bluuebunny/crossref_metadata_2025 huggingface dataset:
Liposomes Under Shear: Structure, Dynamics, and Drug Delivery Applications
Authors: Karaz Selcan , Senses Erkan
Published: February 2023

The targeted delivery to specific locations while not causing damage to healthy tissues efficiently remains a challenge in drug delivery systems. Through addressing this issue, stimuli‐responsive materials have been under investigation. As one of the fundamental forces associated with blood flow, shear stress is taken as an advantage to design shear‐sensitive drug carriers. Although blood flow is modeled as laminar flow under normal conditions, in case of constrictions caused by endothelial shear stress, cardiovascular diseases, or angiogenesis due to tumor formation, local shear stress can dramatically increase. To date, shear‐sensitive materials have been investigated under two main categories: shear‐disaggregated and shear‐deformed nanoparticles based on their structural mechanism after exposure to high‐shear stress. Among them, liposomes are promising materials with their soft and deformable structure, high biocompatibility, controlled‐release properties, and sensitivity to shear stress. Herein, in this review, the effects of shear stress on liposomes in terms of their structural changes, flow regimes, rheological properties, and drug delivery applications are discussed. It is believed that this work provides a basis for designing more effective drug delivery systems considering the complexity of the human body.
Functionalized Gold Nanoclusters Promote Stress Response in COS‐7 Cells
Authors: Linklater Denver P. , Le Guével Xavier , Kosyer Erim , Rubanov Sergey , Bryant Gary , Hanssen Eric , Baulin Vladimir A. , Pereiro Eva , Perera Palalle G.Tharushi , Wandiyanto Jason V. , Angulo Ana , Juodkazis Saulius , Ivanova Elena P.
Published: February 2023

Ultrasmall gold nanoclusters (AuNC) show great promise for application in theranostics due to their unique optical and physicochemical properties; however, the associated nanotoxicology concerns need to be carefully considered because of their high diffusion across the cellular barrier. Herein, new insights into the role of surface modification of 2 nm AuNC on their toxicity with impact on the metabolism of COS‐7 fibroblast‐like cells are revealed. AuNCs are chemically modified with either a monodentate‐thiolated molecule (AuNC‐MHA) or a modified‐bidentate sulfobetaine zwitterionic molecule (AuNC‐ZwBuEt). Uptake and localization inside fibroblasts and the resultant influence on cell ultrastructure are carefully evaluated using scanning transmission electron microscopy (STEM) and cryo‐soft‐X‐ray tomography (cryo‐SXT). At concentrations of ≥25 μg Au mL−1, AuNC‐ZwBuEt are cytotoxic toward COS‐7 cells and are observed to cross the nuclear membrane. Cryo‐SXT analysis shows that fibroblasts develop an acute stress response in the form of swollen mitochondria, nuclear membrane blebbing, and large cytoplasmic vacuoles as early as 1 h postexposure. By contrast, AuNC‐MHA are not cytotoxic toward COS‐7 cells. Endosomal escape and translocation of the AuNC‐ZwBuEt into the nucleus and other organelles may be the cause for the observed cytotoxicity and highlight the need for further study of metal nanocluster‐cell interactions.
A Polymer Bio–Photoelectrolytic Platform for Electrical Signal Measurement and for Light Modulation of Ion Fluxes and Proliferation in a Neuroblastoma Cell Line
Authors: Ciocca Manuela , Marcozzi Serena , Mariani Paolo , Lacconi Valentina , Di Carlo Aldo , Cinà Lucio , Rosato-Siri Marcelo D. , Zanon Alessandra , Cattelan Giada , Avancini Enrico , Lugli Paolo , Priya Shashank , Camaioni Antonella , Brown Thomas M.
Published: February 2023

Light control of living systems is an emerging field in bioelectronics, in regenerative medicine and cell‐based therapy. Herein, the design of a semitransparent bio–photoelectrolytic platform for control of a neuroblastoma cell line via light pulses is laid out. The platform is based on conjugated polymer films interfaced with a biological electrolyte solution confined in a compact chamber. Human SH‐SY5Y neuroblastoma cells are cultured for 3 days on the organic semiconductor and subjected to a pulsed light protocol. At the end of the culture time, proliferative activity of cells on the polymer film subjected to light pulses is reduced by 50% compared to the cultures kept in dark. An increase in intracellular Ca2+ level is observed, indicating a significant perturbation of the equilibrium potential of the cells. It is shown that the platform, in a sandwich‐type closed architecture with two transparent electrodes, can provide a tool for the initial recording of bioelectrical photovoltage signals (mV) that can complement analysis with more sophisticated electrophysiological tools. Obtained results can pave the way to new noninvasive photomanipulation techniques to stimulate/control living cells and their proliferation through both optical and electrical stimulation and probes, for application in the fields of biosensing and biomedicine.
Dried blood spot characterization of sex‐based metabolic responses to acute running exercise
Authors: Cendali Francesca , D'Alessandro Angelo , Nemkov Travis
Published: February 2023

