bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex Mediates Relationships Between Regional Tau Pathology and Cognitive Decline
Authors: Buckley Rachel F. , Scott Matthew R. , Jacobs Heidi I. L. , Schultz Aaron P. , Properzi Michael J. , Amariglio Rebecca E. , Hohman Timothy J. , Mayblyum Danielle V. , Rubinstein Zoe B. , Manning Lyssa , Hanseeuw Bernard J. , Mormino Elizabeth C. , Rentz Dorene M. , Johnson Keith A. , Sperling Reisa A.
Published: August 2020

Objective

The goal of this study was to examine sex differences in tau distribution across the brain of older adults, using positron emission tomography (PET), and investigate how these differences might associate with cognitive trajectories.

Methods

Participants were 343 clinically normal individuals (women, 58%; 73.8 [8.5] years) and 55 individuals with mild cognitive impairment (MCI; women, 38%; 76.9 [7.3] years) from the Harvard Aging Brain Study and the Alzheimer's Disease Neuroimaging Initiative. We examined 18F‐Flortaucipir (FTP)‐positron emission tomography (PET) signal across 41 cortical and subcortical regions of interest (ROIs). Linear regression models estimated the effect of sex on FTP‐signal for each ROI after adjusting for age and cohort. We also examined interactions between sex*Aβ‐PET positive / negative (+ / −) and sex*apolipoprotein ε4 (APOEε4) status. Linear mixed models estimated the moderating effect of sex on the relationship between a composite of sex‐differentiated tau ROIs and cognitive decline.

Results

Women showed significantly higher FTP‐signals than men across multiple regions of the cortical mantle (p < 0.007). β‐amyloid (Aβ)‐moderated sex differences in tau signal were localized to medial and inferio‐lateral temporal regions (p < 0.007); Aβ + women exhibited greater FTP‐signal than other groups. APOEε4‐moderated sex differences in FTP‐signal were only found in the lateral occipital lobe. Women with higher FTP‐signals in composite ROI exhibited faster cognitive decline than men (p = 0.04).

Interpretation

Tau vulnerability in women is not just limited to the medial temporal lobe and significantly contributed to greater risk of faster cognitive decline. Interactive effects of sex and Aβ were predominantly localized in the temporal lobe, however, sex differences in extra‐temporal tau highlights the possibility of accelerated tau proliferation in women with the onset of clinical symptomatology. ANN NEUROL 2020;88:921–932
Multilayer polyimide nanocomposite films synthesis process optimization impact on nanoparticles dispersion and their dielectric performance
Authors: Akram Shakeel , Castellon Jérôme , Agnel Serge , Zhou Kai , Habas Jean‐Pierre , Nazir Muhammad Tariq
Published: August 2020

The preparation of polyimide (PI)/nanocomposite films and their thickness are a complex process with some ambiguous variables that are involved in the synthesis process. Therefore, it is crucial to understand those variables and reveal the chemistry behind them. Several methods have been probed until an optimal synthesis process was found. A detailed synthesis process optimization is described in this article to understand all variables, which can influence the molecular weight of polyamic acide (PAA) solution, the thickness of films, and nanoparticles dispersion. The spin coating technique was used to control the thickness of single and multilayer PI/nanocomposite films, which reveals that the thickness of the casted PI film depends on several factors, such as the viscosity, molecular weight of the PAA solution, and the spin speed of spin coater. Factors, which can influence the molecular weight of PAA solution, are discussed in detail. After completing the synthesis process, the single and multilayer PI nanocomposite films are characterized experimentally. The results reveal that using a thin layer of nanocomposite on PI film in the form of a multilayer structure improves the nanoparticles dispersion and thereafter its dielectric properties.
Respiratory Diseases as Risk Factors for Seropositive and Seronegative Rheumatoid Arthritis and in Relation to Smoking
Authors: Kronzer Vanessa L. , Westerlind Helga , Alfredsson Lars , Crowson Cynthia S. , Nyberg Fredrik , Tornling Göran , Klareskog Lars , Holmqvist Marie , Askling Johan
Published: August 2020

Objective

The link and interplay between different airway exposures and rheumatoid arthritis (RA) risk are unclear. This study was undertaken to determine whether respiratory disease is associated with development of RA, and specifically to examine this relationship by RA serostatus and smoking exposure.

Methods

Using data from the Epidemiological Investigation of Rheumatoid Arthritis study, this analysis included 1,631 incident RA cases and 3,283 matched controls recruited from 2006 to 2016. Linking these individuals to the National Patient Register provided information on past acute or chronic, upper or lower respiratory disease diagnoses. For each disease group, we estimated adjusted odds ratios (ORadj) with 95% confidence intervals (95% CI) for RA, using logistic regression models adjusted for age, sex, residential area, body mass index, and education both overall and stratified by anti–citrullinated protein antibody (ACPA)/rheumatoid factor (RF) status and by smoking status.

Results

Respiratory disease diagnoses were associated with risk of RA, with an ORadj of 1.2 for acute upper respiratory disease (95% CI 0.8–1.7), 1.4 for chronic upper respiratory disease (95% CI 1.1–1.9), 2.4 for acute lower respiratory disease (95% CI 1.5–3.6), and 1.6 for chronic lower respiratory disease (95% CI 1.5–3.6). These associations were present irrespective of RF or ACPA status, though the association was somewhat stronger for ACPA/RF–positive than ACPA/RF–negative RA. The association between any respiratory disease and RA was stronger for nonsmokers (ORadj 2.1 [95% CI 1.5–2.9]) than for smokers (ORadj 1.2 [95% CI 0.9–1.5]).

