bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal characterisation of profile features
Authors: Blateyron François , Leroy Bertrand
Published: November 2020

Segmentation of profile features is mainly described in two standards: ISO 4287 for profile elements, used to calculate RSm and Rc, and ISO 12085 for profile motifs, used to calculate R&W parameters. These methods are commonly criticised for their unstability, although they provide valuable results when used in an adequate context [25]. A new profile segmentation based on watersheds is now introduced in ISO 21920-2 and ISO 16610-45, adapted from areal segmentation [ISO 25178-2, [22]. The areal feature parameters, chap. 3 in Characterisation of Areal Surface Texture, Leach Ed. Springer], with the hope to solve most of the existing problems. However, there are very few comparisons between these methods and almost no recommendations for the configuration of the watershed segmentation. This paper discusses the validity of applying segmentation methods on certain profiles and proposes a validity criterion. It then investigates algorithmic differences between the watershed segmentation and the classical Motifs method, compares the results between the two methods, and suggests guidelines and good practices to obtain significant correlations.
Micro mean-field Monte Carlo (MMFMC) method for Heisenberg ferromagnet with arbitrary spin and single-ion anisotropy
Authors: Khamdao Yongpao , Du An
Published: November 2020

We proposed a micro mean-field Monte Carlo (MMFMC) method based on Metropolis single spin flip algorithm to calculate the thermodynamic properties of three-dimensional ferromagnet describerd by Heisenberg model. In MMFMC method, the actions of the neighboring spins on the selected spin is replaced approximately by their expected values multiplied by the exchange interactions between them, thus each spin is in a quantum state obtained by solving single spin Hamitonian in every MC step. The magnetization, internal energy, specific heat, longitudinal and transverse susceptibilities are calculated for SC, BCC and FCC ferromagnets with arbitray spin quantum number and single-ion anisotropy. it is found that the system shows phase transition phenomenon from paramagnetic to ferromagnetic phase with temperature decreasing, and the Curie temperatures obtained are consistent with those obtained by other theories.
Study on the enhanced tribological performance for titanium alloys by PEG oil/Zn-nanoparticles
Authors: Quan Xin , Xie Hongmei , Xu Xiangjun , Tang Jinzhu
Published: November 2020

This work developed an effective and promising lubricant containing Zn nanoparticles and polyethylene glycol (PEG) base oil to deal with the tough problem of boundary lubrication for steel/Ti6Al4V. Tribological tests were carried out to investigate the boundary lubrication performances and the generation process of boundary protective films on the worn surface. Results showed that low and steady friction coefficient curves could be obtained by PEG suspensions with Zn nanoparticles after a very short ‘run-in’ period, and the main wear volume of Ti6Al4V was occurred during the ‘run-in’ period. The ZnO boundary protective films generated on the counterfaces of the Ti6Al4V disk and steel ball during the friction process. This strong and steady oxide films could effectively prevent direct contact between frictional pairs and provide excellent boundary lubrication performances. This work will contribute to the development of high performance lubricants for titanium alloys
Corrosion behavior of Inconel 625 deposited metal in molten KCl-MgCl2
Authors: Yang Taisen , Su Yunhai , Liu Hongyu , Dai Zhiyong , Liang Xuewei , Wu Xinggang
Published: November 2020

In order to investigate the corrosion behavior of Inconel 625 deposited metal in molten KCl and MgCl2, the corrosion behavior of deposited metal immersed in molten salt for 60 h at 700 °C and 900 °C was studied by static corrosion immersion method. X-ray diffraction (XRD) and Geminisem300 were used to systematically study the phase composition, corrosion morphology and element distribution of the deposited metal. The results show that: the corrosion weight loss of the deposited metal showed an increasing trend at both temperatures, but the increasing range was different in different time intervals. The corrosion weight loss of the deposited metal increased slowly in the first 10 h, and increased sharply in the 10 h–60 h. It can be found that 10 h is the cut-off point of corrosion behavior. The corrosion rate is 0.03 mm/year at 700 °C and 0.50 mm/year at 900 °C for 10 h. The corrosion resistance of the deposited metal at 700 °C is better than that at 900 °C, which is due to the formation of dense MgO on the surface of the deposited metal at 700 °C, which hinders the corrosion reaction; at 900 °C, the content of CrCl3 on the surface of the deposited metal increases, resulting in a ‘shell breaking effect’, which destroys the MgO shell and forms NiCr2O4 with spinel structure. Its corrosion resistance is thus weakened.
Assessing the cost-effectiveness of DNA origami nanostructures for targeted delivery of anti-cancer drugs to tumours
Authors: Coleridge Edward L , Dunn Katherine E
Published: November 2020

Chemotherapy drugs are generally cytotoxic and can cause major side effects, including vomiting/nausea, fatigue, hair loss and pain. The use of targeted nanostructures to deliver drugs directly to tumours has the potential to reduce the side effects by decreasing the exposure of healthy cells and reducing the amount of drug needed. DNA can be used as a structural material to build drug-delivering nanorobots, but questions remain over the practicality of this approach. Here we show that it is potentially feasible for DNA nanostructure drug delivery to be more cost-effective than the drug-only approach. Our result suggests that the barriers to the development of DNA nanostructure-based drug delivery are likely to be primarily technical, regulatory and ethical rather than financial, as the potential exists for this to be a profitable therapeutic approach.
Constrained optimization towards marker-based tumor tracking in VMAT
Authors: Omotayo Azeez , Venkataraman Sankar , McCurdy Boyd
Published: November 2020

