bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain–computer interfaces based on code-modulated visual evoked potentials (c-VEP): a literature review
Authors: Martínez-Cagigal Víctor , Thielen Jordy , Santamaría-Vázquez Eduardo , Pérez-Velasco Sergio , Desain Peter , Hornero Roberto
Published: November 2021

Objective. Code-modulated visual evoked potentials (c-VEP) have been consolidated in recent years as robust control signals capable of providing non-invasive brain–computer interfaces (BCIs) for reliable, high-speed communication. Their usefulness for communication and control purposes has been reflected in an exponential increase of related articles in the last decade. The aim of this review is to provide a comprehensive overview of the literature to gain understanding of the existing research on c-VEP-based BCIs, since its inception (1984) until today (2021), as well as to identify promising future research lines. Approach. The literature review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. After assessing the eligibility of journal manuscripts, conferences, book chapters and non-indexed documents, a total of 70 studies were included. A comprehensive analysis of the main characteristics and design choices of c-VEP-based BCIs was discussed, including stimulation paradigms, signal processing, modeling responses, applications, etc. Main results. The literature review showed that state-of-the-art c-VEP-based BCIs are able to provide an accurate control of the system with a large number of commands, high selection speeds and even without calibration. In general, a lack of validation in real setups was observed, especially regarding the validation with disabled populations. Future work should be focused toward developing self-paced c-VEP-based portable BCIs applied in real-world environments that could exploit the unique benefits of c-VEP paradigms. Some aspects such as asynchrony, unsupervised training, or code optimization still require further research and development. Significance. Despite the growing popularity of c-VEP-based BCIs, to the best of our knowledge, this is the first literature review on the topic. In addition to providing a joint discussion of the advances in the field, some future lines of research are suggested to contribute to the development of reliable plug-and-play c-VEP-based BCIs.
Avalanche transport of energetic-ions in magnetic confinement plasmas: nonlinear multiple wave-number simulation
Authors: Zhu X.L. , Chen W. , Podestà M. , Wang F. , Liu D. , Wang Z.X.
Published: November 2021

Large burst activity, identified as toroidal Alfvén eigenmode (TAE) avalanche, occurs frequently in neutral-beam heated plasmas in National Spherical Torus Experiment (NSTX). Based on the typical experimental observation of TAE avalanche on NSTX, a self-consistent nonlinear multiple wave-number (k
∥ ≃ n/R, where n toroidal mode-number and R major radius) simulation associated with TAE avalanches is performed using the experimental parameters and profiles before the occurrence of TAE avalanche as the M3D-K input. The wave–wave nonlinear coupling among different modes and the resonant interaction between different modes and energetic-ions during TAE avalanches are identified in the nonlinear multiple wave-number simulations. The resonance overlap during the TAE avalanche is clearly observed in the simulation. It is found that the effective wave–wave coupling and a sufficiently strong drive are two important ingredients for the onset of TAE avalanches. TAE avalanche is considered to be a strongly nonlinear process and it is always accompanied by the simultaneous rapid frequency-chirping and large amplitude bursting of multiple modes and significant energetic-ion losses. The experimental phenomenon is observed on NSTX and is qualitatively reproduced by the simulation results in this work. These findings indicate that the onset of avalanche is triggered by nonlinearity of the system, and are also conducive to understanding the underlying mechanism of avalanche transport of energetic particles in the future burning plasmas, such as International Thermonuclear Experiment Reactor.
Recent progress in modeling ICRF-edge plasma interactions with application to ASDEX Upgrade
Authors: Zhang W. , Bilato R. , Bobkov V. , Cathey A. , Di Siena A. , Hoelzl M. , Messiaen A. , Myra J.R. , Suárez López G. , Tierens W. , Usoltceva M. , Wright J.C. , the ASDEX Upgrade Team  , the EUROfusion MST1 Team
Published: November 2021

This paper summarizes recent progress in modeling the interaction between ion cyclotron range of frequency (ICRF) waves and edge plasma with application to ASDEX Upgrade. The basic theories, the development of ICRF and edge plasma codes, the integrated modeling methods and some key results are reviewed. In particular, the following physical aspects are discussed: (1) ICRF power coupling; (2) slow wave propagation; (3) ICRF-rectified sheath; (4) ICRF-induced convection; (5) ICRF-edge turbulence interaction. Moreover, comprehensive integrated modeling strategies by including all necessary codes in one package and solving multiple physical issues self-consistently are discussed.
Hydrodynamics of weak integrability breaking
Authors: Bastianello Alvise , De Luca Andrea , Vasseur Romain
Published: November 2021

We review recent progress in understanding nearly integrable models within the framework of generalized hydrodynamics (GHD). Integrable systems have infinitely many conserved quantities and stable quasiparticle excitations: when integrability is broken, only a few residual conserved quantities survive, eventually leading to thermalization, chaotic dynamics and conventional hydrodynamics. In this review, we summarize recent efforts to take into account small integrability breaking terms, and describe the transition from GHD to standard hydrodynamics. We discuss the current state of the art, with emphasis on weakly inhomogeneous potentials, generalized Boltzmann equations and collision integrals, as well as bound-state recombination effects. We also identify important open questions for future works.
Analog pile-up circuit technique using a single capacitor for the readout of Skipper-CCD detectors
Authors: Sofo Haro M. , Chavez C. , Lipovetzky J. , Alcalde Bessia F. , Cancelo G. , Chierchie F. , Estrada J. , Fernandez Moroni G. , Stefanazzi L. , Tiffenberg J. , Uemura S.
Published: November 2021