Conclusion

Respiratory diseases increase the risk for both seropositive and seronegative RA, but only among nonsmokers. These findings raise the hypothesis that smoking and airway disease are associated with RA development through partly different mechanisms.
The Association Between Physician Gender and Career Advancement Among Academic Rheumatologists in the United States
Authors: Jorge April , Bolster Marcy , Fu Xiaoqing , Blumenthal Daniel M. , Gross Nate , Blumenthal Kimberly G. , Wallace Zachary
Published: August 2020

Objective

To determine the potential association between physician gender and academic advancement among US rheumatologists.

Methods

We performed a nationwide, cross‐sectional study of all rheumatologists practicing in the US in 2014 using a comprehensive database of all licensed physicians. Among academic rheumatologists, we estimated gender differences in faculty rank, adjusting for differences in physician age, years since residency graduation, publications, National Institutes of Health (NIH) grants, registered clinical trials, and appointment at a top 20 medical school using a multivariate logistic regression model. We also estimated gender differences in leadership positions (i.e., division director and fellowship program director).

Results

Among 6,125 total practicing rheumatologists, 941 (15%) had academic faculty appointments in 2014. Women academic rheumatologists (41.4%) were younger and had completed residency more recently than men. Women had fewer total publications, publications on which they were the first or last author, and NIH grants. In fully adjusted analyses, women were less likely to be full or associate professors than men, with an adjusted odds ratio (OR) of 0.78 (95% confidence interval [95% CI] 0.62–0.99]). Women in rheumatology had similar odds as men of being a fellowship program director or division director (adjusted OR 0.99 [95% CI 0.69–1.43] and adjusted OR 0.96 [95% CI 0.66–1.41], respectively).

Conclusion

Among academic rheumatologists, women are less likely than men to be full or associate professors but have similar odds of being fellowship program directors or division directors, when adjusting for several factors known to influence faculty promotion. These differences suggest barriers to academic promotion despite representation in leadership positions within rheumatology divisions.
On the future of the individual longitudinal age‐crime curve
Authors: Le Blanc Marc
Published: August 2020

Background

This article serves as our memorial for the outstanding contribution of Rolf Loeber to developmental criminology. His salient paper on the future of the study of the age‐crime curve (2012) is the focal point.

Aims

Follow some research trails that Rolf Loeber proposed in his 2012 paper.

Methods

Recent data on official offending from the Montréal Two Samples Four Generations Cross‐sectional and Longitudinal Studies (MTSFGCLS) are analysed. The data were gathered for two generations of juvenile court males; five birth cohorts born around 1960 and followed from age 8 to 61, and five birth cohorts born around 1980, males and females traced from age 12 to 45. The age‐crime curves are presented for the total prevalence. Epidemiological data are displayed for career descriptors: number of years active in offending, frequency, variety, onset, offset and duration.

Results

The age‐crime curves of the two generations display the habitual shape reported in the literature. The epidemiological data shows that the population sample has a much lower curve in comparison to the court sample; this sort of difference is also observed between females and males.

Conclusion

The difference between the two generations in the age‐crime curves are interpreted in light of three evolutions in Québec from 1960 to 2000: (a) a radical change in the delinquency law, social and criminal justice policies, and treatment for juvenile delinquents; (b) a reduction of the juvenile and adult crime rates; (c) a significant increase in the wellbeing of the population on education, health and welfare services.
From brown, red, and black rice to beer: Changes in phenolics, γ‐aminobutyric acid, and physicochemical attributes
Authors: dos Santos Jaqueline Pozzada , Acunha Tanize dos Santos , Prestes Dejalmo Nolasco , Rombaldi Cesar Valmor , El Halal Shanise Lisie Mello , Vanier Nathan Levien
Published: August 2020

Background and objectives

Many breweries have attempted to widen their offers by developing innovative products that meets consumer demands. Brown‐, red‐, and black‐pericarp rice were malted and used for brewing. The color, the physicochemical properties, the γ‐aminobutyric acid (GABA), the phenolics profile, and the free radical scavenging capacity of raw rice, rice malt, and obtained beers were evaluated.

Findings

The beer made from black rice malt showed 18 times more nitrogen content when compared to brown rice beer. Regarding GABA content, the beer obtained from red‐pericarp rice was the best, exhibiting more than 20 μg/g. Catechin was detected in beer made with brown‐ and red‐pericarp rice, and protocatechuic acid was detected in beer made from black‐pericarp rice. Beer from black‐pericarp rice kept cyanidin‐3‐O‐glucoside (40.54 μg/ml) above the quantification limit, while other anthocyanins that were initially detected in black rice and its malt were lost during brewing.

Conclusions

Work may support future studies regarding the use of pigmented rice genotypes for the development of craft beers with unique physicochemical and nutritional properties.

