bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficiency in alcohol dehydrogenase 2 reduces arsenic in rice grains by suppressing silicate transporters
Authors: Hayashi Shimpei , Kuramata Masato , Abe Tadashi , Yamaguchi Noriko , Takagi Hiroki , Tanikawa Hachidai , Iino Manaka , Sugimoto Kazuhiko , Ishikawa Satoru
Published: February 2021

Paddy fields are anaerobic and facilitate arsenite (As(III)) elution from the soil. Paddy-field rice accumulates arsenic (As) in its grains because silicate transporters actively assimilate As(III) during the reproductive stage. Reducing the As level in rice grains is an important challenge for agriculture. Using a forward genetic approach, we isolated a rice (Oryza sativa) mutant, low arsenic line 3 (las3), whose As levels were decreased in aerial tissues, including grains. The low-As phenotype was not observed in young plants before heading (emergence of the panicle). Genetic analyses revealed that a deficiency in alcohol dehydrogenase (ADH) 2 by mutation is responsible for the phenotype. Among the three rice ADH paralogues, ADH2 was the most efficiently produced in root tissue under anaerobic conditions. In wild-type (WT), silicon and As concentrations in aerial tissues increased with growth. However, the increase was suppressed in las3 during the reproductive stage. Accordingly, the gene expression of two silicate transporters, Lsi1 and Lsi2, was increased in WT around the time of heading, whereas the increase was suppressed in las3. These results indicate that the low-As phenotype in las3 is due to silicate transporter suppression. Measurement of intracellular pH by 31P-nuclear magnetic resonance revealed intracellular acidification of las3 roots under hypoxia, suggesting that silicate transporter suppression in las3 might arise from an intracellular pH decrease, which is known to be facilitated by a deficiency in ADH activity under anaerobic conditions. This study provides valuable insight into reducing As levels in rice grains.
Structure of double pionic atoms
Authors: Tani Akari , Ikeno Natsumi , Jido Daisuke , Nagahiro Hideko , Fujioka Hiroyuki , Itahashi Kenta , Hirenzaki Satoru
Published: February 2021

We study theoretically the structure of double pionic atoms, in which two negatively charged pions ($\pi^-$) are bound in the atomic orbits. The double pionic atom is considered to be an interesting system from the point of view of the multi-bosonic systems. In addition, it could be possible to deduce valuable information on the isospin $I = 2$$\pi\pi$ interaction and the pion–nucleus strong interaction. In this paper, we take into account the $\pi\pi$ strong and electromagnetic interactions, and evaluate the effects on the binding energies by perturbation theory for the double pionic atoms in heavy nuclei. We investigate several combinations of two pionic states and find that the order of magnitude of the energy shifts due to the $\pi\pi$ interaction is around 10 keV for the strong interaction and around 100 keV for the electromagnetic interaction for the ground states.
Sleep health and cognitive function among people with and without HIV: the use of different machine learning approaches
Authors: De Francesco Davide , Sabin Caroline A , Winston Alan , Rueschman Michael N , Doyle Nicki D , Anderson Jane , Vera Jaime H , Boffito Marta , Sachikonye Memory , Mallon Patrick W G , Haddow Lewis , Post Frank A , Redline Susan , Kunisaki Ken M
Published: February 2021

Study Objectives

We investigated associations between actigraphy-assessed sleep measures and cognitive function in people with and without HIV using different analytical approaches to better understand these associations and highlight differences in results obtained by these approaches.

Methods

Cognitive and 7-day/night actigraphy data were collected from people with HIV (PWH) and lifestyle-similar HIV-negative individuals from HIV and sexual health clinics in the United Kingdom/Ireland. A global cognitive T-score was obtained averaging the standardized individual cognitive test scores accounting for sociodemographics. Average and SD of 11 sleep measures over 7 days/nights were obtained. Rank regression, partial least-squares (PLS) regression, random forest, sleep dimension construct, and latent class analysis (LCA) were applied to evaluate associations between global T-scores and sleep measures.

Results

In 344 PWH (median age 57 years, 86% males), average sleep duration, efficiency, and wake after sleep onset were not associated with global T-scores according to rank regression (p = 0.51, p = 0.09, p = 0.16, respectively). In contrast, global T-scores were associated with average and SD of length of nocturnal awakenings, SD of maintenance efficiency, and average out-of-bed time when analyzed by PLS regression and random forest. No associations were found when using sleep dimensions or LCA. Overall, findings observed in PWH were similar to those seen in HIV-negative individuals (median age 61 years, 67% males).

Conclusions

Using multivariable analytical approaches, measures of sleep continuity, timing, and regularity were associated with cognitive performance in PWH, supporting the utility of newer methods of incorporating multiple standard and novel measures of sleep-wake patterns in the assessment of health and functioning.
On the classic paradox of infinity and a related function
Authors: Wijeratne Chanakya , Zazkis Rina
Published: February 2021

In this study we consider a classic paradox of infinity and its variations and suggest how the sources of misleading intuition can be analysed using the concept of uniform convergence of functions. We then examine how six mathematics honour students engage with a variation of the paradox. Despite their advanced mathematical training, the participants experienced considerable difficulty in addressing the presented paradoxical situation. Drawing on data from written responses and individual interviews, we describe the students’ approaches in an attempt to reconcile their intuitive perceptions with their mathematical computations.
Hydroquinone exposure accumulates neutral lipid by the activation of CDP-DAG pathway in Saccharomyces cerevisiae
Authors: Raj Abhishek , Nachiappan Vasanthi
Published: February 2021

