bluuebunny/crossref_metadata_2025 huggingface dataset:
Valorization of rubberwood waste into porous carbon
Authors: Songthan R , Somsongkul V , Kongmark C
Published: March 2022

Rubberwood is one of the main Thailand goods exports. In each year, about 45,000 hectares of rubber tree are cut down, only about 30% of them is appropriated for furniture production while most of the rest is used as woodfuel. This research work focuses on the valorization of rubberwood waste into porous carbon and the optimization of carbonization process for the production of hierarchical porous carbon. Rubberwood wastes obtained from a rubberwood processing industry (in Thailand’s southern region) were treated with H3PO4 and subjected to two different carbonization methods. In the first method, the rubberwood was carbonized at 500°C for 1 h (PC-1step). The second method consisted of two steps of heat treatment, the rubberwood was pre-carbonized at 200°C for 15 min and subsequently carbonized at 500°C for 45 min (PC-2step). The physical properties of the porous carbon were investigated using thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, and N2 adsorption-desorption isotherm techniques. The porous carbons obtained from both carbonization methods have hierarchical porous structures comprising the naturally existing tubular macropores (diameter 4-20 μm) and the micropores (diameter 0.3-1 nm) generated during carbonization process. The PC-2step provides a specific surface area of 336.2 m2 g-1 and a pore volume of 0.093 cm3 g-1, which are almost twice those of the PC-1step. It is possible that the pre-carbonization at 200°C would allow a slow and gradual evaporation of moisture within the wood, thus preserving pore walls in the materials. The obtained hierarchical porous carbons can be used in many applications such as energy storage, waste water treatment, air purification and metal recovery.
Design of experiments approach to developing a robust ink for bioprinting
Authors: Hegab Rachel , Van Volkenburg Tessa , Ohiri Korine , Sebeck Natalie , Bessling Seneca , Theodore Mellisa , Rossick Katelyn , Pellicore Matthew , Benkoski Jason , Patrone Julia
Published: March 2022

Despite advancements in tissue engineering, the methods used to generate three-dimensional (3D) in vitro models for rapid screening and characterization studies remain time and labor intensive. Bioprinting offers an opportunity to offset these limitations by providing a scalable, high-throughput method with precise control over biomaterial scaffold and cellular deposition. However, the process of formulating bioinks can be complex in terms of balancing the mechanical integrity of a bioscaffold and viability of cells. One key factor, especially in alginate-based bioinks, is the rate of bioscaffold dissolution. It must allow cells to replace the bioscaffold with extracellular matrix (ECM), yet remain durable during extended tissue culture. This study uses a Design of Experiments (DoE) approach to understand the dependencies of multiple variables involved in the formulation and processing of an alginate-based bioink. The focus of the DoE was to understand the effects of hydrogel composition on bioink durability while maintaining cell viability. Three ingredients were varied in all: alginate, nanocellulose, and fibrinogen. Their effects on the bioink were then measured with respect to extrudability, strength, and stiffness as determined by dynamic mechanical analysis (DMA). The DoE demonstrated that mechanical integrity increased with increasing alginate concentration. In contrast, fibrinogen and nanofibril concentration had no statistically significant effect. The optimized ink containing fibroblasts was printable using multiple nozzle sizes while also supporting fibroblast cell viability. DMA characterization further showed that the composition of the cell culture medium did not modulate the degradation rate of the hydrogel. Ultimately, the study outlines a methodology for formulating a bioink that will result in robust bioscaffolds for in vitro model development.
Effective persistency evaluation via exact excursion distributions for random processes and fields
Authors: Lindgren G , Podgórski K , Rychlik I
Published: March 2022

Finding the probability that a stochastic system stays in a certain region of its state space over a specified time—a long-standing problem both in computational physics and in applied and theoretical mathematics—is approached through the extended and multivariate Rice formula. In principle, it applies to any smooth process multivariate both in argument and in value given that efficient numerical implementations of the high-dimensional integration are available. The computational method offers an exact integral representation yielding remarkably accurate results and provides an alternative method of computing persistency probability and exponent for a physical system. It can be viewed as an implementation of path integration for a smooth Gaussian process with an arbitrary covariance. Its high accuracy is due to efficient computation of expectations with respect to high-dimensional nearly singular Gaussian distributions. For Gaussian processes, the computations are effective and more precise than those based on the Rice series expansions and the independent interval approximation. For the benchmark diffusion process, it produces the persistency exponent that is essentially the same as the recently obtained analytical value and surpasses accuracy, interpretability as well as control of the error, previous methods including the independent or Markovian approximation. The method solves the two-step excursion dependence for a stationary differentiable Gaussian process, in both theoretical and numerical sense. The solution is based on exact expressions for the probability density for one and two successive excursion lengths. The numerical routine RIND computes the densities using recent advances in scientific computing and is easily accessible for a general covariance function, via a simple numerical interface. The work offers also analytical results that explain the effectiveness of the implemented methodology and elaborates its utilization for non-Gaussian processes.
A modular fabrication process for thin-film lithium niobate modulators with silicon photonics
Authors: Mere Viphretuo , Valdez Forrest , Wang Xiaoxi , Mookherjea Shayan
Published: March 2022

