bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal Effects of Air Pollution on Mortality Rate in Massachusetts
Authors: Wei Yaguang , Wang Yan , Wu Xiao , Di Qian , Shi Liuhua , Koutrakis Petros , Zanobetti Antonella , Dominici Francesca , Schwartz Joel D
Published: June 2020

Air pollution epidemiology studies have primarily investigated long- and short-term exposures separately, have used multiplicative models, and have been associational studies. Implementing a generalized propensity score adjustment approach with 3.8 billion person-days of follow-up, we simultaneously assessed causal associations of long-term (1-year moving average) and short-term (2-day moving average) exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5), ozone, and nitrogen dioxide with all-cause mortality on an additive scale among Medicare beneficiaries in Massachusetts (2000–2012). We found that long- and short-term PM2.5, ozone, and nitrogen dioxide exposures were all associated with increased mortality risk. Specifically, per 10 million person-days, each 1-μg/m3 increase in long- and short-term PM2.5 exposure was associated with 35.4 (95% confidence interval (CI): 33.4, 37.6) and 3.04 (95% CI: 2.17, 3.94) excess deaths, respectively; each 1–part per billion (ppb) increase in long- and short-term ozone exposure was associated with 2.35 (95% CI: 1.08, 3.61) and 2.41 (95% CI: 1.81, 2.91) excess deaths, respectively; and each 1-ppb increase in long- and short-term nitrogen dioxide exposure was associated with 3.24 (95% CI: 2.75, 3.77) and 5.60 (95% CI: 5.24, 5.98) excess deaths, respectively. Mortality associated with long-term PM2.5 and ozone exposure increased substantially at low levels. The findings suggested that air pollution was causally associated with mortality, even at levels below national standards.
No acclimation: instantaneous responses to temperature maintain homeostatic photosynthetic rates under experimental warming across a precipitation gradient in Ulmus americana
Authors: Smith Nicholas G , McNellis Risa , Dukes Jeffrey S
Published: June 2020

Past research has shown that plants possess the capacity to alter their instantaneous response of photosynthesis to temperature in response to a longer-term change in temperature (i.e. acclimate). This acclimation is typically the result of processes that influence net photosynthesis (Anet), including leaf biochemical processes such as the maximum rate of Rubisco carboxylation (Vcmax) and the maximum rate of photosynthetic electron transport (Jmax), stomatal conductance (gs) and dark respiration (Rd). However, these processes are rarely examined in the field or in concert with other environmental factors, such as precipitation amount. Here, we use a fully factorial warming (active heating up to +4 °C; mean = +3.1 °C) by precipitation (−50 % ambient to 150 % ambient) manipulation experiment in an old-field ecosystem in the north-eastern USA to examine the degree to which Ulmus americana saplings acclimate through biochemical and stomatal adjustments. We found that rates of Anet at ambient CO2 levels of 400 µmol mol−1 (A400) did not differ across climate treatments or with leaf temperatures from 20 to 30 °C. Canopy temperatures rarely reached above 30 °C in any treatment, suggesting that seasonal carbon assimilation was relatively homeostatic across all treatments. Assessments of the component processes of A400 revealed that decreases in gs with leaf temperature from 20 to 30 °C were balanced by increases in Vcmax, resulting in stable A400 rates despite concurrent increases in Rd. Photosynthesis was not affected by precipitation treatments, likely because the relatively dry year led to small treatment effects on soil moisture. As temperature acclimation is likely to come at a cost to the plant via resource reallocation, it may not benefit plants to acclimate to warming in cases where warming would not otherwise reduce assimilation. These results suggest that photosynthetic temperature acclimation to future warming will be context-specific and that it is important to consider assimilatory benefit when assessing acclimation responses.
IBDkin: fast estimation of kinship coefficients from identity by descent segments
Authors: Zhou Ying , Browning Sharon R , Browning Brian L
Published: June 2020

Motivation

Estimation of pairwise kinship coefficients in large datasets is computationally challenging because the number of related individuals increases quadratically with sample size.

Results

We present IBDkin, a software package written in C for estimating kinship coefficients from identity by descent (IBD) segments. We use IBDkin to estimate kinship coefficients for 7.95 billion pairs of individuals in the UK Biobank who share at least one detected IBD segment with length ≥ 4 cM.

Availability and implementation

https://github.com/YingZhou001/IBDkin.

Supplementary information

Supplementary data are available at Bioinformatics online.
Gene regulation inference from single-cell RNA-seq data with linear differential equations and velocity inference
Authors: Aubin-Frankowski Pierre-Cyril , Vert Jean-Philippe
Published: June 2020

Motivation

Single-cell RNA sequencing (scRNA-seq) offers new possibilities to infer gene regulatory network (GRNs) for biological processes involving a notion of time, such as cell differentiation or cell cycles. It also raises many challenges due to the destructive measurements inherent to the technology.

Results

In this work, we propose a new method named GRISLI for de novo GRN inference from scRNA-seq data. GRISLI infers a velocity vector field in the space of scRNA-seq data from profiles of individual cells, and models the dynamics of cell trajectories with a linear ordinary differential equation to reconstruct the underlying GRN with a sparse regression procedure. We show on real data that GRISLI outperforms a recently proposed state-of-the-art method for GRN reconstruction from scRNA-seq data.