Benzene metabolites (HQ and BQ) are toxic compounds and their presence in human cause alteration in cellular respiration and kidney damage. In the current study, Saccharomyces cerevisiae has been used as a model organism and acute exposure of hydroquinone (HQ) decreased cell growth and increased reactive oxygen species (ROS). The expression of apoptosis regulatory genes (YCA1, NUC1, YSP1 and AIF1) were increased with HQ exposure in the wild-type cells. HQ exposure in the wild-type cells altered both the phospholipid and neutral lipid levels. Phosphatidylcholine is a vital membrane lipid that has a vital role in membrane biogenesis and was increased significantly with HQ. The neutral lipid results were supported with lipid droplets data and mRNA expression study. The phospholipid knockouts (Kennedy pathway) accumulated neutral lipids via the CDP-DAG (cytidine-diphosphate-diacylglycerol) pathway genes both in the presence and absence of HQ.
Preferences and patterns of response to public health advice during the COVID-19 pandemic
Authors: Nov Oded , Dove Graham , Balestra Martina , Lawrence Katharine , Mann Devin , Wiesenfeld Batia
Published: February 2021

With recurring waves of the Covid-19 pandemic, a dilemma facing public health leadership is whether to provide public advice that is medically optimal (e.g., most protective against infection if followed), but unlikely to be adhered to, or advice that is less protective but is more likely to be followed. To provide insight about this dilemma, we examined and quantified public perceptions about the tradeoff between (a) the stand-alone value of health behavior advice, and (b) the advice’s adherence likelihood. In a series of studies about preference for public health leadership advice, we asked 1,061 participants to choose between (1) strict advice that is medically optimal if adhered to but which is less likely to be broadly followed, and (2) relaxed advice, which is less medically effective but more likely to gain adherence - given varying infection expectancies. Participants’ preference was consistent with risk aversion. Offering an informed choice alternative that shifts volition to advice recipients only strengthened risk aversion, but also demonstrated that informed choice was preferred as much or more than the risk-averse strict advice.
Transcranial direct current stimulation (tDCS) targeting the medial prefrontal cortex (mPFC) modulates functional connectivity and enhances inhibitory safety learning in obsessive-compulsive disorder (OCD)
Authors: Adams Thomas G. , Cisler Josh M. , Kelmendi Benjamin , George Jamilah R. , Kichuk Stephen A. , Averill Christopher L. , Anticevic Alan , Abdallah Chadi G. , Pittenger Christopher
Published: February 2021

Background

Psychotherapy based on fear extinction is a mainstay of treatment for obsessive-compulsive disorder (OCD). The default mode network (DMN) is important to safety signal processing, fear extinction, and exposure-based therapies. The medial prefrontal cortex (mPFC) is an anchor of the DMN. Neuromodulation targeting the mPFC might augment therapeutic learning and thereby enhance response to exposure-based therapies.

Methods

To characterize the effects of mPFC neuromodulation, 17 community volunteers completed resting-state fMRI scans before and after receiving 20 minutes of frontopolar multifocal transcranial direct current stimulation (tDCS). To examine the effects of tDCS on therapeutic learning, 24 patients with OCD were randomly assigned (double-blind, 50:50) to receive active or sham tDCS immediately before completing a two-day exposure and response prevention (ERP) challenge.

Results

After tDCS, frontal pole functional connectivity with regions in the anterior insula and basal ganglia decreased, while connectivity in the middle and superior frontal gyri increased (ps<.001, corrected). Functional connectivity between DMN and salience network (SN) increased after tDCS (ps<.001). OCD patients who received active tDCS exhibited more rapid within- and between-trial therapeutic extinction learning (ps<.05) during the ERP challenge compared to those who received sham tDCS.

Conclusion

tDCS targeting the mPFC may modulate SN and DMN functional connectivity and can accelerate therapeutic learning. Though limited by small samples, these promising findings motivate further exploration of the effects of tDCS on neural and behavioral targets associated with exposure-based treatments for OCD and for other anxiety and related disorders.
The detection of SARS-CoV-2 in autolysed samples from an exhumed decomposed body: Implications to virus survival, genome stability and spatial distribution in tissues
Authors: Prasad Mahadeshwara , Nachappa Somanna Ajjamada , Anand Niveditha , Rudresh Deepika Udayawara , Singh Yashika , Gangani Surabhi P. , Bhansali Forum K. , Sharma Basista Rabina , Senathipathi Deep Nithun , Byrappa Shashidhar H. , Halami Prakash M. , Veeranna Ravindra P. ,   CSIR,   CFTRI
Published: February 2021

