bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting evolutionary patterns of cancers using consensus trees
Authors: Christensen Sarah , Kim Juho , Chia Nicholas , Koyejo Oluwasanmi , El-Kebir Mohammed
Published: September 2020

Motivation

While each cancer is the result of an isolated evolutionary process, there are repeated patterns in tumorigenesis defined by recurrent driver mutations and their temporal ordering. Such repeated evolutionary trajectories hold the potential to improve stratification of cancer patients into subtypes with distinct survival and therapy response profiles. However, current cancer phylogeny methods infer large solution spaces of plausible evolutionary histories from the same sequencing data, obfuscating repeated evolutionary patterns.

Results

To simultaneously resolve ambiguities in sequencing data and identify cancer subtypes, we propose to leverage common patterns of evolution found in patient cohorts. We first formulate the Multiple Choice Consensus Tree problem, which seeks to select a tumor tree for each patient and assign patients into clusters in such a way that maximizes consistency within each cluster of patient trees. We prove that this problem is NP-hard and develop a heuristic algorithm, Revealing Evolutionary Consensus Across Patients (RECAP), to solve this problem in practice. Finally, on simulated data, we show RECAP outperforms existing methods that do not account for patient subtypes. We then use RECAP to resolve ambiguities in patient trees and find repeated evolutionary trajectories in lung and breast cancer cohorts.

Availability and implementation

https://github.com/elkebir-group/RECAP.

Supplementary information

Supplementary data are available at Bioinformatics online.
Long-term Infective Endocarditis Mortality Associated With Injection Opioid Use in the United States: A Modeling Study
Authors: Barocas Joshua A , Eftekhari Yazdi Golnaz , Savinkina Alexandra , Nolen Shayla , Savitzky Caroline , Samet Jeffrey H , Englander Honora , Linas Benjamin P
Published: September 2020

Background

The expansion of the US opioid epidemic has led to significant increases in infections, such as infective endocarditis (IE), which is tied to injection behaviors. We aimed to estimate the population-level IE mortality rate among people who inject opioids and compare the risk of IE death against the risks of death from other causes.

Methods

We developed a microsimulation model of the natural history of injection opioid use. We defined injection behavior profiles by both injection frequency and injection techniques. We accounted for competing risks of death and populated the model with primary and published data. We modeled cohorts of 1 million individuals with different injection behavior profiles until age 60 years. We combined model-generated estimates with published data to project the total expected number of IE deaths in the United States by 2030.

Results

The probabilities of death from IE by age 60 years for 20-, 30-, and 40-year-old men with high-frequency use with higher infection risk techniques compared to lower risk techniques for IE were 53.8% versus 3.7%, 51.4% versus 3.1%, and 44.5% versus 2.2%, respectively. The predicted population-level attributable fraction of 10-year mortality from IE among all risk groups was 20%. We estimated that approximately 257 800 people are expected to die from IE by 2030.

Conclusions

The expected burden of IE among people who inject opioids in the United States is large. Adopting a harm reduction approach, including through expansion of syringe service programs, to address injection behaviors could have a major impact on decreasing the mortality rate associated with the opioid epidemic.
The Presence of (1→3)-β-D-Glucan as Prognostic Marker in Patients After Major Abdominal Surgery
Authors: White P Lewis , Posso Raquel , Parr Christian , Price Jessica S , Finkelman Malcolm , Barnes Rosemary A
Published: September 2020

Background

While the serological detection of (1→3)-β-D-glucan (BDG) can indicate invasive fungal disease (IFD), false positivity occurs. Nevertheless, the presence of BDG can still be recognized by the host’s innate immune system and persistent BDG antigenemia, in the absence of IFD, can result in deleterious proinflammatory immune responses.

Methods

During the XXX (INTENSE) study into the preemptive use of micafungin to prevent invasive candidiasis (IC) after abdominal surgery, the serum burden of BDG was determined to aid diagnosis of IC. Data from the INTENSE study were analyzed to determine whether BDG was associated with organ failure and patient mortality, while accounting for the influences of IC and antifungal therapy.

Results

A BDG concentration >100 pg/mL was associated with a significantly increased Sequential Organ Failure Assessment score (≤100 pg/mL: 2 vs >100 pg/mL: 5; P < .0001) and increased rates of mortality (≤100 pg/mL: 13.7% vs >100 pg/mL: 39.0%; P = .0002). Multiple (≥2) positive results >100 pg/mL or a BDG concentration increasing >100 pg/mL increased mortality (48.1%). The mortality rate in patients with IC and a BDG concentration >100 pg/mL and ≤100 pg/mL was 42.3% and 25.0%, respectively. The mortality rate in patients without IC but a BDG concentration >100 pg/mL was 37.3%. The use of micafungin did not affect the findings.

Conclusions

The presence of persistent or increasing BDG in the patient’s circulation is associated with significant morbidity and mortality after abdominal surgery, irrespective of IC. The potential lack of a specific therapeutic focus has consequences when trying to manage these patients, and when designing clinical trials involving patients where host-associated BDG concentrations may be elevated.