This study proposes that incorporating marker-based visibility constraints into the optimization of volumetric modulated arc therapy (VMAT) will generate treatment plans which not only ensure a higher chance of successfully applying real-time tumor tracking techniques, but also simultaneously satisfy dosimetric objectives. This was applied clinically and investigated for multiple disease sites (10 prostate, 5 liver, and 5 lung) using a radiotherapy optimization software (MonArc), where these new constraints were added to conventional dosimetric constraints. For all the investigated sites, three fiducial markers were located inside or around the planning target volume (PTV), and VMAT plans were created for each patient. We modified MonArc to analyze the multi-leaf collimator (MLC) beam’s-eye-view at all control points in the gantry arc, while including marker-based visibility constraints of type ‘hard’ (i.e. requiring 100% visibility of all markers, HC) and ‘soft’ (i.e. penalizes visibility for one marker [SCI] or two markers [SCII] only) in the optimization process. Dose distributions resulting from the constrained plans (HC, SCI, and SCII) were compared to the non-constrained plan (NC—plans optimized without visibility constraints) using several quantitative dose metrics including the conformity index, homogeneity index, doses to PTV and to organs-at-risk (OAR). Generally, the NC plan produced the best PTV dose conformity and the least OAR doses for the entire patient datasets, followed by the SC and then HC plans, with all the optimization approaches typically achieving acceptable dose metrics. Across the three disease sites, visibility of all three markers in MLC apertures increased from 32% to 100% of available control points as visibility constraints strengthened. Although dose metrics showed some deterioration for constrained plans (−6% for SCI up to −15% for HC using the PTV average index), the required dosimetric objectives were still satisfied in at least 90% of patients. In conclusion, we demonstrated that marker and tumour visibility constraints can be incorporated with dosimetric objectives to produce treatment plans satisfying both objectives, which should ensure greater success when applying real-time tracking for VMAT delivery.
APC regulation of ESRP1 and p120-catenin isoforms in colorectal cancer cells
Authors: Faux Maree C. , King Lauren E. , Kane Serena R. , Love Christopher , Sieber Oliver M. , Burgess Antony W.
Published: November 2020

Re-expression of wild-type APC promotes a p120-catenin isoform switch that restores an epithelial phenotype in colorectal cancer (CRC) cells. This switch is mediated by a change in Wnt-induced transcriptional control and an increase in the master epithelial regulator ESRP1. ESRP1 expression is down-regulated in primary CRCs with truncated APC.
pHLARE: a new biosensor reveals decreased lysosome pH in cancer cells
Authors: Webb Bradley A. , Aloisio Francesca M. , Charafeddine Rabab A. , Cook Jessica , Wittmann Torsten , Barber Diane L.
Published: November 2020

Dyes for measuring lysosome pH (pHlys) cannot be propagated in cells for longitudinal or in vivo studies. We report a new genetically encoded ratiometric pHlys biosensor, pHLARE (pH Lysosomal Activity REporter), which we use to show decreased pHlys with inhibiting mTORC1 (mammalian target of rapamycin complex 1) activity and in cancer cells of different tissues and genetic signatures.
Altered Inferior Parietal Functional Connectivity is Correlated with Praxis and Social Skill Performance in Children with Autism Spectrum Disorder
Authors: Wymbs Nicholas F , Nebel Mary Beth , Ewen Joshua B , Mostofsky Stewart H
Published: November 2020

Children with autism spectrum disorder (ASD) have difficulties perceiving and producing skilled gestures, or praxis. The inferior parietal lobule (IPL) is crucial to praxis acquisition and expression, yet how IPL connectivity contributes to autism-associated impairments in praxis as well as social-communicative skill remains unclear. Using resting-state functional magnetic resonance imaging, we applied independent component analysis to test how IPL connectivity relates to praxis and social-communicative skills in children with and without ASD. Across all children (with/without ASD), praxis positively correlated with connectivity of left posterior-IPL with the left dorsal premotor cortex and with the bilateral posterior/medial parietal cortex. Praxis also correlated with connectivity of right central-IPL connectivity with the left intraparietal sulcus and medial parietal lobe. Further, in children with ASD, poorer praxis and social-communicative skills both correlated with weaker right central-IPL connectivity with the left cerebellum, posterior cingulate, and right dorsal premotor cortex. Our findings suggest that IPL connectivity is linked to praxis development, that contributions arise bilaterally, and that right IPL connectivity is associated with impaired praxis and social-communicative skills in autism. The findings underscore the potential impact of IPL connectivity and impaired skill acquisition on the development of a range of social-communicative and motor functions during childhood, including autism-associated impairments.
Tuning and external validation of an adult congenital heart disease risk prediction model
Authors: Geenen Laurie W , Opotowsky Alexander R , Lachtrupp Cara , Baggen Vivan J M , Brainard Sarah , Landzberg Michael J , van Klaveren David , Lingsma Hester F , Boersma Eric , Roos-Hesselink Jolien W
Published: November 2020

Aims

Adequate risk prediction can optimize the clinical management in adult congenital heart disease (ACHD). We aimed to update and subsequently validate a previously developed ACHD risk prediction model.