Here we report for the first time the SARS-CoV-2 detection in autolysed samples from an exhumed decomposed body post-thirty six days after death. Both naso-oropharyngeal swabs and visceral samples from the lung, intestine, liver, and kidney were collected from the body exhumed post-fifteen days after burial, stored in viral transport medium and in saturated salt solution respectively. Naso-oropharyngeal swabs showed the presence of the SARS-CoV-2 genome as identified by the amplification of viral E, N, RdRP, or ORF1ab genes by RT-PCR. Subsequent examination of tissues reveal the detection of the virus genome in the intestine and liver, while no detection in the kidney and lung. These results signify the genome stability and implicate the virus survival in decomposed swab samples and in tissues and thereafter in storage solution. Further results also indicate spatial distribution of the virus in tissues during the early stage of infection in the subject with no respiratory distress. Considering the presence of cool, humid, and moist location of the exhumation, the presence of virus genome might also indicate that SARS-CoV-2 can persist for more than seven days on the surface of dead bodies similar to the Ebola virus, confirming that transmission from deceased subjects is possible for an extended period after death. These results further reaffirm the robustness of the RT-PCR aiding in the detection of viruses or their genome in decomposed samples when other methods of detection could not be useful.
Homologous and heterologous serological response to the N-terminal domain of SARS-CoV-2
Authors: Lv Huibin , Tsang Owen Tak-Yin , So Ray T. Y. , Wang Yiquan , Yuan Meng , Liu Hejun , Yip Garrick K. , Teo Qi Wen , Lin Yihan , Liang Weiwen , Wang Jinlin , Ng Wilson W. , Wilson Ian A. , Peiris J. S. Malik , Wu Nicholas C. , Mok Chris K. P.
Published: February 2021

The increasing numbers of infected cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious threats to public health and the global economy. Most SARS-CoV-2 neutralizing antibodies target the receptor binding domain (RBD) and some the N-terminal domain (NTD) of the spike protein, which is the major antigen of SARS-CoV-2. While the antibody response to RBD has been extensively characterized, the antigenicity and immunogenicity of the NTD protein are less well studied. Using 227 plasma samples from COVID-19 patients, we showed that SARS-CoV-2 NTD-specific antibodies could be induced during infection. As compared to the serological response to SARS-CoV-2 RBD, the SARS-CoV-2 NTD response is less cross-reactive with SARS-CoV. Furthermore, neutralizing antibodies are rarely elicited in a mice model when NTD is used as an immunogen. We subsequently demonstrate that NTD has an altered antigenicity when expressed alone. Overall, our results suggest that while NTD offers an alternative strategy for serology testing, it may not be suitable as an immunogen for vaccine development.
Physiological and ecological consequences of the water optical properties degradation on reef corals
Authors: López-Londoño Tomás , Galindo-Martínez Claudia T. , Gómez-Campo Kelly , González-Guerrero Luis A. , Roitman Sofia , Pollock F. Joseph , Pizarro Valeria , López-Victoria Mateo , Medina Mónica , Iglesias-Prieto Roberto
Published: February 2021

Degradation of water optical properties due to anthropogenic disturbances is a common phenomenon in coastal waters globally. Although this condition is associated with multiple drivers that affect corals health in multiple ways, its effect on light availability and photosynthetic energy acquisition has been largely neglected. Here, we describe how declining the water optical quality in a coastal reef exposed to a turbid plume of water originating from a man-made channel compromise the functionality of the keystone coral speciesOrbicella faveolata. We found highly variable water optical conditions with significant effects on the light quantity and quality available for corals. Reduction of light penetration into the water column elicits the development of low-light phenotypes close to theoretical limits of photoacclimation despite their occurrence at shallow depths. Predicted photosynthetic energy depletion with increasing depth is associated with patterns of colony mortality and contraction of the habitable space for the population. A numerical model illustrates the potential effect the progressive degradation of water optical properties on the gradual mortality and population decline ofO. faveolata. Our findings suggest that preserving the water optical properties seeking to maximize light penetration into the water column may have an extraordinary impact on coral reefs conservation, mostly toward the deeper portions of reefs.
Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance
Authors: Pandya Deep , Shah Myra , Kaplan Fuat , Martino Candice , Levy Gillian , Kazanjian Mia , Batter Stephen , Martignetti John , Frank Richard C.
Published: February 2021

Neuroendocrine prostate cancer (NEPC) is a highly aggressive histologic subtype of prostate cancer associated with a poor prognosis. Its incidence is expected to increase as castration-resistant disease emerges from the widespread use of potent androgen receptor-targeting therapies, such as abiraterone and enzalutamide. Defects in homologous recombination repair genes, such as BRCA1/2, are also being increasingly detected in individuals with advanced prostate cancer. We present the case of a 65-yr-old man with a germline BRCA2 mutation who developed explosive treatment-emergent, small-cell neuroendocrine prostate cancer. He achieved a complete response to platinum-containing chemotherapy, but a limited remission duration with the use of olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, as maintenance therapy. Upon relapse, tumor genomic profiling revealed a novel 228-bp deletion in exon 11 of the BRCA2 gene. The addition of the anti-PD1 drug pembrolizumab to olaparib was ineffective. This case highlights the ongoing challenges in treating neuroendocrine prostate cancer, even in the setting of homologous recombination repair deficiency.
Polo: an open-source graphical user interface for crystallization screening
Authors: Holleman Ethan T. , Duguid Erica , Keefe Lisa J. , Bowman Sarah E. J.
Published: February 2021