With Skipper-CCD detectors it is possible to take multiple samples of the charge packet collected on each pixel. After averaging the samples, the noise can be extremely reduced allowing the exact counting of electrons per pixel. In this work we present an analog circuit that, with a minimum number of components, applies a double slope integration (DSI) and at the same time averages the multiple samples, producing at its output the pixel value with sub-electron noise. For this purpose, we introduce the technique of using the DSI integrator capacitor to add the skipper samples. An experimental verification using discrete components is presented, together with an analysis of its noise sources and limitations. After averaging 400 samples it was possible to reach a readout noise of 0.18 e-
rms/pix, comparable to other available readout systems. Due to its simplicity and significant reduction of the sampling requirements, this circuit technique is of particular interest in particle experiments and cameras with a high density of Skipper-CCDs.
The interplay between (electro)chemical and (chemo)mechanical effects in the cycling performance of thiophosphate-based solid-state batteries
Authors: Teo Jun Hao , Strauss Florian , Walther Felix , Ma Yuan , Payandeh Seyedhosein , Scherer Torsten , Bianchini Matteo , Janek Jürgen , Brezesinski Torsten
Published: November 2021

Solid-state batteries (SSBs) are a promising next step in electrochemical energy storage but are plagued by a number of problems. In this study, we demonstrate the recurring issue of mechanical degradation because of volume changes in layered Ni-rich oxide cathode materials in thiophosphate-based SSBs. Specifically, we explore superionic solid electrolytes (SEs) of different crystallinity, namely glassy 1.5Li2S-0.5P2S5-LiI and argyrodite Li6PS5Cl, with emphasis on how they affect the cyclability of slurry-cast cathodes with NCM622 (60% Ni) or NCM851005 (85% Ni). The application of a combination of ex situ and in situ analytical techniques helped to reveal the benefits of using a SE with a low Young’s modulus. Through a synergistic interplay of (electro)chemical and (chemo)mechanical effects, the glassy SE employed in this work was able to achieve robust and stable interfaces, enabling intimate contact with the cathode material while at the same time mitigating volume changes. Our results emphasize the importance of considering chemical, electrochemical, and mechanical properties to realize long-term cycling performance in high-loading SSBs.
Variant Library Annotation Tool (VaLiAnT): an oligonucleotide library design and annotation tool for saturation genome editing and other deep mutational scanning experiments
Authors: Barbon Luca , Offord Victoria , Radford Elizabeth J , Butler Adam P , Gerety Sebastian S , Adams David J , Tan Hong Kee , Waters Andrew J
Published: November 2021

Motivation

CRISPR/Cas9-based technology allows for the functional analysis of genetic variants at single nucleotide resolution whilst maintaining genomic context. This approach, known as saturation genome editing (SGE), a form of deep mutational scanning, systematically alters each position in a target region to explore its function. SGE experiments require the design and synthesis of oligonucleotide variant libraries which are introduced into the genome. This technology is applicable to diverse fields such as disease variant identification, drug development, structure–function studies, synthetic biology, evolutionary genetics and host–pathogen interactions. Here, we present the Variant Library Annotation Tool (VaLiAnT) which can be used to generate variant libraries from user-defined genomic coordinates and standard input files. The software can accommodate user-specified species, reference sequences and transcript annotations.

Results

Coordinates for a genomic range are provided by the user to retrieve a corresponding oligonucleotide reference sequence. A user-specified range within this sequence is then subject to systematic, nucleotide and/or amino acid saturating mutator functions. VaLiAnT provides a novel way to retrieve, mutate and annotate genomic sequences for oligonucleotide library generation. Specific features for SGE library generation can be employed. In addition, VaLiAnT is configurable, allowing for cDNA and prime editing saturation library generation, with other diverse applications possible.

Availability and implementation

VaLiAnT is a command line tool written in Python. Source code, testing data, example input and output files and executables are available (https://github.com/cancerit/VaLiAnT) in addition to a detailed user manual (https://github.com/cancerit/VaLiAnT/wiki). VaLiAnT is licensed under AGPLv3.

Supplementary information

Supplementary data are available at Bioinformatics online.
Biobox: a toolbox for biomolecular modelling
Authors: Rudden Lucas S P , Musson Samuel C , Benesch Justin L P , Degiacomi Matteo T
Published: November 2021

Motivation

The implementation of biomolecular modelling methods and analyses can be cumbersome, often carried out with in-house software reimplementing common tasks, and requiring the integration of diverse software libraries.

Results

We present Biobox, a Python-based toolbox facilitating the implementation of biomolecular modelling methods.

Availability and implementation

Biobox is freely available on https://github.com/degiacom/biobox, along with its API and interactive Jupyter notebook tutorials.
Faecal immunochemical test to triage patients with possible colorectal cancer symptoms: meta-analysis
Authors: Saw Kai Sheng , Liu Chen , Xu William , Varghese Chris , Parry Susan , Bissett Ian
Published: November 2021

Background

This review evaluated the utility of single quantitative faecal immunochemical test (FIT) as a triaging tool for patients with symptoms of possible colorectal cancer, the effect of symptoms on FIT accuracy, and the impact of triaging incorporating FIT on service provision.