We report advancements in the fabrication of electro-optic Mach-Zehnder modulators made by bonding an unetched thin film of lithium niobate (LN) to a second chip with rib waveguides in another material, such as silicon. Devices were fabricated after storing bonded silicon-LN chips in a common laboratory environment for more than three years. The chips survived the full processing flow and yielded modulators with greater than 50 GHz 3 dB electro-optic bandwidth, and

V

π

L

less than 3 V cm at 1550 nm and equivalent performance to freshly-bonded and processed chips. Furthermore, we demonstrate the co-integration of hybrid bonded thin-film LN modulators and silicon photonics based high quality-factor ring resonators and higher-order coupled microring optical filters. The silicon microring resonators are used for photon-pair generation at 1550 nm using spontaneous four-wave mixing. These results show the feasibility of a modular modulator fabrication procedure, where the planarization and bonding steps are performed for a batch of chips at one time and smaller sub-batches are customized by end users at a much later time according to their needs and convenience.
Synergistic enhancement in electrical conductivity of polymer composites simultaneously filled with multi-walled carbon nanotube and pitch-based carbon fiber via one-step solvent-free fabrication
Authors: Kang Hyoseop , Kim Ki Hoon , Kim Geon Su , Lee Hyeseong , Jang Ji-un , Kim Seong Yun
Published: March 2022

Recently, studies have been reported to synergistically improve the electrical conductivity of polymer composites by simultaneously incorporating hybrid fillers, but systematic studies on filler loading and ratio are still scarce. In this study, a one-step process was proposed to induce the incorporation of uniformly dispersed fillers with a high content, and synergistic improvement in the electrical conductivity of polymer composites was studied by applying two types of carbon fillers: nano-sized multi-walled carbon nanotube (MWCNT) and micro-sized pitch-based carbon fiber (PCF). Based on the proposed process, it was possible to fabricate a polymer composite in which the filler was uniformly dispersed within 40 wt%. The electrical conductivity of the composite containing up to 10 wt% MWCNT which was the percolation plateau content and 30 wt% PCF was 3940 S m−1, showing the maximum performance. This result was improved by 595% and 586%, respectively, compared to the electrical conductivity of the composite containing only 40 wt% MWCNT or PCF. These findings can contribute to expanding the application of conductive composites in the fields of antistatic or electromagnetic interference shielding by providing insight into the optimal design of hybrid filler systems to improve the electrical conductivity of composites.
Influence of Fe3+ ions on the optical properties and photocatalytic ability of spin coated Fe3+ doped brookite TiO2 thin films
Authors: Komaraiah Durgam , Radha Eppa , Sivakumar J , Sayanna R
Published: March 2022

The spin coating process has been used to deposit pure and Fe3+ doped brookite titania films onto glass substrates. In essence, such as films annealed at 500 °C are found to be orthorhombic crystal structure with brookite phase. X-ray diffractometer measurements revealed that Fe ions are incorporated into cation sites of TiO2. The crystallite size reduces with the doping of Fe3+ ions. The scanning electron microscope images show highly uniform, crack free films and the particles size is found to be within the range of 150–200 nm. Energy-dispersive x-ray spectroscopy analysis Fe3+ doped TiO2 films confirmed good stoichiometry of chemical compositions. The Raman spectra of brookite TiO2 exhibit a very strong characteristic band at 153cm−1. The optical band gap was found to be declined from 3.08 eV to 2.54 eV with adding the Fe ions into TiO2 matrix. The EPR studies approve incorporation of Fe3+ in the crystal lattice of brookite by substituting Ti4+ and generation of defects, and Ti3+ states. Photocatalytic ability of films has been studied by degradation of methyl orange solution under illumination of visible light. The 7% Fe doped brookite film was exhibited high catalytic activity compared to other pure and doped films.
Pollen dispersal and genetic diversity of Yucca valida (Asparagaceae), a plant involved in an obligate pollination mutualism
Authors: Alamo-Herrera C Rocio , Arteaga Maria Clara , Bello-Bedoy Rafael , Rosas-Pacheco Fernando
Published: March 2022

In insect-pollinated plants, gene flow through pollen depends on the behaviour of pollinators when moving pollen, as well as the spatial distribution of the plants. For the perennial species Yucca valida, we evaluated gene flow mediated by its obligate pollinator, the yucca-moth Tegeticula baja. We also estimated genetic diversity and population structure throughout the plant’s geographical distribution. Using nuclear microsatellites, we genotyped 405 individuals, representing 105 trees and progenies from 15 plants (300 seedlings). We estimated outcrossing rate, pollen donors, dispersion distance and genetic autocorrelation index, as well as diversity and differentiation indexes. We found that Y. valida has a mostly outcrossing mating system. Gene flow through pollen occurs over short distances (42 m) within a small reproductive neighbourhood (1.4 ha) where individuals are genetically related. Each mother plant’s progeny has at least 2.8 pollen donors. Despite the inbreeding detected, interaction among yucca life-history traits may maintain high levels of genetic diversity and low differentiation among Y. valida populations. The spatial scale at which gene flow operates is essential in understanding the distribution of genetic variation within and between populations.
OnF-modelling-based empirical Bayes estimation of variances
Authors: Kwon Yeil , Zhao Zhigen
Published: March 2022

We consider the problem of empirical Bayes estimation of multiple variances when provided with sample variances. Assuming an arbitrary prior on the variances, we derive different versions of the Bayes estimators using different loss functions. For one particular loss function, the resulting Bayes estimator relies on the marginal cumulative distribution function of the sample variances only. When replacing it with the empirical distribution function, we obtain an empirical Bayes version called the $F$-modelling-based empirical Bayes estimator of variances. We provide theoretical properties of this estimator, and further demonstrate its advantages through extensive simulations and real data analysis.
Outcome and prognosis after adrenal metastasectomy: nationwide study
Authors: Vlk Elizabeth , Ebbehoj Andreas , Donskov Frede , Poulsen Per Løgstrup , Rashu Badal Sheiko , Bro Lasse , Aagaard Mikael , Rolighed Lars
Published: March 2022

Background

Data regarding adrenal metastasectomy are limited. Here, clinical outcomes, safety, and prognostic factors in patients undergoing adrenal metastasectomy were evaluated in a large nationwide study.

