bluuebunny/crossref_metadata_2025 huggingface dataset:
Commons as Polanyian countermovement in neoliberal market society. A case study in Belgium
Authors: Holemans Dirk
Published: April 2021

Over the last two decades, scholars have witnessed a remarkable wave of new commons. They have mostly been conceptualized either as pragmatic management of common-pool resources or as a radical political idea and praxis. We assert that enriching the literature with a Polanyian perspective allows to go beyond the binary conception and affords a better understanding of the societal relevance of commons. Conceptualizing commons as part of a countermovement aimed at the gradual decommodification and re-embedding of markets, results in a more dynamic view on how commons function in the interplay of the social force of capitalism and the forces that limit or reverse it. This also shows the relevance of commons as interstitial alternative practices. The framework is illustrated by a case study on commons established in Belgium in 2015–2016. It shows that instead of focussing primarily on contentious action, commoners concentrate on establishing alternatives that prefigure the desired future society.
The Precentral Insular Cortical Network for Speech Articulation
Authors: Tomaiuolo Francesco , Campana Serena , Voci Loredana , Lasaponara Stefano , Doricchi Fabrizio , Petrides Michael
Published: April 2021

Apraxia of speech is a motor disorder characterized by the impaired ability to coordinate the sequential articulatory movements necessary to produce speech. The critical cortical area(s) involved in speech apraxia remain controversial because many of the previously reported cases had additional aphasic impairments, preventing localization of the specific cortical circuit necessary for the somatomotor execution of speech. Four patients with “pure speech apraxia” (i.e., who had no aphasic and orofacial motor impairments) are reported here. The critical lesion in all four patients involved, in the left hemisphere, the precentral gyrus of the insula (gyrus brevis III) and, to a lesser extent, the nearby areas with which it is strongly connected: the adjacent subcentral opercular cortex (part of secondary somatosensory cortex) and the most inferior part of the central sulcus where the orofacial musculature is represented. There was no damage to rostrally adjacent Broca’s area in the inferior frontal gyrus. The present study demonstrates the critical circuit for the coordination of complex articulatory movements prior to and during the execution of the motor speech plans. Importantly, this specific cortical circuit is different from those that relate to the cognitive aspects of language production (e.g., Broca’s area on the inferior frontal gyrus).
Analysis of Hospitalized and Severe Dengue Cases Over the 6 years of Follow-up of the Tetravalent Dengue Vaccine (CYD-TDV) Efficacy Trials in Asia and Latin America
Authors: Forrat Rémi , Dayan Gustavo H , DiazGranados Carlos A , Bonaparte Matthew , Laot Thelma , Capeding Maria Rosario , Sanchez Leilani , Coronel Diana Leticia , Reynales Humberto , Chansinghakul Danaya , Hadinegoro Sri Rezeki S , Perroud Ana Paula , Frago Carina , Zambrano Betzana , Machabert Tifany , Wu Yukun , Luedtke Alexander , Price Brenda , Vigne Claire , Haney Owen , Savarino Stephen J , Bouckenooghe Alain , Noriega Fernando
Published: April 2021

Background

CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post hoc analysis assessed hospitalized and severe virologically confirmed dengue (VCD) over the complete 6-year follow-up of 3 CYD-TDV efficacy studies (CYD14, CYD15, and CYD23/CYD57).

Methods

The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years). Baseline dengue serostatus was measured or inferred using several methods. Hospitalized VCD cases were characterized in terms of clinical signs and symptoms and wild-type viremia level. Antibody persistence was assessed up to 5 years after the last injection.

Results

In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over 6 years compared to placebo (HR [95% confidence interval] multiple imputation from month 0 method, .19 [.12–.30] and .15 [.06–.39]; other methods were consistent). Vaccine protection was observed over the different study periods, being highest during the first 2 years. Evidence for a decreased risk of hospitalized and severe VCD was also observed in seropositive participants aged 6–8 years. Clinical signs and symptoms, and quantified dengue viremia from participants with hospitalized VCD were comparable between groups.

Conclusions

CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire 6-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6–8 year-olds.

Clinical Trials Registration: NCT00842530, NCT01983553, NCT01373281, NCT01374516.
Refractory and Resistant Cytomegalovirus After Hematopoietic Cell Transplant in the Letermovir Primary Prophylaxis Era
Authors: Sassine Joseph , Khawaja Fareed , Shigle Terri Lynn , Handy Victoria , Foolad Farnaz , Aitken Samuel L , Jiang Ying , Champlin Richard , Shpall Elizabeth , Rezvani Katy , Ariza-Heredia Ella J , Chemaly Roy F
Published: April 2021

Background

Cytomegalovirus (CMV) reactivation is one of the most common infectious complications after allogeneic hematopoietic cell transplant (HCT) and may result in significant morbidity and mortality. Primary prophylaxis with letermovir demonstrated a reduction in clinically significant CMV infections (CS-CMVi) in clinical trials of CMV-seropositive HCT recipients. This study aims at exploring the effect of primary letermovir prophylaxis in this population on the incidence and outcomes of refractory or resistant CMV infections.

Methods

This is a single-center, retrospective cohort study of 537 consecutive CMV-seropositive allogeneic HCT recipients cared for between March 2016 and October 2018. Baseline demographics, HCT characteristics, CMV infections, treatment, and mortality data were collected from the electronic medical record. CMV outcomes were defined according to the recently standardized definitions for clinical trials. Characteristics and outcomes were assessed according to receipt of primary letermovir prophylaxis.