Polo is a Python-based graphical user interface designed to streamline viewing and analysis of images to monitor crystal growth, with a specific target to enable users of the High-Throughput Crystallization Screening Center at Hauptman-Woodward Medical Research Institute (HWI) to efficiently inspect their crystallization experiments. Polo aims to increase efficiency, reducing time spent manually reviewing crystallization images, and to improve the potential of identifying positive crystallization conditions. Polo provides a streamlined one-click graphical interface for the Machine Recognition of Crystallization Outcomes (MARCO) convolutional neural network for automated image classification, as well as powerful tools to view and score crystallization images, to compare crystallization conditions, and to facilitate collaborative review of crystallization screening results. Crystallization images need not have been captured at HWI to utilize Polo's basic functionality. Polo is free to use and modify for both academic and commercial use under the terms of the copyleft GNU General Public License v3.0.
Upscaling X-ray nanoimaging to macroscopic specimens
Authors: Du Ming , Di Zichao , Gürsoy Dogˇa , Xian R. Patrick , Kozorovitskiy Yevgenia , Jacobsen Chris
Published: February 2021

Upscaling X-ray nanoimaging to macroscopic specimens has the potential for providing insights across multiple length scales, but its feasibility has long been an open question. By combining the imaging requirements and existing proof-of-principle examples in large-specimen preparation, data acquisition and reconstruction algorithms, the authors provide imaging time estimates for howX-ray nanoimaging can be scaled to macroscopic specimens. To arrive at this estimate, a phase contrast imaging model that includes plural scattering effects is used to calculate the required exposure and corresponding radiation dose. The coherent X-ray flux anticipated from upcoming diffraction-limited light sources is then considered. This imaging time estimation is in particular applied to the case of the connectomes of whole mouse brains. To image the connectome of the whole mouse brain, electron microscopy connectomics might require years, whereas optimized X-ray microscopy connectomics could reduce this to one week. Furthermore, this analysis points to challenges that need to be overcome (such as increased X-ray detector frame rate) and opportunities that advances in artificial-intelligence-based `smart' scanning might provide. While the technical advances required are daunting, it is shown that X-ray microscopy is indeed potentially applicable to nanoimaging of millimetre- or even centimetre-size specimens.
Crystal structure and Hirshfeld surface analysis of 3-[(1E)-(4-{4-[(E)-(3-hydroxybenzylidene)amino]phenoxy}phenylimino)methyl]phenol
Authors: Mohamed Shaaban K. , Mague Joel T. , Akkurt Mehmet , Hawaiz Farouq E. , Elgarhy Sahar M. I. , Al-Taifi Elham A.
Published: February 2021

In the crystal, the molecule of the title compound, C26H20N2O3, has crystallographically imposed twofold rotation symmetry. The crystal packing consists of layers parallel to the ab plane formed by O—H...N and C—H...O hydrogen bonds. Between the layers, C—H...π interactions are observed.
Structural investigation of N-[2-(4-fluoro-3-phenoxybenzoyl)hydrazinecarbothioyl]benzamide and N-[2-(4-fluoro-3-phenoxybenzoyl)hydrazinecarbothioyl]-4-methoxybenzamide
Authors: Dey Dhananjay , Shruti I. , Chopra Deepak , Mohan T. P.
Published: February 2021

The compound N-[2-(4-fluoro-3-phenoxybenzoyl)hydrazinecarbothioyl]benzamide, C21H16FN3O3S, crystallizes in the monoclinic centrosymmetric space group P21/c and its molecular conformation is stabilized via an intramolecular N—H...O hydrogen bond. The corresponding para-methoxy derivative, namely, N-[2-(4-fluoro-3-phenoxybenzoyl)hydrazinecarbothioyl]-4-methoxybenzamide, C22H18FN3O4S, crystallizes in the monoclinic centrosymmetric space group C2/c. The supramolecular network mainly comprises N—H...O, N—H...S and C—H...O hydrogen bonds, which contribute towards the formation of the crystal structures for the two molecules. The different intermolecular interactions have been further analysed using Hirshfeld surface analysis and fingerprint plots.
China investment policy – ensuring the mice will be caught
Authors: Lewis Ian K. , Zhou Mirror , Wang Elfie J.Y.
Published: February 2021

Purpose

This article analyses China’s attempts at economic revival, which, starting with the Foreign Investment Law, were under way before COVID-19 but which were given extra impetus by the onset of the pandemic.

Design/methodology/approach

The thought is that the Foreign Investment Law lacks detail, so this article looks at the three ideas with which the State Council is seeking to underpin it: key Industries, promoting investment and equal treatment. It also considers Shanghai’s experience as the first major municipality to implement the State Council’s guidance.

Findings

China is committed to more transparency and to opening more of its economy to foreign investors, even if it will continue to be selective about which industries it wishes to encourage. The central government wants other regional and local jurisdictions to follow Shanghai’s lead and implement its guidance, as well as bring forward more measures to make the environment more favorable for foreign investment. At the same time, the article notes that China faces some hostility from other nations and groupings, such as the US, UK and the EU, from which it would expect to receive investment.

Practical implications

Investors can expect more specific reforms in the different areas of the economy that China wishes to develop while recognizing that it needs foreign expertise to do so.

Originality/value

Insight from experienced corporate lawyers who are resident in China and have first-hand experience of the measures aimed at economic recovery.
Big data doesn’t mean big money!
Authors: Sweeney Patrick
Published: February 2021

Purpose

Design/methodology/approach

Information paper

Findings

Provide information

Originality/value

Original review
Reflections on the theme issue outcomes: tourism sustainability in natural, residential and mountain locations: What are the current issues and questions?
Authors: Teare Richard
Published: February 2021

Purpose

Profiles the WHATT theme issue: “Tourism sustainability in natural, residential and mountain locations: What are the current issues and questions?” with reference to the experiences of the theme editors and writing team.