Methods

Patients undergoing adrenal metastasectomy between 2000 and 2018 were identified in the Danish National Pathology Registry. Medical records were reviewed to confirm eligibility and to collect clinical data. The primary outcome was overall survival (OS). Cox multivariable regression analyses were? adjusted for baseline factors.

Results

In total, 435 patients underwent adrenal metastasectomy; the primary cancer origins were renal (n = 195, 45 per cent), lung (n = 121, 28 per cent), colorectal (n = 50, 11 per cent), and other (n = 69, 16 per cent). The median (interquartile range; i.q.r.) age was 66 (59–71) years, and 280 (64 per cent) were men. The 5-year OS was 31 per cent. The 30-day mortality was 1.8 per cent. Complications were more frequent and severe in patients who underwent open surgery compared with laparoscopic surgery (Clavien–Dindo III–V, 31.5 per cent versus 11.8 per cent respectively, P < 0.001). Factors associated with poor survival included non-radical pR2 resection (hazard ratio (HR) 3.57, 95 per cent c.i. 1.96 to 6.48), tumour size more than 50 mm (HR 1.79, 95 per cent c.i. 1.26 to 2.52), lung cancer origin (HR 1.77, 95 per cent c.i. 1.31 to 2.40), open surgical approach (HR 1.33, 95 per cent c.i. 1.04 to 1.71), presence of extra-adrenal metastases (HR 1.31, 95 per cent c.i. 1.01 to 1.71), and increasing Charlson co-morbidity index factors (HR 1.14 per one-point increase, 95 per cent c.i. 1.03 to 1.27).

Conclusion

Adrenal metastasectomy is safe and may result in long-term survival in a subset of patients. Non-radical resection, large tumour size, lung cancer origin, open approach, presence of extra-adrenal metastases, and co-morbidity were associated with inferior outcomes.
Efficacy and safety of drugs used for ‘assisted dying’
Authors: Worthington Ana , Finlay Ilora , Regnard Claud
Published: March 2022

Background

‘Assisted dying’ is practiced in some European countries and US states. Legislation suggests that there exists an easily prescribed drug which consistently brings about death quickly and painlessly. Evidence from jurisdictions where ‘assisted dying’ is practiced, however, reveals that hastening patient death is not so simple.

Sources of data

This report is a collation of assisted suicide and euthanasia drug protocols published by the Canadian Association of MAiD Assessors and Providers and the Royal Dutch Medical Association, annual data reports from the USA and Canada and relevant academic publications pertaining to methods of ‘assisted dying’ in the USA, Belgium, Canada and Switzerland.

Areas of agreement

A wide variety of lethal drug combinations are used for people who want their life ended, and the prevalence of complications and failures in intentionally ending life suggest that ‘assisted dying’ applicants are at risk of distressing deaths.

Areas of controversy

The efficacy and safety of ‘assisted dying’ drugs are currently difficult to assess, as clinician reporting is often very low.

Growing points

The findings from this report reveal that little attention has been given to the problem of unmonitored prescribing and administering of lethal drug combinations, whose mode of action is unclear.

Areas timely for developing research

In order to properly assess the efficacy and safety of ‘assisted dying’, a more thorough means of data collection regarding the drugs used must be implemented and research is urgently needed into their mode of action.
Hamstring, bone-patellar tendon-bone, quadriceps and peroneus longus tendon autografts for primary isolated posterior cruciate ligament reconstruction: a systematic review
Authors: Migliorini Filippo , Pintore Andrea , Vecchio Gianluca , Oliva Francesco , Hildebrand Frank , Maffulli Nicola
Published: March 2022

Introduction

Several autografts are available to reconstruct the posterior cruciate ligament (PCL).

Source of data

Current scientific literature published in PubMed, Google scholar, Embase and Scopus.

Areas of agreement

Hamstring, bone-patellar tendon-bone (BPTB), quadriceps and peroneus longus (PLT) are the most common tendon autografts used for primary isolated PCL reconstruction.

Areas of controversy

The optimal tendon source for PCL reconstruction remains nevertheless debated. Identifying the most suitable tendon autograft could assist the surgeon during primary PCL reconstruction.

Growing points

The present study compared the outcome of PCL reconstruction using hamstring, BPTB, quadriceps and PLT autografts. The focus was on patient-reported outcome measures (PROMs), joint laxity, range of motion and complications.