Significance and novelty

The study is in line with current approaches for assessing beer attributes as a function of different rice genotypes, providing knowledge for the scientific world and brewing industry.
Secondary syphilis mimicking sarcoidosis
Authors: Li Wencheng , Barnes Erin , McNeil Candice , Palavecino Elizabeth
Published: August 2020

Secondary syphilis may mimic sarcoidosis due to atypical clinical and pathological presentations. Differential diagnosis of these two is critical since the clinical courses and treatments are different. Highly clinical suspicion and utilization of confirmatory tests in high‐risk patients are the key for the differential diagnosis.
Modelling mechanism of Ca2+ removal from dicyandiamide using dynamic ion exchange method
Authors: Huang Meiying , Ren Yongsheng , Jiang Demin , Qi Junsheng
Published: August 2020

Based on breakthrough theory and fractal porous medium theory (FPM), the paper investigates the modelling mechanism of Ca2+ removal in dicyandiamide by dynamic ion exchange. In this work, parameters within consideration included the flow rate of dicyandiamide crystallization mother liquor, the height‐diameter ratio of the resin layer, and the temperature on Ca2+ exchange. It was found that the removal efficiency of Ca2+ reached 97.32%. Meanwhile, the through function of the process was obtained, and the behaviour of the dynamic process was modelled and simulated. In addition, using FPM theory, the calculation equation of the spectral dimension of the fractal surface of the resin in the ion exchange process was observed as linear and a mathematical model was established. This paper analyses the dynamics equation of the ideal surface and the fractal surface. According to the analytic results, it was linear relation on the ideal surface and power function on the fractal surface.
Efficient parallel implementations to compute the diameter of a graph
Authors: Takafuji Daisuke , Nakano Koji , Ito Yasuaki
Published: August 2020

The Floyd‐Warshall algorithm is a well‐known algorithm to compute the distance of all pairs of nodes of a graph. The Blocked Floyd‐Warshall algorithm, a variant of the Floyd‐Warshall has been proposed to accelerate the Floyd‐Warshall algorithm by means of a graphics processing unit (GPU) architecture. The previously published GPU implementations for the Blocked Floyd‐Warshall algorithm perform many separated kernel calls for costly barrier synchronization. The main contribution of this article is to present efficient implementations of the Blocked Floyd‐Warshall algorithm, which performs no barrier synchronization and invokes only one kernel call. Experimental results using NVIDIA Tesla V100 show that our implementation runs 1.05‐1.31 times faster than the previously published one. Our implementation with SIMD functions also runs 1.00‐1.28 times faster than it. Second, we propose efficient GPU implementations to execute the Blocked Floyd‐Warshall algorithm for many graphs at the same time. From the experimental results, our single kernel implementation runs 1.03‐1.60 times faster than multiple kernel one. In terms of implementations with SIMD functions, our single kernel implementation runs 1.01‐1.89 times faster than it. We also propose the low‐latency implementations for many graphs. Finally, we implemented the parallel Floyd‐Warshall algorithm on the multicore processors.
Physiologically Based Pharmacokinetic Modeling of Central Nervous System Pharmacokinetics of CDK4/6 Inhibitors to Guide Selection of Drug and Dosing Regimen for Brain Cancer Treatment
Authors: Li Jing , Jiang Jun , Wu Jianmei , Bao Xun , Sanai Nader
Published: August 2020

A better understanding of the human central nervous system (CNS) pharmacokinetics is critical to the selection of the right drug and refinement of dosing regimen for more effective treatment of primary and metastatic brain cancer. Using the physiologically‐based pharmacokinetic (PBPK) modeling approach, we systematically compared the CNS pharmacokinetics of three cyclin D‐cyclin dependent kinase 4 and 6 (CDK4/6) inhibitors (ribociclib, palbociclib, and abemaciclib) in patients with cancer. A PBPK model platform was developed and verified for predicting plasma and CNS pharmacokinetics. Target engagement ratio (TER), defined as the ratio of the average steady‐state unbound drug brain concentration to the in vitro half‐maximal inhibitory concentration (IC50) for CDK4/6 inhibition, was used as a crude predictor of efficacy. As compared with ribociclib and palbociclib, abemaciclib penetrated into the human brain to a larger extent, but at a slower rate, and was retained in the brain longer. Following the standard dosing regimens, the predicted CDK4/6 TERs were 26/5.2 for abemaciclib, 2.4/0.62 for ribociclib, and 0.36/0.27 for palbociclib. Simulations suggested that abemaciclib achieved comparable TERs following twice daily or daily dosing; ribociclib may sufficiently inhibit both CDK4 and CDK6 at the maximum tolerated dose; whereas, palbociclib achieved TERs < 0.5 even at a dose 50% higher than the standard dose. In conclusion, the PBPK modeling, supported by available preclinical and clinical evidence, suggests that abemaciclib is the best CDK4/6 inhibitor for brain cancer treatment, whereas palbociclib is not recommended. The model refined dosing regimen is 300 mg daily on a 4‐weeks‐on schedule for abemaciclib, and 900 mg daily on a 3‐weeks‐on/1‐week‐off schedule for ribociclib.
Lignin Source and Structural Characterization
Authors: Sun Run‐Cang
Published: August 2020

Invited for this month's cover is the group of Run‐Cang Sun at Dalian Polytechnic University. The image shows that lignin has the potential to produce energy, chemicals, and materials. The Essay itself is available at 10.1002/cssc.202001324.
Novel combination immunotherapy for pancreatic cancer: potent anti‐tumor effects with CD40 agonist and interleukin‐15 treatment
Authors: Van Audenaerde Jonas RM , Marcq Elly , von Scheidt Bianca , Davey Ashleigh S , Oliver Amanda J , De Waele Jorrit , Quatannens Delphine , Van Loenhout Jinthe , Pauwels Patrick , Roeyen Geert , Lardon Filip , Slaney Clare Y , Peeters Marc , Kershaw Michael H , Darcy Phillip K , Smits Evelien LJM
Published: August 2020

Objectives

With the poorest 5‐year survival of all cancers, improving treatment for pancreatic cancer is one of the biggest challenges in cancer research. We sought to explore the potential of combining both priming and activation of the immune system. To achieve this, we combined a CD40 agonist with interleukin‐15 and tested its potential in pancreatic cancer.

