bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of adaptive designs with respect to a performance score
Authors: Herrmann Carolin , Kieser Meinhard , Rauch Geraldine , Pilz Maximilian
Published: April 2022

Adaptive designs are an increasingly popular method for the adaptation of design aspects in clinical trials, such as the sample size. Scoring different adaptive designs helps to make an appropriate choice among the numerous existing adaptive design methods. Several scores have been proposed to evaluate adaptive designs. Moreover, it is possible to determine optimal two‐stage adaptive designs with respect to a customized objective score by solving a constrained optimization problem. In this paper, we use the conditional performance score by Herrmann et al. (2020) as the optimization criterion to derive optimal adaptive two‐stage designs. We investigate variations of the original performance score, for example, by assigning different weights to the score components and by incorporating prior assumptions on the effect size. We further investigate a setting where the optimization framework is extended by a global power constraint, and additional optimization of the critical value function next to the stage‐two sample size is performed. Those evaluations with respect to the sample size curves and the resulting design's performance can contribute to facilitate the score's usage in practice.
RAD18 confers radioresistance of esophagus squamous cell carcinoma through regulating p‐DNA‐PKcs
Authors: Li Xiaoqing , Zou Shitao , Zhou Liangsu , Gao Aidi , Xu Jing , He Chao , Zhou Jundong , Wu Shuhua , Chen Yihong
Published: April 2022

Background

Radiotherapy has recently become more common for the treatment of esophageal squamous cell carcinoma (ESCC). Radioresistance, on the other hand, continues to be a major issue because it interferes with the effectiveness of ESCC radiation. It has been demonstrated that RAD18, an E3 ubiquitin‐protein ligase that regulates translesion DNA synthesis (TLS), is implicated in the regulation of genomic integrity and DNA damage response.

Methods

In the present study, immunohistochemical staining and western blotting were utilized to determine RAD18 expression in ESCC tissues and cells. ESCC cell proliferation was determined using a colony formation assay. Immunofluorescence staining, comet assay, and homologous recombination (HR)/non‐homologous end‐joining (NHEJ) assays were conducted to examine the effect of RAD18 on the DNA damage response in ESCC cells.

Results

We found that high RAD18 expression was positively associated with a poorer prognosis in patients with ESCC who received radiotherapy. Downregulation of RAD18 expression significantly increased the sensitivity of ESCC cells to irradiation. Moreover, RAD18 knockdown prolonged the repair kinetics of γH2AX foci and resulted in longer comet tails. Furthermore, loss of RAD18 expression markedly decreased non‐homologous end‐joining (NHEJ) activity, but it did not affect homologous recombination (HR)‐mediated double‐strand break repair in ESCC cells. RAD18 upregulated p‐DNA‐dependent protein kinase complex (p‐DNA‐PKc) expression in vivo and in vitro.

Conclusions

These data indicated that RAD18 may regulate radioresistance by facilitating NHEJ via phosphorylation of DNA‐PKcs in ESCC cells, providing a novel radiotherapy target for ESCC.
Guillain‐Barré syndrome after mRNA‐1273 (Moderna) COVID‐19 vaccination: A case report
Authors: Anjum Zauraiz , Iyer Charoo , Naz Sidra , Jaiswal Vikash , Nepal Gaurav , Laguio‐vila Maryrose , Anandaram Sanjay , Thapaliya Sahil
Published: April 2022

Guillain‐Barre syndrome (GBS) is an acquired inflammatory polyradiculoneuropathy that often follows infection with a virus or bacteria and in rare occasions, vaccination may precede GBS. We present a case of 80‐year‐old male patient who presented with chief complaints of progressive, ascending bilateral lower extremity paresthesia and weakness following first dose of Moderna vaccine. His symptoms got exacerbated after 2nd dose. Clinical examination and investigation findings including lumbar puncture, nerve conduction study, and electromyography were consistent with the diagnosis of GBS. The patient received treatment with intravenous immunoglobulin and there was significant improvement toward the end of 5th day. Though rare, this case report suggest that physician should remain vigilant for GBS following COVID‐19 vaccination.
Estimating design operating characteristics in Bayesian adaptive clinical trials
Authors: Golchi Shirin
Published: April 2022