Metabolomics and lipidomics techniques are capable of comprehensively measuring hundreds to thousands of small molecules in single analytical runs and have been used to characterize responses to exercise traditionally using venipuncture‐produced liquid samples. Advanced microsampling devices offer an alternative by circumventing the requirement to maintain frozen samples. This approach combines a microneedle puncture for blood draw with microfluidic sample collection onto a dried carrier and has thus far been employed for targeted measurements of a few analytes. To demonstrate the utility of advanced dried microsampling to characterize metabolomic and lipidomic changes during exercise, we obtained samples before and after a 2‐mile run from twelve (8 male, 4 female) healthy volunteers with various ranges in activity levels. Results highlighted significant changes in whole blood levels of several metabolites associated with energy (glycolysis and Tricarboxylic Acid cycle) and redox (Pentose Phosphate Pathway) metabolism. Lipid changes during this same period were individualized and less uniform. Sex‐based differences in response to running highlighted reliance on carbohydrate or fat substrate utilization in males or females, respectively. The results presented herein illustrate the ability of this approach to monitor circulating metabolome and lipidome profiles from field sampled blood in response to exercise.
Modified Dirac Fermions in the Crystalline Xenon and Graphene Moiré Heterostructure
Authors: Im Suji , Im Hayoon , Kim Kyoo , Lee Ji‐Eun , Hwang Jinwoong , Mo Sung‐Kwan , Hwang Choongyu
Published: February 2023

The interface between two‐dimensional (2D) crystals often forms a Moiré superstructure that imposes a new periodicity, which is a key element in realizing complex electronic phases as evidenced in twisted bilayer graphene. Acombined angle‐resolved photoemission spectroscopy measurements and first‐principles calculations reveal the formation of a Moiré superstructure between a 2D Dirac semi‐metallic crystal, graphene, and a 2D insulating crystal of noble gas, xenon. Incommensurate diffraction pattern and folded Dirac cones around the Brillouin zone center imply the formation of hexagonal crystalline array of xenon atoms. The velocity of Dirac fermions increases upon the formation of the 2D xenon crystal on top of graphene due to the enhanced dielectric screening by the xenon over‐layer. These findings not only provide a novel method to produce a Moiré superstructure from the adsorption of noble gas on 2D materials, but also to control the physical properties of graphene by the formation of a graphene‐noble gas interface.
Towards an integrated decision‐making support framework for the sustainable production and use of biomass
Authors: Ebadian Mahmood , Gonzales‐Calienes Giovanna , Shadbahr Jalil , Vazifehkoorabbasloo Zahra , Bensebaa Farid
Published: February 2023

The decision‐making landscape to maximize the use of sustainable biomass resources, and achieve long‐term environmental and socioeconomic benefits, is complex with a high level of uncertainty in biomass supply and logistics, technical and economic performance of the biorefinery routes, lifecycle performance of the finished products, and other sustainability criteria. Numerous decision‐making support models have been developed but these models usually assess only a few specific aspects of technology, regulations, economic, environment, and society. Decision‐making support models with a limited capability to capture environmental and socioeconomic performance of the biorefining pathways are not able to identify the best available biorefining routes. This study reviews and discusses recent progress on the harmonization, standardization, and integration of the existing decision‐making support models that aim to improve the comparability of the results of these models when different pathways are being assessed and align the decisions made at the strategic, tactical and operational levels. With the growing number of climate‐change policies and greenhouse gas (GHG) emission reduction targets, national and international efforts to harmonize the input databases, the model assumptions and system boundaries, and the integration of the existing models have been increasing. However, the deployment of the integrated frameworks among the bioeconomy stakeholders that are capable of evaluating and identifying the promising biorefining routes with significant economic, social and environmental benefits is still not a common practice. This study proposes an integrated decision‐making support framework to identify cost‐competitive, low‐carbon fuel production pathways that are technically viable and can potentially provide maximum GHG emission reduction.
Evo‐devo beyond development: Generalizing evo‐devo to all levels of the phenotypic evolution
Authors: Salazar‐Ciudad Isaac , Cano‐Fernández Hugo
Published: February 2023

A foundational idea of evo‐devo is that morphological variation is not isotropic, that is, it does not occur in all directions. Instead, some directions of morphological variation are more likely than others from DNA‐level variation and these largely depend on development. We argue that this evo‐devo perspective should apply not only to morphology but to evolution at all phenotypic levels. At other phenotypic levels there is no development, but there are processes that can be seen, in analogy to development, as constructing the phenotype (e.g., protein folding, learning for behavior, etc.). We argue that to explain the direction of evolution two types of arguments need to be combined: generative arguments about which phenotypic variation arises in each generation and selective arguments about which of it passes to the next generation. We explain how a full consideration of the two types of arguments improves the explanatory power of evolutionary theory. Also see the video abstract here: https://youtu.be/Egbvma_uaKc
Pheochromocytoma disguised as gestational hypertensive disease during pregnancy: A case report
Authors: Kumari Swati , Lamichhane Ramesh , Giri Subarna , Chaudhary Saroj , Neupane Shanta , Dangol Neha
Published: February 2023

Pheochromocytoma is often diagnosed prior to pregnancy. Sometimes, the disease may be diagnosed for the first‐time during pregnancy masking itself as a hypertensive disease in pregnancy. Early diagnosis and timely, appropriate management reduce possible maternal and fetal complications. We identified a case of pheochromocytoma during pregnancy misdiagnosed as preeclampsia.
A patient with leishmaniasis presenting with longstanding pancytopenia and hepatosplenomegaly
Authors: Onsongo Simon , Mulwa Evelyne , Mutiso Bonface
Published: February 2023