Availability and implementation

The MATLAB code of GRISLI is available at: https://github.com/PCAubin/GRISLI.

Supplementary information

Supplementary data are available at Bioinformatics online.
A rapid and low-cost method for genomic DNA extraction from the cyanobacterium Synechocystis
Authors: Harrison Dale J A , Thompson Elinor P
Published: June 2020

A two-step method is reported for preparation of genomic DNA from the model cyanobacterium Synechocystis that can be performed with minimal equipment and reagents in about an hour. High yields of genetic material can be obtained (200–450 ng/μl) with reasonable purity. A further ethanol precipitation step can be included but is not necessary if template is simply required for polymerase chain reaction (PCR) or digestion. This new protocol is helpful for amplification of genes of interest in early-stage research projects and for low throughput screening of transformants. It is more reliable than colony PCR of Synechocystis cultures, and less involved and cheaper than existing clean-DNA preparation methods. It represents an unusually simple and reliable extraction protocol for the growing body of research making use of this cyanobacterium.
A Māori specific RFC1 pathogenic repeat configuration in CANVAS, likely due to a founder allele
Authors: Beecroft Sarah J , Cortese Andrea , Sullivan Roisin , Yau Wai Yan , Dyer Zoe , Wu Teddy Y , Mulroy Eoin , Pelosi Luciana , Rodrigues Miriam , Taylor Rachael , Mossman Stuart , Leadbetter Ruth , Cleland James , Anderson Tim , Ravenscroft Gianina , Laing Nigel G , Houlden Henry , Reilly Mary M , Roxburgh Richard H
Published: June 2020

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative disease with onset in mid- to late adulthood. The genetic basis for a large proportion of Caucasian patients was recently shown to be the biallelic expansion of a pentanucleotide (AAGGG)n repeat in RFC1. Here, we describe the first instance of CANVAS genetic testing in New Zealand Māori and Cook Island Māori individuals. We show a novel, possibly population-specific CANVAS configuration (AAAGG)10-25(AAGGG)exp, which was the cause of CANVAS in all patients. There were no apparent phenotypic differences compared with European CANVAS patients. Presence of a common disease haplotype among this cohort suggests this novel repeat expansion configuration is a founder effect in this population, which may indicate that CANVAS will be especially prevalent in this group. Haplotype dating estimated the most recent common ancestor at ∼1430 ce. We also show the same core haplotype as previously described, supporting a single origin of the CANVAS mutation.
Tumor protein expression of the DNA repair gene BRCA1 and lethal prostate cancer
Authors: Stopsack Konrad H , Gerke Travis , Zareba Piotr , Pettersson Andreas , Chowdhury Dipanjan , Ebot Ericka M , Flavin Richard , Finn Stephen , Kantoff Philip W , Stampfer Meir J , Loda Massimo , Fiorentino Michelangelo , Mucci Lorelei A
Published: June 2020

DNA repair genes are commonly altered in metastatic prostate cancer, but BRCA1 mutations are rare. Preliminary studies suggest that higher tumor expression of the BRCA1 protein may be associated with worse prognosis. We undertook a prospective study among men with prostate cancer in the Health Professionals Follow-up Study and evaluated BRCA1 via immunohistochemical staining on tissue microarrays. BRCA1 was expressed in 60 of 589 tumors. Prevalence of BRCA1 positivity was 43% in the 14 men with metastases at diagnosis compared with 9% in non-metastatic tumors [difference, 33 percentage points; 95% confidence interval (CI), 7–59]. BRCA1-positive tumors had 2.16-fold higher Ki-67 proliferative indices (95% CI, 1.18–3.95), higher tumor aneuploidy as predicted from whole-transcriptome profiling, and higher Gleason scores. Among the 575 patients with non-metastatic disease at diagnosis, we evaluated the association between BRCA1 expression and development of lethal disease (metastasis or cancer-specific death, 69 events) during long-term follow-up (median, 18.3 years). A potential weak association of BRCA1 positivity with lethal disease (hazard ratio, 1.61; 95% CI, 0.82–3.15) was attenuated when adjusting for age, Gleason score and clinical stage (hazard ratio, 1.11; 95% CI, 0.54–2.29). In summary, BRCA1 protein expression is a feature of more proliferative and more aneuploid prostate tumors and is more common in metastatic disease. While not well suited as a prognostic biomarker in primary prostate cancer, BRCA1 protein expression may be most relevant in advanced disease.
Automatic Encoding of a View-Centered Background Image in the Macaque Temporal Lobe
Authors: Chen He , Naya Yuji
Published: June 2020