Methods and results

A prediction model was developed in a prospective cohort study including 602 moderately or severely complex ACHD patients, enrolled as outpatients at a tertiary centre in the Netherlands (2011–2013). Multivariable Cox regression was used to develop a model for predicting the 1-year risks of death, heart failure (HF), or arrhythmia (primary endpoint). The Boston ACHD Biobank study, a prospectively enrolled cohort (n = 749) of outpatients who visited a referral centre in Boston (2012–2017), was used for external validation. The primary endpoint occurred in 153 (26%) and 191 (28%) patients in the derivation and validation cohorts over median follow-up of 5.6 and 2.3 years, respectively. The final model included 5 out of 14 pre-specified predictors with the following hazard ratios; New York Heart Association class ≥II: 1.92 [95% confidence interval (CI) 1.28–2.90], cardiac medication 2.52 (95% CI 1.72–3.69), ≥1 reintervention after initial repair: 1.56 (95% CI 1.09–2.22), body mass index: 1.04 (95% CI 1.01–1.07), log2 N-terminal pro B-type natriuretic peptide (pmol/L): 1.48 (95% CI 1.32–1.65). At external validation, the model showed good discrimination (C-statistic 0.79, 95% CI 0.74–0.83) and excellent calibration (calibration-in-the-large = −0.002; calibration slope = 0.99).

Conclusion

These data support the validity and applicability of a parsimonious ACHD risk model based on five readily available clinical variables to accurately predict the 1-year risk of death, HF, or arrhythmia. This risk tool may help guide appropriate care for moderately or severely complex ACHD.
Anatomic resection has superior long-term survival compared with wedge resection for second primary lung cancer after prior lobectomy
Authors: Baig Mirza Zain , Razi Syed S , Stroever Stephanie , Weber Joanna F , Connery Cliff P , Bhora Faiz Y
Published: November 2020

OBJECTIVES

The extent of surgical resection for early-stage second primary lung cancer (SPLC) in patients with a previous lobectomy is unclear. We sought to compare anatomic lung resections (lobectomy and segmentectomy) and wedge resections for small peripheral SPLC using a population-based database.

METHODS

The Surveillance, Epidemiology and End Results database was queried for all patients with ≤2 cm peripheral SPLC diagnosed between 2004 and 2015 who underwent prior lobectomy for the first primary and surgical resection only for the SPLC. American College of Chest Physicians guidelines were used to classify SPLC. Kaplan–Meier analysis and multivariable Cox regression were used to compare overall survival.

RESULTS

A total of 356 patients met the inclusion criteria with 203 (57%) treated with wedge resection and 153 (43%) treated with anatomic resection. Significantly better median survival was observed with anatomic resection than with wedge resection using a Kaplan–Meier analysis (124 vs 63 months; P < 0.001). With multivariable Cox regression, improved long-term survival was observed for anatomic resection (hazard ratio: 0.44, confidence interval: 0.27–0.70; P = 0.001). Improvement in survival was demonstrated with wedge resection when lymph node sampling was done. Lastly, we calculated the average treatment effect on the treated with inverse probability weighting for a subgroup of patients and found that those with wedge resection and lymph node sampling had shorter long-term survival times.

CONCLUSIONS

Anatomic resections may provide better long-term survival than wedge resections for patients with early-stage peripheral SPLC after prior lobectomy. Significant improvement in survival was observed with wedge resection for SPLC when adequate lymph node dissection was performed.
The role of integrated community case management projects in strengthening health systems: case study analysis in Ethiopia, Malawi and Mozambique
Authors: Story William T , Pritchard Susannah , Hejna Emily , Olivas Elijah , Sarriot Eric
Published: November 2020

Integrated community case management (iCCM) has now been implemented at scale globally. Literature to-date has focused primarily on the effectiveness of iCCM and the systems conditions required to sustain iCCM. In this study, we sought to explore opportunities taken and lost for strengthening health systems through successive iCCM programmes. We employed a systematic, embedded, multiple case study design for three countries—Ethiopia, Malawi and Mozambique—where Save the Children implemented iCCM programmes between 2009 and 2017. We used textual analysis to code 62 project documents on nine categories of functions of health systems using NVivo 11.0. The document review was supplemented by four key informant interviews. This study makes important contributions to the theoretical understanding of the role of projects in health systems strengthening by not only documenting evidence of systems strengthening in multi-year iCCM projects, but also emphasizing important deficiencies in systems strengthening efforts. Projects operated on a spectrum, ranging from gap-filling interventions, to support, to actual strengthening. While there were natural limits to the influence of a project on the health system, all successive projects found constructive opportunities to try to strengthen systems. Alignment with the Ministry of Health was not always static and simple, and ministries themselves have shown pluralism in their perspectives and orientations. We conclude that systems strengthening remains ‘everybody’s business’ and places demands for realism and transparency on government and the development architecture. While mid-size projects have limited decision space, there is value in better defining where systems strengthening contributions can actually be made. Furthermore, systems strengthening is not solely about macro-level changes, as operational and efficiency gains at meso and micro levels can have value to the system. Claims of ‘systems strengthening’ are, however, bounded within the quality of evaluation and learning investments.
Is the fourth industrial revolution a continuation of the third industrial revolution or something new under the sun? Analyzing technological regimes using US patent data
Authors: Lee Jongho , Lee Keun
Published: November 2020

