by a wide literature, but postmortem studies and interpretations of autopsy findings are lacking or limited to few cases, few matrices analyzed or a small number of analytes. The present study describes the development and full in-house validation of a sensitive and simple method based on an optimized rapid clean-up procedure combined with a robust and highly sensitive liquid chromatography coupled with tandem mass spectrometry (LC–MS-MS) technique, designed to simultaneous determination of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC), 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid (THC-COOH) and 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid glucuronated (THC-COOH gluc.) in postmortem samples: central blood (CB), femoral blood (FB) and brain tissue (BR). The developed method was validated and applied to 24 postmortem cases involving cannabinoids. In this study, we presented a full optimization and validation of target analyses for each matrix. The procedure had proven to be reliable and accurate. This study adds new data, particularly about the cannabinoids concentrations in BR samples. Combined pattern (CB, FB, BR) can be used in the interpretation of postmortem cases, proving and strengthening the assessments made on blood data. BR matrix is a helpful supplement in the investigation of the role of cannabinoids as crucial or contributory factor in leading to death.
Measurements of Cardiac Output and Management of Blood Transfusions During Burn Surgery—An Observational Prospective Study
Authors: Stefansson Jakob Skúlason , Christensen Rasmus , Ottosen Camilla Ikast , Rasmussen Lars Simon
Published: October 2020

Burn surgery can cause extensive bleeding, which lead to perioperative blood transfusions. The purpose of this study was to investigate whether blood transfusions during burn surgery, guided by standard monitoring with inspection of the operative field, measurements of blood pressure, heart rate, hourly diuresis, and concentrations of hemoglobin and lactate could sustain the preoperative cardiac output (CO) till end of surgery. We investigated 15 patients ≥18 years of age scheduled for burn surgery, where the perioperative monitoring included an arterial line. After induction of anesthesia and before start of surgery, we measured baseline values of CO with the minimally invasive LiDCOrapid, mean arterial pressure, and concentrations of hemoglobin and lactate in arterial blood. We measured these values every 30 minutes through surgery. The primary outcome was change in CO from baseline till end of surgery. Secondary outcomes included the change in concentrations of hemoglobin and lactate from baseline till end of surgery. We found no statistically significant change in CO from baseline till end of surgery (6.6 [±2.4] liters/min; 7.2 [±3.2] liters/min; P = .26). We found a statistically significant decrease in concentration of hemoglobin (7.2 [±0.8] mmol/liter; 6.2 [±0.9] mmol/liter; P = .0002), and a statistically significant increase in concentration of lactate (1.3 [±0.5] mmol/liter; 1.7 [±1] mmol/liter; P = .02). The perioperative blood transfusion guided by standard monitoring seemed to sustain CO from baseline till end of surgery; however, further research is needed to confirm this.
Pediatric Treadmill Friction Burns to the Hand: Outcomes of an Initial Nonoperative Approach
Authors: Batra Nikita , Zheng Yinan , Alberto Emily C , Ahmed Omar Z , Cheng Megan , Shupp Jeffrey W , Burd Randall S
Published: October 2020

Treadmill burns that occur from friction mechanism are a common cause of hand burns in children. These burns are deeper and more likely to require surgical intervention compared to hand burns from other mechanisms. The purpose of this study was to identify the factors associated with healing time using an initial nonoperative approach. A retrospective chart review was performed examining children (<15 years) who were treated for treadmill burns to the hand between 2012 and 2019. Patient age, burn depth, total body surface area of the hand injury, and time to healing were recorded. Topical wound management strategies (silver sheet, silver cream, non-silver sheet, and non-silver cream) and associated treatment durations were determined. For patients with burns to bilateral hands, the features, treatment, and outcomes of each hand were assessed separately. Cox regression analysis was used to evaluate the association between time to healing and patient characteristics and treatment type. Seventy-seven patients with 86 hand burns (median age 3 years, range 1–11) had a median total body surface area per hand burn of 0.8% (range 0.1–1.5%). Full-thickness burns (n = 47, 54.7%) were associated with longer time to healing compared to partial-thickness burns (HR 0.28, CI 0.15–0.54, P < .001). Silver sheet treatment was also associated with more rapid time to healing compared to treatment with a silver cream (HR 2.64, CI 1.01–6.89, P = .047). Most pediatric treadmill burns can be managed successfully with a nonoperative approach. More research is needed to confirm the superiority of treatment with silver sheets compared to treatment with silver creams.
The Role of Antennae in Heat Detection and Feeding Behavior in the Bed Bug (Hemiptera: Cimicidae)
Authors: Gaire Sudip , Schal Coby , Mick Russell , DeVries Zachary
Published: October 2020