Results

Of 537 patients identified, 123 received letermovir for primary prophylaxis during the first 100 days after HCT; 414 did not. In a multivariate analysis, primary prophylaxis with letermovir was associated with reductions in CS-CMVi (hazard ratio [HR] 0.26; 95% confidence interval [CI], 0.16–0.41), CMV end-organ disease (HR 0.23; 95% CI, 0.10–0.52), refractory or resistant CMV infection (HR 0.15; 95% CI, 0.04–0.52), and nonrelapse mortality at week 48 (HR 0.55; 95% CI, 0.32–0.93). There was neither resistant CMV nor CMV-related mortality in the primary letermovir prophylaxis group.

Conclusions

Primary letermovir prophylaxis effectively prevents refractory or resistant CMV infections and decreases nonrelapse mortality at week 48, as well as CS-CMVi and CMV disease after allogeneic HCT.
Agricultural pesticides and ectoparasites: potential combined effects on the physiology of a declining aerial insectivore
Authors: Sigouin Audrey , Bélisle Marc , Garant Dany , Pelletier Fanie
Published: April 2021

Agricultural pesticides usage has been increasing globally. These compounds have been developed to disrupt pest species physiology, but because their specificity is limited, they can also have adverse effects on non-target organisms. Recent studies have shown that the damaging toxicological effects of pesticides can be amplified in stressful environments. However, few studies have documented these effects in natural settings where organisms are simultaneously exposed to pesticides and to other environmental stressors such as parasites. In this study, we assessed both pesticide and ectoparasite effects on the physiology of a free-ranging bird. We measured physiological markers including haematocrit, bacteria-killing ability (BKA) and leucocyte counts, as well as exposure to haematophagous Protocalliphora larvae, in tree swallow nestlings (Tachycineta bicolor), a declining aerial insectivore, in southern Québec, Canada, for over 3 years. We found that combined exposure to pesticides and Protocalliphora larvae was negatively related to haematocrit, suggesting possible synergistic effects. However, we found no such relationships with BKA and leucocyte counts, highlighting the complexity of physiological responses to multiple stressors in natural settings. Populations of several aerial insectivores are declining, and although sublethal pesticide effects on physiology are suspected, our results suggest that exposure to other factors, such as parasitism, should also be considered to fully assess these effects, especially because pesticides are increasingly present in the environment.
Neuroprotective strategies in acute aortic dissection: an analysis of the UK National Adult Cardiac Surgical Audit
Authors: Benedetto Umberto , Dimagli Arnaldo , Cooper Graham , Uppal Rakesh , Mariscalco Giovanni , Krasopoulos George , Goodwin Andrew , Trivedi Uday , Kendall Simon , Sinha Shubhra , Fudulu Daniel , Angelini Gianni D , Tsang Geoffrey , Akowuah Enoch ,   the UK Aortic Surgery
Published: April 2021

OBJECTIVES

The risk of brain injury following surgery for type A aortic dissection (TAAD) remains substantial and no consensus has still been reached on which neuroprotective technique should be preferred. We aimed to investigate the association between neuroprotective strategies and clinical outcomes following TAAD repair.

METHODS

Using the UK National Adult Cardiac Surgical Audit, we identified 1929 patients undergoing surgery for TAAD (2011–2018). Deep hypothermic circulatory arrest (DHCA) only, unilateral (uACP), bilateral antegrade cerebral perfusion (bACP) and retrograde cerebral perfusion were used in 830, 117, 760 and 222 patients, respectively. The primary end point was a composite of death and/or cerebrovascular accident (CVA). Generalized linear mixed model was used to adjust the effect of neuroprotective strategies for other confounders.

RESULTS

The use of bACP was associated with longer circulatory arrest (CA) compared to other strategies. There was a trend towards lower incidence of death and/or CVA using uACP only for shorter CA. In particular, primary end point rate was 27.7% overall and 26.5%, 12.5%, 28.0% and 22.9% for CA <30 min and 28.6%, 30.4%, 33.3% and 33.0% for CA ≥30 min with DHCA only, uACP, bACP and retrograde cerebral perfusion, respectively. The use of DHCA only was associated with five-fold [odds ratio (OR) 5.35, 95% confidence interval (CI) 1.36–21.02] and two-fold (OR 1.77, 95% CI 1.01–3.09) increased risk of death and/or CVA compared to uACP and bACP, respectively, but the effect of uACP was significantly associated with CA duration (hazard ratio 0.97, 95% CI 0.94–0.99; P = 0.04).

CONCLUSIONS

In TAAD repair, the use of uACP and bACP was associated with a lower adjusted risk of death and/or CVA when compared to DHCA. uACP can offer some advantage but only for a shorter CA duration.
Aerobic growth physiology ofSaccharomyces cerevisiaeon sucrose is strain-dependent
Authors: Rodrigues Carla Inês Soares , Wahl Aljoscha , Gombert Andreas K
Published: April 2021

Present knowledge on the quantitative aerobic physiology of the yeast Saccharomyces cerevisiae during growth on sucrose as sole carbon and energy source is limited to either adapted cells or to the model laboratory strain CEN.PK113-7D. To broaden our understanding of this matter and open novel opportunities for sucrose-based biotechnological processes, we characterized three strains, with distinct backgrounds, during aerobic batch bioreactor cultivations. Our results reveal that sucrose metabolism in S. cerevisiae is a strain-specific trait. Each strain displayed distinct extracellular hexose concentrations and invertase activity profiles. Especially, the inferior maximum specific growth rate (0.21 h-1) of the CEN.PK113-7D strain, with respect to that of strains UFMG-CM-Y259 (0.37 h-1) and JP1 (0.32 h-1), could be associated to its low invertase activity (0.04–0.09 U/mgDM). Moreover, comparative experiments with glucose or fructose alone, or in combination, suggest mixed mechanisms of sucrose utilization by the industrial strain JP1, and points out the remarkable ability of the wild isolate UFMG-CM-259 to grow faster on sucrose than on glucose in a well-controlled cultivation system. This work hints to a series of metabolic traits that can be exploited to increase sucrose catabolic rates and bioprocess efficiency.
Intrinsic non-uniqueness of the acoustic full waveform inverse problem
Authors: Lyu Chao , Capdeville Yann , Al-Attar David , Zhao Liang
Published: April 2021