Perceptual processing along the ventral visual pathway to the hippocampus (HPC) is hypothesized to be substantiated by signal transformation from retinotopic space to relational space, which represents interrelations among constituent visual elements. However, our visual perception necessarily reflects the first person’s perspective based on the retinotopic space. To investigate this two-facedness of visual perception, we compared neural activities in the temporal lobe (anterior inferotemporal cortex, perirhinal and parahippocampal cortices, and HPC) between when monkeys gazed on an object and when they fixated on the screen center with an object in their peripheral vision. We found that in addition to the spatially invariant object signal, the temporal lobe areas automatically represent a large-scale background image, which specify the subject’s viewing location. These results suggest that a combination of two distinct visual signals on relational space and retinotopic space may provide the first person’s perspective serving for perception and presumably subsequent episodic memory.
Powassan Virus Infection Likely Acquired Through Blood Transfusion Presenting as Encephalitis in a Kidney Transplant Recipient
Authors: Taylor Lindsay , Condon Taryn , Destrampe Eric M , Brown Jennifer A , McGavic Jeanette , Gould Carolyn V , Chambers Trudy V , Kosoy Olga I , Burkhalter Kristen L , Annambhotla Pallavi , Basavaraju Sridhar V , Groves Jamel , Osborn Rebecca A , Weiss John , Stramer Susan L , Misch Elizabeth A
Published: June 2020

A kidney transplant patient without known tick exposure developed encephalitis 3 weeks after transplantation. During the transplant hospitalization, the patient had received a blood transfusion from an asymptomatic donor later discovered to have been infected with Powassan virus. Here, we describe a probable instance of transfusion-transmitted Powassan virus infection.
Crisis Communication and Public Perception of COVID-19 Risk in the Era of Social Media
Authors: Malecki Kristen M C , Keating Julie A , Safdar Nasia
Published: June 2020

A number of important principles in effective risk communication established in the late 20th century can provide important scientific insight into patient response to the risks posed by coronavirus disease 2019 (COVID-19). Early risk communication scholars found acceptability of risk was shaped by 2 key components: hazard and outrage. The number of people who are exposed, infected, and fall ill can be considered the hazard. How the public and patients and respond to messages regarding risk mitigation relates to outrage. Social and cultural factors, immediacy, uncertainty, familiarity, personal control, scientific uncertainty, and trust in institutions and media all shape perception and response to risk mesaging. Outrage factors influence the ever-changing public understanding of COVID-19 risk. In concert, hazard and outrage along with cultural and economic context shape adherence to, and overall acceptance of, personal mitigation strategies including wearing facemasks and social distancing among the general public. The spread of misinformation on social media also provides both challenges and opportunities for clinicians. Social media offers an opportunity for experts to quickly convey true information about hazards, but offers others the opportunity to counter this with the spread of misinformation and exacerbate outrage. We propose strategies for infectious diseases clinicians to apply risk communication principles and frameworks to improve patient care and public message development in response to COVID-19.
Coronavirus Disease 2019 and Antimicrobial Resistance: Parallel and Interacting Health Emergencies
Authors: Nieuwlaat Robby , Mbuagbaw Lawrence , Mertz Dominik , Burrows Lori L , Bowdish Dawn M E , Moja Lorenzo , Wright Gerard D , Schünemann Holger J
Published: June 2020

The coronavirus disease 2019 (COVID-19) pandemic and antimicrobial resistance (AMR) are parallel and interacting health emergencies that provide the opportunity for mutual learning. As their measures and consequences are comparable, the COVID-19 pandemic helps to illustrate the potential long-term impact of AMR, which is less acute but not less crucial. They may also impact each other as there is a push to use existing antimicrobials to treat critically ill COVID-19 patients in the absence of specific treatments. Attempts to manage the spread of COVID-19 may also lead to a slowdown in AMR. Understanding how COVID-19 affects AMR trends and what we can expect if these trends remain the same or worsen will help us to plan the next steps for tackling AMR. Researchers should start collecting data to measure the impact of current COVID-19 policies and programs on AMR.
Pseudomonas aeruginosa Strain-sharing in Early Infection Among Children With Cystic Fibrosis
Authors: Stapleton Patrick J , Izydorcyzk Conrad , Clark Shawn , Blanchard Ana , Wang Pauline W , Yau Yvonne , Waters Valerie , Guttman David S
Published: June 2020

Background

We previously identified Pseudomonas aeruginosa isolates with characteristics typical of chronic infection in some early infections in children with cystic fibrosis (CF), suggesting that these isolates may have been acquired from other patients. Our objective was to define the extent of P. aeruginosa strain-sharing in early CF infections and its impact on antibiotic eradication treatment failure rates.

Methods

We performed whole genome sequencing on isolates from early pediatric CF pulmonary infections and from the following comparator groups in the same hospital: chronic CF infection, sink drains, sterile site infections, and asymptomatic carriage. Univariate logistic regression was used to assess factors associated with treatment failure.

Results

In this retrospective, observational study, 1029 isolates were sequenced. The CF clones strain B and clone C were present. In 70 CF patients with early infections, 14 shared strains infected 29 (41%) patients over 5 years; 16% (n = 14) of infections had mixed strains. In the 70 children, approximately one-third of shared-strain infections were likely due to patient-to-patient transmission. Mixed-strain infections were associated with strain-sharing (odds ratio, 8.50; 95% confidence interval, 2.2–33.4; P = .002). Strain-sharing was not associated with antibiotic eradication treatment failure; however, nosocomial strain transmission was associated with establishment of chronic infection in a CF sibling pair.