Areas timely for developing research

All autografts are viable options for PCL reconstruction, with BTB and hamstring autografts demonstrating superior PROMs. However, further clinical investigations are required to determine the ideal autograft construct.
Mining Frequent Serial Positioning Episode Rules with Forward and Backward Search Technique from Event Sequences
Authors: K Poongodi , Kumar Dhananjay
Published: March 2022

A large event sequence can generate episode rules that are patterns which help to identify the possible dependencies existing among event types. Frequent episodes occurring in a simple sequence of events are commonly used for mining the episodes from a sequential database. Mining serial positioning episode rules (MSPER) using a fixed-gap episode occurrence suffers from unsatisfied scalability with complex sequences to test whether an episode occurs in a sequence. Large number of redundant nodes was generated in the MSPER-trie-based data structure. In this paper, forward and backward search algorithm (FBSA) is proposed here to detect minimal occurrences of frequent peak episodes. An extensive correlation of parameter settings and the generating procedure of fixed-gap episodes are carried out. To generate a fixed-gap episode and estimate the variance that decides the parameter selection in event sequences, Spearman’s correlation coefficient is used for verifying the sequence of occurrences of the episodes. MFSPER with FBSA is developed to eliminate the frequent sequence scans and redundant event sets. The MFSPER–FBSA stores the minimal occurrences of frequent peak episodes from the event sequences. The experimental evaluation on benchmark datasets shows that the proposed technique outperforms the existing methods with respect to memory, execution time, recall and precision.
Magnetic resonance imaging contrast-enhancement with superparamagnetic iron oxide nanoparticles amplifies macrophage foam cell apoptosis in human and murine atherosclerosis
Authors: Segers Filip M E , Ruder Adele V , Westra Marijke M , Lammers Twan , Dadfar Seyed Mohammadali , Roemhild Karolin , Lam Tin Sing , Kooi Marianne Eline , Cleutjens Kitty B J M , Verheyen Fons K , Schurink Geert W H , Haenen Guido R , van Berkel Theo J C , Bot Ilze , Halvorsen Bente , Sluimer Judith C , Biessen Erik A L
Published: March 2022

Aims

(Ultra) Small superparamagnetic iron oxide nanoparticles, (U)SPIO, are widely used as magnetic resonance imaging contrast media and assumed to be safe for clinical applications in cardiovascular disease. As safety tests largely relied on normolipidaemic models, not fully representative of the clinical setting, we investigated the impact of (U)SPIOs on disease-relevant endpoints in hyperlipidaemic models of atherosclerosis.

Methods and results

RAW264.7 foam cells, exposed in vitro to ferumoxide (dextran-coated SPIO), ferumoxtran (dextran-coated USPIO), or ferumoxytol [carboxymethyl (CM) dextran-coated USPIO] (all 1 mg Fe/mL) showed increased apoptosis and reactive oxygen species accumulation for ferumoxide and ferumoxtran, whereas ferumoxytol was tolerated well. Pro-apoptotic (TUNEL+) and pro-oxidant activity of ferumoxide (0.3 mg Fe/kg) and ferumoxtran (1 mg Fe/kg) were confirmed in plaque, spleen, and liver of hyperlipidaemic ApoE−/− (n = 9/group) and LDLR−/− (n = 9–16/group) mice that had received single IV injections compared with saline-treated controls. Again, ferumoxytol treatment (1 mg Fe/kg) failed to induce apoptosis or oxidative stress in these tissues. Concomitant antioxidant treatment (EUK-8/EUK-134) largely prevented these effects in vitro (−68%, P < 0.05) and in plaques from LDLR−/− mice (−60%, P < 0.001, n = 8/group). Repeated ferumoxtran injections of LDLR−/− mice with pre-existing atherosclerosis enhanced plaque inflammation and apoptosis but did not alter plaque size. Strikingly, carotid artery plaques of endarterectomy patients who received ferumoxtran (2.6 mg Fe/kg) before surgery (n = 9) also showed five-fold increased apoptosis (18.2 vs. 3.7%, respectively; P = 0.004) compared with controls who did not receive ferumoxtran. Mechanistically, neither coating nor particle size seemed accountable for the observed cytotoxicity of ferumoxide and ferumoxtran.

Conclusions

Ferumoxide and ferumoxtran, but not ferumoxytol, induced apoptosis of lipid-laden macrophages in human and murine atherosclerosis, potentially impacting disease progression in patients with advanced atherosclerosis.
Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction
Authors: Shin Junchul , Tkachenko Svyatoslav , Chaklader Malay , Pletz Connor , Singh Kanwardeep , Bulut Gamze B , Han Young min , Mitchell Kelly , Baylis Richard A , Kuzmin Andrey A , Hu Bo , Lathia Justin D , Stenina-Adognravi Olga , Podrez Eugene , Byzova Tatiana V , Owens Gary K , Cherepanova Olga A
Published: March 2022

Aims

Until recently, the pluripotency factor Octamer (ATGCAAAT)-binding transcriptional factor 4 (OCT4) was believed to be dispensable in adult somatic cells. However, our recent studies provided clear evidence that OCT4 has a critical atheroprotective role in smooth muscle cells. Here, we asked if OCT4 might play a functional role in regulating endothelial cell (EC) phenotypic modulations in atherosclerosis.