Clinical Trials Registration

NCT01122368.
Measurement of free glucocorticoids: quantifying corticosteroid binding capacity and its variation within and among mammal and bird species
Authors: Delehanty Brendan , Bossart Gregory D , Champagne Cory , Crocker Daniel E , Elliott Kyle H , Fair Patricia A , Houser Dorian , Newman Amy E M , Boonstra Rudy
Published: September 2020

Plasma glucocorticoid (CORT) levels are one measure of stress in wildlife and give us insight into natural processes relevant to conservation issues. Many studies use total CORT concentrations to draw conclusions about animals’ stress state and response to their environment. However, the blood of tetrapods contains corticosteroid-binding globulin (CBG), which strongly binds most circulating CORT. Only free CORT (CORT not bound by CBG) leaves the circulation and exerts biological effects on CORT-sensitive tissues. Measuring free CORT concentrations provides insight to an animal’s stress response that cannot be revealed by simply measuring total CORT. To calculate free CORT concentrations in plasma or serum samples, one needs three measurements: the binding affinity of CBG for CORT (which varies by species), the total CORT concentration in the sample and the maximum corticosteroid binding capacity (MCBC) of CBG in the sample. Here, we detail the measurement of CBG binding capacity. We compare and contrast the three main methods to measure MCBC: charcoal, cell harvester and dialysis. Each is defined by the means by which free and bound CORT are separated. We weigh the relative merits and challenges of each. We conclude that sample volume, species and taxon binding specificity, and availability of equipment are the primary considerations in selecting the appropriate separation method. For most mammals, the charcoal method is recommended. For birds, the harvester method has critical advantages over the charcoal method. The dialysis method is widely regarded as the gold standard and has lower equipment costs but is more time-intensive and costly in terms of radioactive isotope needed and is less suited to processing large numbers of samples. The binding capacity of CBG varies tremendously within and among the bird and marine mammal species studied, and we discuss the implication of this variation for understanding the role of stress in wildlife.
Prevalence and clinical implications of valvular calcification on coronary computed tomography angiography
Authors: Williams Michelle C , Massera Daniele , Moss Alastair J , Bing Rong , Bularga Anda , Adamson Philip D , Hunter Amanda , Alam Shirjel , Shah Anoop S V , Pawade Tania , Roditi Giles , van Beek Edwin J R , Nicol Edward D , Newby David E , Dweck Marc R
Published: September 2020

Aims

Valvular heart disease can be identified by calcification on coronary computed tomography angiography (CCTA) and has been associated with adverse clinical outcomes. We assessed aortic and mitral valve calcification in patients presenting with stable chest pain and their association with cardiovascular risk factors, coronary artery disease, and cardiovascular outcomes.

Methods and results

In 1769 patients (58 ± 9 years, 56% male) undergoing CCTA for stable chest pain, aortic and mitral valve calcification were quantified using Agatston score. Aortic valve calcification was present in 241 (14%) and mitral calcification in 64 (4%). Independent predictors of aortic valve calcification were age, male sex, hypertension, diabetes mellitus, and cerebrovascular disease, whereas the only predictor of mitral valve calcification was age. Patients with aortic and mitral valve calcification had higher coronary artery calcium scores and more obstructive coronary artery disease. The composite endpoint of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke was higher in those with aortic [hazard ratio (HR) 2.87; 95% confidence interval (CI) 1.60–5.17; P < 0.001] or mitral (HR 3.50; 95% CI 1.47–8.07; P = 0.004) valve calcification, but this was not independent of coronary artery calcification or obstructive coronary artery disease.

Conclusion

Aortic and mitral valve calcification occurs in one in six patients with stable chest pain undergoing CCTA and is associated with concomitant coronary atherosclerosis. Whilst valvular calcification is associated with a higher risk of cardiovascular events, this was not independent of the burden of coronary artery disease.
Richafort’s Requiem: beyond Josquin
Authors: Bloxam M Jennifer
Published: September 2020

All polyphonic Requiem settings have a commemorative purpose, but none is more multi-layered in its memorializing aims and strategies than that by Jean Richafort (c.1480–c.1550). This piece is unique among Renaissance Requiems in drawing its materials and procedures from an earlier composer’s oeuvre: Richafort mined no fewer than three works by Josquin des Prez. Indeed, Richafort’s Requiem is so deeply indebted to Josquin that Gustave Reese suggested it was ‘written on the death of Josquin’ in 1521.

This article revisits this exquisite piece of music in order to look more deeply into its commemorative nature and purpose. First, essential musical and textual details germane to its function as tribute are identified, building on John Milsom’s essay ‘Sense and sound in Richafort’s Requiem’ in Early Music, xxx (2002). The association of this Requiem with Josquin’s death is assessed, and other possibilities for the work’s genesis suggested. Finally, ways in which this setting serves a purpose beyond the memorialization of any one individual is explored by situating it within the ritual context of the Funeral Mass, and evidence offered to suggest that certain compositional decisions made by Richafort were designed to commemorate Christ’s redeeming death and resurrection as the key to every Christian’s salvation.
SWinvert: a workflow for performing rigorous 1-D surface wave inversions
Authors: Vantassel Joseph P , Cox Brady R
Published: September 2020