This study has compared the technological regimes of the Fourth Industrial Revolution (4IR) and the Third Industrial Revolution (3IR) technologies. If we limit the comparison based on absolute values representing diverse elements of the technological regime, 4IR technologies are more original and science-based and have a longer technological cycle time (TCT). However, all these differences turn insignificant or reversed when the comparison is made using normalized values of variables reflecting over-time trends. Moreover, 4IR technologies, including artificial intelligence (AI), have an impact on subsequent innovations in less wide fields (lower degree of generality) compared with 3IR, which means that they may not be counted as a new general-purpose technology. Furthermore, a longer TCT of 4IR technologies, including AI, means that they tend to keep citing 3IR technologies or older. In this sense, 4IR technologies are not much a radical break from past technologies but tend to be evolutionary, whereas 3IR technologies correspond to a more radical break from the past technologies because they have a shorter TCT and rely less on old technologies. At the aggregate level, technologies in the 21st century heavily rely on science, combining knowledge from more diverse fields (higher originality) and becoming longer cycled but having impact on less diverse fields (lower generality), which is true not just in a few technologies commonly associated with the so-called 4IR but across the board of technologies. Finally, although five representative 4IR technologies do not command radically different technological regimes compared with 3IR technologies, they are still outstanding, that is, they have higher originality, generality, and shorter TCT compared with the average technologies in the 2010s.
X-ray Transform in Asymptotically Conic Spaces
Authors: Guillarmou Colin , Lassas Matti , Tzou Leo
Published: November 2020

In this article, we study the properties of the geodesic X-ray transform for asymptotically Euclidean or conic Riemannian metrics and show injectivity under non-trapping and no conjugate point assumptions. We also define a notion of lens data for such metrics and study the associated inverse problem.
A Novel Encochleated Formulation Improves Atovaquone Activity in a Murine Model of Pneumocystis Pneumonia
Authors: Cushion Melanie T , Kumar Parag , Lu Ruying , Ashbaugh Alan , Adeojo Lilian W , Alfaro Raul , Mannino Raphael , Tramont Edmund , Kovacs Joseph A
Published: November 2020

Although atovaquone is effective in treating and preventing Pneumocystis pneumonia (PCP), its use is limited by nonlinear absorption and adverse events. The current study was undertaken to examine the activity of encochleated atovaquone (eATQ), a novel lipid-crystal nanoparticle formulation, in a mouse model of PCP. eATQ 100–200 mg was superior to commercially available atovaquone at 14 days in decreasing total Pneumocystis nuclei and asci. eATQ plus anidulafungin reduced nuclei significantly better than commercial atovaquone plus anidulafungin. eATQ is a novel formulation of atovaquone that warrants further evaluation for treatment and prevention of PCP.
Salmonella enterica serovar Typhi H58 clone has been endemic in Zimbabwe from 2012 to 2019
Authors: Mashe Tapfumanei , Leekitcharoenphon Pimlapas , Mtapuri-Zinyowera Sekesai , Kingsley Robert A , Robertson V , Tarupiwa Andrew , Kock Marleen M , Makombe Evidence P , Chaibva Blessmore V , Manangazira Portia , Phiri Isaac , Nyadundu Simon , Chigwena Chriswell T , Mufoya Last P , Thilliez Gaetan , Midzi Stanely , Mwamakamba Lusubilo W , Hamblion Esther L , Matheu Jorge , Jensen Jacob D , Aarestrup Frank M , Hendriksen Rene S , Ehlers Marthie M
Published: November 2020

Background

Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control.

Objectives

To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics.

Methods

A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis.

Results

A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, β-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (4.3.1.1), with a maximum pair-wise distance of 22 SNPs.

Conclusions

This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi 4.3.1.1 (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance.
Enhancing filter-based parenthetic abbreviation extraction methods
Authors: Turki Houcemeddine , Hadj Taieb Mohamed Ali , Ben Aouicha Mohamed
Published: November 2020

This letter discusses the limitations of the use of filters to enhance the accuracy of the extraction of parenthetic abbreviations from scholarly publications and proposes the usage of the parentheses level count algorithm to efficiently extract entities between parentheses from raw texts as well as of machine learning-based supervised classification techniques for the identification of biomedical abbreviations to significantly reduce the removal of acronyms including disallowed punctuations.
Surgical challenges in multimodal treatment of N2-stage IIIA non-small cell lung cancer
Authors: Yamaguchi Masafumi , Nakagawa Kazuo , Suzuki Kenji , Takamochi Kazuya , Ito Hiroyuki , Okami Jiro , Aokage Keiju , Shiono Satoshi , Yoshioka Hiroshige , Aoki Tadashi , Tsutani Yasuhiro , Okada Morihito , Watanabe Shun-ichi ,   Lung Cancer Surgical Study Group (LCSSG) of the Japan Clinical Oncology Group (JCOG)
Published: November 2020