In the context of seismic imaging, full waveform inversion (FWI) is increasingly popular. Because of its lower numerical cost, the acoustic approximation is often used, especially at the exploration geophysics scale, both for tests and for real data. Moreover, some research domains such as helioseismology face true acoustic media for which FWI can be useful. In this work, an argument that combines particle relabelling and homogenization is used to show that the general acoustic inverse problem based on band-limited data is intrinsically non-unique. It follows that the results of such inversions should be interpreted with caution. To illustrate these ideas, we consider 2-D numerical FWI examples based on a Gauss–Newton iterative inversion scheme and demonstrate effects of this non-uniqueness in the local optimization context.
Seismic event detection in urban Singapore using a nodal array and frequency domain array detector: earthquakes, blasts and thunderquakes
Authors: Lythgoe Karen , Loasby Aidan , Hidayat Dannie , Wei Shengji
Published: April 2021

Detection of seismic events at or below the noise level is enabled by the use of dense arrays of receivers and corresponding advances in data analysis methods. It is not only important to detect tectonic events, but also events from man-made, non-earthquake sources and events that originate from coupling between the solid Earth and the atmosphere. In urban environments with high ambient noise levels the effectiveness of event detection methods is unclear, particularly when deployment restrictions result in an irregular receiver array geometry. Here, we deploy a dense nodal array for 1 month in the highly populated city state of Singapore. We develop a new detection method based on image processing that we call spectrogram stacking, which detects anomalous, coherent spectral energy across the array. It simultaneously detects multiple classes of signal with differing spectral content and aids event classification, so it is particularly useful for signal exploration when signal characteristics are unknown. Our approach detects more local events compared to the traditional short-term average over long-term average and waveform similarity methods, while all methods detect similar numbers of teleseismic and regional earthquakes. Local events are principally man-made non-earthquake sources, with several events from the same location exhibiting repeating waveforms. The closest earthquake occurs in peninsular Malaysia, in an area where no earthquakes have previously been detected. We also detect ground motion over a wide frequency range from discrete thunder events that show complex coupling between acoustic and elastic wavefield propagation. We suggest that care should be taken deciphering local high-frequency tectonic events in areas prone to thunder storms.
Dahaan: a framework for delivering evidence-informed dentistry recommendations and dental public health advocacy in Iran
Authors: Sofi-Mahmudi Ahmad , Moradi Sara , Shakiba Maryam , Iranparvar Pouria , Sadr Soroush
Published: April 2021

Although health is mostly determined by socio-political factors, the need for providing reliable health recommendations to the public should not be neglected. There has been a considerable void in delivering evidence-informed oral health recommendations in Iran; whilst there is a significant gap in oral health knowledge among socioeconomic classes, recommendations are neither fully compatible with each other nor up-to-date. To fill in this void, we started Dahaan (meaning “mouth” in Persian) with the aim of providing the latest easily accessed evidence-informed dentistry recommendations and advocating dental public health in the Iranian community. In this paper, we as the authors present the performance and achievements of this group, which is a member of the NCD Alliance and the Informed Health Choices project with a reasonable number of readers across the country, and illustrate the way ahead towards our goals.
Longitudinal Assessment of SARS-CoV-2 Antinucleocapsid and Antispike-1-RBD Antibody Testing Following PCR-Detected SARS-CoV-2 Infection
Authors: El-Khoury Joe M , Schulz Wade L , Durant Thomas J S
Published: April 2021

Background

SARS-CoV-2 serologic assays are becoming increasingly available and may serve as a diagnostic aid in a multitude of settings relating to past infection status. However, there is limited literature detailing the longitudinal performance of EUA-cleared serologic assays in US populations, particularly in cohorts with a remote history of PCR-confirmed SARS-CoV-2 infection (e.g., >2 months).

Methods

We evaluated the diagnostic sensitivities and specificities of the Elecsys® Anti-SARS-CoV-2 (anti-N) and Elecsys Anti-SARS-CoV-2 S (anti-S1-RBD) assays, using 174 residual clinical samples up to 267 days post-PCR diagnosis of SARS-CoV-2 infection (n = 154) and a subset of samples obtained prior to the COVID-19 pandemic as negative controls (n = 20).

Results

The calculated diagnostic sensitivities for the anti-N and anti-S1-RBD assays were 89% and 93%, respectively. Of the 154 samples in the SARS-CoV-2-positive cohort, there were 6 discrepant results between the anti-N and anti-S1-RBD assays, 5 of which were specimens collected ≥200 days post-PCR positivity and only had detectable levels of anti-S1-RBD antibodies. When only considering specimens collected ≥100 days post-PCR positivity (n = 41), the sensitivities for the anti-N and anti-S1-RBD assays were 85% and 98%, respectively.