SWinvert is a workflow developed at The University of Texas at Austin for the inversion of surface wave dispersion data. SWinvert encourages analysts to investigate inversion uncertainty and non-uniqueness in shear wave velocity (Vs) by providing a systematic procedure and specific actionable recommendations for surface wave inversion. In particular, the workflow encourages the use of multiple layering parametrizations to address the inversion's non-uniqueness, multiple global searches for each parametrization to address the inverse problem's non-linearity and quantification of Vs uncertainty in the resulting profiles. While the workflow uses the Dinver module of the popular open-source Geopsy software as its inversion engine, the principles presented are of relevance to analysts using other inversion programs. To illustrate the effectiveness of the SWinvert workflow and to develop a set of benchmarks for use in future surface wave inversion studies, synthetic experimental dispersion data for 12 subsurface models of varying complexity are inverted. While the effects of inversion uncertainty and non-uniqueness are shown to be minimal for simple subsurface models characterized by broad-band dispersion data, these effects cannot be ignored in the Vs profiles derived for more complex models with band-limited dispersion data. To encourage adoption of the SWinvert workflow, an open-source Python package (SWprepost), for pre- and post-processing of surface wave inversion data, and an application on the DesignSafe-Cyberinfrastructure (SWbatch), for performing batch-style surface wave inversions with Dinver using high-performance computing, have been developed and released in conjunction with this work. The SWinvert workflow is shown to provide a methodical procedure and a powerful set of tools for performing rigorous surface wave inversions and quantifying the uncertainty in the resulting Vs profiles.
Iterative passive-source location estimation and velocity inversion using geometric-mean reverse-time migration and full-waveform inversion
Authors: Lyu Bin , Nakata Nori
Published: September 2020

Passive-seismic provides useful information for reservoir monitoring and structural imaging; for example, the locations of microseismic events are helpful to understand the extension of the hydraulic fracturing. However, passive-seismic imaging still faces some challenges. First, it is not easy to know where the passive-seismic events happened, which is known as passive-source locating. Additionally, the accuracy of the subsurface velocity model will influence the accuracy of the estimated passive-source locations and the quality of the structural imaging obtained from the passive-seismic data. Therefore the velocity inversion using the passive-seismic data is required to provide the velocity with higher accuracy. Focusing on these challenges, we develop an iterative passive-source location estimation and velocity inversion method using geometric-mean reverse-time migration (GmRTM) and full-waveform inversion (FWI). In each iteration, the source location is estimated using a high-resolution GmRTM method, which provides a better focusing of passive-source imaging compared to conventional wavefield scanning method. The passive-source FWI is then followed to optimize the velocity model using the estimated source location provided by GmRTM. The source location estimation and velocity inversion are implemented sequentially. We evaluate this iterative method using the Marmousi model data set. The experiment result and sensitivity analysis indicate that the proposed method is effective to locate the sources and optimize velocity model in the areas with complicated subsurface structures and noisy recordings.
From the Adriatic to Northern Norway—geographic differences in moult increment and moult probability of the European lobster (Homarus gammarus), across the natural range
Authors: Coleman Matthew T , Agnalt Anne-Lisbeth , Emmerson Jack , Laurens Martial , Porter Joanne S , Bell Michael C
Published: September 2020

This study collated existing data on lobster moult increment from studies across the range of Homarus gammarus, together with new tagging data from Orkney, United Kingdom. Generalized additive models were used to investigate geographical differences in absolute moult increment and moult probability. Absolute moult increment was seen to differ significantly between regions and between sexes and showed a non-linear relationship with pre-moult size. Smaller absolute moult increments were observed at southern and northern latitudes with larger increments observed in the centre of the species range. Temperature was identified as a significant factor explaining differences in absolute moult increment between regions, consistent with there being a thermal optimum for growth for in H. gammarus. Moult and double moult probabilities decline with pre-moult size, with greatest probability of moulting occurring around day 250. Probability of double moulting increased with mean annual sea surface temperature. Regionally variable growth patterns, and localized adaptation to abiotic variables such as temperature, should therefore be taken into account when defining lobster stock assessment and fishery management areas.
Tuna aggregation dynamics at Drifting Fish Aggregating Devices: a view through the eyes of commercial echosounder buoys
Authors: Baidai Yannick , Dagorn Laurent , Amandè Monin J , Gaertner Daniel , Capello Manuela
Published: September 2020

This study addresses novel questions on the dynamics of tuna aggregations around floating objects, using echosounder buoys data collected throughout the drifts of newly deployed Drifting Fish Aggregating Devices (DFADs) in the Atlantic Ocean (AO) and Indian Ocean (IO). Time series of presence/absence of tunas were obtained by supervised classification of acoustic data. To avoid biases related to the variability in individual DFAD soak times, a new approach was developed to estimate the average colonization time of new DFADs by tuna aggregations. We showed that tunas colonize DFADs after an average of 16 days in the AO, and 40 days in the IO. Moreover, the analysis indicated that the time span during which tuna aggregations occupy DFADs is driven by a time-independent process with short- and long-term residence modes. On average, DFADs were continuously occupied by tuna aggregations for 6 and 9 days in the IO and AO, respectively. The time between two consecutive aggregations at the same DFAD averaged 9 days in the IO and 5 days in the AO. Throughout their soak time after being colonized, DFADs remained occupied for a larger proportion of time in the AO (63%) than in the IO (45%).
Transcatheter mitral valve replacement: tissue in-growth after 4 weeks
Authors: Lutter Georg , Bax Lennart , Liu Yazhou , Hansen Jan-Hinnerk , Frank Derk , Freitag-Wolf Sandra , Simionescu Agneta , Sathananthan Janarthanan , Puehler Thomas
Published: September 2020

OBJECTIVES

Tissue reaction to transcatheter mitral valve replacement in the mitral annulus remains to be elucidated.