Locally advanced non-small cell lung cancer, especially mediastinal lymph node metastasis-positive stage IIIA-N2 cancer, is a heterogeneous disease state characterized by anatomically locally advanced disease with latent micrometastases. Thus, surgical resection or radiotherapy alone has historically failed to cure this disease. During the last three decades, persistent efforts have been made to develop a suitable treatment modality to overcome these problems using chemotherapy and/or radiotherapy with surgical resection. However, the role of surgical resection remains unclear, and the standard treatment for stage IIIA-N2 disease is concurrent chemoradiotherapy. In general, adjuvant chemotherapy is indicated for completely resected pathological stage IB disease or lymph node metastasis-positive pathological stage II or IIIA disease. Platinum-based doublet cytotoxic chemotherapy is currently the standard regimen. Additionally, post-operative radiotherapy might be indicated for post-operatively proven mediastinal lymph node metastasis; i.e. clinical N0–1 and pathological N2 disease. With the remarkable progression that has recently been made in the field of chemotherapy, such as advances in molecular targeting agents and immune checkpoint inhibitors, the basic policy of chemotherapy has been shifting to personalized treatment based on the individual patient’s oncogene driver mutation status, immune status and other parameters. The same trend is being seen in the treatment of stage IIIA-N2 disease. We should consider the past and upcoming results of several clinical trials to optimize the coming era of personalized treatment.
Eight New Species of Sucking Lice (Psocodea: Phthiraptera) From Endemic Murine Rodents in Australia and an Updated Identification Key
Authors: Wang Wei , Durden Lance A , Weaver Haylee , Shao Renfu
Published: November 2020

Based on a comprehensive study of museum specimens, eight new species of sucking lice of the genus Hoplopleura Enderlein, 1904 (Psocodea: Phthiraptera: Hoplopleuridae), are described from six genera of Australian Old Endemic rodents: Conilurus Ogilby, 1838 (Rodentia: Muridae), Leggadina Thomas, 1910 (Rodentia: Muridae), Leporillus Thomas, 1906 (Rodentia: Muridae), Mesembriomys Palmer, 1906 (Rodentia: Muridae), Pogonomys Milne-Edwards, 1877 (Rodentia: Muridae), and Xeromys Thomas, 1889 (Rodentia: Muridae). The description of these new species increases the number of sucking louse species from endemic Australian rodents from 13 to 21 and extends the records of sucking lice to all of the 14 genera of endemic rodents in Australia. Our results show that sucking lice are much more diverse among rodents in Australia than previously known. Furthermore, the Australian Hoplopleura species are host specific—each Hoplopleura species, including the eight new species described in the present study, parasitizes only a single host species, except Hoplopleura irritans Kuhn and Ludwig, 1967 (Psocodea: Phthiraptera: Hoplopleuridae) and Hoplopleura melomydis Weaver, 2017 (Psocodea: Phthiraptera: Hoplopleuridae), each of which is found on two host species. An updated dichotomous key for identifying Australian Hoplopleura species is included.
Organ-specific expression and epigenetic traits of genes encoding digestive enzymes in the lance-leaf sundew (Drosera adelae)
Authors: Arai Naoki , Ohno Yusuke , Jumyo Shinya , Hamaji Yusuke , Ohyama Takashi
Published: November 2020

Over the last two decades, extensive studies have been performed at the molecular level to understand the evolution of carnivorous plants. As fruits, the repertoire of protein components in the digestive fluids of several carnivorous plants have gradually become clear. However, the quantitative aspects of these proteins and the expression mechanisms of the genes that encode them are still poorly understood. In this study, using the Australian sundew Drosera adelae, we identified and quantified the digestive fluid proteins. We examined the expression and methylation status of the genes corresponding to major hydrolytic enzymes in various organs; these included thaumatin-like protein, S-like RNase, cysteine protease, class I chitinase, β-1, 3-glucanase, and hevein-like protein. The genes encoding these proteins were exclusively expressed in the glandular tentacles. Furthermore, the promoters of the β-1, 3-glucanase and cysteine protease genes were demethylated only in the glandular tentacles, similar to the previously reported case of the S-like RNase gene da-I. This phenomenon correlated with high expression of the DNA demethylase DEMETER in the glandular tentacles, strongly suggesting that it performs glandular tentacle-specific demethylation of the genes. The current study strengthens and generalizes the relevance of epigenetics to trap organ-specific gene expression in D. adelae. We also suggest similarities between the trap organs of carnivorous plants and the roots of non-carnivorous plants.
A willow UDP-glycosyltransferase involved in salicinoid biosynthesis
Authors: Kulasekaran Satish , Cerezo-Medina Sergio , Harflett Claudia , Lomax Charlotte , de Jong Femke , Rendour Amelie , Ruvo Gianluca , Hanley Steven J , Beale Michael H , Ward Jane L
Published: November 2020