Design/methodology/approach

The author has used structured questions to enable the theme editors to reflect on the rationale for the theme issue question, the starting-point, the selection of the writing team and material and the editorial process.

Findings

This paper identifies some of the key challenge for sustainable tourism in natural spaces and mountain areas with reference to the issues that impede sustainability and possible solutions.

Practical implications

The theme issue outcomes provide indicators and action points for tourism industry stakeholders and for teaching and research in sustainable tourism development.

Originality/value

This paper draws on discussion and applies research to identify and assess the scope and scale of action needed to address tourism sustainability in a diverse range of locations, with particular reference to Europe. Taken together, the theme issue collection of articles provides a rich picture of the changes that are needed and key actions for the future.
Self-determination and financial well-being: mediating role of financial attitude among retirees in Nigeria
Authors: Soepding Benard Alkali , Munene John C. , Orobia Laura
Published: February 2021

Purpose

Little is known about how self-determination and financial attitude are linked to retirees’ financial well-being in Nigerian context. Drawing from the theory of reasoned action, the purpose of this paper is to examine the connection of self-determination, financial attitude and financial well-being. Also, this paper examines the mediating role of financial attitude between self-determination and financial well-being.

Design/methodology/approach

A cross-sectional study was used in collecting quantitative data from 399 retirees drawn from North Central Nigeria. Hypotheses are tested through structural equation modelling using the Analysis of Moments of Structures (AMOS) software, version 23.

Findings

Results from the research indicate that financial attitude serves as a trajectory through which self-determination leads to financial well-being. Therefore, self-determination and financial attitude significantly contribute to the financial well-being of retirees.

Research limitations/implications

The use of a cross-sectional design may undermine the causal conclusions of the findings. This study adds to existing research on financial well-being by showing that financial attitude is significant in attaining financial well-being and how self-determination variable impact financial well-being.

Originality/value

This study contributes to literature by establishing the mediating role of financial attitude in the relationship between self-determination and financial well-being. Thus, instead of concentrating on only the direct effects of self-determination and financial well-being, the indirect effect of financial attitude is tested.
Choosing Wisely in radiation therapy for breast cancer: Time lag in adoption of hypofractionated radiation therapy in Victoria
Authors: Ong Wee Loon , Khor Richard , Chao Michael , Milne Roger L , Millar Jeremy , Foroudi Farshad
Published: February 2021

Introduction

To evaluate the adoption of hypofractionated radiotherapy (HFRT) for breast cancer (BC) in Victoria, Australia.

Methods

This is a population‐based cohort of women with BC who had breast RT as captured in the Victorian Radiotherapy Minimum Data Set between 2012 and 2017. We defined HFRT as < 25 fractions of RT. The pattern of HFRT use over time was evaluated with the Cochrane–Armitage test for trend. Factors associated with HFRT were identified using multivariable logistic regression.

Results

12,717 women were included in the study. Overall, 6,653 (52%) patients had HFRT. HFRT use increased from 35% in 2012 to 66% in 2017 (P‐trend < 0.001). Older women were more likely to have HFRT (74% for women aged ≥ 70 years vs. 27% for women aged < 50 years; P < 0.001). Women who had nodal irradiation were less likely to have HFRT compared with those who did not (13% vs. 57%; P < 0.001). HFRT use was more common in public than private institutions (57% vs. 46%, P < 0.001), and in metropolitan than regional centres (54% vs. 46%, P < 0.001). In multivariable analyses, the progressive increase in HFRT use over time was independent of other covariates – women treated in 2017 were 7.3 times (95% CI = 6.3–8.6, P < 0.001) more likely to be treated with HFRT than in 2012. Age at RT, nodal irradiation, area of residence and institutional type and locations were all independently associated with HFRT use.

Conclusion

This large Australian contemporary population‐based study demonstrates increasing use of HFRT for BC. However, large sociodemographic and institutional provider‐related variations in practice still exist.
Right atrial cardiac angiosarcoma treated with concurrent proton beam therapy and paclitaxel: A novel approach to a rare disease
Authors: Mangla Ankit , Gupta Amit , Mansur David B. , Abboud Salim , Rothermel Luke D. , Oliveira Guilherme H.
Published: February 2021

Cardiac angiosarcoma is a rare malignancy with an aggressive course and poor prognosis. We present a 26‐year old man who came to our clinic with shortness of breath and was diagnosed with a right‐sided atrial mass. He underwent urgent resection of the mass. The pathology confirmed the mass to be cardiac angiosarcoma with positive microscopic margins (R1 resection). Since reresection was not feasible, the patient started treatment with concurrent paclitaxel (80 mg/m2 weekly) and proton beam therapy (61 Cobalt equivalent delivered over five weeks). After completing the concurrent chemotherapy and radiation therapy, he was treated with adjuvant chemotherapy using gemcitabine (900 mg/m2 on Days 1 and 8) and docetaxel (100 mg/m2 on Day 8) every three weeks. After three cycles, the patient developed severe dermatitis, and hence further chemotherapy was withheld. The patient is alive at 26 months since receiving his surgery and 18 months since the completion of treatment. Patients with cardiac angiosarcoma who undergo R1 resection have a median survival of six months. More radical approaches such as orthotopic heart‐lung transplant or prolonged durations of chemotherapy lead to minimal improvement in survival at the cost of increased morbidity. Here, we describe a novel approach to a rare disease that resulted in prolonged survival and led to a better quality of life without any long‐term morbidity to the patient.
Mediastinal undifferentiated pleomorphic sarcoma with pleural effusion cytopathologically misdiagnosed as epithelial malignant pleural mesothelioma: An autopsy case report
Authors: Matsumoto Kinnosuke , Nakamura Yukihiro , Inagaki Yuji , Taniguchi Yoshihiko , Tamiya Akihiro , Matsuda Yoshinobu , Kasai Takahiko , Atagi Shinji
Published: February 2021