METHODS

Trileaflet porcine pericardial valves were sewn onto self-expanding d-shaped nitinol stents, which were delivered transapically and in an off-pump fashion into the mitral position of 10 pigs. After at least 4 weeks of follow-up, gross pathological assessment and histological examination were performed. The specimens were stained with Movat’s pentachrome, Elastica-van-Gieson and von Kossa staining. The leucocytes, B cells, T cells or macrophages were detected by specific immunohistochemical staining.

RESULTS

Proper stent positioning in the mitral annulus was achieved in 9/10 animals. Nine of 10 animals survived the desired observation period. In all but one, the mitral valve stent was well integrated into the left atrium and perpendicularly embedded into the annulus by 85 ± 24%. One animal had minor fractures in the nitinol struts and another animal showed tearing of 1 of 4 tethers. Histological examination demonstrated no major tissue reaction with the nitninol struts but well-preserved overall structures around the mitral annulus in 8/9 cases.

CONCLUSIONS

This is the first report demonstrating good in-growth of transcatheter-delivered anatomically shaped mitral valve stents after at least 4 weeks of follow-up. Histological examination demonstrated progressive healing and neointimalization.
Central Diagonal Sections of the n-Cube
Authors: Bartha Ferenc Ágoston , Fodor Ferenc , González Merino Bernardo
Published: September 2020

We prove that the volume of central hyperplane sections of a unit cube in $\mathbb{R}^n$ orthogonal to a main diagonal of the cube is a strictly monotonically increasing function of the dimension for $n\geq 3$. Our argument uses an integral formula that goes back to Pólya [ 20] (see also [ 14] and [ 3]) for the volume of central sections of the cube and Laplace’s method to estimate the asymptotic behavior of the integral. First, we show that monotonicity holds starting from some specific $n_0$. Then, using interval arithmetic and automatic differentiation, we compute an explicit bound for $n_0$ and check the remaining cases between $3$ and $n_0$ by direct computation.
Live Attenuated Varicella Vaccine: Prevention of Varicella and of Zoster
Authors: Gershon Anne A , Gershon Michael D , Shapiro Eugene D
Published: September 2020

Michiaki Takahashi developed the live attenuated varicella vaccine in 1974 . This was the first, and is still the only, herpesvirus vaccine. Early studies showed promise, but the vaccine was rigorously tested on immunosuppressed patients because of their high risk of fatal varicella; vaccination proved to be lifesaving. Subsequently, the vaccine was found to be safe and effective in healthy children. Eventually, varicella vaccine became a component of measles mumps rubella vaccine, 2 doses of which are administered in the USA to ~90% of children. The incidence of varicella has dropped dramatically in the USA since vaccine-licensure in 1995. Varicella vaccine is also associated with a decreased incidence of zoster and is protective for susceptible adults. Today, immunocompromised individuals are protected against varicella due to vaccine-induced herd immunity. Latent infection with varicella zoster virus occurs after vaccination; however, the vaccine strain is impaired for its ability to reactivate.
How effective are electronic medication systems in reducing medication error rates and associated harm among hospital inpatients? A systematic review and meta-analysis
Authors: Gates Peter J , Hardie Rae-Anne , Raban Magdalena Z , Li Ling , Westbrook Johanna I
Published: September 2020

Objective

To conduct a systematic review and meta-analysis to assess: 1) changes in medication error rates and associated patient harm following electronic medication system (EMS) implementation; and 2) evidence of system-related medication errors facilitated by the use of an EMS.

Materials and Methods

We searched Medline, Scopus, Embase, and CINAHL for studies published between January 2005 and March 2019, comparing medication errors rates with or without assessments of related harm (actual or potential) before and after EMS implementation. EMS was defined as a computer-based system enabling the prescribing, supply, and/or administration of medicines. Study quality was assessed.

Results

There was substantial heterogeneity in outcomes of the 18 included studies. Only 2 were strong quality. Meta-analysis of 5 studies reporting change in actual harm post-EMS showed no reduced risk (RR: 1.22, 95% CI: 0.18–8.38, P = .8) and meta-analysis of 3 studies reporting change in administration errors found a significant reduction in error rates (RR: 0.77, 95% CI: 0.72–0.83, P = .004). Of 10 studies of prescribing error rates, 9 reported a reduction but variable denominators precluded meta-analysis. Twelve studies provided specific examples of system-related medication errors; 5 quantified their occurrence.