Leishmaniasis is a common cause of pancytopenia and hepatosplenomegaly in tropical and subtropical regions. A high index of suspicion is required to diagnose and manage patients with leishmaniasis. Travel history should always be elicited in a patient with suggestive clinical presentation.
A tale about an unusual cause of pygalgia in non‐radiographic axial spondyloarthritis
Authors: Dhahri Rim , Bettaieb Hiba , Slouma Maroua , Khrifech Yasmine , Mallat Youssef , Amri Khalil , Harbaoui Ahmed , Metoui Leila , Gharsallah Imen , Louzir Bassem
Published: February 2023

Schwannoma are tumors of Schwann cells of the peripheral nerve sheath. Sacral location is rarely reported especially in spondyloarthritis patients. Herein, we report a case of uncommon pygalgia in a 25‐year‐old man with history of a non‐radiographic axial spondyloarthritis and in whom the diagnosis of sacral Schwannoma was established.
Process Simulation of Twin‐Screw Granulator: Effect of Screw Configuration on Size Distribution
Authors: Arthur Tony B. , Sekyi Nana K. G. , Rahmanian Nejat , Pu Jaan
Published: February 2023

The effect of screw configuration on granule size distribution (GSD) using gPROMS FormulatedProduct (gFP) software to perform optimization, estimation of complex processes, and analyses is evaluated. Twin‐screw granulation modeling was used to investigate the contribution of screw configuration and liquid‐to‐solid (L/S) ratio on GSD. Lactose and Avicel were the granulating materials. Twelve different configurations were investigated under three feed rates as consistent with literature and at various L/S ratios. Results indicate that kneading elements promote the recovery of 100–1000 µm granules while reducing the production of oversized granules. Higher feed rates support the production of fines and agglomerates, while a low feed rate produces 100–1000 µm granules.
Efficient resolution of 4‐chlormandelic acid enantiomers using lipase@UiO‐67(Zr) zirconium–organic frameworks in organic solvent
Authors: Zhong Long‐Jin , Jiang Bihui , Tang Kewen
Published: February 2023

A new biocatalyst PCL@UiO‐67(Zr) was successfully synthesized by immobilized lipases on metal–organic frameworks (MOFs) materials. Compare with free lipases, zirconium foundation organic framework material UiO‐67(Zr) modification on immobilized lipases Pseudomonas cepacia lipase (PCL) great boosts their enantioselectivity in the kinetic resolution racemic 4‐chloro‐mandelic acid (4‐ClMA) on the organic solvent. The acquired bio‐composite PCL@UiO‐67(Zr) was fully characterized by powder X‐ray diffraction (PXRD), Fourier transform infrared (FT‐IR) spectroscopy, N2 adsorption–desorption isotherm and aperture distribution map, and scanning electron microscopy (SEM). The catalytic performance of PCL@UiO‐67(Zr), such as temperature, reaction time, and lipase quantity, were deeply explored. The experiment results showed resolution racemic 4‐ClMA optimum conditions that 20 mmol/L of (R, S)‐4‐chloromandelic acid, 120 mmol/L vinyl acetate, 30‐mg immobilized lipases PCL@UiO‐67(Zr), 2 mL of MTBE, 500 rpm, and under the 55°C reaction 18 h. In this optimum conditions, c and eep could reach up to 47.6% and 98.7%, respectively.
Allergy screening with extract‐based skin prick tests demonstrates higher sensitivity over in vitro molecular allergy testing
Authors: Gureczny Tobias , Heindl Benjamin , Klug Livia , Wantke Felix , Hemmer Wolfgang , Wöhrl Stefan
Published: February 2023

Background

As extract‐based skin testing as well as in vitro tests for major allergens have their own advantages, both procedures are usually performed in routine settings. In times of shortages in medical staff and supplies, we asked ourselves, how many patients would be underdiagnosed, if only one test could be used.

Methods

In a retrospective analysis, we investigated a cohort of 2646 patients seen by a single physician in a large Austrian outpatient allergy clinic in 2018. Only patients with an allergen source‐specific history and pairs of extract‐based skin prick (SPT) and in vitro molecular allergy tests to major allergens were included.

Results

For all tested allergen sources, sensitivity was higher for SPT than for sIgE‐based molecular allergy testing. Concerning 1006 birch pollen‐allergic patients, 791 (78.6%) had positive results with both tests, while 153 (15.2%) only with the SPT and 62 (6.2%) only with the sIgE to Bet v1. The other allergen sources showed similar results: For house dust mite 816/1120 (72.9%), grass pollen 1077/1416 (76.1%) and cat 433/622 (69.6%) remained test‐positive with both procedures, whereas in 276 (24.6%), 224 (15.8%) and 173 (27.8%) times only the SPT and 28 (2.5%), 115 (8.1%) and 16 (2.6%) times only the sIgE to Der p1/2/23, Phl p1/5 and Fel d1 showed a positive result. Each comparison was statistically significant (each p < 0.0001, Chi‐squared test).