Methods and results

Specifically, we show that EC-specific Oct4 knockout resulted in increased lipid, LGALS3+ cell accumulation, and altered plaque characteristics consistent with decreased plaque stability. A combination of single-cell RNA sequencing and EC-lineage-tracing studies revealed increased EC activation, endothelial-to-mesenchymal transitions, plaque neovascularization, and mitochondrial dysfunction in the absence of OCT4. Furthermore, we show that the adenosine triphosphate (ATP) transporter, ATP-binding cassette (ABC) transporter G2 (ABCG2), is a direct target of OCT4 in EC and establish for the first time that the OCT4/ABCG2 axis maintains EC metabolic homeostasis by regulating intracellular heme accumulation and related reactive oxygen species production, which, in turn, contributes to atherogenesis.

Conclusions

These results provide the first direct evidence that OCT4 has a protective metabolic function in EC and identifies vascular OCT4 and its signalling axis as a potential target for novel therapeutics.
How has the Ascend programme contributed to strengthening health systems for sustainable country-driven neglected tropical disease programming?
Authors: Rowan Sinead , Amodu-Agbi Perpetua , Weil Olivier , Northway Diane , Ene Nkem , Gwom Anita , Pavluck Alexandre
Published: March 2022

The Ascend West and Central Africa programme, a UK aid-funded programme, was implemented across 12 countries. The programme focused on strengthening national health systems for sustainable neglected tropical disease (NTD) control and elimination. This commentary presents how Ascend's approach contributed to developing country-driven sustainable systems for NTDs and offers learnings to inform future sustainable NTD programming.
Effect of a prioritization score on the inter-hospital transfer time management of severe COVID-19 patients: a quasi-experimental intervention study
Authors: Solà-Muñoz Silvia , Azeli Youcef , Trenado Josep , Jiménez Xavier , Bisbal Roger , López Àngels , Morales Jorge , García Xaime , Sánchez Bernat , Fernández José , Soto Maria Ángeles , Ferreres Yolanda , Cantero Cristina , Jacob Javier
Published: March 2022

Background

The overburdening of the healthcare system during the coronavirus disease 19 (COVID-19) pandemic is driving the need to create new tools to improve the management of inter-hospital transport for patients with a severe COVID-19 infection.

Objective

The aim of this study was to analyse the usefulness of the application of a prioritization score (IHTCOVID-19) for inter-hospital transfer of patients with COVID-19 infection.

Methods

The study has a quasi-experimental design and was conducted on the Medical Emergency System, the pre-hospital emergency department of the public company belonging to the Autonomous Government of Catalonia that manages urgent healthcare in the region. Patients with a severe COVID-19 infection requiring inter-hospital transport were consecutively included. The pre-intervention period was from 1 to 31 March 2020, and the intervention period with the IHTCOVID-19 score was from 1 to 30 April 2020 (from 8 am to 8 pm). The prioritization score comprises four priority categories, with Priority 0 being the highest and Priority 3 being the lowest. Inter-hospital transfer (IHT) management times (alert-assignment time, resource management time and total central management time) and their variability were evaluated according to whether or not the IHTCOVID-19 score was applied.

Results

A total of 344 IHTs were included: 189 (54.9%) in the pre-intervention period and 155 (45.1%) in the post-intervention period. The majority of patients were male and the most frequent age range was between 50 and 70 years. According to the IHTCOVID-19 score, 12 (3.5%) transfers were classified as Priority 0, 66 (19.4%) as Priority 1, 247 (71.8%) as Priority 2 and 19 (5.6%) as Priority 3. Overall, with the application of the IHTCOVID-19 score, there was a significant reduction in total central management time [from 112.4 (inter-quartile range (IQR) 281.3) to 89.8 min (IQR 154.9); P = 0.012]. This significant reduction was observed in Priority 0 patients [286.2 (IQR 218.5) to 42.0 min (IQR 58); P = 0.018] and Priority 1 patients [130.3 (IQR 297.3) to 75.4 min (IQR 91.1); P = 0.034]. After applying the IHTCOVID-19 score, the average time of the process decreased by 22.6 min, and variability was reduced from 618.1 to 324.0 min.

Conclusion

The application of the IHTCOVID-19 score in patients with a severe COVID-19 infection reduces IHT management times and variability.
The Cosmopolitan Silk Road Worldview: Developing an Interfaith Ethic of Hospitality in Ancient Buddhist and Christian Writings
Authors: Chong Alan
Published: March 2022

The ancient Silk Roads are reputed for demonstrating a more tolerant Asia–Europe interaction than is believed possible today among modern nation-states. What is the Silk Roads’ contribution to global thought? Along the original Silk Roads, a cosmopolitan ethic of hospitality to foreigners emerged from a confluence of hostile secular attitudes as well as accommodation of differences within each religion's conception of ecumenism and standardization. This is manifest in the writings of Marco Polo, a quintessential traveller along the ancient overland Silk Road, assorted Christian monks serving as Papal representatives to the Mongols, and two Buddhist pilgrims, Fa-Hsien and I-Tsing of China. In treating these underappreciated writings as contributions to global thought from Asia, the author identifies three indelible elements that add up to an amorphous cosmopolitanism in progress: the role of violence in managing social order, piety through ritual, and the custom of travellers and hosts exchanging gifts.
Population pharmacokinetics of intravenous cefotaxime indicates that higher doses are required for critically ill children
Authors: Hartman Stan J. F. , Upadhyay Parth J. , Mathôt Ron A. A. , van der Flier Michiel , Schreuder Michiel F. , Brüggemann Roger J. , Knibbe Catherijne A. , de Wildt Saskia N.
Published: March 2022

Background

Cefotaxime is frequently used in critically ill children, however pharmacokinetic (PK) studies to support adequate dosing in this patient population are limited.