Undifferentiated pleomorphic sarcoma (UPS) is a new disease in the World Health Organization's classification of tumors of soft tissue and bone published in 2013. Primary mediastinal UPS is rare, especially with pleural effusion. Herein, we describe the pathological findings of pleural effusion followed by mediastinal UPS, which was initially misdiagnosed as epithelial malignant pleural mesothelioma (MPM). The cytopathological findings of the pleural effusion cell block often contribute to the diagnosis of various malignant tumors. However, these findings may lead to misdiagnosis of highly invasive mediastinal tumors such as UPS. A biopsy for primary mediastinal lesions should be performed because MPM rarely mimics mediastinal tumors with pleural effusion.
Improving outcomes for people with mild cognitive impairment: An Australian mixed‐methods pilot study
Authors: Theodoro de Freitas Luciana , Pain Tilley , Barnett Fiona
Published: February 2021

Objective

This pilot study tested the feasibility and acceptability of an innovative functional task exercise program to ameliorate mild cognitive impairment.

Methods

The functional task exercise program was trialled on community‐dwelling adults aged 60 years or older. The 10‐week program was conducted in regional Australia and evaluated for acceptability and feasibility. Outcomes were assessed pre‐ and post‐ intervention and at three‐month follow‐up. Structured interviews were conducted with caregivers and participants at the end of the program.

Results

Acceptability was demonstrated, with approximately 80% of the 23 participants completing the program. Clinical improvements were demonstrated in several cognitive and functional measures using an uncontrolled pre‐post test design. Qualitative findings suggest feasibility as the program was viewed positively by participants and caregivers.

Conclusion

The functional exercise program was acceptable, was feasible and improved outcomes in an Australian context. Research is urgently needed to identify and treat people with mild cognitive impairment living in the community.
Commons and cooperatives: A new governance of collective action
Authors: Guttmann Alexandre
Published: February 2021

The Social and Solidarity Economy (SSE) is emerging as a social movement capable of moving society beyond the imbalances of the capitalist market economy and its top‐down regulation by the state. But the SSE's progress has been slow while unresolved challenges (e.g., climate, inequality) continue to intensify. Among communitarian responses to these challenges, the commons have shown great potential as a shared governance mechanism for the responsible management of common‐pool resources. To the extent that this success encourages broader applicability for commons, we focus also on commoning as crucial social practice rooted in collective action and adaptive governance. Adding this dimension of activism opens the possibility of enriching the SSE both in theory and practice for the purpose of strengthening its institutional make‐up, in particular cooperatives occupying a central position in SSE. Commoning enables us to conceive of tangible connections between commons and cooperatives as complementary modes of anti‐capitalist organization. We can illustrate this complementarity by analyzing how Ostrom's “design principles” for commons can help strengthen the ICA's Cooperative Principles. Useful lessons can be learned from concrete examples of commons–cooperative alliances, such as Ecuador's Buen Vivir initiative, the Enercoop PACA project in France, and Oakland's OmniCommons space.
Syntaxonomy and biogeography of the Irano‐Turanian mires and springs
Authors: Naqinezhad Alireza , Nowak Arkadiusz , Świerszcz Sebastian , Jalili Adel , Kamrani Asghar , Wheeler Bryan D. , Shaw Susan C. , Attar Farideh , Nobis Marcin , Nowak Sylwia , Hájek Michal
Published: February 2021

Aims

To develop the first comprehensive syntaxonomic classification for patchy montane mire and spring vegetation across the Irano‐Turanian phytogeographical region in Iran, Tajikistan and Kyrgyzstan and to explore the effects of the main environmental and geographic gradients on their distribution.

Location

Alborz Mountain range (Iran), Pamir‐Alai Mountains (Tajikistan) and Tian Shan Mountains (Kyrgyzstan); total area about 3,000,000 km2.

Methods

A database of 1,015 vegetation relevés including a total of 675 vascular and bryophyte taxa was established, covering the large mountains ranges of the Irano‐Turanian regions in Iran, Tajikistan and Kyrgyzstan, at altitudes ranging from 1,300 to 4,505 m a.s.l. A semi‐supervisedk‐means analysis was performed. Additional analyses were carried out to show differences among predefined vegetation groups in terms of phytogeographical, climatic and compositional factors.

Results

Two large groups of mire communities, referable to mires and springs were identified. Twenty associations, one subassociation and four alliances of these wetlands, belonging to three orders and three classes, were defined. Among them, ten associations, one subassociation and two alliances were formally described as new syntaxa. Moreover, a new orderCaricetalia orbicularis, that comprises phytogeographically unique vegetation of the Irano‐Turanian mires, is proposed.