Conclusions

Screening for allergy with major molecular allergens has lower sensitivity when compared with extract‐based skin tests. A combination of both is required for an optimal sensitivity.
Janus liquid marbles: Fabrication techniques, recent developments, and applications
Authors: Lekshmi Bindhu Sunilkumar , Varanakkottu Subramanyan Namboodiri
Published: February 2023

Liquid marbles (LMs) are nonsticky droplets stabilized by hydrophobic solid particles that are adsorbed at the liquid–air interface. LMs are emerging as a potential platform in digital microfluidics, sensing applications, storage unit, biological incubation, and cosmetic applications. Incorporating multifunctional particles to form Janus liquid marble (JLM) could enhance the capabilities of the pristine LM. JLMs are multifunctional next‐generation LMs comprising two hemispherical domains of distinct physicochemical properties such as size, hydrophobicity, electrical conductivity, surface functionalization, stimuli‐responsivity, and so on. The JLMs offer precise control on the manipulability and enhanced performance over pristine LMs. Though the properties, applications, and progress of LMs are detailed in the recent literature, a focused review encompassing the fabrication, recent developments, potential applications of JLMs, and the challenges regarding its reliable fabrication remains a gap in the literature. The review provides insights into the importance of JLMs, systematically discussing the fabrication strategies, applications, challenges, and future directions.
Improvement in output power of vibration generators based on piezoelectric elements by using internal capacitor cancel control rectifier
Authors: Minami Masataka , Nakagaki Akito , Hase Genki
Published: February 2023

Recently, energy harvesting has attracted increasing attention. The present study focuses on vibration generators based on piezoelectric elements by proposing an internal capacitor cancel control (ICCC) rectifier to improve the output power. The proposed rectifier cancels the internal capacitor to improve the output power while retaining the maximum output power. Accordingly, this paper experimentally demonstrates the improvement in output power by using the ICCC rectifier compared to conventional circuits and the previous proposed circuit.
DNA methylation‐based age prediction with bloodstains using pyrosequencing and random forest regression
Authors: Yang Fenglong , Qian Jialin , Qu Hongzhu , Ji Zhimin , Li Junli , Hu Wenjing , Cheng Feng , Fang Xiangdong , Yan Jiangwei
Published: February 2023

The use of DNA methylation to predict chronological age has shown promising potential for obtaining additional information in forensic investigations. To date, several studies have reported age prediction models based on DNA methylation in body fluids with high DNA content. However, it is often difficult to apply these existing methods in practice due to the low amount of DNA present in stains of body fluids that are part of a trace material. In this study, we present a sensitive and rapid test for age prediction with bloodstains based on pyrosequencing and random forest regression. This assay requires only 0.1 ng of genomic DNA and the entire procedure can be completed within 10 h, making it practical for forensic investigations that require a short turnaround time. We examined the methylation levels of 46 CpG sites from six genes using bloodstain samples from 128 males and 113 females aged 10–79 years. A random forest regression model was then used to construct an age prediction model for males and females separately. The final age prediction models were developed with seven CpG sites (three for males and four for females) based on the performance of the random forest regression. The mean absolute deviation was less than 3 years for each model. Our results demonstrate that DNA methylation‐based age prediction using pyrosequencing and random forest regression has potential applications in forensics to accurately predict the biological age of a bloodstain donor.
An optimized live bacterial delivery vehicle safely and efficaciously delivers bacterially transcribed therapeutic nucleic acids
Authors: Mora Darcy S. O. , Cox Madeline , Magunda Forgivemore , Williams Ashley B. , Linke Lyndsey
Published: February 2023

There is an unmet need for delivery platforms that realize the full potential of next‐generation nucleic acid therapeutics. The in vivo usefulness of current delivery systems is limited by numerous weaknesses, including poor targeting specificity, inefficient access to target cell cytoplasm, immune activation, off‐target effects, small therapeutic windows, limited genetic encoding and cargo capacity, and manufacturing challenges. Here we characterize the safety and efficacy of a delivery platform comprising engineered live, tissue‐targeting, non‐pathogenic bacteria (Escherichia coli SVC1) for intracellular cargo delivery. SVC1 bacteria are engineered to specifically bind to epithelial cells via a surface‐expressed targeting ligand, to allow escape of their cargo from the phagosome, and to have minimal immunogenicity. We describe SVC1's ability to deliver short hairpin RNA (shRNA), localized SVC1 administration to various tissues, and its minimal immunogenicity. To validate the therapeutic potential of SVC1, we used it to deliver influenza‐targeting antiviral shRNAs to respiratory tissues in vivo. These data are the first to establish the safety and efficacy of this bacteria‐based delivery platform for use in multiple tissue types and as an antiviral in the mammalian respiratory tract. We expect that this optimized delivery platform will enable a variety of advanced therapeutic approaches.
Challenges in Recycling Spent Lithium‐Ion Batteries: Spotlight on Polyvinylidene Fluoride Removal
Authors: Wang Mengmeng , Liu Kang , Yu Jiadong , Zhang Qiaozhi , Zhang Yuying , Valix Marjorie , Tsang Daniel C.W.
Published: February 2023