Conclusions

Although early P. aeruginosa CF infection is thought to reflect acquisition of diverse strains from community reservoirs, we identified frequent early CF strain-sharing that was associated with the presence of mixed strains and instances of possible patient-to-patient transmission.
On Enabling Attribute-Based Encryption to Be Traceable Against Traitors
Authors: Liu Zhen , Huang Qiong , Wong Duncan S
Published: June 2020

Attribute-based encryption (ABE) is a versatile one-to-many encryption primitive, which enables fine-grained access control over encrypted data. Due to its promising applications in practice, ABE schemes with high efficiency, security and expressivity have been continuously emerging. On the other hand, due to the nature of ABE, a malicious user may abuse its decryption privilege. Therefore, being able to identify such a malicious user is crucial towards the practicality of ABE. Although some specific ABE schemes in the literature enjoys the tracing function, they are only proceeded case by case. Most of the ABE schemes do not support traceability. It is thus meaningful and important to have a generic way of equipping any ABE scheme with traceability. In this work, we partially solve the aforementioned problem. Namely, we propose a way of transforming (non-traceable) ABE schemes satisfying certain requirements to fully collusion-resistant black-box traceable ABE schemes, which adds only $O(\sqrt{\mathcal{K}})$ elements to the ciphertext where ${\mathcal{K}}$ is the number of users in the system. And to demonstrate the practicability of our transformation, we show how to convert a couple of existing non-traceable ABE schemes to support traceability.
Out-of-hours primary care in 26 European countries: an overview of organizational models
Authors: Steeman Luca , Uijen Maike , Plat Erik , Huibers Linda , Smits Marleen , Giesen Paul
Published: June 2020

Background

Various models exist to organize out-of-hours primary care (OOH-PC). We aimed to provide an up-to-date overview of prevailing organizational models in the European Union (EU), implemented changes over the last decade and future plans. This baseline overview may provide information for countries considering remodelling their OOH-PC system.

Methods

A cross-sectional web-based questionnaire among 93 key informants from EU countries, Norway and Switzerland. Key informants with expertise in the field of primary health care were invited to participate. Themes in the questionnaire were the existing organizational models for OOH-PC, model characteristics, major organizational changes implemented in the past decade and future plans.

Results

All 26 included countries had different coexisting OOH-PC models, varying from 3 to 10 models per country. ‘GP cooperative was the dominant model in most countries followed by primary care centre and rota group’. There was a large variation in characteristics between the models, but also within the models, caused by differences between countries and regions. Almost all countries had implemented changes over the past 10 years, mostly concerning the implementation of telephone triage and a change of organizational model by means of upscaling and centralization of OOH-PC. Planned changes varied from fine-tuning the prevailing OOH-PC system to radical nationwide organizational transitions in OOH-PC.

Conclusions

Different organizational models for OOH-PC exist on international and national level. Compared with a decade ago, more primary care-oriented organizational models are now dominant. There is a trend towards upscaling and centralization; it should be evaluated whether this improves the quality of health care.
Seismo-electric conversion in shale: experiment and analytical modelling
Authors: Peng Rong , Di Bangrang , Glover Paul W J , Wei Jianxin , Lorinczi Piroska , Liu Zichun , Li Huafei
Published: June 2020

The development of seismo-electric exploration techniques relies critically upon the strength of the seismo-electric conversion. However, there have been very few seismo-electric measurements or modelling on shales, despite shales accounting for the majority of unconventional reservoirs. We have carried out seismo-electric measurements on Sichuan Basin shales (permeability 0.00147–0.107 mD), together with some comparative measurements on sandstones (permeability 0.2–60 mD). Experimental results show that the amplitudes of the seismo-electric coupling coefficient in shales are comparable to that exhibited by sandstones, and are approximately independent of frequency in the seismic frequency range (<1 kHz). Numerical modelling has also been used to examine the effects of varying (i) dimensionless number, (ii) porosity, (iii) permeability, (iv) tortuosity and (v) zeta potential on seismo-electric conversion in porous media. It was found that while changes in dimensionless number and permeability seem to have little effect, seismo-electric coupling coefficient is highly sensitive to changes in porosity, tortuosity and zeta potential. Numerical modelling suggests that the origin of the seismo-electric conversion in shales is enhanced zeta potentials caused by clay minerals, which are highly frequency dependent. This is supported by a comparison of our numerical modelling with our experimental data, together with an analysis of seismo-electric conversion as a function of clay mineral composition from XRD measurements. The sensitivity of seismo-electric coupling to the clay minerals suggests that seismo-electric exploration may have potential for the characterization of clay minerals in shale gas and shale oil reservoirs.
Multiscale crustal deformation around the southeastern margin of the Tibetan Plateau from GNSS observations
Authors: Xu Keke , Liu Jie , Liu Xifeng , Liu Jipeng , Zhao Fuling
Published: June 2020