Methods

Response to this combination regimen was assessed in pancreatic ductal adenocarcinoma mouse models, and a thorough analysis of the tumor microenvironment was performed.

Results

We demonstrated profound reduction in tumor growth and increased survival of mice with the majority of mice being cured when both agents were combined, including an unprecedented 8‐fold dose reduction of CD40 agonist without losing any efficacy. RNAseq analysis showed involvement of natural killer (NK) cell‐ and T‐cell‐mediated anti‐tumor responses and the importance of antigen‐presenting cell pathways. This combination resulted in enhanced infiltration of tumors by both T cells and NK cells, as well as a striking increase in the ratio of CD8+ T cells over Tregs. We also observed a significant increase in numbers of dendritic cells (DCs) in tumor‐draining lymph nodes, particularly CD103+ DCs with cross‐presentation potential. A critical role for CD8+ T cells and involvement of NK cells in the anti‐tumor effect was highlighted. Importantly, strong immune memory was established, with an increase in memory CD8+ T cells only when both interleukin‐15 and the CD40 agonist were combined.

Conclusion

These novel preclinical data support initiation of a first‐in‐human clinical trial with this combination immunotherapy strategy in pancreatic cancer.
Evaluating spectral cytometry for immune profiling in viral disease
Authors: Niewold Paula , Ashhurst Thomas Myles , Smith Adrian Lloyd , King Nicholas Jonathan Cole
Published: August 2020

In conventional fluorescence cytometry, each fluorophore present in a panel is measured in a target detector, through the use of wide band‐pass optical filters. In contrast, spectral cytometry uses a large number of detectors with narrow band‐pass filters to measure a fluorophore's signal across the spectrum, creating a more detailed fluorescent signature for each fluorophore. The spectral approach shows promise in adding flexibility to panel design and improving the measurement of fluorescent signal. However, few comparisons between conventional and spectral systems have been reported to date. We therefore sought to compare a modern conventional cytometry system with a modern spectral system, and to assess the quality of resulting datasets from the point of view of a flow cytometry user. Signal intensity, spread, and resolution were compared between the systems. Subsequently, the different methods of separating fluorophore signals were compared, where compensation mathematically separates multiple overlapping fluorophores and unmixing relies on creating a detailed fluorescent signature across the spectrum to separate the fluorophores. Within the spectral data set, signal spread and resolution were comparable between compensation and unmixing. However, for some highly overlapping fluorophores, unmixing resolved the two fluorescence signals where compensation did not. Finally, data from mid‐ to large‐size panels were acquired and were found to have comparable resolution for many fluorophores on both instruments, but reduced levels of spreading error on our spectral system improved signal resolution for a number of fluorophores, compared with our conventional system. Furthermore, autofluorescence extraction on the spectral system allowed for greater population resolution in highly autofluorescent samples. Overall, the implementation of a spectral cytometry approach resulted in data that are comparable to that generated on conventional systems, with a number of potential advantages afforded by the larger number of detectors, and the integration of the spectral unmixing approach. © 2020 International Society for Advancement of Cytometry
Trade‐offs in moving citizen‐based anuran call surveys online during the SARS‐CoV‐2 pandemic: Lessons from rural Appalachia, USA
Authors: Smith Walter H. , Hamed Michael Kevin
Published: August 2020

Citizen science approaches provide adaptable methodologies for enhancing the natural history knowledge of understudied taxa and engaging underserved populations with biodiversity. However, transitions to remote, virtual training, and participant recruitment in response to public health crises like the SARS‐CoV‐2 pandemic have the potential to disrupt citizen science projects. We present a comparison of outputs from a citizen science initiative built around call surveys for the Mountain Chorus Frog (Pseudacris brachyphona), an understudied anuran, in Appalachian Virginia, USA, prior to and during the SARS‐CoV‐2 pandemic. A transition to virtual training in this initiative did not lead to a decrease in scientific output and led to unexpected natural history insight about our focal taxon; however, a reliance on virtual instruction did decrease overall participation by local residents, particularly for rural K‐12 students. We discuss the trade‐offs exhibited by the adaptation of our initiative to a virtual format and provide recommendations for other citizen science initiatives facing similar restrictions in the face of current and future public health crises.
High levels of phenological asynchrony between specialized pollinators and plants with short flowering phases
Authors: Maglianesi María A. , Hanson Paul , Brenes Emanuel , Benadi Gita , Schleuning Matthias , Dalsgaard Bo
Published: August 2020