Objectives

To characterize cefotaxime PK in critically ill children and evaluate exposures achieved by current and alternative dosing regimens.

Methods

Children (0–18 years) admitted to the paediatric ICU, receiving intravenous cefotaxime (100–150 mg/kg/day, interval 6–8 h) were included (Clinicaltrials.gov NCT03248349). Total plasma cefotaxime concentrations were measured on multiple study days. Population-PK analysis was performed using nonlinear mixed effects modelling (NONMEM™). Dose evaluations were performed using typical patients across the paediatric age range and target attainment was determined for MICs of 0.5, 2 and 4 mg/L.

Results

479 cefotaxime plasma concentrations from 52 children (median age 1.6, range 0.03–17.7 years) were used to describe cefotaxime PK. We describe a two-compartment structural model with interindividual variability, including bodyweight as covariate for volume of distribution and clearance. Model predicted exposure for 150 mg/kg/day (current dose) showed trough concentrations <0.5 mg/L in patients >4 years of age. The maximum cefotaxime doses (200 mg/kg/day, interval 6 h) proved adequate for MICs ≤0.5 mg/L across the whole age range. Similar daily doses with increased frequency (interval 4 h) covered MICs up to 2 mg/L, while a loading dose followed by continuous infusion regimens are needed to adequately treat MICs of 4 mg/L.

Conclusions

Higher cefotaxime doses are required for adequate exposure for most pathogens in critically ill children. A higher dose frequency or continuous infusion is advisable to improve target attainment for intermediately susceptible pathogens.
Functional properties of miscanthus fiber and prebiotic blends in extruded canine diets
Authors: Finet Shannon , He Fei , Clark Lindsay. V , de Godoy Maria Regina Cattai
Published: March 2022

Dietary fiber has become increasingly recognized as a key factor in maintaining gastrointestinal health. Dietary fiber sources are often comprised of several different fiber fractions, each with unique physicochemical properties. These properties can have varying physiological effects on the gastrointestinal tract that include modulation of microbiota, production of fermentation-derived metabolites, and laxation. The objectives of this study were 1) to determine the effects of a novel dietary fiber source, miscanthus grass fiber (MF), and prebiotic and fiber blends on gastrointestinal tolerance, apparent total tract digestibility, fecal metabolites, and fecal microbiota and 2) to evaluate the palatability of extruded diets containing MF in comparison to traditional dietary fiber sources. All animal procedures were approved by the University of Illinois Institutional Animal Care and Use Committee. Six dietary treatments were formulated to meet or exceed the AAFCO nutrient profile of 2018 and included either cellulose (CO), beet pulp (BP), MF, or a blend of MF and tomato pomace, MF and resistant starch, or MF and fructooligosaccharide. A total of 12 adult neutered female beagles (mean age 5.8 ± 1.1 yr; mean body weight 10.9 ± 1.0 kg; mean body condition score 5.7 ± 0.7) were randomly assigned to one of the six treatment diets in a replicated 6 × 6 Latin square design. Each dog was fed their assigned diet for a treatment period of 21 d with 17 d of diet adaptation followed by 4 d of total and fresh fecal collection. All diets were well accepted and digested by the dogs. Dogs fed BP had greater fecal total short-chain fatty acid concentration than the CO treatment (P < 0.05), while the dogs fed diets containing MF were intermediate. In a two-bowl palatability trial, no significant preference was observed between the extruded diets containing MF and CO (P > 0.05). However, a significant preference for the extruded diet containing BP over the diet containing only MF was observed (P < 0.05). The α-diversity of fecal microbial communities was not impacted by treatment (P > 0.05), but β-diversity indicated that dogs fed the BP diet differed from the other treatment groups (P < 0.05). The data from this study suggest that miscanthus grass can be successfully utilized in fiber blends in extruded diets for adult dogs, with modulatory effects similar to the traditional dietary fiber source, cellulose.
The Development of Acute Kidney Injury in Burn Patients Undergoing Computed Tomography With Intravenous Contrast
Authors: Burgess Jessica , Jenkins Ciara , Kopelman, Tammy , Foster Kevin , Collins Jay
Published: March 2022

Acute kidney injury (AKI) is a major complication of significant burn injuries and a significant cause of patient morbidity and mortality. Patients that sustain traumatic burn injuries may require computed tomography (CT) imaging as part of their initial trauma management. This multicenter retrospective chart review of patients admitted to two level I trauma centers with ≥10% TBSA burns between 2014 and 2017 aims to determine if patients with greater than 10% TBSA burns that received CT imaging with intravenous contrast were more likely to develop acute kidney injury during their admission. A total of 439 patients were included in the study. The average age was 45.3 years and average TBSA was 23.2%. Sixty-seven of the 439 patients underwent CT scans with IV contrast on admission. The rate of AKI between patients who did or did not receive CT scans was not statistically significant (9.1 vs 6.0%, P = 0.40). Patients who developed an AKI had higher TBSA (45.6 vs 21.1%, P < .01), amount of fluids per TBSA given within the first 24 hours (457.4 vs 321.6, P < .01), and mortality (71.1 vs 6.2%, P < .01) than those who did not develop an AKI. There was no significant difference in the development of acute kidney injury in burn patients who received CT scans with IV contrast on admission. Although there is a risk of contrast induced nephropathy, the risk is not increased in burn patients and this should not prevent a thorough evaluation to rule out additional life-threatening injuries in the burn trauma patient.
Design principle for effective mechanical boundary using a resonance band gap under elastic waves
Authors: Shin Yong Chang , Jo Soo-Ho , Yoon Heonjun , Youn Byeng D
Published: March 2022