In the recycling of retired lithium‐ion batteries (LIBs), the cathode materials containing valuable metals should be first separated from the current collector aluminum foil to decrease the difficulty and complexity in the subsequent metal extraction. However, strong the binding force of organic binder polyvinylidene fluoride (PVDF) prevents effective separation of cathode materials and Al foil, thus affecting metal recycling. This paper reviews the composition, property, function, and binding mechanism of PVDF, and elaborates on the separation technologies of cathode material and Al foil (e.g., physical separation, solid‐phase thermochemistry, solution chemistry, and solvent chemistry) as well as the corresponding reaction behavior and transformation mechanisms of PVDF. Due to the characteristic variation of the reaction systems, the dissolution, swelling, melting, and degradation processes and mechanisms of PVDF exhibit considerable differences, posing new challenges to efficient recycling of spent LIBs worldwide. It is critical to separate cathode materials and Al foil and recycle PVDF to reduce environmental risks from the recovery of retired LIBs resources. Developing fluorine‐free alternative materials and solid‐state electrolytes is a potential way to mitigate PVDF pollution in the recycling of spent LIBs in the EV era.
A fast linkage method for population GWAS cohorts with related individuals
Authors: Zajac Gregory J. M. , Gagliano Taliun Sarah A. , Sidore Carlo , Graham Sarah E. , Åsvold Bjørn O. , Brumpton Ben , Nielsen Jonas B. , Zhou Wei , Gabrielsen Maiken , Skogholt Anne H. , Fritsche Lars G. , Schlessinger David , Cucca Francesco , Hveem Kristian , Willer Cristen J. , Abecasis Gonçalo R.
Published: February 2023

Linkage analysis, a class of methods for detecting co‐segregation of genomic segments and traits in families, was used to map disease‐causing genes for decades before genotyping arrays and dense SNP genotyping enabled genome‐wide association studies in population samples. Population samples often contain related individuals, but the segregation of alleles within families is rarely used because traditional linkage methods are computationally inefficient for larger datasets. Here, we describe Population Linkage, a novel application of Haseman–Elston regression as a method of moments estimator of variance components and their standard errors. We achieve additional computational efficiency by using modern methods for detection of IBD segments and variance component estimation, efficient preprocessing of input data, and minimizing redundant numerical calculations. We also refined variance component models to account for the biases in population‐scale methods for IBD segment detection. We ran Population Linkage on four blood lipid traits in over 70,000 individuals from the HUNT and SardiNIA studies, successfully detecting 25 known genetic signals. One notable linkage signal that appeared in both was for low‐density lipoprotein (LDL) cholesterol levels in the region near the gene APOE (LOD = 29.3, variance explained = 4.1%). This is the region where the missense variants rs7412 and rs429358, which together make up the ε2, ε3, and ε4 alleles each account for 2.4% and 0.8% of variation in circulating LDL cholesterol. Our results show the potential for linkage analysis and other large‐scale applications of method of moments variance components estimation.
Bayesian multivariant fine mapping using the Laplace prior
Authors: Walters Kevin , Yaacob Hannuun
Published: February 2023

Currently, the only effect size prior that is routinely implemented in a Bayesian fine‐mapping multi‐single‐nucleotide polymorphism (SNP) analysis is the Gaussian prior. Here, we show how the Laplace prior can be deployed in Bayesian multi‐SNP fine mapping studies. We compare the ranking performance of the posterior inclusion probability (PIP) using a Laplace prior with the ranking performance of the corresponding Gaussian prior and FINEMAP. Our results indicate that, for the simulation scenarios we consider here, the Laplace prior can lead to higher PIPs than either the Gaussian prior or FINEMAP, particularly for moderately sized fine‐mapping studies. The Laplace prior also appears to have better worst‐case scenario properties. We reanalyse the iCOGS case–control data from the CASP8 region on Chromosome 2. Even though this study has a total sample size of nearly 90,000 individuals, there are still some differences in the top few ranked SNPs if the Laplace prior is used rather than the Gaussian prior. R code to implement the Laplace (and Gaussian) prior is available at https://github.com/Kevin‐walters/lapmapr.
Brain metabolites measured with magnetic resonance spectroscopy in pediatric concussion and orthopedic injury: An Advancing Concussion Assessment in Pediatrics (A‐CAP) study
Authors: La Parker L. , Joyce Julie M. , Bell Tiffany K. , Mauthner Micaela , Craig William , Doan Quynh , Beauchamp Miriam H. , Zemek Roger , Yeates Keith Owen , Harris Ashley D.
Published: February 2023

Millions of children sustain a concussion annually. Concussion disrupts cellular signaling and neural pathways within the brain but the resulting metabolic disruptions are not well characterized. Magnetic resonance spectroscopy (MRS) can examine key brain metabolites (e.g., N‐acetyl Aspartate (tNAA), glutamate (Glx), creatine (tCr), choline (tCho), and myo‐Inositol (mI)) to better understand these disruptions. In this study, we used MRS to examine differences in brain metabolites between children and adolescents with concussion versus orthopedic injury. Children and adolescents with concussion (n = 361) or orthopedic injury (OI) (n = 184) aged 8 to 17 years were recruited from five emergency departments across Canada. MRS data were collected from the left dorsolateral prefrontal cortex (L‐DLPFC) using point resolved spectroscopy (PRESS) at 3 T at a mean of 12 days post‐injury (median 10 days post‐injury, range 2–33 days). Univariate analyses for each metabolite found no statistically significant metabolite differences between groups. Within each analysis, several covariates were statistically significant. Follow‐up analyses designed to account for possible confounding factors including age, site, scanner, vendor, time since injury, and tissue type (and interactions as appropriate) did not find any metabolite group differences. In the largest sample of pediatric concussion studied with MRS to date, we found no metabolite differences between concussion and OI groups in the L‐DLPFC. We suggest that at 2 weeks post‐injury in a general pediatric concussion population, brain metabolites in the L‐DLPFC are not specifically affected by brain injury.
A study on a new fiscal risk‐sharing system to make Eurozone an OCA
Authors: Kim Wi‐Dae
Published: February 2023