Species phenology plays a key role in determining mutualistic interactions, such as those between plants and pollinators. Notably, temporal synchrony shapes the patterns of interactions by influencing the probability of encounters between interacting partners; thus, species phenology greatly contributes to structuring ecological communities. In these communities, specialized species are expected to show a high level of synchrony with their partners; however, the relationship between species phenology and specialization remains largely unexplored. In three localities in the tropical mountains of Costa Rica, we quantified the level of phenological synchrony in plant–pollinator networks and tested whether phenological synchrony is associated with the degree of pollinator specialization on plant partners. We also tested the relationship between pollinator specialization and the length of the flowering phase of the visited plants. Across all three studied networks, our results show a strong asynchrony between interacting plant and pollinator species. We also found that more specialized pollinators were more asynchronous with their plant partners and, moreover, that specialized pollinators preferably visited plant species with shorter flowering phases compared to generalized pollinators. These patterns suggest that specialized pollinators may be more vulnerable to mutualistic disruptions because they depend primarily on short‐lived resources and have a high risk of phenological mismatch. This discovery has important consequences for specialized species’ potential to survive and adapt to changes in the phenology of their interacting partners, which is highly relevant in a time characterized by changing climates and associated shifts in species phenology.
Trait‐based variation in host contribution to pathogen transmission across species and resource supplies
Authors: Welsh Miranda E. , Cronin James Patrick , Mitchell Charles E.
Published: August 2020

Two key knowledge gaps currently limit the development of more predictive and general models of pathogen transmission: (1) the physiological basis of heterogeneity in host contribution to pathogen transmission (reservoir potential) remains poorly understood and (2) a general means of integrating the ecological dynamics of host communities has yet to emerge. If the traits responsible for differences in reservoir potential also modulate host community dynamics, these traits could be used to predict pathogen transmission as host communities change. In two greenhouse experiments, across 23 host species and two levels of resource supply, the reservoir potential of plant hosts increased significantly along the Leaf Economics Spectrum, a global axis of plant physiological trait covariation that features prominently in models of plant community ecology. This indicates that the traits of the Leaf Economics Spectrum underlie broad differences in reservoir potential across host species and resource supplies. Therefore, host traits could be used to integrate epidemiological models of pathogen transmission with ecological models of host community change.
The extension of the one‐dimensional two‐fluid slug capturing method to simulate slug flow in vertical pipes
Authors: Leporini Mariella , Bonzanini Arianna , Ferrari Marco , Poesio Pietro
Published: August 2020

While many studies have been conducted on the application of the one‐dimensional (1D) two‐fluid model in horizontal and nearly horizontal pipes under slug flow condition, very few works have been carried out on the mechanistic simulation of the slug flow regime in vertical pipe configurations.

This article presents the extension of a novel numerical scheme for slug capturing in pipes in vertical slug flows. The original numerical scheme includes an 1D transient, hyperbolic five‐equation two‐fluid model, and it has been embodied in a computer code called 5ESCARGOTS (5 Equations for Slug Capturing Analysis by a Roe solver in Gas and Oil Transient Simulation).

This article demonstrates that the model is able to properly automatically capture and simulate the slug generation even in vertical flow. It shows that when appropriate closure relations are used for interfacial shear forces, the model is able to properly characterize the vertical slug flow.

Numerous simulations have been carried out for different pipe configurations and flow conditions leading to slug flow. First, a qualitative discussion of the numerical results is proposed underlining that the model is able to properly simulate the evolution of the slug flow in vertical pipes. Experimental flow pattern maps have also been numerically computed and it has been demonstrated that the model correctly simulates slug conditions. Moreover, slug frequency, velocity, and average liquid holdup, computed numerically, have been compared with experimental data in order to quantitatively validate the model. It is shown that the numerical results agree fairly well with the experimental data. A sensitivity analysis on the mesh size and on the inlet boundary conditions has also been carried out.
Macronutrient composition of street food in Central Asia: Bishkek, Kyrgyzstan
Authors: Albuquerque Gabriela , Lança de Morais Inês , Gelormini Marcello , Sousa Sofia , Casal Susana , Pinho Olívia , Moreira Pedro , Breda João , Lunet Nuno , Padrão Patrícia
Published: August 2020

Background

Urban areas in central Asia are currently undergoing nutrition transition. Street food is very popular, but the specific foods available and their nutritional composition are unknown. The aim was to describe the availability and macronutrient composition of street foods in Bishkek, Kyrgyzstan.

Results

Trained interviewers collected data on street food vending sites’ characteristics and food availability (n = 596). Samples of the most commonly available foods and drinks were collected (n = 80 homemade; n = 40 industrial). Macronutrients were quantified through chemical analysis. Fruit, beverages, and food other than fruit were available in 4.0%, 61.7%, and 81.0% of the vending sites, respectively. Among those selling food other than fruit, 56.5% sold only homemade (e.g., bread, main dishes, snacks, pastries, sandwiches, and cakes), 23.3% both homemade and industrial and 20.2% only industrial foods (e.g., bread, snacks, pastries, cakes, and cookies). Homemade foods presented the highest energy/serving (median kcal/serving: 357 versus 145, p < .001). A high content in saturated and trans‐fatty acids was observed in some homemade traditional dishes and snacks, reaching, respectively, 30.2 g/serving and 2.9 g/serving (in homemade manty, a traditional dish). Tea and soft drinks were available in over 50% of the vending sites selling beverages.