The common bed bug (Cimex lectularius L.) is an obligate hematophagous ectoparasite that has significant impacts on human health and well-being. All life stages of bed bugs (except eggs) feed solely on blood, which is required to molt and reproduce. Bed bugs use multiple cues to locate their hosts, including heat, CO2, and body odors. Of these cues, detection of heat appears limited to a short distance of <3 cm. However, it remains unclear if bed bugs can detect radiant heat, what structure(s) are responsible for heat detection, and if heat detection via the antennae is required for feeding. In this study, bed bug response to radiant heat was evaluated using the two-choice T-maze assay with the heat source either in contact with the surface (i.e., conduction) or not in contact (i.e., radiation) in nonantennectomized bed bugs. Further, we systematically ablated the bed bug’s antennal segments (distal tip, first segment, and all four segments) and assessed their responses to heat and feeding in a unique two-choice T-maze assay and individual feeding assays, respectively. Our two-choice assays with contact to or no contact with the surface indicated that bed bugs cannot detect radiant heat. Later, we found that the distal tip of the terminal antennal segment is responsible for orientation toward a heat source. However, >50% of the bed bugs fed even when the entire antenna was removed, suggesting redundancy in sensory cues that drive feeding. These results will be used to better understand the role heat plays in bed bug host attraction and design of traps.
Effects of Low Temperature Exposure on Diapause, Development, and Reproductive Fitness of the Emerald Ash Borer (Coleoptera: Buprestidae): Implications for Voltinism and Laboratory Rearing
Authors: Duan Jian J , Schmude Jonathan M , Larson Kristi M
Published: October 2020

The emerald ash borer (EAB), Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), native to Northeast Asia, is the most destructive invasive ash (Fraxinus spp.) pest in the United States. In the present study, we evaluated the effect of exposure of diapausing mature fourth instars (J-shaped larvae, JL) of EAB to cool temperatures, either 1.7 or 12.8°C for 1–9 mo, on their post-chill development including adult emergence, longevity, and lifetime fecundity under standard rearing conditions (26 ± 0.5°C, 16:8 h L:D). In addition, we determined the effect of different stages of the larvae chilled at 12.8°C for 3 mo on the subsequent post-chill development to EAB adults. Findings from the study revealed that a period (≥2 mo) of chill at 12.8°C is required for the termination of the EAB diapause. However, chill treatment of the larvae at the near zero temperature (1.7°C) does not result in the post-diapause larval development to adults, regardless of the chill time (1–9 mo). In addition, our results showed that chill treatment of immature young larvae (L1–L4 prior to JL) results in little production of EAB adults, indicating that EAB diapause predominantly as JL. Findings of this study may be useful to laboratory rearing of EAB from eggs through continuous generations and help us understand the pest’s voltinism resulting from the diapause and post-diapause development under different climatic conditions.
Fanning the Flames of Hate: Social Media and Hate Crime
Authors: Müller Karsten , Schwarz Carlo
Published: October 2020

This paper investigates the link between social media and hate crime. We show that antirefugee sentiment on Facebook predicts crimes against refugees in otherwise similar municipalities with higher social media usage. To establish causality, we exploit exogenous variation in the timing of major Facebook and internet outages. Consistent with a role for “echo chambers,” we find that right-wing social media posts contain narrower and more loaded content than news reports. Our results suggest that social media can act as a propagation mechanism for violent crimes by enabling the spread of extreme viewpoints.
The devil in the tiers1
Authors: Feldman Robin
Published: October 2020