Conclusions

Based on our results and comparison between the Irano‐Turanian and other phytogeographical regions, we propose a first comprehensive syntaxonomic synopsis for the Irano‐Turanian mires and springs. Despite some identical character species and their vicariant nature, the Irano‐Turanian, Euro‐Siberian and Mediterranean mires and springs show considerable compositional differences. Irano‐Turanian wetlands contain a large and distinct set of endemic plant species, which are mixed with Euro‐Siberian species in the west and north, but predominate in the eastern locations. They have a patchy pattern and scattered distribution and serve as inland hotspots of wetland vegetation in the vast dry landscape of southwest and Central Asia.
The effect of aging on infliximab exposure and response in patients with inflammatory bowel diseases
Authors: Kantasiripitak Wannee , Verstockt Bram , Alsoud Dahham , Lobatón Triana , Thomas Debby , Gils Ann , Vermeire Séverine , Ferrante Marc , Dreesen Erwin
Published: February 2021

Aims

Controversies regarding infliximab treatment in elderly patients with inflammatory bowel diseases remain. We evaluated the effect of patient's age on infliximab exposure, efficacy and safety.

Methods

Retrospective case‐control data of patients receiving infliximab induction treatment were analysed. A population pharmacokinetic model was developed to estimate individual pharmacokinetic parameters. A logistic regression model was used to investigate the effect of exposure on endoscopic remission. Repeated time‐to‐event models were developed to describe the hazard of safety events over time.

Results

A total of 104 patients (46 elderly, ≥65 years) were included. A two‐compartment population pharmacokinetic model with linear elimination adequately described the data. Infliximab clearance decreased with older age, higher serum albumin, lower fat‐free mass, lower C‐reactive protein and absence of immunogenicity. Yet, infliximab exposure was not significantly different between elderly and nonelderly. Regardless of age, an infliximab trough concentration at week (w)14 of 15.6 mg/L was associated with a 50% probability of attaining endoscopic remission between w6 and w22. Infliximab exposure during induction treatment was not a risk factor of (severe) adverse events. The hazard of severe adverse events and malignancy increased by 2% and 7%, respectively, with increasing year of age. Concomitant immunomodulator use increased the hazard of infection by 958%, regardless of age.

Conclusions

Elderly patients attained infliximab exposure and endoscopic remission similarly to nonelderly patients. Therefore, the same infliximab trough concentration target can be used in therapeutic drug monitoring. The hazards of severe adverse events and malignancy increased with age, but not with infliximab exposure.
The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer
Authors: Fujii Atsushi , Masuda Takaaki , Iwata Michio , Tobo Taro , Wakiyama Hiroaki , Koike Kensuke , Kosai Keisuke , Nakano Takafumi , Kuramitsu Shotaro , Kitagawa Akihiro , Sato Kuniaki , Kouyama Yuta , Shimizu Dai , Matsumoto Yoshihiro , Utsunomiya Tohru , Ohtsuka Takao , Yamanishi Yoshihiro , Nakamura Masafumi , Mimori Koshi
Published: February 2021

Targeting mutated oncogenes is an effective approach for treating cancer. The 4 main driver genes of pancreatic ductal adenocarcinoma (PDAC) are KRAS, TP53, CDKN2A, and SMAD4, collectively called the “big 4” of PDAC, however they remain challenging therapeutic targets. In this study, ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 (ASAP2), one of the ArfGAP family, was identified as a novel driver gene in PDAC. Clinical analysis with PDAC datasets showed that ASAP2 was overexpressed in PDAC cells based on increased DNA copy numbers, and high ASAP2 expression contributed to a poor prognosis in PDAC. The biological roles of ASAP2 were investigated using ASAP2‐knockout PDAC cells generated with CRISPR‐Cas9 technology or transfected PDAC cells. In vitro and in vivo analyses showed that ASAP2 promoted tumor growth by facilitating cell cycle progression through phosphorylation of epidermal growth factor receptor (EGFR). A repositioned drug targeting the ASAP2 pathway was identified using a bioinformatics approach. The gene perturbation correlation method showed that niclosamide, an antiparasitic drug, suppressed PDAC growth by inhibition of ASAP2 expression. These data show that ASAP2 is a novel druggable driver gene that activates the EGFR signaling pathway. Furthermore, niclosamide was identified as a repositioned therapeutic agent for PDAC possibly targeting ASAP2.
The declining wealth of the middle class, 1983–2016
Authors: Wolff Edward N.
Published: February 2021

This article considers trends in wealth at the middle and top of the distribution, with a particular focus on the period around the Great Recession. It illustrates that leverage rates of middle class families relative to high‐wealth families were beneficial to relative rates of return of middle class families for most periods since 1983 but was extremely detrimental during the Great Recession. It also considers the savings rates over time among high‐wealth and middle class families, showing that dissaving slowed the recovery in wealth—especially among the middle class. Differential leverage was also a key factor explaining wealth inequality trends.
Sodium‐glucose cotransporter‐2 inhibitors and the risk of urinary tract infection among diabetic patients in Japan: Target trial emulation using a nationwide administrative claims database
Authors: Takeuchi Yoshinori , Kumamaru Hiraku , Hagiwara Yasuhiro , Matsui Hiroki , Yasunaga Hideo , Miyata Hiroaki , Matsuyama Yutaka
Published: February 2021

Aim

To assess the risk of urinary tract infection (UTI) occurrence associated with sodium‐glucose cotransporter‐2 (SGLT2) inhibitor use relative to biguanide use in diabetes in a population‐based cohort study using a target trial emulation framework.