Conclusion

The high availability of street food in Bishkek highlights its importance for this urban population. Traditional snacks, dishes, and beverages coexist with more westernized products. The variability in energy, macronutrients, and lipid profile of homemade and industrial products reflects heterogeneous culinary practices and ingredients. Policies promoting the availability of healthy foods and ingredients should be implemented.
Characterizing seasonal groundwater storage in alpine catchments using time‐lapse gravimetry, water stable isotopes and water balance methods
Authors: Arnoux Marie , Halloran Landon J. S. , Berdat Eléonore , Hunkeler Daniel
Published: August 2020

Alpine areas play a major role in water supply in downstream valleys by releasing water during warm and dry periods. However, the hydrogeology of alpine catchments, which are particularly exposed to the effects of climate change, is currently not well understood. Increasing our knowledge of alpine hydrogeological processes is thus of considerable importance for any forward‐looking hydrological investigations in alpine areas. The objectives of this study are to quantify seasonal groundwater storage variations in a small Swiss alpine catchment and to evaluate the capabilities of time‐lapse gravimetry in the identification of zones of high groundwater storage fluctuations. Time‐lapse gravimetric measurements enable rapid localisation of zones of dynamic groundwater storage changes and help to highlight aquifers with a higher storage decrease. Temperature sensors enable measurement of the temporal trend in stream and spring drying in the post‐snowmelt period. Stable isotope measurements allow us to identify the origin of surface water exiting the catchment. The results improve our comprehension of a conceptual schema highlighting two different hydrogeological systems: (a) a shallow, rapidly depleted one fed directly by snowmelt and (b) a deeper one, with a slower recession, fed by main recharge during peak snowmelt and emerging at the lower part of the catchment below the talus and moraine of the catchment where bedrock is exposed. These dynamics confirm the high variability of storage in the talus and moraine aquifers and highlight the dominant role of Quaternary deposits and their connectivity to store water over seasonal and multi‐year time‐scales. The mechanisms explaining the importance of Quaternary deposits are the combination of moraine and talus with different permeabilities allowing the storage of sufficient quantities of water permitting continuous release during drier periods of the year.
Addressing the variation in adjuvant chemotherapy treatment for colorectal cancer: Can a regional intervention promote national change?
Authors: Taylor John C. , Swinson Daniel , Seligmann Jenny F. , Birch Rebecca J. , Dewdney Alice , Brown Victoria , Dent Joanna , Rossington Hannah L. , Quirke Philip , Morris Eva J. A. ,   YCR BCIP Study Group
Published: August 2020

Analysis of routine population‐based data has previously shown that patterns of surgical treatment for colorectal cancer can vary widely, but there is limited evidence available to determine if such variation is also seen in the use of chemotherapy. This study quantified variation in adjuvant chemotherapy across both England using cancer registry data and in more detail across the representative Yorkshire and Humber regions. Individuals with Stages II and III colorectal cancer who underwent major resection from 2014 to 2015 were identified. Rates of chemotherapy were calculated from the Systemic Anticancer Treatment database using multilevel logistic regression. Additionally, questionnaires addressing different clinical scenarios were sent to regional oncologists to investigate the treatment preferences of clinicians. The national adjusted chemotherapy treatment rate ranged from 2% to 46% (Stage II cancers), 19% to 81% (Stage III cancers), 24% to 75% (patients aged <70 years) and 5% to 46% (patients aged ≥70 years). Regionally, the rates of treatment and the proportions of treated patients receiving combination chemotherapy varied by stage (Stage II 4%‐26% and 0%‐55%, Stage III 48%‐71% and 40%‐84%) and by age (<70 years 35%‐68% and 49%‐91%; ≥70 years 15%‐39% and 6%‐75%). Questionnaire responses showed significant variations in opinions for high‐risk Stage II patients with both deficient and proficient mismatch repair tumours and Stage IIIB patients aged ≥70 years. Following a review of the evidence, open discussion in our region has enabled a consensus agreement on an algorithm for colorectal cancer that is intended to reduce variation in practice.
Loss of the cystine/glutamate antiporter in melanoma abrogates tumor metastasis and markedly increases survival rates of mice
Authors: Sato Mami , Onuma Kunishige , Domon Mio , Hasegawa Shun , Suzuki Ami , Kusumi Ryosuke , Hino Remi , Kakihara Nahoko , Kanda Yusuke , Osaki Mitsuhiko , Hamada Junichi , Bannai Shiro , Feederle Regina , Buday Katalin , Angeli José Pedro Friedmann , Proneth Bettina , Conrad Marcus , Okada Futoshi , Sato Hideyo
Published: August 2020

The cystine/glutamate antiporter, system xc−, is essential for the efficient uptake of cystine into cells. Interest in the mechanisms of system xc− function soared with the recognition that system xc− presents the most upstream node of ferroptosis, a recently described form of regulated necrosis relevant for degenerative diseases and cancer. Since targeting system xc− hold the great potential to efficiently combat tumor growth and metastasis of certain tumors, we disrupted the substrate‐specific subunit of system xc−, xCT (SLC7A11) in the highly metastatic mouse B16F10 melanoma cell line and assessed the impact on tumor growth and metastasis. Subcutaneous injection of tumor cells into the syngeneic B16F10 mouse melanoma model uncovered a marked decrease in the tumor‐forming ability and growth of KO cells compared to control cell lines. Strikingly, the metastatic potential of KO cells was markedly reduced as shown in several in vivo models of experimental and spontaneous metastasis. Accordingly, survival rates of KO tumor‐bearing mice were significantly prolonged in contrast to those transplanted with control cells. Analyzing the in vitro ability of KO and control B16F10 cells in terms of endothelial cell adhesion and spheroid formation revealed that xCT expression indeed plays an important role during metastasis. Hence, system xc− emerges to be essential for tumor metastasis in mice, thus qualifying as a highly attractive anticancer drug target, particularly in light of its dispensable role for normal life in mice.
microRNA‐377 acts as a suppressor in esophageal squamous cell carcinoma through CBX3‐dependent P53/P21 pathway
Authors: He Zhisheng , Chen Junjing , Chen Xiaoliang , Wang Huanyuan , Tang Lang , Han Chunbin
Published: August 2020