Conclusions

The anti-S1-RBD assay demonstrated superior sensitivity at time points more remote to the PCR detection date, with 6 more specimens from the SARS-CoV-2-positive cohort detected, 5 of which were collected more than 200 days post-PCR positivity. While analytical differences and reagent lot-to-lot variability are possible, this may indicate that, in some instances, anti-S1-RBD antibodies may persist longer in vivo and may be a better target for detecting remote SARS-CoV-2 infection.
Validation of the Thermo Scientific™ SARS-CoV-2 RT-PCR Detection Workflow for the Detection of SARS-CoV-2 from Stainless-Steel Environmental Surface Swabs: AOAC Performance Tested MethodSM 012103
Authors: Stephenson Patrick , Crabtree David , Evans Katharine , Salavirta Heikki , Brzoska Pius , Leonte Ana-Maria , Manolis Amanda , Sohier Daniele
Published: April 2021

Background

The Thermo Scientific™ SARS-CoV-2 reverse transcription–polymerase chain reaction (RT-PCR) Detection Workflow, packaged with Applied Biosystems™ TaqMan™ 2019-nCoV Assay Kit v1 targets three different SARS-CoV-2 genomic regions in a single RT-PCR reaction.

Objective

To validate the Thermo Scientific SARS-CoV-2 RT-PCR Workflow, for the detection of SARS-CoV-2 virus on stainless-steel surfaces as part of the AOAC Performance Tested MethodSM Emergency Response Validation program.

Method

The Applied Biosystems TaqMan 2019-nCoV Assay Kit v1, as part of the Thermo Scientific SARS-CoV-2 RT-PCR Workflow, was evaluated for specificity using in silico analysis of 15 764 SARS-CoV-2 sequences and 65 exclusivity organisms. The Thermo Scientific SARS-CoV-2 RT-PCR Workflow was evaluated in an unpaired study for one environmental surface (stainless steel) and compared to the U.S. Centers for Disease Control and Prevention 2019-Novel Coronavirus RT-PCR Diagnostic Panel, Instructions for Use (Revision 4, Effective 6/12/2020).

Results

In silico analysis showed that, of the 15 756 target SARS-CoV-2 genomes analyzed, 99% of the strains/isolates are perfectly matched to at least two of the three assays, and more than 90% have 100% homology to all three assays (ORF1ab, N-gene, S-gene) in the SARS-CoV-2 Kit. None of the 65 non-target strain genomes analyzed showed matching sequences. In the matrix study, the Thermo Scientific SARS-CoV-2 workflow showed comparable detection to the centers of disease control and prevention (CDC) method.

Conclusions

The Thermo Scientific SARS-CoV-2 RT-PCR Workflow is an effective procedure for detection of RNA from SARS-CoV-2 virus from stainless steel.

Highlights

The workflow provides equivalent performance results with the two tested RNA extraction platforms and the two tested RT-PCR instruments.
Natural diet of the endemic freshwater crab Aegla castro Schmitt, 1942 (Decapoda: Anomura: Aeglidae)
Authors: de Almeida Karin C R , Moreira João M N C , Páez Fernanda P , Marçal Ingrid C , Teixeira Gustavo M
Published: April 2021

We characterized the natural diet and feeding dynamics of Aegla castroSchmitt, 1942 (Aeglidae), an endemic freshwater crab. Research was undertaken on the trophic spectrum of the species by analyzing the stomach contents of individuals collected in a stream in southeastern Brazil, and evaluating the diet through the index of relative importance (IRI). Seasonal and circadian variations in diet composition were analyzed, and the feeding dynamics investigated through repletion index (RI) analysis. We analyzed a total of 240 stomachs and identified 20 main food categories of the diet, which were studied throughout the seasons. Aegla castro maintained a constant RI throughout the year, with a peak of food activity between midnight (00) and 0600. The species was characterized as an omnivorous generalist and opportunist. The high overlay in the diet composition of adults of both sexes and juveniles indicates that they share the same food resources, even though they seem to exploit them in different quantities and frequencies. Future research should focus on the species of Aegla whose diets have not yet been described, and use available data to inform trophic network analyses and models.
Histopathological atlas of desmoplastic reaction characterization in colorectal cancer
Authors: Ueno Hideki , Kajiwara Yoshiki , Ajioka Yoich , Sugai Tamotsu , Sekine Shigeki , Ishiguro Megumi , Takashima Atsuo , Kanemitsu Yukihide
Published: April 2021

Emergent scientific evidence indicates the central role of cancer-associated fibroblasts in determining whether the microenvironment of cancer works as friend or foe of the host; however, there is no unified histological evaluation framework of fibrotic stroma in colorectal cancers. Myxoid stroma and keloid-like collagen are site-specific histopathological features generated by cancer-associated fibroblasts, which appear exclusively in the tumor front during desmoplastic reaction. On the basis of these two stromal components, desmoplastic reaction is categorized into three patterns—immature, intermediate and mature—using hematoxylin and eosin staining. In January 2020, a prospective randomized clinical trial, JCOG1805, to elucidate the value of adjuvant chemotherapy in stage II colorectal cancer patients with pathological risk factors of recurrence was launched in Japan, in which intermediate/immature desmoplastic reaction is one of the four risk factors selected as inclusion criteria. This paper covers the diagnostic criteria for the desmoplastic reaction classification being used in the JCOG1805 study.
Comparative Effectiveness of Digital Breast Tomosynthesis for Breast Cancer Screening Among Women 40-64 Years Old
Authors: Richman Ilana B , Long Jessica B , Hoag Jessica R , Upneja Akhil , Hooley Regina , Xu Xiao , Kunst Natalia , Aminawung Jenerius A , Kyanko Kelly A , Busch Susan H , Gross Cary P
Published: April 2021

Background

Digital breast tomosynthesis (DBT) may have a higher cancer detection rate and lower recall compared with 2-dimensional (2 D) mammography for breast cancer screening. The goal of this study was to evaluate screening outcomes with DBT in a real-world cohort and to characterize the population health impact of DBT as it is widely adopted.