The salicinoids are phenolic glycosides that are characteristic secondary metabolites of the Salicaceae, particularly willows and poplars. Despite the well-known pharmacology of salicin, that led to the development of aspirin >100 years ago, the biosynthetic pathways leading to salicinoids have yet to be defined. Here, we describe the identification, cloning, and biochemical characterization of SpUGT71L2 and SpUGT71L3—isozymic glycosyltransferases from Salix purpurea—that function in the glucosylation of ortho-substituted phenols. The best substrate in vitro was salicyl-7-benzoate. Its product, salicyl-7-benzoate glucoside, was shown to be endogenous in poplar and willow. Together they are inferred to be early intermediates in the biosynthesis of salicortin and related metabolites in planta. The role of this UDP-glycosyltransferase was confirmed via the metabolomic analysis of transgenic plants produced by RNAi knockdown of the poplar orthologue (UGT71L1) in the hybrid clone Populus tremula×P. alba, INRA 717-1B4.
Utility of Intraoperative Fluoroscopic Positioning of Total Hip Arthroplasty Components Using a Posterior and Direct Anterior Approach
Authors: Belyea Christopher M , Lansford Jefferson L , Yim Duke G
Published: November 2020

Introduction

Positioning of implant components for total hip arthroplasty (THA) is important for polyethylene liner wear, prosthesis joint stability, and range of motion. The introduction of fluoroscopy for the direct anterior approach has been shown to improve physician accuracy for component positioning. Few studies compare the use of intraoperative fluoroscopy for THA component positioning in posterior THA. The purpose of this project is to retrospectively evaluate the effect of intraoperative fluoroscopy on component positioning for THA using posterior and direct anterior approach (DAA).

Materials and Methods

A retrospective review of postoperative weight-bearing X-ray films of THAs was performed over a 2-year period where a single fellowship–trained total joint surgeon introduced direct anterior approach into his practice while expanding the intraoperative use of fluoroscopy for all THA procedures, regardless of approach. Component position was evaluated through radiographic measurement of acetabular cup inclination (goal of 40 degrees), limb length discrepancy (goal of 0 mm), and femoral component offset difference (goal of 0 mm). Radiographic analysis was performed by two independent providers. Statistical analysis was performed using Student’s t-tests.

Results

A total of 107 patients with an average age of 62 years were identified during the 2-year period surrounding the THA practice change, adding fluoroscopy to posterior and DAA THA. Three cohorts were identified: cohort A: 44 patients who underwent posterior THAs without the use of intraoperative fluoroscopy, cohort B: 35 patients who underwent direct anterior approach THAs with the use of intraoperative fluoroscopy, and cohort C: 18 patients who underwent posterior THAs with the use of intraoperative fluoroscopy. The use of intraoperative fluoroscopy for the posterior approach versus unguided posterior approach increased accuracy of both cup inclination (44 degrees vs 50 degrees, P < .05) and femoral offset (4 mm vs 7 mm, P < .05). A comparison of DAA with fluoroscopy versus posterior approach without fluoroscopy showed improvement in cup inclination (48 degrees vs 50 degrees, P < .05). Fluoroscopy with posterior approach versus fluoroscopy with DAA was found to have improved cup inclination (44 degrees vs 48 degrees, P < .05).

Conclusion

Intraoperative use of fluoroscopy can improve component positioning for posterior THA.
dadi.CUDA: Accelerating Population Genetics Inference with Graphics Processing Units
Authors: Gutenkunst Ryan N
Published: November 2020

dadi is a popular but computationally intensive program for inferring models of demographic history and natural selection from population genetic data. I show that running dadi on a Graphics Processing Unit can dramatically speed computation compared with the CPU implementation, with minimal user burden. Motivated by this speed increase, I also extended dadi to four- and five-population models. This functionality is available in dadi version 2.1.0, https://bitbucket.org/gutenkunstlab/dadi/.
The in vitro ToxTracker and Aneugen Clastogen Evaluation extension assay as a tool in the assessment of relative genotoxic potential of e-liquids and their aerosols
Authors: Czekala Lukasz , Chapman Fiona , Simms Liam , Rudd Kathryn , Trelles Sticken Edgar , Wieczorek Roman , Bode Lisa Maria , Pani Jutta , Moelijker Nynke , Derr Remco , Brandsma Inger , Hendriks Giel , Stevenson Matthew , Walele Tanvir
Published: November 2020