This article seeks to add a new element to the 5‐decade debate over the theory of Optimal Currency Area. In the euro area, the accumulation of economic imbalances caused by the loss of the automatic adjustment functions of the exchange rate have served as a structural background to limit its self‐sustaining resilience during financial shocks. To enhance the stability of Optimal Currency Area (OCA) through the revitalization of those functions, this article argues that if the euro area had adopted some form of fiscal risk‐sharing mechanisms, which could have generated a similar economic effect as if they had maintained a flexible F/X system as that which had existed in pre‐euro days, the fiscal crisis hypothetically could have been more easily overcome within a shorter period with less financial support. The result suggests that if ‘Adjustment Fund for Foreign Exchange rate Loss (AFFEL)’, originally devised within these pages, had operated, the interest rates in crisis‐hit members could have been significantly lower than actual levels during the crisis, while safely maintaining the euro system.
Inflation expectations and nonlinearities in the Phillips curve
Authors: Doser Alexander , Nunes Ricardo , Rao Nikhil , Sheremirov Viacheslav
Published: February 2023

This paper examines the presence of nonlinearities in the Phillips curve. We allow for a flexible form of nonlinearity and estimate a threshold regression model with the number and location of thresholds determined directly from the data. Over the estimation period starting in the late 1960s, we document that the linear model cannot be rejected if we properly control for inflation expectations. More precisely, not controlling for consumer expectations may lead the econometrician to overestimate the degree of nonlinearity. Our results hold with aggregate data, regional data, and controlling for cost‐push shocks directly or using instrumental variables.
Using arbitrary precision arithmetic to sharpen identification analysis for DSGE models
Authors: Qu Zhongjun , Tkachenko Denis
Published: February 2023

We introduce arbitrary precision arithmetic to resolve practical difficulties arising in the identification analysis of dynamic stochastic general equilibrium (DSGE) models. A three‐step procedure is proposed to address local and global identification and the empirical distance between models. The method is applied to monetary and fiscal policy interaction models, revealing exact observational equivalence in a small‐scale model between an indeterminate passive monetary and fiscal policy regime and determinate regimes, and near observational equivalence in a medium‐scale model. Additionally, the method yields new insights for a model with news shocks, demonstrating that wage markup shocks can be replaced by unanticipated moving average shocks, resulting in near observational equivalence.
Low Early Antifactor Xa Target Achievement Rate of Low‐Molecular‐Weight Heparin for Treating Venous Thromboembolism in Patients in Intensive Care
Authors: Zhang Li , Zhang Lei , Li Ping , Liu Chenwei , Zheng Qiwen , Wang Yan
Published: February 2023

This study aimed to evaluate whether early antifactor Xa (anti‐Xa) achieved the target range when venous thromboembolism (VTE) was treated with low‐molecular‐weight heparin (LMWH), based on body weight and renal function in patients treated in intensive care units (ICUs). Anti‐Xa levels in patients treated with LMWH for VTE in ICU and medical wards between January 1, 2021, and June 30, 2022, were retrospectively assessed. The demographics, laboratory parameters, and early anti‐Xa peak levels of patients were collected. All patients were followed up for 3 months to collect VTE recurrence/bleeding events. Univariate and multivariate linear regression analyses were used to identify the factors affecting anti‐Xa levels. A total of 108 patients were enrolled in this study, including 70 patients in ICU and 38 patients on medical wards. The early anti‐Xa level (0.36 vs 0.61 IU/mL, P < .001) and target achievement rate (21.4% vs 39.5%, P = .015) of patients in ICU were lower than those in medical wards. Multivariate linear regression showed that only antithrombin (AT) significantly affected anti‐Xa levels in patients in ICU (β = 0.008, 95%CI 0.005 to 0.011, P < .001). There was no significant difference in VTE recurrence events (11.8% vs 7.5%, P = .628) and bleeding events (29.4% vs 17.0%, P = .304) between the early anti‐Xa within‐target group and the early anti‐Xa below‐target group. Low anti‐Xa peak levels are common in patients in ICU. AT activity should be monitored when using LMWH in critically ill patients.
Extracellular vesicles and high‐density lipoproteins: Exercise and oestrogen‐responsive small RNA carriers
Authors: Karvinen Sira , Korhonen Tia‐Marje , Sievänen Tero , Karppinen Jari E. , Juppi Hanna‐Kaarina , Jakoaho Veera , Kujala Urho M. , Laukkanen Jari A. , Lehti Maarit , Laakkonen Eija K.
Published: February 2023

Decreased systemic oestrogen levels (i.e., menopause) affect metabolic health. However, the detailed mechanisms underlying this process remain unclear. Both oestrogens and exercise have been shown to improve metabolic health, which may be partly mediated by circulating microRNA (c‐miR) signalling. In recent years, extracellular vesicles (EV) have increased interest in the field of tissue crosstalk. However, in many studies on EV‐carried miRs, the co‐isolation of high‐density lipoprotein (HDL) particles with EVs has not been considered, potentially affecting the results. Here, we demonstrate that EV and HDL particles have distinct small RNA (sRNA) content, including both host and nonhost sRNAs. Exercise caused an acute increase in relative miR abundancy in EVs, whereas in HDL particles, it caused an increase in transfer RNA‐derived sRNA. Furthermore, we demonstrate that oestrogen‐based hormonal therapy (HT) allows the acute exercise‐induced miR‐response to occur in both EV and HDL particles in postmenopausal women, while the response was absent in nonusers.
Early intervention model of inpatient diabetes care improves glycemia following hospitalization
Authors: Kyi Mervyn , Colman Peter , Gonzalez Vicky , Hall Candice , Cheuk Nathan , Fourlanos Spiros
Published: February 2023