Prescription drug spending in the USA has soared, fueled by rising drug prices. A critical mechanism for restraining drug prices is the formulary tiering system. Although tiering should reflect the cost of a drug—and reward patients who choose less-expensive drugs—something is seriously amiss. Using Medicare claims data from roughly one million patients between 2010 and 2017, this article finds troubling amounts of distorted tiering and wasted cost. Increasingly, generics are shifted to more expensive—and therefore less accessible—tiers. The percentage of generics on the least-expensive tier drops from 73% to 28%; the percentage of drugs on inappropriate tiers rises from 47% to 74%. Considering only costs paid by patients and the federal Low-Income Subsidy Program, tier misplacement cumulatively costs society $13.25 billion over the time period. An unruly problem demands a disruptive solution. This article advances the counterintuitive regulatory reform that tiering should be based on a drug’s list price. Yes, list price—that roundly dismissed figure—should become the touchstone. This would deter incentive-distorting rebate schemes while recognizing that many people already pay list price. It is a remarkably streamlined approach for cutting through a wide swath of perverse incentives and manipulations.
The effects of an experimental drought on the ecophysiology and fruiting phenology of a tropical rainforest palm
Authors: Vogado Nara O , Liddell Michael J , Laurance Susan G W , Campbell Mason J , Cheesman Alexander W , Engert Jayden E , Palma Ana C , Ishida Françoise Y , Cernusak Lucas A
Published: October 2020

Aims

Anthropogenic climate change is predicted to increase mean temperatures and rainfall seasonality. How tropical rainforest species will respond to this climate change remains uncertain. Here, we analysed the effects of a 4-year experimental throughfall exclusion (TFE) on an Australian endemic palm (Normambya normanbyi) in the Daintree rainforest of North Queensland, Australia. We aimed to understand the impact of a simulated reduction in rainfall on the species’ physiological processes and fruiting phenology.

Methods

We examined the fruiting phenology and ecophysiology of this locally abundant palm to determine the ecological responses of the species to drought. Soil water availability was reduced overall by ~30% under a TFE experiment, established in May 2015. We monitored monthly fruiting activity for 8 years in total (2009–2018), including 4 years prior to the onset of the TFE. In the most recent year of the study, we measured physiological parameters including photosynthetic rate, stomatal conductance and carbon stable isotopes (δ 13C, an integrated measure of water use efficiency) from young and mature leaves in both the dry and wet seasons.

Important Findings

We determined that the monthly fruiting activity of all palms was primarily driven by photoperiod, mean solar radiation and mean temperature. However, individuals exposed to lower soil moisture in the TFE decreased significantly in fruiting activity, photosynthetic rate and stomatal conductance. We found that these measures of physiological performance were affected by the TFE, season and the interaction of the two. Recovery of fruiting activity in the TFE palms was observed in 2018, when there was an increase in shallow soil moisture compared with previous years in the treatment. Our findings suggest that palms, such as the N. normanbyi, will be sensitive to future climate change with long-term monitoring recommended to determine population-scale impacts.
The Polycomb group methyltransferase StE(z)2 and deposition of H3K27me3 and H3K4me3 regulate the expression of tuberization genes in potato
Authors: Kumar Amit , Kondhare Kirtikumar R , Malankar Nilam N , Banerjee Anjan K
Published: October 2020