In vitro (geno)toxicity assessment of electronic vapour products (EVPs), relative to conventional cigarette, currently uses assays, including the micronucleus and Ames tests. Whilst informative on induction of a finite endpoint and relative risk posed by test articles, such assays could benefit from mechanistic supplementation. The ToxTracker and Aneugen Clastogen Evaluation analysis can indicate the activation of reporters associated with (geno)toxicity, including DNA damage, oxidative stress, the p53-related stress response and protein damage. Here, we tested for the different effects of a selection of neat e-liquids, EVP aerosols and Kentucky reference 1R6F cigarette smoke samples in the ToxTracker assay. The assay was initially validated to assess whether a mixture of e-liquid base components, propylene glycol (PG) and vegetable glycerine (VG) had interfering effects within the system. This was achieved by spiking three positive controls into the system with neat PG/VG or phosphate-buffered saline bubbled (bPBS) PG/VG aerosol (nicotine and flavour free). PG/VG did not greatly affect responses induced by the compounds. Next, when compared to cigarette smoke samples, neat e-liquids and bPBS aerosols (tobacco flavour; 1.6% freebase nicotine, 1.6% nicotine salt or 0% nicotine) exhibited reduced and less complex responses. Tested up to a 10% concentration, EVP aerosol bPBS did not induce any ToxTracker reporters. Neat e-liquids, tested up to 1%, induced oxidative stress reporters, thought to be due to their effects on osmolarity in vitro. E-liquid nicotine content did not affect responses induced. Additionally, spiking nicotine alone only induced an oxidative stress response at a supraphysiological level. In conclusion, the ToxTracker assay is a quick, informative screen for genotoxic potential and mechanisms of a variety of (compositionally complex) samples, derived from cigarettes and EVPs. This assay has the potential for future application in the assessment battery for next-generation (smoking alternative) products, including EVPs.
Characterization of the first tetrameric transcription factor of the GntR superfamily with allosteric regulation from the bacterial pathogenAgrobacterium fabrum
Authors: Vigouroux Armelle , Meyer Thibault , Naretto Anaïs , Legrand Pierre , Aumont-Nicaise Magali , Di Cicco Aurélie , Renoud Sébastien , Doré Jeanne , Lévy Daniel , Vial Ludovic , Lavire Céline , Moréra Solange
Published: November 2020

A species-specific region, denoted SpG8-1b allowing hydroxycinnamic acids (HCAs) degradation is important for the transition between the two lifestyles (rhizospheric versus pathogenic) of the plant pathogen Agrobacterium fabrum. Indeed, HCAs can be either used as trophic resources and/or as induced-virulence molecules. The SpG8-1b region is regulated by two transcriptional regulators, namely, HcaR (Atu1422) and Atu1419. In contrast to HcaR, Atu1419 remains so far uncharacterized. The high-resolution crystal structures of two fortuitous citrate complexes, two DNA complexes and the apoform revealed that the tetrameric Atu1419 transcriptional regulator belongs to the VanR group of Pfam PF07729 subfamily of the large GntR superfamily. Until now, GntR regulators were described as dimers. Here, we showed that Atu1419 represses three genes of the HCAs catabolic pathway. We characterized both the effector and DNA binding sites and identified key nucleotides in the target palindrome. From promoter activity measurement using defective gene mutants, structural analysis and gel-shift assays, we propose N5,N10-methylenetetrahydrofolate as the effector molecule, which is not a direct product/substrate of the HCA degradation pathway. The Zn2+ ion present in the effector domain has both a structural and regulatory role. Overall, our work shed light on the allosteric mechanism of transcription employed by this GntR repressor.
Unusual presentation of pulmonary blastomycosis complicated by amphotericin-induced refractory electrolyte abnormalities
Authors: Tobar Pool , Sanchez-Nadales Alejandro , Caldeira Elena , Saad Peguy
Published: November 2020

Blastomyces dermatitidis is an endemic mold infection commonly seen in the midwestern of the USA and rarely affects pregnant women. The most common presentation is a pulmonary infection with variable degrees of severity. Of note, the clinical and radiographic findings of pulmonary blastomycosis can be mistaken for other pulmonary pathologies, thus earning the title of ‘the great pretender’. The treatment of choice of infected pregnant patients is amphotericin B, which is known to produce electrolyte imbalances. However, it infrequently causes severe, prolonged and profound hypokalemia and hypomagnesemia. We present the case of a 27-year-old pregnant patient with pulmonary blastomycosis presenting with a lung mass suspicious of malignancy and treated with amphotericin B with subsequent prolonged refractory hypokalemia and hypomagnesemia.

Keywords

pulmonary blastomycosis

pregnancy

biopsy

computed tomography angiography

liposomal amphotericin B
Juvenile idiopathic arthritis in a premature baby: rare case report
Authors: Doya Leen Jamel , Bijow Fareeda Wasfy , Dayoub Adnan
Published: November 2020

Juvenile idiopathic arthritis (JIA) is chronic arthritis in children and adolescents. It is clinically diagnosed, which includes children under the age of 16 with arthritis for at least six weeks. Cases younger than six months of age are extremely rare. Here we report a rare case in the literature about Juvenile idiopathic arthritis in a premature baby, presenting at 21 days of age. The diagnosis was made according to clinical symptoms, laboratory analyses and duration of disease.
Primary cutaneous B-cell lymphoma—leg type in a young adult with HIV: a case report
Authors: Contreras-Chavez Pamela , Sanchez-Nadales Alejandro , Babets Igor , Sajjad-Hassan Romesa , Lansigan Frederick
Published: November 2020

Primary cutaneous B-cell lymphoma is a very rare entity. Skin lesions mainly occur on the lower extremities. Sheets of immunoblasts and centroblasts are characteristic findings at histologic examination. This case report highlights diagnostic and therapeutic strategies for primary cutaneous B-Cell lymphoma-leg type.
Decision Responsiveness and the Legitimacy of Public Agencies
Authors: Seyd Ben , Cichocka Aleksandra , Panayiotou Orestis
Published: November 2020