Discussion and Conclusion

Despite the wide-scale adoption of EMS in hospitals around the world, the quality of evidence about their effectiveness in medication error and associated harm reduction is variable. Some confidence can be placed in the ability of systems to reduce prescribing error rates. However, much is still unknown about mechanisms which may be most effective in improving medication safety and design features which facilitate new error risks.
Comparative analysis reveals gravity is involved in the MIZ1-regulated root hydrotropism
Authors: Li Ying , Yuan Wei , Li Luocheng , Dai Hui , Dang Xiaolin , Miao Rui , Baluška František , Kronzucker Herbert J , Lu Congming , Zhang Jianhua , Xu Weifeng
Published: September 2020

Hydrotropism is the directed growth of roots toward the water found in the soil. However, mechanisms governing interactions between hydrotropism and gravitropism remain largely unclear. In this study, we found that an air system and an agar–sorbitol system induced only oblique water-potential gradients; an agar–glycerol system induced only vertical water-potential gradients; and a sand system established both oblique and vertical water-potential gradients. We employed obliquely oriented and vertically oriented experimental systems to study hydrotropism in Arabidopsis and tomato plants. Comparative analyses using different hydrotropic systems showed that gravity hindered the ability of roots to search for obliquely oriented water, whilst facilitating roots’ search for vertically oriented water. We found that the gravitropism-deficient mutant aux1 showed enhanced hydrotropism in the oblique orientation but impaired root elongation towards water in the vertical orientation. The miz1 mutant exhibited deficient hydrotropism in the oblique orientation but normal root elongation towards water in the vertical orientation. Importantly, in contrast to miz1, the miz1/aux1 double mutant exhibited hydrotropic bending in the oblique orientation and attenuated root elongation towards water in the vertical orientation. Our results suggest that gravitropism is required for MIZ1-regulated root hydrotropism in both the oblique orientation and the vertical orientation, providing further insight into the role of gravity in root hydrotropism.
Cytokinin regulates the activity of the inflorescence meristem and components of seed yield in oilseed rape
Authors: Schwarz Ireen , Scheirlinck Marie-Therese , Otto Elisabeth , Bartrina Isabel , Schmidt Ralf-Christian , Schmülling Thomas
Published: September 2020

The number of flowers and seed-bearing structures formed by the inflorescence meristem and the formation of ovules in the female reproductive part of the flowers are important yield-related traits of crop plants. It has been shown that cytokinin is a pivotal factor regulating these traits. Here, we explore the impact of mutation of CYTOKININ OXIDASE/DEHYDROGENASE (CKX) genes encoding cytokinin-degrading enzymes on these yield-related traits in oilseed rape (Brassica napus L.). We describe the identification of four BnCKX3 and two BnCKX5 genes as regulators of reproductive development in the allotetraploid B. napus. RNA-seq analysis and in situ hybridization showed expression of these genes in reproductive organs. Loss-of-function mutants for each of these CKX gene copies were identified by targeting induced local lesions in genomes (TILLING) and combined by crossing. Sextuple ckx3 ckx5 mutants showed an increased cytokinin concentration and larger and more active inflorescence meristems. They also produced up to 72% more flowers with gynoecia containing 32% more ovules and up to 54% more pods on the main stem. The weight of seeds harvested from the main stem of plants grown in the greenhouse or in the field was increased by 20–32%. Our results show that cytokinin regulates inflorescence meristem and placenta activity in oilseed rape. The work demonstrates the potential to achieve yield enhancement in a dicot crop plant by modulating the cytokinin status through mutagenesis of specific CKX genes.
Nitric oxide production and signalling in algae
Authors: Astier Jeremy , Rossi Jordan , Chatelain Pauline , Klinguer Agnès , Besson-Bard Angélique , Rosnoblet Claire , Jeandroz Sylvain , Nicolas-Francès Valérie , Wendehenne David
Published: September 2020

Nitric oxide (NO) was the first identified gaseous messenger and is now well established as a major ubiquitous signalling molecule. The rapid development of our understanding of NO biology in embryophytes came with the partial characterization of the pathways underlying its production and with the decrypting of signalling networks mediating its effects. Notably, the identification of proteins regulated by NO through nitrosation greatly enhanced our perception of NO functions. In comparison, the role of NO in algae has been less investigated. Yet, studies in Chlamydomonas reinhardtii have produced key insights into NO production through the identification of NO-forming nitrite reductase and of S-nitrosated proteins. More intriguingly, in contrast to embryophytes, a few algal species possess a conserved nitric oxide synthase, the main enzyme catalysing NO synthesis in metazoans. This latter finding paves the way for a deeper characterization of novel members of the NO synthase family. Nevertheless, the typical NO–cyclic GMP signalling module transducing NO effects in metazoans is not conserved in algae, nor in embryophytes, highlighting a divergent acquisition of NO signalling between the green and the animal lineages.
Uncovering Environmental Change in the English Lake District: Using Computational Techniques to Trace the Presence and Documentation of Historical Flora
Authors: Smail Robert , Donaldson Chris , Govaerts Rafaël , Rayson Paul , Stevens Carly
Published: September 2020