We present a multiscale decomposition model for analysing the widespread deformation and complex dynamics mechanism of the southeastern margin of the Tibetan Plateau. We first carry out simulations to test the performance of the model by synthetic Global Navigation Satellite System (GNSS) data for a network, whose geometry distribution is same with actual Crust Movement Observation Network of China in the southeast edge of the Tibetan Plateau. We then estimate the multiscale velocity field and strain rate field using observed data with 240 stations between 1999 and 2007. Results show that the deformation field at the different spatial scale corresponds to the different tectonic driving force and strain accumulation coverage. Tectonic background of the Tibetan Plateau, extrusion of the Sichuan–Yunnan rhombic block, rigid block motion, interior deformation of the block and segmented motion of fault zones are separately displayed in the corresponding scale, which provides a strong support keys to the understanding of the controversial deformation models for the tectonic evolution and uplift mechanisms of the Tibetan Plateau. Our results also show that scale 7 with the coverage of about 50 km can better reflect the seismogenic background of mid-strong earthquakes (>Ms 5.0) of the region. The convergence area of high compression and inflation strain or the high-value area of maximum shear strain at scale 7 is obviously correlated with seismic activities, including 2008 Wenchuan Ms 8.0 earthquake, no significant pre-seismic deformation across fault in other scales. Our research provides a new insight into the nature of tectonic deformation and the seismic risk assessment of the southeastern margin of the Tibetan Plateau.
Health system adaptation to climate change: a Peruvian case study
Authors: Aracena Stephanie , Barboza Marco , Zamora Victor , Salaverry Oswaldo , Montag Doreen
Published: June 2020

Despite mitigation attempts, the trajectory of climate change remains on an accelerated path, with devastating health impacts. As a response to the United Nations Framework Convention on Climate Change call for National Adaptation Plans, Peru has developed a national and decentralized regional adaptation plans. The purpose of this article is to understand the role and priority status of health within the adaptation planning and process. Peru was used as a case study to analyse the policy process in the creation of adaptation plans, encompassing the need to address climate change impacts on health with a particular focus on marginalized people. An actor, content and context policy analyses were conducted to analyse 17 out of 25 regional adaptation plans, which are available. The national adaptation plans (2002, 2015) do not include health as a priority or health adaptation strategies. In a decentralized health care system, regional plans demonstrate an increased improvement of complexity, systematization and structure over time (2009–17). In general, health has not been identified as a priority but as another area of impact. There is no cohesiveness between plans in format, content, planning and execution and only a limited consideration for marginalized populations. In conclusion, the regional departments of Peru stand on unequal footing regarding adapting the health sector to climate change. Findings in the strategies call into question how mitigation and adaption to climate change may be achieved. The lack of local research on health impacts due to climate change and a particular focus on marginalized people creates a policy vacuum. The Peruvian case study resembles global challenges to put health in the centre of national and regional adaptation plans. In-depth cross-country analysis is still missing but urgently needed to learn from other experiences.
Indications and predictors for pacemaker implantation after isolated aortic valve replacement with bioprostheses: the CAREAVR study
Authors: Salmi Samuli J , Nieminen Tuomo , Hartikainen Juha , Biancari Fausto , Lehto Joonas , Nissinen Maunu , Malmberg Markus , Yannopoulos Fredrik , Savolainen Jyri , Airaksinen Juhani , Kiviniemi Tuomas
Published: June 2020

OBJECTIVES

We sought to study the indications, long-term occurrence, and predictors of permanent pacemaker implantation (PPI) after isolated surgical aortic valve replacement with bioprostheses.

METHODS

The CAREAVR study included 704 patients (385 females, 54.7%) without a preoperative PPI (mean ± standard deviation age 75 ± 7 years) undergoing isolated surgical aortic valve replacement at 4 Finnish hospitals between 2002 and 2014. Data were extracted from electronic patient records.

RESULTS

The follow-up was median 4.7 years (range 1 day to 12.3 years). Altogether 56 patients received PPI postoperatively, with the median 507 days from the operation (range 6 days to 10.0 years). The PPI indications were atrioventricular block (31 patients, 55%) and sick sinus syndrome (21 patients, 37.5%). For 4 patients, the PPI indication remained unknown. A competing risks regression analysis (Fine–Gray method), adjusted with age, sex, diabetes, coronary artery disease, preoperative atrial fibrillation (AF), left ventricular ejection fraction, New York Heart Association class, AF at discharge and urgency of operation, was used to assess risk factors for PPI. Only AF at discharge (subdistribution hazard ratio 4.34, 95% confidence interval 2.34–8.03) was a predictor for a PPI.

CONCLUSIONS

Though atrioventricular block is the major indication for PPI after surgical aortic valve replacement, >30% of PPIs are implanted due to sick sinus syndrome during both short-term follow-up and long-term follow-up. Postoperative AF versus sinus rhythm conveys >4-fold risk of PPI.

Clinical trial registration

clinicaltrials.gov Identifier: NCT02626871
Association Between Immunoglobulin E Levels and Kaposi Sarcoma in African Adults With Human Immunodeficiency Virus Infection
Authors: Byakwaga Helen , Barbachano-Guerrero Arturo , Wang Dongliang , McAllister Shane , Naphri Kamal , Laker-Oketta Miriam , Muzoora Conrad , Hunt Peter W , Martin Jeffrey , King Christine A
Published: June 2020