The procedural qualities of decisions made by public agencies are known to shape citizens’ perceptions of decision legitimacy. Existing empirical studies focus on procedures such as whether citizens are consulted, and whether their preferences are taken into account. Less is known about whether decisions made by public agencies are deemed legitimate if they reflect citizens’ broad interests rather than their immediate preferences. Yet, many contemporary issues confront policy-makers with dilemmas of whether to respond to citizens’ demands or instead to act on their interests. Using an experimental approach among a sample of British citizens, we analyse the effects on perceived legitimacy of various aspects of decision responsiveness. We focus in particular on whether public agencies are rewarded if they ignore citizens’ preferences while showing they are acting in their broader interests. Our results show that perceived legitimacy is indeed higher when decisions are seen to reflect citizens’ collective interests. But this boost disappears if individuals disapprove of the agency’s decision. We conclude that acting in citizens’ broad interests is unlikely to stimulate legitimacy among individuals who do not favour a decision’s outcome.
Neutron lifetime measurement with pulsed cold neutrons
Authors: Hirota K , Ichikawa G , Ieki S , Ino T , Iwashita Y , Kitaguchi M , Kitahara R , Koga J , Mishima K , Mogi T , Morikawa K , Morishita A , Nagakura N , Oide H , Okabe H , Otono H , Seki Y , Sekiba D , Shima T , Shimizu H M , Sumi N , Sumino H , Tomita T , Uehara H , Yamada T , Yamashita S , Yano K , Yokohashi M , Yoshioka T
Published: November 2020

The neutron lifetime has been measured by comparing the decay rate with the reaction rate of $^3$He nuclei of a pulsed neutron beam from the spallation neutron source at the Japan Proton Accelerator Research Complex (J-PARC). The decay rate and the reaction rate were determined by simultaneously detecting electrons from the neutron decay and protons from the $^3$He(n,p)$^3$H reaction using a gas chamber, the working gas of which contains diluted $^3$He. The measured neutron lifetime was $898\,\pm\,10\,_{\rm stat}\,^{+15}_{-18}\,_{\rm sys}\,$s.
How Valuable Is Financial Flexibility when Revenue Stops? Evidence from the COVID-19 Crisis
Authors: Fahlenbrach Rüdiger , Rageth Kevin , Stulz René M
Published: November 2020

Firms with greater financial flexibility should be better able to fund a revenue shortfall resulting from the COVID-19 shock and benefit less from policy responses. We find that firms with high financial flexibility within an industry experience a stock price drop that is 26$\%$, or 9.7 percentage points, lower than those with low financial flexibility. This differential return persists as stock prices rebound. Firms more exposed to the COVID-19 shock benefit more from cash holdings. No evidence suggests that recent payouts worsened the average firm’s drop in stock price. Our results cannot be explained by a leverage effect.
The aetiopathogenic significance, clinical relevance and therapeutic implications of vasculopathy in idiopathic inflammatory myopathy
Authors: Pauling John D , Christopher-Stine Lisa
Published: November 2020

It is 120 years since ‘angiomyositis’ was included alongside ‘polymyositis’ and ‘dermatomyositis’ in an attempt to propose a taxonomy that reflected the major clinical characteristics of idiopathic inflammatory myopathy (IIM). Endothelial injury, perivascular inflammation and capillary loss are important histological findings in affected tissues in IIM. Overt vascular clinical features including RP and abnormal nailfold capillaroscopy (NC) are also common in IIM. Despite the presence of endothelial injury, perivascular inflammation and capillary loss in affected tissues in IIM, and the presence of clinical features such as RP and NC abnormalities, the pathogenic and therapeutic implications of vasculopathy in IIM have been somewhat overlooked. RP and NC abnormalities are not always present, providing a valuable opportunity to explore aetiopathogenic factors driving vasculopathy within autoimmune rheumatic disease. The present review examines the aetiopathogenic, prognostic and therapeutic significance of vasculopathy in IIM. We describe the prevalence and clinical relevance of vasculopathy in IIM, and consider how vasculopathy may be better utilized to support improved IIM diagnosis and disease classification. Areas of unmet research need are highlighted where relevant.
Phase III trials of JAK1 selective inhibitors in rheumatoid arthritis
Authors: Mysler Eduardo , Lizarraga Ana
Published: November 2020

Upadacitinib and filgotinib, two JAK1 selective drugs have undergone extensive phase III clinical trials in RA and have demonstrated rapid improvements in disease activity, function and patient reported outcomes. Six global phase III randomized controlled clinical trials (SELECT phase III program) evaluated the efficacy and safety of upadacitinib and four clinical phase III trials (the FINCH program) evaluated the efficacy and safety of filgotinib. This article is a critical review of all these studies with focus on the therapeutic efficacy in RA. The aim is to display the data that could allow the approval of these new drugs for the treatment of RA (upadacitinib has been already approved in most of the markets around the world).
STAT3 phosphorylation inhibition for treating inflammation and new bone formation in ankylosing spondylitis
Authors: Jo Sungsin , Won Eun Jeong , Kim Moon-Ju , Lee Yu Jeong , Jin So-Hee , Park Pu-Reum , Song Ho-Chun , Kim Jahae , Choi Yoo-Duk , Kim Ji-Young , Shim Seung Cheol , Choi Sung Hoon , Park Ye-Soo , Kim Tae-Hwan , Kim Tae-Jong
Published: November 2020

Objective

AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS.

Methods

Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT.

Results

In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively).

Conclusion

Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.