Methods

Five databases were searched. Meta-analyses of the extracted FIT sensitivities and specificities for detection of colorectal cancer at reported f-Hb thresholds were performed. Secondary outcomes included sensitivity and specificity of FIT for advanced colorectal neoplasia and serious bowel disease. Subgroup analysis by FIT brand and symptoms was undertaken.

Results

Fifteen prospective cohort studies, including 28 832 symptomatic patients were included. At the most commonly reported f-Hb positivity threshold of ≥ 10 µg Hb/g faeces (n=13), the summary sensitivity was 88.7% (95% c.i. 85.2 to 91.4) and the specificity was 80.5% (95% c.i. 75.3 to 84.8) for colorectal cancer. At lower limits of detection of ≥ 2 µg Hb/g faeces, the summary sensitivity was 96.8% (95% c.i. 91.0 to 98.9) and the specificity was 65.6% (95% c.i. 59.0 to 71.6). At the upper f-Hb positivity thresholds of ≥ 100 µg Hb/g faeces and ≥ 150 µg Hb/g faeces, summary sensitivities were 68.1% (95% c.i. 59.2 to 75.9) and 66.3% (95% c.i. 52.2 to 78.0), with specificities of 93.4% (95% c.i. 91.3 to 95.1) and 95.1% (95% c.i. 93.6 to 96.3) respectively. FIT sensitivity was comparable between different assay brands. FIT sensitivity may be higher in patients reporting rectal bleeding.

Conclusion

Single quantitative FIT at lower f-Hb positivity thresholds can adequately exclude colorectal cancer in symptomatic patients and provides a data-based approach to prioritization of colonoscopy resources.
Somatosensory awareness in the parietal operculum
Authors: Sirigu Angela , Desmurget Michel
Published: November 2021

This scientific commentary refers to ‘Tonic somatosensory responses and deficits of tactile awareness converge in the parietal operculum’ by Del Vecchio et al. (doi:10.1093/brain/awab384).
Time-dependent cortical plasticity during moderate-intensity continuous training versus high-intensity interval training in rats
Authors: Hugues Nicolas , Pin-Barre Caroline , Pellegrino Christophe , Rivera Claudio , Berton Eric , Laurin Jérôme
Published: November 2021

The temporal pattern of cortical plasticity induced by high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) is required to clarify their relative benefits to prevent neurological disorders. The purpose of this study is to define the time-dependent effects of work-matched HIIT and MICT on cortical plasticity, endurance, and sensorimotor performances over an 8-week training period in healthy rats. Adult healthy rats performed incremental exercise tests and sensorimotor tests before and at 2, 4, and 8 weeks of training. In parallel, cortical markers related to neurotrophic, angiogenic, and metabolic activities were assessed. Results indicate that HIIT induced an early and superior endurance improvement compared to MICT. We found significant enhancement of speed associated with lactate threshold (SLT) and maximal speed (Smax) in HIIT animals. MICT promoted an early increase in brain-derived neurotrophic factor and angiogenic/metabolic markers but showed less influence at 8 weeks. HIIT upregulated the insulin-like growth factor-1 (IGF-1) as well as neurotrophic, metabolic/angiogenic markers at 2 and 8 weeks and downregulated the neuronal K-Cl cotransporter KCC2 that regulates GABAA-mediated transmission. HIIT and MICT are effective in a time-dependent manner suggesting a complementary effect that might be useful in physical exercise guidelines for maintaining brain health.
Esophageal microbiota composition and outcome of esophageal cancer treatment: a systematic review
Authors: Plat Victor D , van Rossen Tessel M , Daams Freek , de Boer Nanne K , de Meij Tim G J , Budding Andries E , Vandenbroucke-Grauls Christina M J E , van der Peet Donald L
Published: November 2021

Background: The role of esophageal microbiota in esophageal cancer treatment is gaining renewed interest, largely driven by novel DNA-based microbiota analysis techniques. The aim of this systematic review is to provide an overview of current literature on the possible association between esophageal microbiota and outcome of esophageal cancer treatment, including tumor response to (neo)adjuvant chemo(radio)therapy, short-term surgery-related complications, and long-term oncological outcome. Methods: A systematic review of literature was performed, bibliographic databases were searched and relevant articles were selected by two independent researchers. The Newcastle-Ottawa scale was used to estimate the quality of included studies. Results: The search yielded 1303 articles, after selection and cross-referencing, five articles were included for qualitative synthesis and four studies were considered of good quality. Two articles addressed tumor response to neoadjuvant chemotherapy and described a correlation between high intratumoral Fusobacterium nucleatum levels and a poor response. One study assessed surgery-related complications, in which no direct association between esophageal microbiota and occurrence of complications was observed. Three studies described a correlation between shortened survival and high levels of intratumoral F. nucleatum, a low abundance of Proteobacteria and high abundances of Prevotella and Streptococcus species. Conclusions: Current evidence points towards an association between esophageal microbiota and outcome of esophageal cancer treatment and justifies further research. Whether screening of the individual esophageal microbiota can be used to identify and select patients with a predisposition for adverse outcome needs to be further investigated. This could lead to the development of microbiota-based interventions to optimize esophageal microbiota composition, thereby improving outcome of patients with esophageal cancer.
Quantification of left atrial fibrosis by 3D late gadolinium-enhanced cardiac magnetic resonance imaging in patients with atrial fibrillation: impact of different analysis methods
Authors: Hopman Luuk H G A , Bhagirath Pranav , Mulder Mark J , Eggink Iris N , van Rossum Albert C , Allaart Cornelis P , Götte Marco J W
Published: November 2021