It has been demonstrated that activated mast cells (MCs) are enriched in Kaposi sarcoma (KS) tumors and contribute to the inflammatory microenvironment. Mechanisms driving MC activation, however, are incompletely understood. We sought to understand whether immunoglobulin E (IgE), a potent activator of MCs, was associated with KS incidence and severity. In a cross-sectional study of untreated human immunodeficiency virus (HIV)–infected adults with or without KS in Uganda, we found that patients with KS had higher plasma IgE levels than those without KS. After adjustment for age, sex, CD4+ T-cell count, and HIV RNA levels, there was a dose-response relationship between plasma IgE levels and the presence and severity of KS. Higher eosinophil counts were also associated with IgE levels, and plasma interleukin 33 concentrations were higher in individuals with KS. These findings suggest that IgE-driven atopic inflammation may contribute the pathogenesis of KS. Therapies targeting IgE-mediated MC activation thus might represent a novel approach for treatment or prevention of KS.
Combination antifungal therapy for breakthrough invasive mould disease in patients with haematological malignancies: when management reasoning eclipses evidence-based medicine
Authors: Garcia-Vidal C , Lewis R E , Kontoyiannis D P
Published: June 2020

Timely diagnosis and treatment of invasive mould disease is challenging in severely immunocompromised patients, particularly for patients who develop breakthrough infections while on antifungal prophylaxis. Currently, there are no high-quality data on how to best diagnose and treat these infections. Many essential decisions affecting the management of breakthrough mould disease are made before a definitive diagnosis is established. In this scenario, sound management reasoning often favours the use of combination antifungal therapy, especially when antifungal resistance, suspicion of undetected sites of infection or pharmacokinetic/pharmacodynamic limitations at the site of infection are likely. In these scenarios, pre-emptive use of antifungal combination therapy with frequent re-evaluation with an aim of de-escalation could be justified for many high-risk patients.
Venous thromboembolism in cancer patients: report of baseline data from the multicentre, prospective Cancer-VTE Registry
Authors: Ohashi Yasuo , Ikeda Masataka , Kunitoh Hideo , Sasako Mitsuru , Okusaka Takuji , Mukai Hirofumi , Fujiwara Keiichi , Nakamura Mashio , Oba Mari S , Kimura Tetsuya , Ibusuki Kei , Sakon Masato
Published: June 2020

Background

The Cancer-VTE Registry evaluates the occurrence and management of venous thromboembolism in Japanese participants with major solid tumors. Using Registry data, we evaluated the frequency of concurrent venous thromboembolism in cancer patients prior to treatment initiation by cancer type.

Methods

The Cancer-VTE Registry is an ongoing (March 2017–September 2020) prospective cohort study using a nationwide, multicentre clinical registry. Participants aged ≥20 years with colorectal, lung, stomach, pancreatic, breast or gynecologic cancer, confirmed staging, ≥6 months life expectancy post-registration and who had undergone venous thromboembolism screening were managed with routine clinical care. Venous thromboembolism frequency at registration was evaluated.

Results

Of 9735 participants, 571 (5.9%) had venous thromboembolism at baseline, including asymptomatic [5.5% (n = 540)] and symptomatic venous thromboembolism [0.3% (n = 31)]. Most participants with venous thromboembolism (n = 506, 5.2%) had deep vein thrombosis only; 65 (0.7%) had pulmonary embolism with/without deep vein thrombosis. The prevalence of distal and proximal deep vein thrombosis was 4.8% (n = 466) and 0.9% (n = 83), respectively. The highest prevalence of venous thromboembolism was for pancreatic cancer (8.5%) and the lowest for breast cancer (2.0%). Venous thromboembolism prevalence increased as cancer stage advanced.

Conclusions

Although there was a marked difference in venous thromboembolism by cancer type, the data suggest that cancer stage is an important risk factor for venous thromboembolism. Thus, metastasis seems a critical risk factor for venous thromboembolism. This is the first demonstration of venous thromboembolism prevalence and risk factors in Japanese cancer patients prior to treatment.

Trial registration

UMIN000024942.
Circulating Tumor DNA Markers for Early Progression on Fulvestrant With or Without Palbociclib in ER+ Advanced Breast Cancer
Authors: O’Leary Ben , Cutts Rosalind J , Huang Xin , Hrebien Sarah , Liu Yuan , André Fabrice , Loibl Sibylle , Loi Sherene , Garcia-Murillas Isaac , Cristofanilli Massimo , Bartlett Cynthia Huang , Turner Nicholas C
Published: June 2020

Background

There are no established molecular biomarkers for patients with breast cancer receiving combination endocrine and CDK4/6 inhibitor (CDK4/6i). We aimed to determine whether genomic markers in circulating tumor DNA (ctDNA) can identify patients at higher risk of early progression on fulvestrant therapy with or without palbociclib, a CDK4/6i.

Methods

PALOMA-3 was a phase III, multicenter, double-blind randomized controlled trial of palbociclib plus fulvestrant (n = 347) vs placebo plus fulvestrant (n = 174) in patients with endocrine-pretreated estrogen receptor–positive (ER+) breast cancer. Pretreatment plasma samples from 459 patients were analyzed for mutations in 17 genes, copy number in 14 genes, and circulating tumor fraction. Progression-free survival (PFS) was compared in patients with circulating tumor fraction above or below a prespecified cutoff of 10% and with or without a specific genomic alteration. All statistical tests were 2-sided.