Stem cells play pivotal roles in esophageal squamous cell carcinoma (ESCC) recurrence and metastasis. The self‐renewal ability of stem cells was associated with specific microRNAs (miRs). Herein, we identified the effects of miR‐377 on ESCC stem cell activities. First, the expression of miR‐377 in ESCC and adjacent normal tissues was determined. The relationship between miR‐377 and chromobox protein homolog 3 (CBX3) was assessed by a dual‐luciferase reporter gene assay. miR‐377 was overexpressed or inhibited in ESCC stem cells to explore its role in ESCC. To further investigate the mechanism of miR‐377 in ESCC, cells were introduced with short hairpin RNA against CBX3 or pifithrin‐α (inhibitor of P53 pathway). Besides, the expression of P21, P53, CD133, CD13, Nanog, sex determining region Y‐Box 2 (Sox2), and octamer‐binding transcription factor 4 (Oct4), cell sphere formation, colony formation, and proliferation were evaluated respectively. Finally, limiting dilution assay in vivo and tumor xenograft in nude mice were conducted to confirm the roles of miR‐377 in vivo. miR‐377 was poorly expressed in ESCC. Overexpression of miR‐377 could suppress the stem‐like trait of ESCC as well as the tumor growth in vivo. miR‐377 targeted CBX3 to activate the P53/P21 pathway. Besides, the expression of stem‐like markers including CD133, CD13, Oct4, Sox2, and Nanog was decreased, and the abilities of cell sphere formation, colony formation, proliferation, and tumorigenicity were significantly reduced by overexpressing miR‐377 or silencing CBX3. The results were reversed after inactivating the P53/P21 pathway. In summary, upregulation of miR‐377 inhibits the self‐renewal of ESCC stem cells by inhibiting CBX3 expression and promoting activation of the P53/P21 pathway.
Isolation, growth kinetics, and immunophenotypic characterization of adult human cardiac progenitor cells
Authors: Rallapalli Suneel , Guhathakurta Soma , Korrapati Purna S.
Published: August 2020

The discovery of cardiac progenitor cells (CPCs) has raised expectations for the development of cell‐based therapy of the heart. Although cell therapy is emerging as a novel treatment for heart failure, several issues still exist concerning an unambiguous definition of the phenotype of CPC types. There is a need to define and validate the methods for the generation of quality CPC populations used in cell therapy applications. Considering the critical roles of cardiac cell progenitors in cellular therapy, we speculate that long term culture might modulate the immunophenotypes of CPCs. Hence, a strategy to validate the isolation and cell culture expansion of cardiac cell populations was devised. Isolation of three subpopulations of human CPCs was done from a single tissue sample using explant, enzymatic isolation, and c‐kit+ immunomagnetic sorting methods. The study assessed the effects of ex vivo expansion on proliferation, immunophenotypes, and differentiation of CPCs. Additionally, we report that an explant culture can take over 2 months to achieve similar cell yields, and cell sorting requires a much larger starting population to match this expansion time frame. In comparison, an enzymatic method is expected to yield equivalent quantities of CPCs in 2–3 weeks, notably at a significantly lower cost, which may intensify their use in therapeutic approaches. We determined that ex vivo expansion caused changes in cellular characteristics, and hence propose validated molecular signatures should be established to evaluate the impact of ex vivo expansion for a safe cell therapy product.
Effects of acute nutritional ketosis during exercise in adults with glycogen storage disease type IIIa are phenotype‐specific: An investigator‐initiated, randomized, crossover study
Authors: Hoogeveen Irene J. , de Boer Foekje , Boonstra Willemijn F. , van der Schaaf Caroline J. , Steuerwald Ulrike , Sibeijn‐Kuiper Anita J. , Vegter Riemer J. K. , van der Hoeven Johannes H. , Heiner‐Fokkema M. Rebecca , Clarke Kieran C. , Cox Pete J. , Derks Terry G. J. , Jeneson Jeroen A. L.
Published: August 2020

Glycogen storage disease type IIIa (GSDIIIa) is an inborn error of carbohydrate metabolism caused by a debranching enzyme deficiency. A subgroup of GSDIIIa patients develops severe myopathy. The purpose of this study was to investigate whether acute nutritional ketosis (ANK) in response to ketone‐ester (KE) ingestion is effective to deliver oxidative substrate to exercising muscle in GSDIIIa patients. This was an investigator‐initiated, researcher‐blinded, randomized, crossover study in six adult GSDIIIa patients. Prior to exercise subjects ingested a carbohydrate drink (~66 g, CHO) or a ketone‐ester (395 mg/kg, KE) + carbohydrate drink (30 g, KE + CHO). Subjects performed 15‐minute cycling exercise on an upright ergometer followed by 10‐minute supine cycling in a magnetic resonance (MR) scanner at two submaximal workloads (30% and 60% of individual maximum, respectively). Blood metabolites, indirect calorimetry data, and in vivo 31P‐MR spectra from quadriceps muscle were collected during exercise. KE + CHO induced ANK in all six subjects with median peak βHB concentration of 2.6 mmol/L (range: 1.6‐3.1). Subjects remained normoglycemic in both study arms, but delta glucose concentration was 2‐fold lower in the KE + CHO arm. The respiratory exchange ratio did not increase in the KE + CHO arm when workload was doubled in subjects with overt myopathy. In vivo 31P MR spectra showed a favorable change in quadriceps energetic state during exercise in the KE + CHO arm compared to CHO in subjects with overt myopathy. Effects of ANK during exercise are phenotype‐specific in adult GSDIIIa patients. ANK presents a promising therapy in GSDIIIa patients with a severe myopathic phenotype.