Aims

Various methods and post-processing software packages have been developed to quantify left atrial (LA) fibrosis using 3D late gadolinium-enhancement cardiac magnetic resonance (LGE-CMR) images. Currently, it remains unclear how the results of these methods and software packages interrelate.

Methods and results

Forty-seven atrial fibrillation (AF) patients underwent 3D-LGE-CMR imaging prior to their AF ablation. LA fibrotic burden was derived from the images using open-source CEMRG software and commercially available ADAS 3D-LA software. Both packages were used to calculate fibrosis based on the image intensity ratio (IIR)-method. Additionally, CEMRG was used to quantify LA fibrosis using three standard deviations (3SD) above the mean blood pool signal intensity. Intraclass correlation coefficients were calculated to compare LA fibrosis quantification methods and different post-processing software outputs. The percentage of LA fibrosis assessed using IIR threshold 1.2 was significantly different from the 3SD-method (29.80 ± 14.15% vs. 8.43 ± 5.42%; P < 0.001). Correlation between the IIR-and SD-method was good (r = 0.85, P < 0.001) although agreement was poor [intraclass correlation coefficient (ICC) = 0.19; P < 0.001]. One-third of the patients were allocated to a different fibrosis category dependent on the used quantification method. Fibrosis assessment using CEMRG and ADAS 3D-LA showed good agreement for the IIR-method (ICC = 0.93; P < 0.001).

Conclusions

Both, the IIR1.2 and 3SD-method quantify atrial fibrotic burden based on atrial wall signal intensity differences. The discrepancy in the amount of LA fibrosis between these methods may have clinical implications when patients are classified according to their fibrotic burden. There was no difference in results between post-processing software packages to quantify LA fibrosis if an identical quantification method including the threshold was used.
A Colonial Celebrity in the New Attention Economy: Cecil Rhodes’s Cape-to-Cairo Telegraph and Railway Negotiations in 1899
Authors: van Waarden Betto
Published: November 2021

In 1899, the British colonialist Cecil Rhodes went to Berlin to negotiate about his fantastical ‘Cape-to-Cairo’ telegraph and railway scheme with his former nemesis, the German emperor Wilhelm II. Why did this initiative of Rhodes, who was held responsible for the disastrous Jameson Raid and no longer occupied any official position, receive so much coverage and legitimacy in the international press? Despite the vast scholarship on Rhodes, there is strikingly little analysis of these negotiations, considering that they were hailed as marking the rehabilitation of Rhodes and the troubled Anglo-German relationship, signalled that Germany would not support the Boers in their conflict with Britain, and led to Germany’s inclusion in the prestigious Rhodes Scholarships scheme. This article analyses the reporting of the negotiations and shows that Rhodes overshadowed other political figures in the competitive ‘attention economy’ of the emerging mass press. Building on the notion of ‘celebrity politics’, it argues that the press attention for him resulted from three interconnected logics: a political logic of agenda-setting and ideological loyalties, a journalistic logic in which scarce access to Rhodes fostered his mythologising, and a mass media logic that increasingly superseded ideological divides. This mass media logic dictated a focus on Rhodes’s personal narrative (infused with literary and colonial themes), personifying politics, and performing these politics in a novel business-like style. This press attention gained Rhodes informal power and shows how, by the end of the nineteenth century, successful politics required the new ability of political figures to attract and leverage media attention. Moreover, it constituted the precondition for the growing cult of Rhodes in the twentieth century, and the subsequent criticism of this cult and its representation of racism in recent times.
Patient-reported diagnostic intervals to colorectal cancer diagnosis in the Midland region of New Zealand: a prospective cohort study
Authors: Blackmore Tania , Chepulis Lynne , Rawiri Keenan , Kidd Jacquie , Stokes Tim , Firth Melissa , Elwood Mark , Weller David , Emery Jon , Lawrenson Ross
Published: November 2021

Background and objectives

New Zealand (NZ) has high rates of colorectal cancer (CRC) but low rates of early detection. The majority of CRC is diagnosed through general practice, where lengthy diagnostic intervals are common. We investigated factors contributing to diagnostic delay in a cohort of patients newly diagnosed with CRC.

Methods

Patients were recruited from the Midland region and interviewed about their diagnostic experience using a questionnaire based on a modified Model of Pathways to Treatment framework and SYMPTOM questionnaire. Descriptive statistics were used to describe the population characteristics. Chi-square analysis and logistic regression were used to analyse factors influencing diagnostic intervals.