Bayesian adaptive designs have gained popularity in all phases of clinical trials with numerous new developments in the past few decades. During the COVID‐19 pandemic, the need to establish evidence for the effectiveness of vaccines, therapeutic treatments, and policies that could resolve or control the crisis emphasized the advantages offered by efficient and flexible clinical trial designs. In many COVID‐19 clinical trials, because of the high level of uncertainty, Bayesian adaptive designs were considered advantageous. Designing Bayesian adaptive trials, however, requires extensive simulation studies that are generally considered challenging, particularly in time‐sensitive settings such as a pandemic. In this article, we propose a set of methods for efficient estimation and uncertainty quantification for design operating characteristics of Bayesian adaptive trials. Specifically, we model the sampling distribution of Bayesian probability statements that are commonly used as the basis of decision making. To showcase the implementation and performance of the proposed approach, we use a clinical trial design with an ordinal disease‐progression scale endpoint that was popular among COVID‐19 trials. However, the proposed methodology may be applied generally in the clinical trial context where design operating characteristics cannot be obtained analytically.
The Impact of CYP2C9*11 Allelic Variant on the Pharmacokinetics of Phenytoin and (S)‐Warfarin
Authors: Wanounou Maor , Shaul Chanan , Abu Ghosh Zahi , Alamia Shoshana , Caraco Yoseph
Published: April 2022

Cytochrome P450 2C9 (CYP2C9) is responsible for the oxidative metabolism of about 15% of commonly used drugs, some of which are characterized by a narrow therapeutic window. CYP2C9 is highly polymorphic, and over 60 alleles have been described. CYP2C9*2 and CYP2C9*3 are the most common polymorphisms among White patients and both are associated with decreased activity. The evidence concerning the functional importance of less frequent variant alleles is scarce. The objective of the current study was to characterize the in vivo activity of CYP2C9 among carriers of CYP2C9*11, one of the "African" alleles and the fourth most common CYP2C9 variant allele among White patients by using two prototype substrates, phenytoin and (S)‐warfarin. Single 300‐mg phenytoin and 20‐mg warfarin doses were given to 150 healthy Ethiopian Jewish participants who were nonsmokers, at least one week apart. (S)‐warfarin oral clearance and phenytoin metabolic ratio (PMR) derived from the ratio of 5‐(4‐hydroxyphenyl)‐5‐phenylhydantoin in 24‐hour urine collection to plasma phenytoin 12 hours (PMR 24/12) or 24 hours (PMR 24/24) post dosing, were used as markers of CYP2C9 activity. PMR 24/12 and PMR 24/24 were reduced by 50% and 62.2%, respectively, among carriers of CYP2C9*1/*11 (n = 13) as compared with carriers of CYP2C9*1/*1 (n = 127) (false discovery rate (FDR) q < 0.001). The respective decrease in (S)‐warfarin oral clearance was 52.6% (FDR q < 0.001). In conclusion, the enzyme encoded by CYP2C9*11 is characterized by a more than 50% decrease in the enzymatic activity, resembling the extent of decrease associated with CYP2C9*3 ("no‐function allele"). Among patients of African ancestry, CYP2C9*11 genetic analysis should be considered prior to prescribing of narrow therapeutic window drugs such as phenytoin, warfarin, nonsteroidal anti‐inflammatory drugs, or siponimod.
Photoresponsive Porphyrin‐DNA Complexes Constructed through Intercalation‐like Binding
Authors: Takada Tadao , Shimogaki Nao , Naruo Moe , Nakamura Mitsunobu , Yamana Kazushige
Published: April 2022

The molecular arrangement of functional chromophores is essential to construct functional nanomaterials. Synthetic DNA has been used as a structural scaffold to control and construct molecular assembly. We now describe the formation of artificial DNA/porphyrin complexes where porphyrins working as photoactive molecules were placed at specific locations on the DNA through a non‐covalent interaction. Spectroscopic analysis by UV/vis, circular dichroism (CD), and melting temperature measurements showed that the binding of water‐soluble porphyrin derivatives with methylpyridinium groups (TMPyP and DMPyP) to DNA can be directed by hydrophobic cavities composed of a pair of abasic site analogs (dS). CD measurements showed that the two porphyrins can be accommodated at two specific sites when the DNA molecule had two cavities, as evidenced by the exciton‐coupled CD spectra of the porphyrins. Photoelectrochemical experiments showed that the DNA complexes accommodating DMPyP at specific locations can respond to light excitation to generate a photocurrent when immobilized on the electrode surface. Our results demonstrated that the control of the porphyrin binding using the dS/dS pair is a useful approach to construct artificial DNA with porphyrin molecules, leading to the design of photoresponsive materials and photoelectrochemical sensors.
Forward Genetic Screens of Human Glycosylation Pathways Using the GlycoGene CRISPR Library
Authors: Kelkar Anju , Groth Theodore , Neelamegham Sriram
Published: April 2022