There is a lack of concrete knowledge about floristic change in Britain before the mid-20th century. Relevant evidence is available, but it is principally contained in disparate historical sources. In this article, we demonstrate how such sources can be efficiently collated and analysed through the implementation of state-of-the-art computational-linguistic and historical-geographic information systems (GIS) techniques. We do so through a case study that focuses on the floristic history of the English Lake District. This region has been selected because of its outstanding cultural and environmental value and because it has been extensively and continuously documented since the late-17th century. We outline how natural language processing (NLP) techniques can be integrated with Kew’s Plants of the World Online database to enable temporal shifts in plant-naming conventions to be more accurately traced across a heterogeneous corpus of texts published between 1682 and 1904. Through collocate analysis and automated geoparsing techniques, the geographies associated with these plant names are then identified and extracted. Finally, we use GIS to demonstrate the potential of this data set for geo-temporal analysis and for revealing the historical distribution of Lake District flora. In outlining our methodology, this article indicates how the spatial and digital humanities can benefit research both in environmental history and in the environmental sciences more widely.
The effect of chronic dosing and p53 status on the genotoxicity of pro-oxidant chemicals in vitro
Authors: Dural Emrah , Shah Ume-Kulsoom , Pritchard Demi , Chapman Katherine Emma , Doak Shareen Heather , Jenkins Gareth James Scott
Published: September 2020

In this study, we have studied the cytotoxicity and genotoxic potency of 3 pro-oxidants; H2O2, menadione and KBrO3 in different dosing scenarios, namely acute (1-day dosing) and chronic (5-days). For this purpose, relative population doubling (RPD%) and mononucleated micronucleus (MN) test were used. TK6 cells and NH32 were employed in in vitro experiments. In the study, the total acute dose was divided into 5 days for each prooxidant chemicals by dose fractionation (1/5th per day) method. Acute dosing was compared to chronic dosing. The oxidative stress caused by the exposure of cells with pro-oxidant chemicals to the cells was determined by an optimized 2′,7′-dichlorofluorescein diacetate (DCFHDA) test method. The antioxidant levels of the cell lines were altered with buthionine sulfoxide (BSO) and N-acetyl cysteine (NAC), and the effect of antioxidant capacity on the MN formation in the cells was observed with this method. In the case of H2O2 and menadione, fractional dosing has been observed to result in lower toxicity and lower genotoxicity. But in the case of KBrO3, unlike the other 2 pro-oxidants, higher MN induction was observed with fractionated doses. DCFHDA test clearly demonstrated ROS induction with H2O2 and menadione but not with KBrO3. Unexpectedly, DCFHDA test demonstrated that KBrO3 did not cause an increase ROS levels in both acute and chronic dosing, suggesting an alternative ROS induction mechanism. It was also observed that, treatment with BSO and NAC, caused increasing and decreasing of MN fold change respectively, allowing further ROS specific mechanisms to be explored. Hence, dose fractionation expectedly caused less MN, cytotoxicity and ROS formation with H2O2 and menadione exposure, but not with KBrO3. This implies a unique mechanism of action for KBrO3 induced genotoxicity. Chronic dosing in vitro may be a valuable approach allowing better understanding of how chemicals damage DNA and pose human hazards.
Tiny noise, big mistakes: adversarial perturbations induce errors in brain–computer interface spellers
Authors: Zhang Xiao , Wu Dongrui , Ding Lieyun , Luo Hanbin , Lin Chin-Teng , Jung Tzyy-Ping , Chavarriaga Ricardo
Published: September 2020

An electroencephalogram (EEG)-based brain–computer interface (BCI) speller allows a user to input text to a computer by thought. It is particularly useful to severely disabled individuals, e.g. amyotrophic lateral sclerosis patients, who have no other effective means of communication with another person or a computer. Most studies so far focused on making EEG-based BCI spellers faster and more reliable; however, few have considered their security. This study, for the first time, shows that P300 and steady-state visual evoked potential BCI spellers are very vulnerable, i.e. they can be severely attacked by adversarial perturbations, which are too tiny to be noticed when added to EEG signals, but can mislead the spellers to spell anything the attacker wants. The consequence could range from merely user frustration to severe misdiagnosis in clinical applications. We hope our research can attract more attention to the security of EEG-based BCI spellers, and more broadly, EEG-based BCIs, which has received little attention before.
COVID-19 prevention and control in China: grid governance
Authors: Wei Yujun , Ye Zhonghua , Cui Meng , Wei Xiaokun
Published: September 2020

The coronavirus disease 2019 (COVID-19) pandemic has spread worldwide and caused negative economic and health effects. China is one of the most seriously affected countries, and it has adopted grid governance measures at the basic level of society, which include city lockdown, household survey and resident quarantine. By the end of April, China had basically brought the pandemic under control within its own borders, and residents’ lives and factory production gradually began to return to normal. In referring to the specific cases of different communities, schools, and enterprises in the four cities of Anhui, Beijing, Shenzhen and Zibo, we analyze grid-based governance measures and we summarize the effectiveness and shortcomings of these measures and discuss foundations and future challenges of grid governance. We do so in the expectation (and hope) that the world will gain a comprehensive understanding of China’s situation and introduce effective measures that enable the prevention and control of COVID-19.
Institutionally embedded research; how academic and governmental practices enable and constrain collaborative research
Authors: Duiveman Robert (R M )
Published: September 2020