Results

Data from 176 patients were analysed, of which 65 (36.9%) experienced a general practitioner (GP) diagnostic interval of >120 days and 96 (54.5%) experienced a total diagnostic interval (TDI) > 120 days. Patients reporting rectal bleeding were less likely to experience a long TDI (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.14–0.78) and appraisal/help-seeking interval (OR, 0.19, 95% CI: 0.06–0.59). Patients <60 were more likely to report a longer appraisal/help-seeking interval (OR, 3.32, 95% CI: 1.17–9.46). Female (OR, 2.19, 95% CI: 1.08–4.44) and Māori patients (OR, 3.18, 95% CI: 1.04–9.78) were more likely to experience a long GP diagnostic interval.

Conclusion

NZ patients with CRC can experience long diagnostic intervals, attributed to patient and health system factors. Young patients, Māori, females, and patients experiencing change of bowel habit may be at particular risk. We need to increase symptom awareness of CRC for patients and GPs. Concentrated efforts are needed to ensure equity for Māori in access to screening, diagnostics, and treatment.
Albumin-Corrected Fructosamine Predicts All-Cause and Non-CVD Mortality Among the Very Elderly Aged 80 Years or Older Without Diabetes
Authors: Zhou Jinhui , Lv Yuebin , Zhao Feng , Wei Yuan , Gao Xiang , Chen Chen , Lu Feng , Liu Yingchun , Li Chengcheng , Wang Jiaonan , Zhang Xiaochang , Gu Heng , Yin Zhaoxue , Cao Zhaojin , Kraus Virginia B , Mao Chen , Shi Xiaoming
Published: November 2021

Background

Several guidelines have suggested alternative glycemic markers for hemoglobin A1c among older adults with limited life expectancy or multiple coexisting chronic illnesses. We evaluated associations between fructosamine, albumin-corrected fructosamine (AlbF), fasting plasma glucose (FPG), and mortality in the diabetic and nondiabetic subpopulations, and compared which marker better predicts mortality among participants aged 80 and older.

Methods

Included were 2 238 subjects from the Healthy Ageing and Biomarkers Cohort Study (2012–2018) and 207 participants had diabetes at baseline. Multivariable Cox proportional hazards regression models investigated the associations of fructosamine, AlbF, FPG, and all-cause, cardiovascular disease (CVD), and non-CVD mortality in the diabetic and nondiabetic subpopulations. Restricted cubic splines explored potential nonlinear relations. C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) evaluated the additive value of different glycemic markers to predict mortality.

Results

Overall, 1 191 deaths were documented during 6 793 person-years of follow-up. In the linear model, per unit increases of fructosamine, AlbF, and FPG were associated with a higher risk of mortality in nondiabetic participants, with hazard ratios of 1.02 (1.00, 1.05), 1.27 (1.14, 1.42), and 1.04 (0.98, 1.11) for all-cause mortality, and 1.04 (1.00, 1.07), 1.38 (1.19, 1.59), and 1.10 (1.01, 1.19) for non-CVD mortality, respectively. Comparisons indicated that AlbF better predicts all-cause and non-CVD mortality in nondiabetic participants with significant improvement in IDI and NRI.

Conclusions

Higher concentrations of fructosamine, AlbF, and FPG were associated with a higher risk of all-cause or non-CVD mortality among the very elderly where AlbF may constitute an alternative prospective glycemic predictor of mortality.
Midlife Work Limitations are Associated with Lower Odds of Survival and Healthy Aging
Authors: Jajtner Katie M , Brucker Debra L , Mitra Sophie
Published: November 2021

Objectives

Health conditions that limit work are associated with myriad socioeconomic disadvantages and around half of Americans could face a work limitation at some point in their working career. Our study examines the relationship between midlife work limitations and two aging outcomes: longevity and healthy aging.

Methods

Using longitudinal data from the Panel Study of Income Dynamics and restricted mortality data, multivariate logistic regressions estimate the odds of desirable aging outcomes around age 65 for individuals with various midlife work limitation histories in samples of around 2,000 individuals.

Results

Midlife work limitations are consistently linked with a lower likelihood of desirable aging outcomes. Temporary limitations are associated with 59% and 69% lower survival and healthy aging odds, respectively. Chronic limitations are associated with approximately 80% lower survival odds and 90% lower healthy aging odds at age 65.

Discussion

Even temporary work limitations can be highly disadvantageous for aging outcomes, emphasizing the need to understand different work limitation histories. Future research should identify underlying mechanisms linking midlife work limitations and less desirable aging outcomes.
Effects of Lamotrigine and Topiramate on Glial Properties in an Astrocyte-Microglia Co-Culture Model of Inflammation
Authors: Faustmann Timo Jendrik , Corvace Franco , Faustmann Pedro M , Ismail Fatme Seval
Published: November 2021

Background

Astrocytes and microglia are involved in the pathophysiology of epilepsy and bipolar disorder with a link to inflammation. We aimed to investigate the effects of the antiepileptic and mood-stabilizing drugs lamotrigine (LTG) and topiramate (TPM) on glial viability, microglial activation, cytokine release, and expression of gap-junctional protein connexin 43 (Cx43) in different set-ups of an in vitro astrocyte-microglia co-culture model of inflammation.

Methods

Primary rat co-cultures of astrocytes containing 5% (M5, representing “physiological” conditions) or 30% (M30, representing “pathological, inflammatory” conditions) of microglia were treated with different concentrations of LTG and TPM for 24 hours. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to measure the glial cell viability. The microglial activation state was analyzed by immunocytochemistry. The pro-inflammatory tumor necrosis factor-α (TNF-α) and anti-inflammatory transforming growth factor-ß1 (TGF-ß1) cytokine levels were measured by enzyme-linked immunosorbent assay. The astroglial Cx43 expression was quantified by western blot.