Trial registration number

ClinicalTrials.gov identifier: NCT03011203.
Stimulated Raman imaging below the diffraction limit with a MHz laser
Authors: Graefe Christian T. , Punihaole David , Lynch Michael J. , Silva W. Ruchira , Frontiera Renee R.
Published: August 2020

Super‐resolution techniques based on Raman spectroscopy could be implemented as label‐free alternatives to fluorescence‐based techniques due to their chemically specific signal and multiplexing potential. In previous work, we developed a stimulated Raman‐based imaging technique that surpassed the diffraction limit using a toroidally shaped pulse to deplete the signal in a spatially defined area. The photophysical principles of depletion and improved spatial resolution were demonstrated using a 1‐kHz laser with high peak power that were able to efficiently drive depletion. However, this laser was not well suited for soft matter samples, which degraded under the intense beams. To improve the biological capabilities of our setup, we have adapted our technique for a 2.04‐MHz laser system. The increased repetition rate produces far more spectra per second, allowing us to decrease the pulse powers while maintaining reasonable acquisition times. Using the 2.04‐MHz laser, we are able to demonstrate strong signal depletion of 62% and resolution enhancements of 52%, which is comparable with the metrics obtained with the 1‐kHz laser. However, further improvements in resolution were not achieved despite increases in the depletion beam energy relative to the other beams. Frequency‐resolved optical gating analysis of the fundamental output of the 2.04 MHz laser indicated an inconsistent pulse phase and duration. We expect that the inconsistent depletion was a result of this pulse profile and conclude that efficient depletion depends on highly reproducible and stable laser pulses.
Design of on‐chip resonator using distributed capacitors in 0.13‐μm (Bi)‐CMOS technology
Authors: Sun Feng , Yang Xinran , Chen Zubin , Tong Xunqian
Published: August 2020

A novel methodology for on‐chip resonator design using broadside‐coupled distributed capacitors is presented in this work. Using this method, a resonance can be generated at any specified frequency by changing the physical dimensions of the distributed capacitors. To prove the concept of the proposed method is feasible in practice, a resonator is designed and fabricated in a standard 0.13‐μm CMOS technology. The measured results show that a resonance can be generated at approximately 47 GHz. The chip size, excluding the pads, is only 0.176 × 0.149 mm2.
Experimental and Monte Carlo characterization of a dynamic collimation system prototype for pencil beam scanning proton therapy
Authors: Smith Blake R. , Pankuch Mark , Hyer Daniel E. , Culberson Wesley S.
Published: August 2020

Purpose

There has been a growing interest in the development of energy‐specific collimators for low‐energy pencil beam scanning (PBS) to reduce the lateral penumbra. One particular device that has been the focus of several recent published works is the dynamic collimation system (DCS), which provides energy‐specific collimation by intercepting the scanned proton beam as it nears to target edge with a set of orthogonal trimmer blades. While several computational studies have shown that this dynamic collimator can provide additional healthy tissue sparing, there has not been any rigorous experimental work to benchmark the theoretical models used in these initial studies. Therefore, it was the purpose of this work to demonstrate an experimental method that could integrate an experimental prototype with a clinical PBS system and benchmark the Monte Carlo methods that have been used to model the DCS.

Methods

An experimental DCS prototype was designed and built in house to actively collimate individual proton beamlets during PBS within a well‐characterized experimental setup. Monte Carlo methods were initially used to assess construction tolerances and later benchmarked against measurements, including integral depth dose and lateral asymmetric beamlet profiles. The experimental apparatus and measurement geometry were modeled using MCNP6 benchmarked from measurements performed at the Northwestern Chicago Proton Center.

Results

Gamma analysis tests were used to evaluate the agreement between the measured and simulated profiles with a strict 1 mm/1% criteria and 5% dose threshold. Excellent agreement was observed between the simulated and measured profiles, which included 1 mm/1% gamma analysis pass rates of at least 100% and 95% for the integral depth dose (IDD) profiles and lateral profiles, respectively. Differences in the relative profile shape were observed experimentally between beamlets collimated on‐ and off‐axis, which was attributed to the partial transmission of the beam through an unfocused collimator. Exposure rates resulting from the activation of the device were monitored with survey meter measurements and were found to agree with Monte Carlo estimates of the exposure rate to within 20%.

Conclusion

A DCS prototype was constructed and integrated into a clinical dose delivery system. While the results of this work are not exhaustive, they demonstrate the effects of beam source divergence, device activation, and beamlet deflection during scanning, which were found to be successfully modeled using Monte Carlo methods and experimentally benchmarked. Excellent agreement was achieved between the simulated and measured lateral spot profiles of collimated beamlets delivered on‐ and off‐axis in PBS. The Monte Carlo models adequately predicted the measured elevated plateau region in the integral depth‐dose profiles from the low‐energy scatter off the collimators.