Methods

This observational study evaluated breast cancer screening outcomes among women screened with 2 D mammography vs DBT. We used deidentified administrative data from a large private health insurer and included women aged 40-64 years screened between January 2015 and December 2017. Outcomes included recall, biopsy, and incident cancers detected. We used 2 complementary techniques: a patient-level analysis using multivariable logistic regression and an area-level analysis evaluating the relationship between population-level adoption of DBT use and outcomes. All statistical tests were 2-sided.

Results

Our sample included 7 602 869 mammograms in 4 580 698 women, 27.5% of whom received DBT. DBT was associated with modestly lower recall compared with 2 D mammography (113.6 recalls per 1000 screens, 99% confidence interval [CI] = 113.0 to 114.2 vs 115.4, 99% CI = 115.0 to 115.8, P < .001), although younger women aged 40-44 years had a larger reduction in recall (153 recalls per 1000 screens, 99% CI = 151 to 155 vs 164 recalls per 1000 screens, 99% CI = 163 to 166, P < .001). DBT was associated with higher biopsy rates than 2 D mammography (19.6 biopsies per 1000 screens, 99% CI = 19.3 to 19.8 vs 15.2, 99% CI = 15.1 to 15.4, P < .001) and a higher cancer detection rate (4.9 incident cancers per 1000 screens, 99% CI = 4.7 to 5.0 vs 3.8, 99% CI = 3.7 to 3.9, P < .001). Point estimates from the area-level analysis generally supported these findings.

Conclusions

In a large population of privately insured women, DBT was associated with a slightly lower recall rate than 2 D mammography and a higher cancer detection rate. Whether this increased cancer detection improves clinical outcomes remains unknown.
Wedding of Molecular Alterations and Immune Checkpoint Blockade: Genomics as a Matchmaker
Authors: Fountzilas Elena , Kurzrock Razelle , Vo Henry Hiep , Tsimberidou Apostolia-Maria
Published: April 2021

The development of checkpoint blockade immunotherapy has transformed the medical oncology armamentarium. But despite its favorable impact on clinical outcomes, immunotherapy benefits only a subset of patients, and a substantial proportion of these individuals eventually manifest resistance. Serious immune-related adverse events and hyperprogression have also been reported. It is therefore essential to understand the molecular mechanisms and identify the drivers of therapeutic response and resistance. In this review, we provide an overview of the current and emerging clinically relevant genomic biomarkers implicated in checkpoint blockade outcome. US Food and Drug Administration–approved molecular biomarkers of immunotherapy response include mismatch repair deficiency and/or microsatelliteinstability and tumor mutational burden of at least 10 mutations/megabase. Investigational genomic-associated biomarkers for immunotherapy response include alterations of the following genes/associated pathways: chromatin remodeling (ARID1A, PBRM1, SMARCA4, SMARCB1, BAP1), major histocompatibility complex, specific (eg, ultraviolet, APOBEC) mutational signatures, T-cell receptor repertoire, PDL1, POLE/POLD1, and neo-antigens produced by the mutanome, those potentially associated with resistance include β2-microglobulin, EGFR, Keap1, JAK1/JAK2/interferon-gamma signaling, MDM2, PTEN, STK11, and Wnt/Beta-catenin pathway alterations. Prospective clinical trials are needed to assess the role of a composite of these biomarkers to optimize the implementation of precision immunotherapy in patient care.
Excision of an unusual tumour of oncocytic origin: a case report
Authors: Howden William B , Gunaratne Dakshika A , Gallagher Richard M
Published: April 2021

This case presents a 46-year-old woman presented with a 5-month history of a gradually enlarging, non-painful swelling her right medial canthus, with magnetic resonance imaging demonstrating a large tumour of her lacrimal sac. The lesion was subsequently excised and the histopathological diagnosis made of a rare primary oncocytoma of the lacrimal sac.
MYB transcription factors GmMYBA2 and GmMYBR function in a feedback loop to control pigmentation of seed coat in soybean
Authors: Gao Ruifang , Han Taotao , Xun Hongwei , Zeng Xiangsheng , Li Penghui , Li Yueqing , Wang Yanan , Shao Yan , Cheng Xin , Feng Xianzhong , Zhao Jian , Wang Li , Gao Xiang
Published: April 2021

Soybean has undergone extensive selection pressures for seed nutrient composition and seed color during domestication, but the major genetic loci controlling seed coat color have not been completely understood, and the transcriptional regulation relationship among the loci remains elusive. Here, two major regulators, GmMYBA2 and GmMYBR, were functionally characterized as an anthocyanin activator and repressor, respectively. Ectopic expression of GmMYBA2 in soybean hairy roots conferred the enhanced accumulation of delphinidin and cyanidin types of anthocyanins in W1t and w1T backgrounds, respectively, through activating anthocyanin biosynthetic genes in the reported loci. The seed coat pigmentation of GmMYBA2-overexpressing transgenic plants in the W1 background mimicked the imperfect black phenotype (W1/w1, i, R, t), suggesting that GmMYBA2 was responsible for the R locus. Molecular and biochemical analysis showed that GmMYBA2 interacted with GmTT8a to directly activate anthocyanin biosynthetic genes. GmMYBA2 and GmMYBR might form a feedback loop to fine-tune seed coat coloration, which was confirmed in transgenic soybeans. Both GmTT8a and GmMYBR that were activated by GmMYBA2 in turn enhanced and obstructed the formation of the GmMYBA2–GmTT8a module, respectively. The results revealed the sophisticated regulatory network underlying the soybean seed coat pigmentation loci and shed light on the understanding of the seed coat coloration and other seed inclusions.
Transcriptomic, proteomic, and physiological studies reveal key players in wheat nitrogen use efficiency under both high and low nitrogen supply
Authors: Meng Xiaodan , Wang Xiaochun , Zhang Zhiyong , Xiong Shuping , Wei Yihao , Guo Jianbiao , Zhang Jie , Wang Lulu , Ma Xinming , Tegeder Mechthild
Published: April 2021