CRISPR‐Cas9‐based forward genetic screens represent a powerful discovery platform to uncover genes regulating specific biological processes. This article describes a method for utilizing a freely available GlycoGene CRISPR library to knock out any gene participating in human glycosylation in arbitrary cell types. The end product is a stable GlycoGene CRISPR knockout cell library, where each cell contains one or more sgRNA and lacks corresponding function. The cell library can be screened using various lectin/antibody reagents. It can also be applied in functional assays to establish glycan structure‐glycogene‐glycopathway relationships. This is a powerful systems glycobiology strategy for dissecting glycosylation pathways and processes. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Scale‐up and NGS validation of the GlycoGene CRISPR plasmid library

Basic Protocol 2: Preparation of a GlycoGene CRISPR lentivirus pool and an isogenic cell line stably expressing Cas9 nuclease

Basic Protocol 3: Preparation of a GlycoGene CRISPR cell library, self‐inactivation of Cas9, and library validation by NGS

Basic Protocol 4: Enrichment of lectin‐binding or non‐binding cells and related multiplex NGS data acquisition

Basic Protocol 5: Bioinformatics pathway analysis
Characterization of neurological disease progression in a canine model of CLN5 neuronal ceroid lipofuscinosis
Authors: Meiman Elizabeth J. , Kick Grace Robinson , Jensen Cheryl A. , Coates Joan R. , Katz Martin L.
Published: April 2022

Golden Retriever dogs with a frameshift variant in CLN5 (c.934_935delAG) suffer from a progressive neurodegenerative disorder analogous to the CLN5 form of neuronal ceroid lipofuscinosis (NCL). Five littermate puppies homozygous for the deletion allele were identified prior to the onset of disease signs. Studies were performed to characterize the onset and progression of the disease in these dogs. Neurological signs that included restlessness, unwillingness to cooperate with the handlers, and proprioceptive deficits first became apparent at approximately 12 months of age. The neurological signs progressed over time and by 21 to 23 months of age included general proprioceptive ataxia, menace response deficits, aggressive behaviors, cerebellar ataxia, intention tremors, decreased visual tracking, seizures, cognitive decline, and impaired prehension. Due to the severity of these signs, the dogs were euthanized between 21 and 23 months of age. Magnetic resonance imaging revealed pronounced progressive global brain atrophy with a more than sevenfold increase in the volume of the ventricular system between 9.5 and 22.5 months of age. Accompanying this atrophy were pronounced accumulations of autofluorescent inclusions throughout the brain and spinal cord. Ultrastructurally, the contents of these inclusions were found to consist primarily of membrane‐like aggregates. Inclusions with similar fluorescence properties were present in cardiac muscle. Similar to other forms of NCL, the affected dogs had low plasma carnitine concentrations, suggesting impaired carnitine biosynthesis. These data on disease progression will be useful in future studies using the canine model for therapeutic intervention studies.
Response Surface Optimization of Enzyme Pretreatment Improves Yield of Ethanol‐Extracted Lipids from Nannochloropsis oceanica
Authors: Zhao Kangyu , Zhang Liwei , Zhang Meilan , Tian Hua , He Dongping , Zheng Jingcheng
Published: April 2022