Polycomb repressive complex (PRC) group proteins regulate various developmental processes in plants by repressing target genes via H3K27 trimethylation, and they function antagonistically with H3K4 trimethylation mediated by Trithorax group proteins. Tuberization in potato has been widely studied, but the role of histone modifications in this process is unknown. Recently, we showed that overexpression of StMSI1, a PRC2 member, alters the expression of tuberization genes in potato. As MSI1 lacks histone-modification activity, we hypothesized that this altered expression could be caused by another PRC2 member, StE(z)2, a potential H3K27 methyltransferase in potato. Here, we demonstrate that a short-day photoperiod influences StE(z)2 expression in the leaves and stolons. StE(z)2 overexpression alters plant architecture and reduces tuber yield, whereas its knockdown enhances yield. ChIP-sequencing using stolons induced by short-days indicated that several genes related to tuberization and phytohormones, such as StBEL5/11/29, StSWEET11B, StGA2OX1, and StPIN1 carry H3K4me3 or H3K27me3 marks and/or are StE(z)2 targets. Interestingly, we observed that another important tuberization gene, StSP6A, is targeted by StE(z)2 in leaves and that it has increased deposition of H3K27me3 under long-day (non-induced) conditions compared to short days. Overall, our results show that StE(z)2 and deposition of H3K27me3 and/or H3K4me3 marks might regulate the expression of key tuberization genes in potato.
Complex DNA sequence readout mechanisms of the DNMT3B DNA methyltransferase
Authors: Dukatz Michael , Adam Sabrina , Biswal Mahamaya , Song Jikui , Bashtrykov Pavel , Jeltsch Albert
Published: October 2020

DNA methyltransferases interact with their CpG target sites in the context of variable flanking sequences. We investigated DNA methylation by the human DNMT3B catalytic domain using substrate pools containing CpX target sites in randomized flanking context and identified combined effects of CpG recognition and flanking sequence interaction together with complex contact networks involved in balancing the interaction with different flanking sites. DNA methylation rates were more affected by flanking sequences at non-CpG than at CpG sites. We show that T775 has an essential dynamic role in the catalytic mechanism of DNMT3B. Moreover, we identify six amino acid residues in the DNA-binding interface of DNMT3B (N652, N656, N658, K777, N779, and R823), which are involved in the equalization of methylation rates of CpG sites in favored and disfavored sequence contexts by forming compensatory interactions to the flanking residues including a CpG specific contact to an A at the +1 flanking site. Non-CpG flanking preferences of DNMT3B are highly correlated with non-CpG methylation patterns in human cells. Comparison of the flanking sequence preferences of human and mouse DNMT3B revealed subtle differences suggesting a co-evolution of flanking sequence preferences and cellular DNMT targets.
Arabidopsis ECERIFERUM2-LIKEs Are Mediators of Condensing Enzyme Function
Authors: Haslam Tegan M , Kunst Ljerka
Published: October 2020

Condensing enzymes catalyze the committed reaction of fatty acid elongation and determine the chain length of fatty acids accepted and produced by the elongation complex. While necessary for the elongation of very-long-chain fatty acids (VLCFAs), identified plant condensing enzymes cannot efficiently produce VLCFAs longer than 28 carbons, which are precursors for the most abundant cuticular waxes of most plant species that have been surveyed. The eceriferum2 (cer2) mutant of Arabidopsis thaliana has a severe wax-deficient phenotype and specifically lacks waxes longer than 28 carbons, but the CER2 protein does not share sequence similarity with condensing enzymes. Instead, CER2 is homologous to BAHD acyltransferases. Heterologous expression in yeast previously demonstrated that CER2, and a small clade of BAHD acyltransferases with high sequence identity to CER2, can extend the chain-length specificity of the condensing enzyme CER6. This biochemical function is distinct from that of the broader BAHD acyltransferase family. The product specificity and physiological functions of individual CER2-LIKE proteins are unique. Here, we demonstrate that CER2 physically interacts with the fatty acid elongase. We cloned chimeric CER2-LIKE proteins and expressed these in yeast cells to identify the features that define the substrate specificities of CER2-LIKEs. We generated homology-based structural models to compare CER2-LIKEs and BAHD acyltransferases. In addition, based on the current phylogenetic analysis of the CER2-LIKE clade, we describe two further Arabidopsis CER2-LIKE genes, CER2-LIKE3 and CER2-LIKE4. We used yeast expression and mutant analysis to characterize these genes. Collectively, these results expand our knowledge of the functions of CER2-LIKEs, the BAHD acyltransferase family and cuticular wax metabolism.