Methods

Using a Japanese nationwide administrative claims database, we constructed a cohort of patients aged ≥40 years who were dispensed SGLT2 inhibitors, dipeptidyl peptidase‐4 (DPP‐4) inhibitors or biguanides between April 2014 and March 2015. For computational ease, we randomly sampled 100% of SGLT2 inhibitor users, 3% of DPP‐4 inhibitor users, and 20% of biguanide users; new antidiabetic drug initiators were analysed. We estimated the intention‐to‐treat (ITT) hazard ratios (HRs) of UTI with inverse probability of treatment (IPT)‐weighted Coxʼs proportional hazards models that ignored subsequent treatment changes. Treatment weights were computed using patient sex, age, medications, medical history and hospitalization history. We also estimated per‐protocol (PP) HRs using IPT‐ and inverse probability of censoring‐weighted Coxʼs models that adjusted for nonrandom treatment changes.

Results

We analysed 11 364 SGLT2 inhibitor initiators, 9035 DPP‐4 inhibitor initiators, and 10 359 biguanide initiators. When compared with biguanide initiators, SGLT2 inhibitor initiators had a crude HR of 1.14 (95% confidence interval [CI] 1.05‐1.24), an ITT HR of 0.94 (95% CI 0.86‐1.03), and a PP HR of 0.90 (95% CI 0.78‐1.03); and DPP‐4 inhibitor initiators had a crude HR of 1.13 (95% CI 1.04‐1.23), an ITT HR of 0.85 (95% CI 0.77‐0.94), and a PP HR of 0.83 (95% CI 0.71‐0.95).

Conclusion

Use of SGLT2 inhibitors or DPP‐4 inhibitors did not increase the risk of UTI compared with biguanide use. Accounting for treatment changes did not substantially influence the estimated effects.
Revisiting My Self‐Quarantine Experience through a Data‐Driven Approach
Authors: Lee Sheng‐Hung
Published: February 2021

One constructive possibility was that as a designer, I could authentically capture my personal self‐quarantine experience to identify user pain points, and improve the school's quarantine procedures to help more people in the future.

Undeterred by an unplanned quarantine, a student uses technology and questions the experience from four perspectives in hopes of improving it for others.
What Didn't Happen to Me Last Year?
Authors: Middleton Zoë
Published: February 2021

Covid had begun to creep across America and change the way we operated in business. I missed the non‐stop hustle and bustle, always on the go, wheels‐up lifestyle.

Hers was a world of travel. The pandemic may have changed that, but this designer expanded her horizons in 2020 in ways she never imagined.
Opportunities to improve ecosystem‐based fisheries management by recognizing and overcoming path dependency and cognitive bias
Authors: Fulton Elizabeth Ann
Published: February 2021

The rate of change in marine ecosystems and the speed with which pressure on those systems is escalating are much faster than rates of institutional change or management responses. The continued promulgation of a century‐old management approach (i.e., single species maximum sustainable yield), despite decades of scientific warnings regarding its flaws, highlights how fisheries management and science can be constrained by path dependency and psychological traps. Major disruptions to the functioning of fisheries created by climate and SARS‐CoV‐2 (COVID‐19) present an opportunity to take a step back and introduce alternative approaches more appropriate to the extant conditions in the majority of global fisheries. This reset point, in combination with a proliferation of cheaper technological options, provides the opportunity for fisheries in emerging economies to reach a sustainable position without retracing the steps, or holding to the assumptions behind the fisheries management approaches applied in regions such as Europe, North America or Australia.
Signaling at the endosome: cryo‐EM structure of a GPCR–G protein–beta‐arrestin megacomplex
Authors: Nguyen Anthony H. , Lefkowitz Robert J.
Published: February 2021

G protein‐coupled receptors (GPCRs) are a large class of cell‐surface receptor involved in cellular signaling that are currently the target of over one third of all clinically approved therapeutics. Classically, an agonist‐bound, active GPCR couples to and activates G proteins through the receptor intracellular core. To attenuate G protein signaling, the GPCR is phosphorylated at its C‐terminal tail and/or relevant intracellular loops, allowing for the recruitment of β‐arrestins (βarrs). βarrs then couple to the receptor intracellular core in order to mediate receptor desensitization and internalization. However, our laboratory and others have observed that some GPCRs are capable of continuously signaling through G protein even after internalization. This mode of sustained signaling stands in contrast with our previous understanding of GPCR signaling, and its molecular mechanism is still not well understood. Recently, we have solved the structure of a GPCR–G protein–βarr megacomplex by cryo‐electron microscopy. This ‘megaplex’ structure illustrates the independent and simultaneous coupling of a G protein to the receptor intracellular core, and binding of a βarr to a phosphorylated receptor C‐terminal tail, with all three components maintaining their respective canonically active conformations. The structure provides evidence for the ability of a GPCR to activate G protein even while being bound to and internalized by βarr. It also reveals that the binding of G protein and βarr to the same GPCR is not mutually exclusive, and raises a number of future questions to be answered regarding the mechanism of sustained signaling.