Admission to hospital provides an opportunity to optimize long‐term diabetes management, but clinical inertia is common. We previously reported the randomized study of a proactive inpatient diabetes service (RAPIDS), investigating an early intervention model of care and demonstrated improved in‐hospital glycemia and clinical outcomes. This follow‐up study assessed whether proactive care in hospital improved postdischarge HbA1c. In a subgroup of 298 RAPIDS trial participants with type 2 diabetes, age <80 years, and admission HbA1c ≥ 7.0%, diabetes treatment intensification occurred more often in early intervention versus usual care groups (37% vs. 19% [p = .001]), adjusted odds ratio 3.2 (95% confidence interval [CI]: 1.7–6.0). There was a greater change in HbA1c in the early intervention group (mean −0.9% [95% CI −1.3 to −0.4]) versus the usual care group (−0.3% [−0.6 to −0.1]), p = .029. The value of acute care by dedicated inpatient diabetes teams can extend beyond improving inpatient clinical outcomes and can lead to sustained improvement in glycemia.
Provider perspectives on service delivery modifications to maintain access to HIV pre‐exposure prophylaxis during the COVID‐19 pandemic: qualitative results from a PrEP implementation project in Kenya
Authors: Velloza Jennifer , Roche Stephanie D. , Owidi Emmah J. , Irungu Elizabeth M. , Dollah Annabell , Kwach Benn , Thuo Nicholas B. , Morton Jennifer F. , Mugo Nelly , Bukusi Elizabeth A. , O'Malley Gabrielle , Ngure Kenneth , Baeten Jared M. , Mugwanya Kenneth K. ,   for the Partners Scale‐Up Project Team
Published: February 2023

Introduction

HIV pre‐exposure prophylaxis (PrEP) is an essential prevention strategy being scaled up for priority populations in Kenya, including for HIV serodiscordant couples. The COVID‐19 pandemic posed challenges to PrEP rollout. We conducted a qualitative study of PrEP providers to understand how clinics adjusted PrEP delivery during the COVID‐19 pandemic.

Methods

Since 2017, the Partners Scale‐Up Project has integrated PrEP into 25 HIV clinics in Central and Western Kenya. We conducted qualitative interviews with 40 purposively sampled clinic personnel. We interviewed personnel once during the first pandemic wave (May–Aug 2020) and again after some decline in COVID‐19 rates (Nov–Jan 2021). We analysed data using inductive memo‐writing and summarized data by themes along the PrEP delivery cascade, guided by the Framework for Reporting Adaptation and Modifications (FRAME).

Results

We interviewed 27 clinical officers, five nurses, four health records and information officers, and four counsellors from Central (n = 20) and Western (n = 20) Kenya. About half (n = 19) were female, with a median age of 32 (IQR: 29–34) and 2.3 years of experience delivering PrEP (IQR: 2–3). All participants reported clinic changes in PrEP demand creation and service delivery during the pandemic. Modifications occurred during PrEP implementation and sustainment phases, were partly reactive to the pandemic and also facilitated by interim Ministry of Health guidance on PrEP delivery during COVID, and were made by PrEP delivery teams, clients and clinic managers. Commonly reported modifications included dispensing multiple‐month PrEP refills, intensifying phone‐based client engagement and collaborating with other HIV clinics to ensure that clients with prolonged stays in other regions could continue to access PrEP. Some clinics also adopted practices to streamline visits, such as within clinical‐room PrEP dispensing, pre‐packing PrEP and task‐shifting. Most providers liked these changes and hoped they would continue after the pandemic subsides.

Conclusions

COVID‐19 served as a catalyst for PrEP delivery innovations in Kenya. HIV clinics successfully and rapidly adapted their PrEP demand creation, refill and retention strategies to promote PrEP uptake and effective use. These modified implementation strategies highlight opportunities to streamline the delivery of PrEP, as well as other HIV and chronic care services, and strengthen engagement with populations post‐pandemic.
Glycomics by ion mobility tandem mass spectrometry of chondroitin sulfate disaccharide domain in biglycan
Authors: Sarbu Mirela , Ica Raluca , Sharon Edie , Clemmer David E. , Zamfir Alina D.
Published: February 2023

Biglycan (BGN), a small leucine‐rich repeat proteoglycan, is involved in a variety of pathological processes including malignant transformation, for which the upregulation of BGN was found related to cancer cell invasiveness. Because the functions of BGN are mediated by its chondroitin/dermatan sulfate (CS/DS) chains through the sulfates, the determination of CS/DS structure and sulfation pattern is of major importance. In this study, we have implemented an advanced glycomics method based on ion mobility separation (IMS) mass spectrometry (MS) and tandem MS (MS/MS) to characterize the CS disaccharide domains in BGN. The high separation efficiency and sensitivity of this technique allowed the discrimination of five distinct CS disaccharide motifs, of which four irregulated in their sulfation pattern. For the first time, trisulfated unsaturated and bisulfated saturated disaccharides were found in BGN, the latter species documenting the non‐reducing end of the chains. The structural investigation by IMS MS/MS disclosed that in one or both of the CS/DS chains, the non‐reducing end is 3‐O‐sulfated GlcA in a rather rare bisulfated motif having the structure 3‐O‐sulfated GlcA‐4‐O‐sulfated GalNAc. Considering the role played by BGN in cancer cell spreading, the influence on this process of the newly identified sequences will be investigated in the future.
Biochar‐application rate and method affect nutrient availability and retention in a coarse‐textured, temperate agricultural Cambisol in a microcosm experiment
Authors: Jílková Veronika
Published: February 2023

Background

Agricultural soils often require organic amendments, which improve crop yield and ecosystem services. Biochar has been proven to increase nutrient availability and retention in fine‐textured, tropical soils.