Results

Patients with high ctDNA fraction had worse PFS on both palbociclib plus fulvestrant (hazard ratio [HR] = 1.62, 95% confidence interval [CI] = 1.17 to 2.24; P = .004) and placebo plus fulvestrant (HR = 1.77, 95% CI = 1.21 to 2.59; P = .004). In multivariable analysis, high-circulating tumor fraction was associated with worse PFS (HR = 1.20 per 10% increase in tumor fraction, 95% CI = 1.09 to 1.32; P < .001), as was TP53 mutation (HR = 1.84, 95% CI = 1.27 to 2.65; P = .001) and FGFR1 amplification (HR = 2.91, 95% CI = 1.61 to 5.25; P < .001). No interaction with treatment randomization was observed.

Conclusions

Pretreatment ctDNA identified a group of high-risk patients with poor clinical outcome despite the addition of CDK4/6 inhibition. These patients might benefit from inclusion in future trials of escalating treatment, with therapies that may be active in these genomic contexts.
Prospects for the accelerated improvement of the resilient crop quinoa
Authors: López-Marqués Rosa L , Nørrevang Anton F , Ache Peter , Moog Max , Visintainer Davide , Wendt Toni , Østerberg Jeppe T , Dockter Christoph , Jørgensen Morten E , Salvador Andrés Torres , Hedrich Rainer , Gao Caixia , Jacobsen Sven-Erik , Shabala Sergey , Palmgren Michael
Published: June 2020

Crops tolerant to drought and salt stress may be developed by two approaches. First, major crops may be improved by introducing genes from tolerant plants. For example, many major crops have wild relatives that are more tolerant to drought and high salinity than the cultivated crops, and, once deciphered, the underlying resilience mechanisms could be genetically manipulated to produce crops with improved tolerance. Secondly, some minor (orphan) crops cultivated in marginal areas are already drought and salt tolerant. Improving the agronomic performance of these crops may be an effective way to increase crop and food diversity, and an alternative to engineering tolerance in major crops. Quinoa (Chenopodium quinoa Willd.), a nutritious minor crop that tolerates drought and salinity better than most other crops, is an ideal candidate for both of these approaches. Although quinoa has yet to reach its potential as a fully domesticated crop, breeding efforts to improve the plant have been limited. Molecular and genetic techniques combined with traditional breeding are likely to change this picture. Here we analyse protein-coding sequences in the quinoa genome that are orthologous to domestication genes in established crops. Mutating only a limited number of such genes by targeted mutagenesis appears to be a promising route for accelerating the improvement of quinoa and generating a nutritious high-yielding crop that can meet the future demand for food production in a changing climate.
Forty years in the Wilderness: John Sadler of the Sadler Partbooks
Authors: Range Matthias , Craig-McFeely Julia
Published: June 2020

The identification of the Tudor partbooks Oxford, Bodleian Library, Mss. Mus. e. 1–5 and Ms. Tenbury 1486, and the privately owned Willmott partbook with John Sadler, a priest and schoolmaster active in rural Northamptonshire between 1548 and the early 1590s, has sat uneasily. This is because the John Sadler associated with these books is actually someone quite different: in the first set he entered in the books what has previously been described as a simple monogram of his name, but which is in fact a ‘merchant mark’ identifying him unambiguously as a Norwich merchant. The article discusses the evidence for his identification and the new context for the books. Their relocation invites a new reading and interpretation of their contents, such as their significance as a source of information about the Norwich composer Thomas Morley. The link with the Elizabethan merchant world brings into focus the rather neglected topic of early modern merchants and their involvement with music.
A versatile tool for cluster lensing source reconstruction – I. Methodology and illustration on sources in the Hubble Frontier Field Cluster MACS J0717.5+3745
Authors: Yang Lilan , Birrer Simon , Treu Tommaso
Published: June 2020

We describe a general-purpose method to reconstruct the intrinsic properties of sources lensed by the gravitational potential of foreground clusters of galaxies. The tool lenstruction is implemented in the publicly available multipurpose gravitational lensing software lenstronomy, in order to provide an easy and fast solution to this common astrophysical problem. The tool is based on forward modelling the appearance of the source in the image plane, taking into account the distortion by lensing and the instrumental point spread function. For singly imaged sources, a global lens model in the format of the Hubble Frontier Fields (HFF) lensing maps is required as a starting point. For multiply imaged sources, the tool can also fit and apply first- (deflection), second- (shear, convergence), and third-order (flexion) corrections to the local gravitational potential to improve the reconstruction, depending on the quality of the data. We illustrate the performance and features of the code with two examples of multiply imaged systems taken from the HFF, starting from five different publicly available cluster models. We find that, after our correction, the relative magnification – and other lensing properties – between the multiple images becomes robustly constrained. Furthermore, we find that scatter between models of the reconstructed source size and magnitude is reduced. The code and Jupyter notebooks are publicly available.
Beyond ΛCDM with H i intensity mapping: robustness of cosmological constraints in the presence of astrophysics
Authors: Camera Stefano , Padmanabhan Hamsa
Published: June 2020