The effective use of available nitrogen (N) to improve crop grain yields provides an important strategy to reduce environmental N pollution and promote sustainable agriculture. However, little is known about the common genetic basis of N use efficiency (NUE) at varying N availability. Two wheat (Triticum aestivum L.) cultivars were grown in the field with high, moderate, and low N supply. Cultivar Zhoumai 27 outperformed Aikang 58 independent of the N supply and showed improved growth, canopy leaf area index, flag leaf surface area, grain number, and yield, and enhanced NUE due to both higher N uptake and utilization efficiency. Further, transcriptome and proteome analyses were performed using flag leaves that provide assimilates for grain growth. The results showed that many genes or proteins that are up- or down-regulated under all N regimes are associated with N and carbon metabolism and transport. This was reinforced by cultivar differences in photosynthesis, assimilate phloem transport, and grain protein/starch yield. Overall, our study establishes that improving NUE at both high and low N supply requires distinct adjustments in leaf metabolism and assimilate partitioning. Identified key genes/proteins may individually or concurrently regulate NUE and are promising targets for maximizing crop NUE irrespective of the N supply.
Modelling synchrotron self-Compton and Klein–Nishina effects in gamma-ray burst afterglows
Authors: Jacovich Taylor E , Beniamini Paz , van der Horst Alexander J
Published: April 2021

We present an implementation of a self-consistent way of modelling synchrotron self-Compton (SSC) effects in gamma-ray burst afterglows, with and without approximated Klein–Nishina suppressed scattering for the afterglow modelling code boxfit, which is currently based on pure synchrotron emission. We discuss the changes in spectral shape and evolution due to SSC effects, and comment on how these changes affect physical parameters derived from broad-band modelling. We show that SSC effects can have a profound impact on the shape of the X-ray light curve using simulations including these effects. This leads to data that cannot be simultaneously fit well in both the X-ray and radio bands when considering synchrotron-only fits, and an inability to recover the correct physical parameters, with some fitted parameters deviating orders of magnitude from the simulated input parameters. This may have a significant impact on the physical parameter distributions based on previous broad-band modelling efforts.
The rare X-ray flaring activity of the ultraluminous X-ray source NGC 4559 X7
Authors: Pintore Fabio , Motta S , Pinto C , Bernardini M G , Rodriguez-Castillo G , Salvaterra R , Israel G L , Esposito P , Ambrosi E , Salvaggio C , Zampieri L , Wolter A
Published: April 2021

Ultraluminous X-ray sources are considered amongst the most extremely accreting objects in the local Universe. The recent discoveries of pulsating neutron stars in ULXs strengthened the scenario of highly super-Eddington accretion mechanisms on stellar mass compact objects. In this work, we present the first long-term light curve of the source NGC 4559 X7 using all the available Swift/XRT, XMM–Newton, Chandra, and NuSTAR data. Because of the high quality 2019 XMM–Newton and NuSTAR observations, we investigated in an unprecedented way the spectral and temporal properties of NGC 4559 X7. The source displayed flux variations of up to an order of magnitude and an unusual flaring activity. We modelled the spectra from NGC 4559 X7 with a combination of two thermal components, testing also the addition of a further high energy cut-off power law. We observed a spectral hardening associated with a luminosity increase during the flares, and a spectral softening in the epochs far from the flares. Narrow absorption and emission lines were also found in the RGS spectra, suggesting the presence of an outflow. Furthermore, we measured hard and (weak) soft lags with magnitudes of a few hundreds of seconds whose origin is possibly due to the accretion flow. We interpret the source properties in terms of a super-Eddington accretion scenario assuming the compact object is either a light stellar mass black hole or a neutron star.
Large dust fractions can prevent the propagation of soundwaves
Authors: David-Cléris Timothée , Laibe Guillaume
Published: April 2021

Dust plays a central role in several astrophysical processes. Hence, the need of dust/gas numerical solutions, and analytical problems to benchmark them. In the seminal dustywave problem, we discover a regime where sound waves cannot propagate through the mixture above a large critical dust fraction. We characterize this regime analytically, making it of use for testing accuracy of numerical solvers at large dust fractions.
Physical origin of the non-physical spin evolution of MAXI J1820 + 070
Authors: Guan J , Tao L , Qu J L , Zhang S N , Zhang W , Zhang S , Ma R C , Ge M Y , Song L M , Lu F J , Li T P , Xu Y P , Chen Y , Cao X L , Liu C Z , Zhang L , Wang Y N , Chen Y P , Bu Q C , Cai C , Chang Z , Chen L , Chen T X , Chen Y B , Cui W W , Du Y Y , Gao G H , Gao H , Gu Y D , Guo C C , Han D W , Huang Y , Huo J , Jia S M , Jiang W C , Jin J , Kong L D , Li B , Li C K , Li G , Li W , Li X , Li X B , Li X F , Li Z W , Liang X H , Liao J Y , Liu B S , Liu H W , Liu H X , Liu X J , Lu X F , Luo Q , Luo T , Ma X , Meng B , Nang Y , Nie J Y , Ou G , Ren X Q , Sai N , Song X Y , Sun L , Tan Y , Wang C , Wang L J , Wang P J , Wang W S , Wang Y S , Wen X Y , Wu B B , Wu B Y , Wu M , Xiao G C , Xiao S , Xiong S L , Yang R J , Yang S , Yang Y J , Yang Y J , Yi Q B , Yin Q Q , You Y , Zhang F , Zhang H M , Zhang J , Zhang P , Zhang W C , Zhang Y F , Zhang Y H , Zhao H S , Zhao X F , Zheng S J , Zheng Y G , Zhou D K
Published: April 2021