Aims

Here we determine how coarse‐textured, temperate soils react to different biochar‐application rates in different tillage systems.

Methods

We conducted a 6‐month laboratory incubation experiment in microcosms filled with a coarse‐textured, temperate agricultural soil to determine the effects of biochar‐application rate (none, low, or high, i.e., 0, 20, or 40 t dw ha−1, respectively) and application method (mixed into the soil or applied to the soil surface) on microbial activity and biomass, and nutrient availability and leaching.

Results

Microbial activity and biomass and contents of carbon, nitrogen, and phosphorus in leachates were higher in biochar‐addition treatments (by 134%, 37%, 372%, 28%, and 801%, respectively) than in the no‐addition treatment. The effect was stronger with the low than with the high biochar‐application rate. Biochar applied by both methods acted as a slow‐release fertilizer, but this effect was stronger when biochar was mixed into the soil. Although available nutrient contents in the soil remained high, nutrient leaching decreased with incubation time. This effect was especially evident when biochar was mixed into the soil.

Conclusions

Biochar is an effective organic amendment in coarse‐textured soils providing available nutrients. On the other hand, nutrient‐retention mechanisms develop slowly after biochar application and may be greater when biochar is mixed into the soil than applied on the soil surface.
An integrated strategy for the geographical origin traceability of Goji berries by antioxidants characteristic fingerprint based online ultra‐performance liquid chromatography‐2,2‐diphenyl‐1‐picrylhydrazyl‐ photodiode array detector‐mass spectrometry combined with multivariate statistics analysis
Authors: Tian Shanming , Yu Yi , Liu Qian , Guo Huanying , Yu Jinqian , Wang Xiao , Zhao Hengqiang
Published: February 2023

Goji berries are now becoming increasingly popular in the human diet due to their potential health benefits. Unscrupulous traders deliberately mislabel with certain origins to gain illegal profits, which seriously affected the consumers’ benefits. In this study, an online ultra‐performance liquid chromatography‐2,2‐diphenyl‐1 ‐picrylhydrazyl‐photodiode array detector‐electrospray ionization‐quadrupole time of flight mass was developed for rapid screening and identification of the antioxidants from Goji berry; then, the antioxidants characteristic fingerprint was established and explored in the origins discrimination of Goji berries from China combined with multivariate statistics analysis. As a result, twenty‐eight compounds were screened from Goji berry extract, 19 of which were identified by accurate molecular and ultraviolet information according to references. Principal components analysis and partial least squares discrimination analysis achieved the accurate classification from the four regions, eight compounds were selected as origin‐related antioxidant markers with variable importance in projection >1 and one‐way analysis of variance (P<0.05), including rutin, rutin di‐hexose, P‐coumaric acid tri‐hexose, dicaffeoylquinic acid isomer, Quercetin‐rhamno‐di‐hexoside, peak14, peak16, and peak27. This study provides a feasible strategy for the geographical origins discrimination of Goji berries based on antioxidant ingredients difference and will be helpful for improving the quality control level of Goji berries.
Analysis of doping control samples using supercritical fluid chromatography‐tandem mass spectrometry: Ready for routine use
Authors: Wuest Bernhard , Gavrilović Ivana , Cowan David , Torre Xavier de la , Botrè Francesco , Parr Maria Kristina
Published: February 2023

Supercritical fluid chromatography is proving to be a good separation and sample preparation tool for various analytical applications and, as such, has gained the attention of the anti‐doping community. Here, the applicability of supercritical fluid chromatography hyphenated to tandem mass spectrometry for routine doping control analysis was tested. A multi‐analyte method was developed to cover 197 drugs and metabolites that are prohibited in sport. More than 1000 samples were analyzed by applying a “dilute and inject” approach after hydrolysis of glucuronide metabolites. Additionally, a comparison with routinely used liquid chromatography‐mass spectrometry was performed with 250 of the 1000 samples and a number of past positive anti‐doping samples. It revealed some features where supercritical fluid chromatography‐tandem mass spectrometry was found to be complementary or advantageous to liquid chromatography‐mass spectrometry for anti‐doping purposes, such as better retention of analytes that are poorly retained in reversed‐phase liquid chromatography. Our results suggest that supercritical fluid chromatography‐tandem mass spectrometry is sensitive (limit of detection <50% relevant minimum required performance level required by the World Anti‐Doping Agency for anti‐doping analysis), reproducible, robust, precise (analytes of interest area coefficient of variation <5%; retention time difference coefficient of variation <1%) and complementary to existing techniques currently used for routine analysis in the World Anti‐Doping Agency accredited laboratories.