Nannochloropsis oceanica are marine microalgae that are rich in eicosapentaenoic acid (EPA); in the future, they may become one of the most effective sources of EPA. The cell walls of N. oceanica contain a three‐layered dense structure called algaenan, which hinders the extraction of intracellular lipids. Here, the main variables for the enzyme pretreatment of N. oceanica are optimized using response surface methodology. Under the optimal variables for enzyme pretreatment, the lipid yield and EPA content are increased to 26.9% and 20.7 g/100 g, respectively. Furthermore, lipidomics analysis is carried out utilizing ultra‐high performance liquid‐quadrupole‐time‐of‐flight mass spectrometry to identify the obtained lipids. After enzyme treatment, the betaine lipids (BL) content significantly increases, probably due to laccase and cellulase promoting the release of BL from membrane structure. In comparison, the hydrolysis of neutral lipids, glycolipids, and phospholipids during the enzyme treatment reduces their respective contents. The results of this study suggest that using compound enzymes to pretreat N. oceanica can effectively increase lipids extraction yields by ethanol and improve the EPA contents in lipids.

Practical applications: This study indicates that enzyme pretreatment can promote the extraction of lipids, especially lipids with EPA, from N. oceanica or other marine microalgae.
Retrospective, cohort review of pharmacists' impact on disparities in care in the management of type 2 diabetes with glucagon‐like peptide‐1 agonists and sodium glucose co‐transporter 2 inhibitors
Authors: Howell Chandler , Schmelz Andrew , Albertson Shelby , Hamm Jay , Meredith Ashley H. , Pence Lauren , Triboletti Jessica , Gonzalvo Jasmine
Published: April 2022

Background

The American Diabetes Association recommend glucagon‐like peptide‐1 (GLP‐1) agonists and sodium glucose co‐transporter 2 (SGLT‐2) inhibitors be considered as first‐line therapy for type 2 diabetes. A secondary analysis of the Look AHEAD study determined these agents are disproportionately prescribed at higher rates to White patients compared with Black patients.

Objectives

The objective of this study is to evaluate if a disparity exists between the prescribing of SGLT‐2 inhibitors and GLP‐1 agonists between White patients and Black patients at an academic, safety‐net health system.

Methods

A single‐center retrospective chart review was conducted on patients seen at a pharmacist‐managed or provider‐managed clinic. The primary outcome is the difference in prescribing of SGLT‐2 inhibitors and GLP‐1 agonists between Black and White patients in the pharmacist and provider‐managed group. Secondary outcomes include differences in prescribing in Hispanic patients and patients with a serious mental illness.

Results

The primary outcome of prescribing rates for GLP‐1 agonists and SGLT‐2 inhibitors did not differ significantly in the pharmacist comanaged group. The primary outcome in the provider managed group did differ significantly. The largest prescribing rate was in the “other” race category. Only two variables were found in the combined datasets to play a role in the prescribing of a GLP‐1 agonist or SGLT‐2 inhibitor. Having only a provider and not a pharmacist involved in care was predictive of not being prescribed either agent (odds ratio = 0.096, P = <.001). Insurance status was the other statistically significant predictor of being prescribed a GLP‐1 agonist or SGLT‐2 inhibitor (odds ratio = 1.592, P = .006).

Conclusion

A clinically significant difference in prescribing based on race did not exist in the pharmacist comanaged group or the provider only managed group. Pharmacist involvement and insurance status appear to have a positive impact on an SGLT‐2 inhibitor or GLP‐1 agonist being prescribed.
Osteomalacia as a Complication of Intravenous Iron Infusion: A Systematic Review of Case Reports
Authors: Vilaca Tatiane , Velmurugan Nalini , Smith Christopher , Abrahamsen Bo , Eastell Richard
Published: April 2022