One representative feature of a locally resonant elastic metamaterial (LREM) is that they can prohibit elastic wave propagation at the frequencies inside a band gap, which means that no energy is transmitted. When an incident wave propagates in a host medium at the frequencies inside band gaps, the incident wave is totally reflected at the interface between the host medium and an LREM. However, it remains unexplored what kind of mechanical boundary (e.g. fixed or free) is formed at the interface between the host medium and the LREM. This study thus aims at finding design principles for effective mechanical boundary (EMB) formation and validating the principles by numerical simulation. Conditions for certain EMBs were derived from the magnitude and phase of the reflection coefficient of the LREM. According to the conditions, an LREM is designed and attached to a host medium. It was confirmed from time-harmonic simulation that the velocity at the interface between the host medium and the LREM approached zero when the effective fixed boundary is formed, while the stress at the interface approached zero when the effective free boundary is formed.
Antidepressant use in Turkey by provinces: panel data analysis
Authors: Oğuzhan Gülpembe , Eren Miraç , Koçkaya Güvenç , Adam Baskı Keziban , Şaylan İsmail Mete , Kurnaz Mustafa , Ökçün Selin
Published: March 2022

Objectives

The objective of this analysis is to show differences in antidepressant use by year and by provinces of Turkey and to understand possible factors that cause these differences.

Methods

The drug data were obtained from the IMS Health Turkey Medical Index, and the per capita usage was calculated by proportioning with the population. Provinces with combined data were excluded from the study. Sixty provinces with complete data obtained from the IMS Health and Turkish Statistical Institute (TUIK) were included in the analysis. Physician visits per capita annual data were extracted from the Ministry of Health statistics. Population and per capita gross domestic product data of provinces were obtained from TUIK. A panel data regression model was established in the study.

Key findings

The model explained 99.25% of the variation in antidepressant consumption unit per person, which is a dependent variable. In our study, it was observed that there was no statistically significant effect of age and income in antidepressant usage. However, per capita physician consultation and the total population have a significant effect on per capita antidepressant use. Therefore, when the other variables are kept constant and the total population increases by 1%, the coefficient of antidepressant use per capita increases by 0.62%.

Conclusions

According to our analysis, in the majority of the provinces, antidepressant use exceeded the expected level. If the population density of Turkey increases, the ratio of antidepressant usage in the total consumption of drugs may grow. It is necessary to investigate whether there is overuse and to determine underlying causes and preventive measures.
Fetal Transfer of Human Metapneumovirus-Neutralizing Antibodies Is Reduced From Mothers Living With HIV-1
Authors: Ramocha Lesego M , van den Hoogen Bernadette G , Baillie Vicky , van Nieuwkoop Stefan , Cutland Clare L , Jones Stephanie , Moultrie Andrew , Izu Alane , Verwey Charl , Madhi Shabir A , Dorfman Jeffrey R
Published: March 2022

Transplacental hMPV-neutralizing antibody transfer was reduced from mothers living with HIV-1. However, a comparison of antibody titers at birth between hMPV hospitalization cases at <6 months and matched controls suggested that reduced maternal antibody might not be the primary cause of the previously reported elevated hMPV risk in HIV-1-exposed infants.
Gastric metastasis from breast cancer presenting as dysphagia
Authors: Fousekis Fotios S , Tepelenis Kostas , Stefanou Stefanos K , Stefanou Christos K , Pappas-Gogos George , Theopistos Vasileios , Evangelou Zoi , Mauri Davide , Christodoulou Dimitrios K
Published: March 2022

Gastric metastasis from breast cancer occurs infrequently and causes non-specific symptoms, usually attributed to the underlying disease. Furthermore, endoscopic findings are almost identical to primary gastric cancer, making the immunohistochemical examination of biopsies necessary for diagnosis. We present the case of a 64-year-old woman who was diagnosed with lobular breast cancer 3 years ago and received chemotherapy with evidence of remission. The patient presented with dyspepsia and progressive dysphagia for the last 6 months, not responsive to PPI treatment. Upper endoscopy revealed partial occlusion of the cardio-esophageal junction and thickened gastric folds resembling linitis plastica. However, immunohistochemical analysis of endoscopic biopsies showed infiltration of gastric mucosa by lobular breast cancer cells, making the diagnosis of gastric metastasis. Therefore, clinicians’ awareness of possible gastric metastasis is warranted in patients with a history of advanced breast cancer and severe gastric symptoms.
C4 trees have a broader niche than their close C3 relatives
Authors: Young Sophie N R , Dunning Luke T , Liu Hui , Stevens Carly J , Lundgren Marjorie R
Published: March 2022