To elucidate how authoritative knowledge is established for better dealing with unstructured urban problems, this article describes how collaborations between researchers and officials become an instrument for conceptualizing and addressing policy problems. A case study is used to describe a research consortium evaluating the controversial practice of ‘Lifestyle’ based housing allocation in the Dutch domain of social-housing. Analyzing this case in key episodes, we see researchers and policymakers selectively draw on established institutional practices—their so called ‘home practices’—to jointly (re-)structure problems. In addition, we find that restructuring problems is not only intertwined with, but also deliberately aimed at (re-)structuring the relations within and between the governmental practices, the actors are embedded in. It is by selectively tinkering with knowledges, values, norms, and criteria that the actors can deliberately enable and constrain the ways a real-world problem is addressed.
Family-based nutrition interventions for obesity prevention among school-aged children: a systematic review
Authors: Perdew Megan , Liu Sam , Naylor Patti-Jean
Published: September 2020

Effective evidence-informed family-based nutrition interventions for childhood obesity management are needed. (a) To assess the number and quality of published randomized controlled trials incorporating family-based nutrition interventions for childhood obesity (ages 5–18 years) management and (b) to identify intervention attributes (e.g., contact time, nutrition curricula, and behavior change strategies) used in successful interventions. Studies that met eligibility criteria were randomized controlled trials and family-based childhood obesity management interventions for children and adolescents ages 5–18 years old that included a healthy eating component and measured child dietary behaviors and/or parent dietary feeding practices. Six databases were searched: CINAHL complete, Cochrane Central Register of Controlled Trials, Health Source: Nursing/Academic Edition, MEDLINE with full text (PubMed), PsycINFO, SPORTDiscus, and ERIC (EBSCO Host). The validated Quality Assessment Tool for Quantitative Studies was used to assess study quality. Eight studies met eligibility criteria. Study quality analysis showed that blinding of the research teams (e.g., analysts, and those focused on data collection) and the use of age appropriate, valid, and reliable instruments were areas of concern. Successful nutrition interventions targeting children 5–18 years old, appear to include setting family-based goals, modifying home food environment, hands-on approaches to teaching nutrition (games, group-based activities), and fruit and vegetable vouchers. This review highlighted a limited amount of moderate to high quality evidence to suggest that family-based nutrition interventions can be successful in improving dietary behaviors and that interventions with positive outcomes had some components of nutrition curricula and strategies in common.
Campus tobacco control policies and cessation interventions in college students: a commentary calling for research and action to address tobacco-related health disparities
Authors: Berg Carla J , Yang Y Tony , Pratt-Chapman Mandi L , Douglas Evans W , Cupertino Ana-Paula , Horn Kimberly , Bernat Debra H , Abroms Lorien C , Tercyak Kenneth P
Published: September 2020

Tobacco-related health disparities (TRHDs) have a significant impact on population health in the USA. Effectively preventing and controlling TRHDs among young adult populations require multiple prevention and cessation points, including within college/university contexts. This commentary addresses current campus tobacco control policies and cessation interventions for U.S. college students, with an emphasis on TRHDs and opportunities for research and research translation to reduce these disparities. This commentary is informed by literature published between 2010 and 2020 regarding (a) prevalence and impact of campus tobacco control policies; and/or (b) behavioral outcomes from cessation interventions for young adults attending colleges. Despite a doubling of college campuses adopting tobacco-free policies from 2012 to 2017, roughly two-thirds continue to operate without such policies. Few policies address alternative tobacco products (e.g., e-cigarettes, cigars/cigarillos, and hookah), and communication about and enforcement of existing policies is extremely limited. A broad range of cessation intervention strategies have targeted individuals in this age group, but with little focus on TRHDs and limited intervention dissemination. Importantly, college students representing populations at risk for TRHDs (e.g., racial/ethnic/sexual/gender minorities, low socioeconomic status) are less likely to be exposed to strong tobacco control policies or supports for cessation. There are untapped opportunities for behavioral medicine approaches to reduce TRHDs in college settings. Research findings regarding multilevel (policy, community-level, and individual-level) interventions must be translated to policy/practice in order to address tobacco use, particularly among vulnerable college student populations.
Population Dynamics and Neuronal Polyploidy in the Developing Neocortex
Authors: Jungas Thomas , Joseph Mathieu , Fawal Mohamad-Ali , Davy Alice
Published: September 2020

The mammalian neocortex is composed of different subtypes of projection neurons that are generated sequentially during embryogenesis by differentiation of neural progenitors. While molecular mechanisms that control neuronal production in the developing neocortex have been extensively studied, the dynamics and absolute numbers of the different progenitor and neuronal populations are still poorly characterized. Here, we describe a medium throughput approach based on flow cytometry and well-known identity markers of cortical subpopulations to collect quantitative data over the course of mouse neocortex development. We collected a complete dataset in a physiological developmental context on two progenitor and two neuron populations, including relative proportions and absolute numbers. Our study reveals unexpected total numbers of Tbr2+ progenitors. In addition, we show that polyploid neurons are present throughout neocortex development.
Uncertainty in Aging and Lifespan Research: Covid-19 as Catalyst for Addressing the Elephant in the Room
Authors: Grote Gudela , Pfrombeck Julian
Published: September 2020