We report on the Insight-HXMT observations of the new black hole X-ray binary MAXI J1820+070 during its 2018 outburst. Detailed spectral analysis via the continuum fitting method shows an evolution of the inferred spin during its high soft sate. Moreover, the hardness ratio, the non-thermal luminosity and the reflection fraction also undergo an evolution, exactly coincident to the period when the inferred spin transition takes place. The unphysical evolution of the spin is attributed to the evolution of the inner disc, which is caused by the collapse of a hot corona due to condensation mechanism or may be related to the deceleration of a jet-like corona. The studies of the inner disc radius and the relation between the disc luminosity and the inner disc radius suggest that, only at a particular epoch, did the inner edge of the disc reach the innermost stable circular orbit and the spin measurement is reliable. We then constrain the spin of MAXI J1820 + 070 to be $a_*=0.2^{+0.2}_{-0.3}$. Such a slowly spinning black hole possessing a strong jet suggests that its jet activity is driven mainly by the accretion disc rather than by the black hole spin.
Impact of CYP2A6 Activity on Nicotine Reinforcement and Cue-Reactivity in Daily Smokers
Authors: Butler Kevin , Chenoweth Meghan J , El-Boraie Ahmed , Giratallah Haidy , Kowalczyk William J , Heishman Stephen J , Tyndale Rachel F , Le Foll Bernard
Published: April 2021

Introduction

Variation in CYP2A6, the primary enzyme responsible for nicotine metabolism, is associated with nicotine dependence, cigarette consumption, and abstinence outcomes in smokers. The impact of CYP2A6 activity on nicotine reinforcement and tobacco cue-reactivity, mechanisms that may contribute to these previous associations, has not been fully evaluated.

Aims and Methods

CYP2A6 activity was indexed using 3 genetic approaches in 104 daily smokers completing forced-choice and cue-induced craving tasks assessing nicotine reinforcement and tobacco cue-reactivity, respectively. First, smokers were stratified by the presence or absence of reduced/loss-of-function CYP2A6 gene variants (normal vs. reduced metabolizers). As nicotine metabolite ratio (NMR) is a reliable biomarker of CYP2A6 activity, our second and third approaches used additional genetic variants identified in genome-wide association studies of NMR to create a weighted genetic risk score (wGRS) to stratify smokers (fast vs. slow metabolizers) and calculate a wGRS-derived NMR.

Results

Controlling for race and sex, normal metabolizers (vs. reduced) selected a greater proportion of puffs from nicotine-containing cigarettes (vs. denicotinized) on the forced-choice task (p = .031). In confirmatory analyses, wGRS-based stratification (fast vs. slow metabolizers) produced similar findings. Additionally, wGRS-derived NMR, which correlated with actual NMR assessed in a subset of participants (n = 55), was positively associated with the proportion of puffs from nicotine-containing cigarettes controlling for race and sex (p = .015). None of the CYP2A6 indices were associated with tobacco cue-reactivity in minimally deprived smokers.

Conclusions

Findings suggest increased nicotine reinforcement is exhibited by smokers with high CYP2A6 activity, which may contribute to heavier smoking and poorer cessation outcomes previously reported in faster metabolizers.

Implications

CYP2A6 activity is a key determinant of smoking behavior and outcomes. Therefore, these findings support the targeting of CYP2A6 activity, either therapeutically or as a clinically relevant biomarker in a precision medicine approach, for tobacco use disorder treatment.
Circadian Clock inArabidopsis thalianaDetermines Flower Opening Time Early in the Morning and Dominantly Closes Early in the Afternoon
Authors: Muroya Mitsuhiko , Oshima Haruka , Kobayashi Shoko , Miura Aya , Miyamura Yohei , Shiota Hajime , Onai Kiyoshi , Ishiura Masahiro , Manabe Katsushi , Kutsuna Shinsuke
Published: April 2021

Many plant species exhibit diurnal flower opening and closing, which is an adaptation influenced by the lifestyle of pollinators and herbivores. However, it remains unclear how these temporal floral movements are modulated. To clarify the role of the circadian clock in flower movement, we examined temporal floral movements in Arabidopsis thaliana. Wild-type (accessions; Col-0, Ler-0 and Ws-4) flowers opened between 0.7 and 1.4 h in a 16-h light period and closed between 7.5 and 8.3 h in a diurnal light period. In the arrhythmic mutants pcl1-1 and prr975, the former flowers closed slowly and imperfectly and the latter ones never closed. Under continuous light conditions, new flowers emerged and opened within a 23–26 h window in the wild-type, but the flowers in pcl1-1 and prr975 developed straight petals, whose curvatures were extremely small. Anti-phasic circadian gene expression of CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), LATE ELONGATED HYPOCOTYLE (LHY) and TIMING OF CAB EXPRESSION 1 (TOC1) occurred in wild-type flowers, but non-rhythmic expression was observed in pcl1-1 and prr975 mutants. Focusing on excised petals, bioluminescence monitoring revealed rhythmic promoter activities of genes expressed (CCA1, LHY and PHYTOCLOCK 1/LUX ARRHYTHMO, PCL1/LUX) in the morning and evening. These results suggest that the clock induces flower opening redundantly with unknown light-sensing pathways. By contrast, flower closing is completely dependent on clock control. These findings will lead to further exploration of the molecular mechanisms and evolutionary diversity of timing in flower opening and closing.
Quantification of morning stiffness to assess disease activity and treatment effects in rheumatoid arthritis
Authors: Boeth Heide , Biesen Robert , Hollnagel Jeremias , Herrmann Sandra , Ehrig Rainald M , Pelli Lorenzo , Taylor William R , Duda Georg N , Buttgereit Frank
Published: April 2021