Randomized control trials (RCTs) have shown that certain intravenous iron preparations can induce high levels of fibroblast growth factor 23 (FGF-23) and persistent hypophosphatemia. Repeated iron infusions may lead to prolonged hypophosphatemia and osteomalacia events not captured by RCTs. Several previous case reports have described skeletal adverse effects after repeated iron infusions. To characterize these effects, we conducted a systematic review of case reports. MEDLINE, Embase, Web of Science, and Cochrane databases were searched in March 2021. We selected case reports of patients ≥16 years old. Study quality was assessed using the tool from Murad and colleagues. We report the results in a narrative summary. We identified 28 case reports, reporting 30 cases. Ages ranged from 28 to 80 years (median 50 years). Most patients (n = 18) received ferric carboxymaltose (FCM), whereas 8 received saccharated ferric oxide (SFO) and 3 received iron polymaltose (IPM). All but 2 cases had more than five infusions (range 2 to 198, median 17). The lowest phosphate levels ranged from 0.16 to 0.77 mmol/L (median 0.36 mmol/L). Intact FGF-23 (iFGF-23) was high when measured. Serum 25OH vitamin D was low in 10 of 21 cases measured and 1,25(OH)2 vitamin D in 12 of 18. Alkaline phosphatase was high in 18 of 22 cases. Bone or muscle pain was reported in 28 of the 30 cases. Twenty patients had pseudofractures, 9 had fractures, and 6 patients had both. All 15 available bone scans showed focal isotope uptake. Case reports tend to report severe cases, so potential reporting bias should be considered. Osteomalacia is a potential complication of repeated iron infusion, especially in patients with gastrointestinal disorders receiving prolonged therapy. Pain and fractures or pseudofractures are common clinical findings, associated with low phosphate, high iFGF-23, high alkaline phosphatase, and abnormal isotope bone scan. Discontinuing or switching the iron formulation was an effective intervention in most cases. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Time‐dependent density functional theory study of the optical properties of tetrahedral aluminum nanoparticles
Authors: Bae Gyun‐Tack , Aikens Christine M.
Published: April 2022

The plasmonic properties of tetrahedral aluminum nanoparticles have been investigated using time‐dependent functional theory (TDDFT) calculations. The excitation energies are calculated for tetrahedral aluminum nanoparticles (Aln, n = 10–120) with different charge states. The BP86/DZ model is used to perform geometric optimization calculations for these clusters. The SAOP/DZ and LB94/DZ levels of theory have been used for the excitation energy calculations of these tetrahedral aluminum clusters. The absorption peaks are red‐shifted upon increasing the size of the aluminum nanoparticles.
Myocardial First‐Pass Perfusion With Increased Anatomic Coverage at 3 T Using Autocalibrated Multiband Imaging
Authors: Zou Lixian , Zheng Yuan , Chen Jialing , Ding Yu , Liu Hui , Liu Yubao , Xu Jian , Zheng Hairong , Liu Xin
Published: April 2022

Background

Myocardial first‐pass perfusion (FPP) imaging is a useful cardiac MRI method for the diagnosis of coronary artery disease. However, conventional 2D multislice FPP acquisitions usually have gaps between myocardium slices, which limits the overall assessment of myocardial ischemia.

Purpose

To increase the anatomic coverage of myocardial FPP imaging at 3 T by implementing both autocalibrated multiband (MB) acquisition and k‐t space acceleration with compress sensing (CS) reconstruction, without the need for additional reference scans.

Study Type

Phantom and prospective human studies.

Phantom/Subjects

A T1MES (T1 Mapping and ECV Standardization in cardiovascular magnetic resonance) phantom and 20 subjects (12 healthy subjects and 8 patients, 10 males, age 42 ± 16 years).

Field Strength/Sequence

A 3 T/saturation recovery prepared gradient echo sequence with contrast administration.

Assessment

Phantom experiments were performed to compare the performance of autocalibrated MB‐FPP with k‐t acceleration using slice‐GRAPPA and CS reconstructions. In vivo experiments were performed to compare the performance of conventional FPP (2.5× acceleration) with autocalibrated MB + CS‐FPP (6× acceleration). In phantom experiments, the error maps were calculated. In in vivo experiments, the contrast ratio (CR) and blurring were quantitatively measured, while image quality, perceived signal‐to‐noise ratio (SNR), and artifact level were qualitatively graded by three cardiologists on a 4‐point scale.

Statistical Tests

Wilcoxon signed‐rank test, paired t‐test. A P value <0.05 was considered statistically significant.

Results

In phantom experiments, residual artifact was reduced using the MB + CS‐FPP reconstruction method compared with using the MB + slice‐GRAPPA reconstruction method. In in vivo experiments, the proposed autocalibrated MB + CS‐FPP method demonstrated significantly higher CR (3.52 ± 0.78 vs 2.91 ± 0.81) and had significantly better perceived SNR (2.69 ± 0.29 vs 2.48 ± 0.31) compared to the conventional sequence. Compared with conventional FPP, MB + CS‐FPP doubled the spatial coverage (MB + CS‐FPP vs conventional FPP) without compromising the image quality (2.69 ± 0.26 vs 2.60 ± 0.30) or increasing the artifact level (2.60 ± 0.26 vs 2.52 ± 0.31).