Results

A significant reduction of the glial cell viability after incubation with LTG or TPM was observed in a concentration-dependent manner under all conditions. LTG caused no significant alterations of the microglial phenotypes. Under pathological conditions, TPM led to a significant concentration-dependent reduction of microglial activation. This correlated with increased astroglial Cx43 expression. TNF-α levels were not affected by LTG and TPM. Treatment with higher concentrations of LTG, but not with TPM, led to a significant increase in TGF-ß1 levels in M5 and M30 co-cultures.

Conclusions

Despite the possible glial toxicity of LTG and TPM, both drugs reduced inflammatory activity, suggesting potential positive effects on the neuroinflammatory components of the pathogenesis of epilepsy and bipolar disorder.
Supporting research, protecting data: one institution’s approach to clinical data warehouse governance
Authors: Walters Kellie M , Jojic Anna , Pfaff Emily R , Rape Marie , Spencer Donald C , Shaheen Nicholas J , Lamm Brent , Carey Timothy S
Published: November 2021

Institutions must decide how to manage the use of clinical data to support research while ensuring appropriate protections are in place. Questions about data use and sharing often go beyond what the Health Insurance Portability and Accountability Act of 1996 (HIPAA) considers. In this article, we describe our institution’s governance model and approach. Common questions we consider include (1) Is a request limited to the minimum data necessary to carry the research forward? (2) What plans are there for sharing data externally?, and (3) What impact will the proposed use of data have on patients and the institution? In 2020, 302 of the 319 requests reviewed were approved. The majority of requests were approved in less than 2 weeks, with few or no stipulations. For the remaining requests, the governance committee works with researchers to find solutions to meet their needs while also addressing our collective goal of protecting patients.
Balancing Bees and Pest Management: Projected Costs of Proposed Bee-Protective Neonicotinoid Regulation in California
Authors: Mace Kevi , Rudder Jessica , Goodhue Rachael , Tolhurst Tor , Tregeagle Daniel , Wei Hanlin , Grafton-Cardwell Beth , Grettenberger Ian , Wilson Houston , Van Steenwyk Robert , Zalom Frank , Steggall John
Published: November 2021

Neonicotinoid insecticides are widely used in agriculture, including in many California specialty crops. With mounting evidence that these insecticides are harmful to bees, state and national governments have increasingly regulated their use. The European Union, Canada, and United States have imposed use restrictions on several neonicotinoids, such as on the timing of applications. In 2020, California proposed a draft regulation to mitigate harm to managed pollinators from four nitroguanidine-substituted neonicotinoids (NGNs): clothianidin, dinotefuran, imidacloprid, and thiamethoxam. We use data on California pesticide use from 2015 to 2017 to analyze the economic and pest management implications of the 2020 draft proposed regulation for seven crops: almond, cherry, citrus, cotton, grape, strawberry, and tomato. From 2015 to 2017, these crops accounted for approximately 85% of total hectares treated with NGNs and 87% of NGN use by kilograms of active ingredient applied in treatments that would have been affected by the proposed regulation. These insecticides often primarily target Hemipteran insect pests. In most cases there are alternatives; however, these are often more expensive per hectare and do not have the same residual effectiveness as the NGNs, which are systemic insecticides. Overall, we estimate that pest management costs for these crops would have increased an estimated $13.6 million in 2015, $12.8 million in 2016, and $11.1 million in 2017 if the 2020 draft proposed regulation had been in effect, representing a 61% to 72% increase in the cost of managing the target pests.
The Attractiveness of α-Copaene to Members of theEuwallacea fornicatus(Coleoptera: Curculionidae) Species Complex in California and Taiwan
Authors: Liu Fang-Ling , Rugman-Jones Paul , Liao Yi-Chang , Fernandez Veronica , Chien Iris , Dodge Christine , Cooperband Miriam F , Tuan Shu-Jen , Stouthamer Richard
Published: November 2021

Species belonging to the Euwallacea fornicatus Eichhoff (Coleoptera: Scolytinae) species complex have invaded the continental U.S. since at least 2003. Three species of this complex are known to have established, two in California (E. fornicatus; and Euwallacea kuroshio), and a third in Florida (Euwallacea perbrevis). Their native ranges are spread across southern and southeast Asia. In Taiwan, all three species occur in sympatry. They attack healthy trees of widely varied species and cause severe damage and death to the trees. The attractant quercivorol is commonly used to promote their detection by passive trapping. Recent studies in Florida have shown that trapping of E. perbrevis can be further improved by adding a synergist, α-copaene, alongside the quercivorol lure. Thus, we were interested in testing the effectiveness of α-copaene for trapping the other invasive members of the complex in California and in an area of Taiwan where all three species co-occur. We found that α-copaene marginally enhanced the trapping of E. perbrevis in Taiwan, but had no effect on the trapping of E. fornicatus or E. kuroshio in either California or Taiwan. We conclude that any enhancing effect of α-copaene is specific to E. perbrevis. This highlights the economic importance of accurate species identification in developing and implementing an efficient, and yet cost-effective, monitoring program for the management of E. fornicatus and E. kuroshio in California and elsewhere.
Structural and environmental predictors of tricolored bat presence and abundance in Texas caves
Authors: Meierhofer Melissa B , Leivers Samantha J , Pierce Brian L , Powers Garrett W , Evans Jonah W , Morrison Michael L
Published: November 2021