Previous studies have demonstrated the ecological sorting of herbaceous C3 and C4 species along gradients of precipitation and temperature: C4 herbaceous species typically occupy drier and warmer environments than their C3 relatives. However, it is unclear if this pattern holds true for C4 tree species, which are unique to Euphorbiaceae and found only on the Hawaiian Islands. Here, we combine occurrence data with local environmental and soil datasets to, for the first time, distinguish the ecological factors associated with photosynthetic diversification in the tree life form. These data are presented within a phylogenetic framework. We show that C3 and C4 trees inhabit similar environments, but that C4 photosynthesis expands the ecological niche in trees relative to that of C3 tree species. In particular, when compared with C3 trees, C4 trees moved into higher elevation habitats with characteristically sparse vegetation (and thus greater sunlight) and cooler temperatures, a pattern which contrasts with that of herbaceous species. Understanding the relationship between C4 photosynthesis and ecological niche in tree species has implications for establishing how C4 photosynthesis has, in this rare instance, evolved in trees, and whether this unique combination of traits could be exploited from an engineering perspective.
Simulations of primary beam effects on the cosmic bispectrum phase observed with the Hydrogen Epoch of Reionization Array
Authors: Charles N , Bernardi G , Bester H L , Smirnov O M , Carilli C , Keller P M , Kern N , Nikolic B , Thyagarajan N , de Lera Acedo E , Fagnoni N , Santos M G
Published: March 2022

The 21 cm transition from neutral hydrogen promises to be the best observational probe of the epoch of reionization (EoR). The main difficulty in measuring the 21 cm signal is the presence of bright foregrounds that require very accurate interferometric calibration. Closure quantities may circumvent the calibration requirements but may be, however, affected by direction-dependent effects, particularly antenna primary beam responses. This work investigates the impact of antenna primary beams affected by mutual coupling on the closure phase and its power spectrum. Our simulations show that primary beams affected by mutual coupling lead to a leakage of foreground power into the EoR window, which can be up to ∼104 times higher than the case where no mutual coupling is considered. This leakage is, however, essentially confined at k < 0.3 h Mpc−1 for triads that include 29 m baselines. The leakage magnitude is more pronounced when bright foregrounds appear in the antenna sidelobes, as expected. Finally, we find that triads that include mutual coupling beams different from each other have power spectra similar to triads that include the same type of mutual coupling beam, indicating that beam-to-beam variation within triads (or visibility pairs) is not the major source of foreground leakage in the EoR window.
Effectiveness of tacrolimus concomitant with biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis
Authors: Terabe Kenya , Takahashi Nobunori , Asai Shuji , Hirano Yuji , Kanayama Yasuhide , Yabe Yuichiro , Oguchi Takeshi , Fujibayashi Takayoshi , Ishikawa Hisato , Hanabayashi Masahiro , Hattori Yosuke , Suzuki Mochihito , Kishimoto Kenji , Ohashi Yoshifumi , Imaizumi Takahiro , Imagama Shiro , Kojima Toshihisa
Published: March 2022

Objectives

The study aimed to investigate the effectiveness and tolerance of biological disease-modifying antirheumatic drugs (bDMARDs) therapy administered concomitantly with tacrolimus (TAC) treatment in patients with rheumatoid arthritis.

Methods

2792 patients who underwent therapy with five bDMARDs (etanercept: ETN, adalimumab, golimumab, tocilizumab, and abatacept: ABT) were enrolled. Among the study subjects, 1582 were concomitant methotrexate (MTX group), 147 were concomitant TAC (TAC group), and 1063 were non-concomitant MTX and TAC (non-MTX/TAC group). The primary outcome was the incident rate of discontinuation of bDMARDs by adverse events (AEs) or loss of efficacy.

Results

Concerning the analysis for each reasons of discontinuation, including AEs and loss of efficacy, the hazards ratio (HR) was significantly lower in the TAC group than in non-MTX/TAC groups (AEs: HR = 0.39, 95% confidence interval, 0.23–0.68, loss of efficacy: HR = 0.49, 95% confidence interval, 0.30–0.78). The loss of efficacy with the use of ETN and ABT was lower in the TAC group than in non-MTX/TAC groups. Concomitant TAC did not induce elevated risk for discontinuation of AEs in all bDMARD analyses.

Conclusions

Concomitant TAC with ABT or ETN showed higher retention rates than bDMARDs therapy without TAC or MTX. AEs did not increase over long-term observation.
scREMOTE: Using multimodal single cell data to predict regulatory gene relationships and to build a computational cell reprogramming model
Authors: Tran Andy , Yang Pengyi , Yang Jean Y H , Ormerod John T
Published: March 2022

Cell reprogramming offers a potential treatment to many diseases, by regenerating specialized somatic cells. Despite decades of research, discovering the transcription factors that promote cell reprogramming has largely been accomplished through trial and error, a time-consuming and costly method. A computational model for cell reprogramming, however, could guide the hypothesis formulation and experimental validation, to efficiently utilize time and resources. Current methods often cannot account for the heterogeneity observed in cell reprogramming, or they only make short-term predictions, without modelling the entire reprogramming process. Here, we present scREMOTE, a novel computational model for cell reprogramming that leverages single cell multiomics data, enabling a more holistic view of the regulatory mechanisms at cellular resolution. This is achieved by first identifying the regulatory potential of each transcription factor and gene to uncover regulatory relationships, then a regression model is built to estimate the effect of transcription factor perturbations. We show that scREMOTE successfully predicts the long-term effect of overexpressing two key transcription factors in hair follicle development by capturing higher-order gene regulations. Together, this demonstrates that integrating the multimodal processes governing gene regulation creates a more accurate model for cell reprogramming with significant potential to accelerate research in regenerative medicine.