Objectives

The clinical parameter of morning stiffness is widely used to assess the status of RA, but its accurate quantitative assessment in a clinical setting has not yet been successful. This lack of individual quantification limits both personalized medication and efficacy evaluation in the treatment of RA.

Methods

We developed a novel technology to assess passive resistance of the MCP III joint (stiffness) and its passive range of motion (PRoM). Within this pilot study, 19 female postmenopausal RA patients and 9 healthy controls were examined in the evening as well as the morning of the following day. To verify the specificity of the biomechanical quantification, 11 patients with RA were assessed both prior to and ∼3 h after glucocorticoid therapy.

Results

While the healthy controls showed only minor changes between afternoon and morning, in RA patients the mean PRoM decreased significantly by 18% (s.d. 22) and stiffness increased significantly by 20% (s.d. 18) in the morning compared with the previous afternoon. We found a significant positive correlation between RA activity and biomechanical measures. Glucocorticoids significantly increased the mean PRoM by 16% (s.d. 11) and reduced the mean stiffness by 23% (s.d. 22).

Conclusion

This technology allowed mechanical stiffness to be quantified in MCP joints and demonstrated high sensitivity with respect to disease status as well as medication effect in RA patients. Such non-invasive, low-risk and rapid assessment of biomechanical joint stiffness opens a novel avenue for judging therapy efficacy in patients with RA and potentially also in other non-RA inflammatory joint diseases.
Genome Sequence Resource for Stagonosporopsis cucurbitacearum, a Cause of Gummy Stem Blight Disease of Watermelon
Authors: Wang Fahao , Qi Jiahui , Tian Miao , Gao Yizhou , Xiong Xiaohui , Wang Jiajing , Song Fengming , Li Dayong
Published: April 2021

Gummy stem blight (GSB), which is caused by three related species of Stagonosporopsis, is a worldwide devastating disease of cucurbit crops including watermelon. Previously S. cucurbitacearum was reported to be the major fungal cause of watermelon GSB in Southern China, where it causes a significant decrease in watermelon yield. Here, we present the draft whole genome sequence, gene prediction and annotation of S. cucurbitacearum strain DBTL4, isolated from diseased watermelon plants. To our knowledge, this is the first publicly available genome sequence of this species, and knowledge of this genome sequence will help further understand the pathogenic mechanism of S. cucurbitacearum to cucurbit plants.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
High-Quality Genome Sequence Resource for Fusarium andiyazi Causing Pokkah Boeng Disease of Sugarcane in China
Authors: Bao Yixue , Pan Kaiyuan , Khan Muhammad Tahir , Chen Baoshan , Zhang Muqing
Published: April 2021

Sugarcane pokkah boeng disease (PBD) is emerging as a prevalent foliar disease in China. This airborne disease is caused by the Fusarium species complex. To investigate the diversity and evolution of Fusarium spp., we performed whole-genome sequencing of Fusarium andiyazi YN28 using a combination of Oxford Nanopore and Illumina technology. The F. andiyazi YN28 genome was sequenced, assembled, and annotated. A high-quality genome was assembled into 24 contigs with an N50 of 2.80 Mb. The genome assembly generated a total size of 44.1 Mb with a GC content of 47.64%. In total, 15,508 genes were predicted, including 794 genes related to the carbohydrate-active enzymes, 397 noncoding RNA, 155 genes associated with transporter classification, 4,550 genes linked to pathogen–host interactions, and 269 genes involved in effector proteins. Collectively, our results will provide insight into the host–pathogen interactions and will facilitate the breeding of new varieties of sugarcane resistant to PBD.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
VNTR Typing of the Bacterial Rice Pathogen Burkholderia glumae Reveals the Coexistence of Several Diverging Lineages in a Single Field in Colombia
Authors: Béna Gilles , Fory Paola A. , Rico Johanna Echeverri , Mosquera Gloria M.
Published: April 2021

Burkholderia glumae is responsible for the panicle blight disease of rice. This disease is present worldwide and can result in significant drop in yields. To estimate the genetic diversity of the bacterial strains present in a rice paddy field in Colombia, we sampled 109 strains from infected panicles. To detect fine genetic relationships among related haplotypes, and to overcome a very low nucleotide diversity detected in previous studies, we designed primers to amplify and sequence several highly variable minisatellite loci, or variable number tandem repeats (VNTRs), as well as part of the Toxoflavin toxA gene in all strains. Results show that the toxA nucleotide diversity defined four lineages and was similar to that detected in several fields in Japan; data suggest that B. glumae has spread from Asia to America without major loss of genetic diversity, and that five VNTR loci discriminated the strains within the field revealing single and multi-infections of the rice panicles with a wide distribution of the haplotypes among the different plots. Even though disease levels vary considerably from year to year, the bacterial genetic diversity is maintained within a field. We do not detect any geographical structuring within the field, nor any effect of the rice cultivar on the observed diversity. The consequences on the origin and evolution of the bacteria are discussed.