The identification of bat colonies is essential to conserve and manage these globally threatened mammals. Caves offer potential roosting locations (hibernacula) to hibernating bat species; however, identifying regions where bat-occupied caves exist can be time-consuming. In Texas, caves are often on privately owned land, creating difficulties for accessing and managing potential hibernacula. The tricolored bat (Perimyotis subflavus), a species susceptible to white-nose syndrome, hibernates in caves in the winter in Texas. We sought to identify and quantify site-specific structural and environmental features that influence the presence and abundance of overwintering tricolored bats. We surveyed caves for bats and recorded environmental and structural features of 116 caves January–February 2016, December–February 2016–2017, January–February 2018, and December–February 2018–2019. We used a zero-inflated Poisson regression to identify which features best explained the presence and abundance of tricolored bats. We found that bat presence increased as cave length decreased, and as Normalized Difference Vegetation Index (NDVI) and external vapor pressure deficit increased. Bat abundance increased as number of portals, cave length, NDVI, and external temperature increased. Combining surface data with subsurface features can assist with identifying specific karst regions and known caves within those regions for survey and management efforts.
Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture
Authors: Kubo Nobuteru , Kobayashi Daijiro , Iwanaga Mototaro , Matsuura Masana , Higuchi Keiko , Eishima Jun , Muramatsu Hiroyuki , Okano Naoko , Shioya Mariko , Onishi Masahiro , Aoki Tetsuya , Oike Takahiro , Ohno Tatsuya ,   Gunma Society for Radiation Oncology (GUSTRO)
Published: November 2021

The promising results of the PACIFIC study led to the approval of consolidation durvalumab for coverage by the National Health Insurance (NHI) in 2018 for patients with locally-advanced unresectable non-small cell lung carcinoma (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT). However, the effect of NHI coverage on the patterns of care for this population remains unclear. Here, we conducted a questionnaire-based survey to determine the patterns of care for patients with stage II–III NSCLC treated with definitive radiotherapy in 2017 (pre-durvalumab era) or in 2019 (post-durvalumab era). Data were obtained from 11 radiotherapy facilities in Gunma prefecture, which has a population of 1.94 million. We identified 80 and 83 patients with stage II–III NSCLC who received definitive radiotherapy in Gunma in 2017 and 2019, respectively. At a given facility, CCRT was the treatment of choice in a significantly greater proportion of patients in 2019 than in 2017 (66% ± 20% vs 51% ± 29%, P = 0.041). Intensity-modulated radiotherapy (IMRT) was more frequent in 2019 than in 2017 (24% vs 1.2%). Carboplatin plus paclitaxel was used for CCRT at higher rate in 2019 than in 2017 (73% vs 44%). Consolidation durvalumab was performed in 73% (40/55) of CCRT-treated patients in 2019, and the treatment was performed for the planned 12 months in 45% (18/40) of patients. These data indicate that NHI coverage of durvalumab might be a possible reason for choosing CCRT in patients with stage II–III NSCLC in the real-world setting.
Roles of acyl-CoA-binding proteins in plant reproduction
Authors: Hamdan Mohd Fadhli , Lung Shiu-Cheung , Guo Ze-Hua , Chye Mee-Len
Published: November 2021

Acyl-CoA-binding proteins (ACBPs) constitute a well-conserved family of proteins in eukaryotes that are important in stress responses and development. Past studies have shown that ACBPs are involved in maintaining, transporting and protecting acyl-CoA esters during lipid biosynthesis in plants, mammals, and yeast. ACBPs show differential expression and various binding affinities for acyl-CoA esters. Hence, ACBPs can play a crucial part in maintaining lipid homeostasis. This review summarizes the functions of ACBPs during the stages of reproduction in plants and other organisms. A comprehensive understanding on the roles of ACBPs during plant reproduction may lead to opportunities in crop improvement in agriculture.
A Balanced Robertsonian Translocation in a Patient with a Janus Kinase 2–Positive Polycythemia Vera
Authors: Strasser Bernhard , Paar Christian , Kiesl David , Tomasits Josef
Published: November 2021

A male patient with a persistent, combined erythrocytosis, leukocytosis, and thrombocytosis without representative evidence of reactive increase emerged as having a myeloproliferative disorder. Molecular-biological assessment yielded Janus kinase 2–positive results, and the patient was diagnosed with polycythemia vera. In addition to these findings, further karyotyping accounted for a Robertsonian translocation. Because this rearrangement was a balanced variant, we concluded that this cytogenetic result might not significantly alter the diagnosis of polycythemia vera.
A quantitative assessment of completeness correction methods and public release of a versatile simulation code
Authors: Leethochawalit Nicha , Trenti Michele , Morishita Takahiro , Roberts-Borsani Guido , Treu Tommaso
Published: November 2021