Mapping the unresolved intensity of the 21-cm emission of neutral hydrogen (H i) is now regarded as one the most promising tools for cosmological investigation in the coming decades. Here, we investigate, for the first time, extensions of the standard cosmological model, such as modified gravity and primordial non-Gaussianity, taking self-consistently into account. The present constraints on the astrophysics of H i clustering in the treatment of the brightness temperature fluctuations. To understand the boundaries within which results thus obtained can be considered reliable, we examine the robustness of cosmological parameter estimation performed via studies of 21-cm intensity mapping, against our knowledge of the astrophysical processes leading to H i clustering. Modelling of astrophysical effects affects cosmological observables through the relation linking the overall H i mass in a bound object, to the mass of the underlying dark matter halo that hosts it. We quantify the biases in estimates of standard cosmological parameters and those describing modified gravity and primordial non-Gaussianity that are obtained if one misconceives the slope of the relation between H i mass and halo mass, or the lower virial velocity cut-off for a dark matter halo to be able to host H i. Remarkably, we find that astrophysical uncertainties will not affect searches for primordial non-Gaussianity – one of the strongest science cases for H i intensity mapping – despite the signal being deeply linked to the H i bias.
A Novel multidimensional Boltzmann neutrino transport scheme for core-collapse supernovae
Authors: Chan Conrad , Müller Bernhard
Published: June 2020

We introduce a new discrete-ordinate scheme for solving the general relativistic (GR) Boltzmann transport equation in the context of core-collapse supernovae (CCSNe). Our algorithm avoids the need to spell out the complicated advection terms in energy and angle that arise when the transport equation is formulated in spherical polar coordinates, in the comoving frame, or in a GR space–time. We instead approach the problem by calculating the advection of neutrinos across momentum space using an intuitive particle-like approach that has excellent conservation properties and fully accounts for Lorentz boosts, GR effects, and grid geometry terms. In order to avoid the need for a global implicit solution, time integration is performed using a locally implicit Lax–Wendroff scheme that correctly reproduces the diffusion limit. This will facilitate the use of our method on massively parallel distributed-memory architectures. We have verified the accuracy and stability of our scheme with a suite of test problems in spherical symmetry and axisymmetry. To demonstrate that the new algorithm works stably in CCSN simulations, we have coupled it to the GR hydrodynamics code coconut and present a first demonstration run of a $20\, \mathrm{M}_\odot$ progenitor with a reduced set of neutrino opacities.
Evolution of α Centauri b’s protoplanetary disc
Authors: Martin Rebecca G , Lissauer Jack J , Quarles Billy
Published: June 2020

With hydrodynamical simulations we examine the evolution of a protoplanetary disc around α Centauri B including the effect of the eccentric orbit binary companion α Centauri A. The initially circular orbit disc undergoes two types of eccentricity growth. First, the eccentricity oscillates on the orbital period of the binary, Porb, due to the eccentricity of the binary orbit. Secondly, for a sufficiently small disc aspect ratio, the disc undergoes global forced eccentricity oscillations on a time-scale of around $20\, P_{\rm orb}$. These oscillations damp out through viscous dissipation leaving a quasi-steady eccentricity profile for the disc that oscillates only on the binary orbital period. The time-averaged global eccentricity is in the range 0.05–0.1, with no precession in the steady state. The periastrons of the gas particles are aligned to one another. The higher the disc viscosity, the higher the disc eccentricity. With N-body simulations we examine the evolution of a disc of planetesimals that forms with the orbital properties of the quasi-steady protoplanetary disc. We find that the average magnitude of the eccentricity of particles increases and their periastrons become misaligned to each other once they decouple from the gas disc. The low planetesimal collision velocity required for planet formation suggests that for planet formation to have occurred in a disc of planetesimals formed from a protoplanetary disc around α Centauri B, said disc’s viscosity must be have been small and planet formation must have occurred at orbital radii smaller than about $2.5\, \rm au$. Planet formation may be easier with the presence of gas.
BUDHiES IV: Deep 21-cm neutral Hydrogen, optical, and UV imaging data of Abell 963 and Abell 2192 at z ≃ 0.2
Authors: Gogate A R , Verheijen M A W , Deshev B Z , van Gorkom J H , Montero-Castaño M , Hulst J M van der , Jaffé Y L , Poggianti B M
Published: June 2020

In this paper, we present data from the Blind Ultra-Deep H i Environmental Survey (BUDHiES), which is a blind 21-cm H i spectral line imaging survey undertaken with the Westerbork Synthesis Radio Telescope. Two volumes were surveyed, each with a single pointing and covering a redshift range of 0.164 < z < 0.224. Within these two volumes, this survey targeted the clusters Abell 963 and Abell 2192, which are dynamically different and offer unique environments to study the process of galaxy evolution within clusters. With an integration time of 117 × 12 h on Abell 963 and 72 × 12 h on Abell 2192, a total of 166 galaxies were detected and imaged in H i. While the clusters themselves occupy only 4 per cent of the 73 400 Mpc3 surveyed by BUDHiES, most of the volume consists of large-scale structures in which the clusters are embedded, including foreground and background overdensities and voids. We present the data processing and source detection techniques and counterpart identification based on a wide-field optical imaging survey using the Isaac Newton Telescope and deep ultraviolet (UV) Galaxy Evolution Explorer (GALEX) imaging. Finally, we present H i and optical catalogues of the detected sources as well as atlases of their global H i properties, which include integrated column density maps, position–velocity diagrams, global H i profiles, and optical and UV images of the H i sources.