Uncertainty is at the center of debates on how to best cope with the Covid-19 pandemic. In our exploration of the role of uncertainty in current aging and lifespan research, we build on an uncertainty regulation framework that includes both reduction and creation of uncertainty as viable self-regulatory processes. In particular, we propose that future time perspective, a key component in models of successful aging, should be reconceptualized in terms of uncertainty regulation. We argue that by proactively regulating the amount of uncertainty one is exposed to, individuals’ future time perspective can be altered. We show how extant research might be (re)interpreted based on these considerations and suggest directions for future research, challenging a number of implicit assumptions about how age and uncertainty are interlinked. We close with some practical implications for individuals and organizations for managing the Covid-19 crisis.
SIRT3 Ablation Deteriorates Obesity-Related Cardiac Remodeling by Modulating ROS-NF-κB-MCP-1 Signaling Pathway
Authors: Guo Xiaobin , Yan Fangying , Li Jingyuan , Zhang Chunmei , Su Hongyan , Bu Peili
Published: September 2020

Obesity and the associated complications are a major public health issue as obesity incidence increases yearly, worldwide. Effects of obesity on heart failure have been reported previously. Obesity-related cardiac remodeling includes structural and functional dysfunctions, in which cardiac inflammation and fibrosis play a key role. The main mitochondrial deacetylase, SIRT3 participates in numerous cellular processes; however, its role in obesity-related cardiac remodeling remains unclear. In our study, high-fat diet (HFD) feeding induced downregulation of SIRT3 protein level in mice. SIRT3-KO mice fed on HFD exhibited higher cardiac dysfunction and cardiac remodeling compared with the wild-type controls. Further study revealed increases in collagen accumulation and inflammatory cytokine expression including MCP-1, IL-6, TGF-β, TNF-α in mice fed on HFD compared with chow diet, with higher levels observed in SIRT3-KO mice. Furthermore, significantly high levels of cardiac MCP-1 expression and macrophage infiltration, and ROS generation and activated NF-κB were observed in HFD-fed SIRT3-KO mice. We presumed that SIRT3 ablation-mediated MCP-1 upregulation is attributed to ROS-NF-κB activation. Thus, we concluded that SIRT3 prevents obesity-related cardiac remodeling by attenuating cardiac inflammation and fibrosis, through modulation of ROS-NF-κB-MCP-1 pathway.
Recurrent Vertebrobasilar Strokes Associated With Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)
Authors: Collía Fernández Alejandra , García Sánchez Juan M. , Rivera-Pérez de Rada Pablo , Fernández-Avellaneda Pedro , Rodrigo Armenteros Patricia , Torre Salaberri Ignacio , Castillo Calvo Beatriz , Gómez Muga Juan J. , Gil Alzueta María d.C. , García-Moncó Juan C.
Published: September 2020

Introduction:

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an ophthalmologic condition of likely immune origin. Typically, it presents as a chorioretinitis with bilateral visual disturbance and characteristic funduscopic lesions of the retinal pigment epithelium. APMPPE has been associated with several systemic and neurological complications, including cerebrovascular diseases.

Case Report:

A 58-year-old woman presented with sudden right hemiparesis and dysarthria, with magnetic resonance imaging evidence of an acute ischemic lesion in the left pons. Five days later, she developed contralateral hemiparesis and evolved into a locked-in syndrome. A new lesion located at the right pontomedullary junction was detected by magnetic resonance imaging. The patient developed a visual deterioration that had started 1 week before admission. An ophthalmologic evaluation showed visual acuity loss (20/200 in both eyes) and characteristic yellow-white lesions in the posterior pole of both eyes. Laboratory analyses were remarkable for positive antinuclear antibodies, an elevated erythrocyte sedimentation rate, and C-reactive protein. The cerebrospinal fluid showed elevated protein levels, lymphocytic pleocytosis, and normal glucose levels. The fundoscopy findings together with recurrent strokes led to the diagnosis of APMPPE and appropriate immunomodulatory treatment with corticosteroids and azathioprine was started.

Conclusions:

This case illustrates the importance of careful evaluation and high clinical suspicion for this entity when dealing with patients with new-onset headache or stroke associated with visual impairment. Proper ophthalmologic evaluation is important so that adequate therapy is established.
Challenges associated with treating and preventing antipsychotic-induced constipation: considerations and cautions when prescribing novel interventions
Authors: Demler Tammie Lee , Krieger Kelly
Published: September 2020

Antipsychotic-induced constipation is a treatment-limiting side effect for patients with serious mental illness (SMI). In addition to increased risk of constipation, due to adverse medication effects, individuals diagnosed with SMI are also prone to lifestyle factors that contribute to this medical complication. The USA Food and Drug Administration (FDA) recently released enhanced warnings about the risk of serious, sometimes fatal, complications associated with constipation caused by the antipsychotic, clozapine. It is likely this heightened warning will prompt providers to seek additional means to prevent and treat antipsychotic-induced constipation, despite having no agent with FDA approval for this specific indication. Off-label prescribing of newer medications for the treatment of antipsychotic-induced constipation is associated with risks, many of which are still unknown, considering the exclusion of patients with SMI in studies measuring nonpsychiatric outcomes.