Having accurate completeness functions is crucial to the determination of the rest-frame ultraviolet luminosity functions (UVLFs) all the way back to the epoch of reionization. Most studies use injection-recovery simulations to determine completeness functions. Although conceptually similar, published approaches have subtle but important differences in their definition of the completeness function. As a result, they implement different methods to determine the UVLFs. We discuss the advantages and limitations of existing methods using a set of mock observations, and then compare the methods when applied to the same set of Hubble Legacy Field (HLF) images. We find that the most robust method under all our mock observations is the one that defines completeness as a function of both input and output magnitude. Other methods considering completeness only as a function of either input or output magnitude may suffer limitations in a presence of photometric scatter and/or steep luminosity functions. In particular, when the flux scatter is ≳ 0.2 mag, the bias in the bright end of the UVLFs is on par with other systematic effects such as the lensing magnification bias. When tested on HLF images, all methods yield UVLFs that are consistent within 2σ confidence, suggesting that UVLF uncertainties in the literature are still dominated by small number statistics and cosmic variance. The completeness simulation code used in this study (GLACiaR2) is publicly released with this paper as a tool to analyse future higher precision data sets such as those expected from the James Webb Space Telescope.
The small boxy/peanut structure of the Milky Way traced by old stars
Authors: Semczuk Marcin , Dehnen Walter , Schönrich Ralph , Athanassoula E
Published: November 2021

We analyse the positions of RR Lyrae stars in the central region of the Milky Way. In addition to the overall bar shape detected previously, we find evidence for a peanut shaped structure, in form of overdensities near ℓ = −2 and 1° at b ∼ −3.5°. The corresponding physical distance between the two peaks of the peanut is $\sim 0.7\,$ kpc, significantly shorter than that found from near-IR images (3.3 kpc) and red-clump stars. Qualitatively this is expected from ‘fractionation’ of bar orbits, which we demonstrate to be matched in a simulation of an inside-out growing disc subsequently forming a bar.
Zinc mediates the interaction between ceruloplasmin and apo-transferrin for the efficient transfer of Fe(III) ions
Authors: Sakajiri Tetsuya , Nakatsuji Masatoshi , Teraoka Yoshiaki , Furuta Kosuke , Ikuta Katsuya , Shibusa Kotoe , Sugano Eriko , Tomita Hiroshi , Inui Takashi , Yamamura Takaki
Published: November 2021

Fe(II) exported from cells is oxidized to Fe(III), possibly by a multicopper ferroxidase (MCF) such as ceruloplasmin (CP), to efficiently bind with the plasma iron transport protein transferrin (TF). As unbound Fe(III) is highly insoluble and reactive, its release into the blood during the transfer from MCF to TF must be prevented. A likely mechanism for preventing the release of unbound Fe(III) is via direct interaction between MCF and TF; however, the occurrence of this phenomenon remains controversial. This study aimed to reveal the interaction between these proteins, possibly mediated by zinc. Using spectrophotometry, isothermal titration calorimetry, and surface plasmon resonance methods, we found that Zn(II)-bound CP bound to iron-free TF (apo-TF) with a Kd of 4.2 μM and a stoichiometry CP:TF of ∼2:1. Computational modeling of the complex between CP and apo-TF predicted that each of the three Zn(II) ions that bind to CP further binds to an acidic amino acid residue of apo-TF to play a role as a cross-linker connecting both proteins. Domain 4 of one CP molecule and domain 6 of the other CP molecule fit tightly into the clefts in the N- and C-lobes of apo-TF, respectively. Upon the binding of two Fe(III) ions to apo-TF, the resulting diferric TF [Fe(III)2TF] dissociated from CP by conformational changes in TF. In human blood plasma, zinc deficiency reduced the production of Fe(III)2TF and concomitantly increased the production of non-TF-bound iron. Our findings suggest that zinc may be involved in the transfer of iron between CP and TF.
Coordination of -1 programmed ribosomal frameshifting by transcript and nascent chain features revealed by deep mutational scanning
Authors: Carmody Patrick J , Zimmer Matthew H , Kuntz Charles P , Harrington Haley R , Duckworth Kate E , Penn Wesley D , Mukhopadhyay Suchetana , Miller Thomas F , Schlebach Jonathan P
Published: November 2021

Programmed ribosomal frameshifting (PRF) is a translational recoding mechanism that enables the synthesis of multiple polypeptides from a single transcript. During translation of the alphavirus structural polyprotein, the efficiency of −1PRF is coordinated by a ‘slippery’ sequence in the transcript, an adjacent RNA stem–loop, and a conformational transition in the nascent polypeptide chain. To characterize each of these effectors, we measured the effects of 4530 mutations on −1PRF by deep mutational scanning. While most mutations within the slip-site and stem–loop reduce the efficiency of −1PRF, the effects of mutations upstream of the slip-site are far more variable. We identify several regions where modifications of the amino acid sequence of the nascent polypeptide impact the efficiency of −1PRF. Molecular dynamics simulations of polyprotein biogenesis suggest the effects of these mutations primarily arise from their impacts on the mechanical forces that are generated by the translocon-mediated cotranslational folding of the nascent polypeptide chain. Finally, we provide evidence suggesting that the coupling between cotranslational folding and −1PRF depends on the translation kinetics upstream of the slip-site. These findings demonstrate how −1PRF is coordinated by features within both the transcript and nascent chain.