Conclusion

Autocalibrated MB + CS‐FPP improved the myocardial coverage and achieved comparable image quality with the same spatial resolution and scan time as conventional FPP and is a promising technique for clinical myocardial perfusion imaging.

Evidence Level

2

Technical Efficacy

Stage 3
Accuracy of conversion formula for effect sizes: A Monte Carlo simulation
Authors: Poom Leo , af Wåhlberg Anders
Published: April 2022

In meta‐analysis, effect sizes often need to be converted into a common metric. For this purpose conversion formulas have been constructed; some are exact, others are approximations whose accuracy has not yet been systematically tested. We performed Monte Carlo simulations where samples with pre‐specified population correlations between the x and y‐variables were drawn from a normally distributed population. A number of commonly used effect size measures and statistics were calculated from each sample. Using several available conversion formula these statistics were converted into Pearson r and Cohen's d and compared to r and d calculated directly from the original data. Converted values were systematically lower than the directly calculated values. While conversions to d were quite accurate, some of the conversions to r resulted in large biases. These systematic errors can in most cases be adjusted for by simply multiplying the converted values with a corresponding correction factor.
Effect of phenolic compounds and hydroxyl content on the physicochemical properties of pine nut oil Pickering emulsions
Authors: Zhao Xin‐lei , Bao Yi‐hong , Guo Yang , Luo Jia‐yuan , Jiang Shi‐long , Yang Xue
Published: April 2022

BACKGROUND

For decades, pine nut oil Pickering emulsions have been stabilized using a covalent composite of two phenolic chemicals (tannic acid, TA; and gallic acid, GA) and whey protein isolate (WPI) following alkali treatment. Based on covalent composite particles being excellent sources of high‐quality stabilizers, this research explored the influence of phenolic addition and hydroxyl content on stability, rheological parameters and characterization of Pickering emulsions.

RESULTS

Tannic acid was more effective in reducing the average particle size of the emulsion, which decreased from 479.4 ± 2.1 nm without addition to between 187.6 ± 5.9 and 368.2 ± 16.8 nm (P < 0.05). The potential values of all the emulsions were between −30 and −50 mV (except for the gallic acid addition of 2.5 g kg−1). When the phenolic addition was 7.5 g kg−1, emulsions demonstrated the best emulsification ability. Pickering emulsion stabilized by WPI‐TA and WPI‐GA particles were successfully generated, according to confocal laser scanning microscopy. Rheological results showed that the increase of phenolic addition contributed to larger elastic modulus (G′), viscosity modulus (G″) and viscosity of emulsions, which was beneficial to the stability of emulsions.

CONCLUSION

Both phenolic compounds significantly improved the physicochemical stability of the emulsions (P < 0.05) and their oxidative stability. Covalently crosslinking phenolic compounds to proteins is a better method to prepare stable emulsions. It is more prominent that TA shows a more significant improvement in emulsion stability due to the number of hydroxyl groups it can provide. This research might serve as a theoretical foundation for enhancing the quality of pine nut oil‐related products. © 2022 Society of Chemical Industry.
Changes in soil organic carbon stocks from 1980‐1990 and 2010‐2020 in the northwest arid zone of China
Authors: Zhang ZiPeng , Ding JianLi , Zhu ChuanMei , Shi Haobo , Chen XiangYue , Han LiJing , Wang JingZhe
Published: April 2022

Soil is the largest carbon reservoir in terrestrial ecosystems, and thus minor changes in it can dramatically affect atmospheric CO2 concentrations. In the northwestern arid zone of China, the prediction of soil organic carbon (SOC) changes is often limited by the scarcity of soil samples and the scale and depth of research, which limit the understanding of carbon cycling processes in arid zone terrestrial ecosystems. Therefore, this study produced digital soil maps of SOC stocks (SOCS) for two periods (1980‐1990 and 2010‐2020) at a 90‐m resolution based on historical soil profile data and a random forest model. The results showed that the prediction accuracy for SOCS in the topsoil (0–30 cm) was superior to that of the subsoil (30–100 cm). Among them, the mean annual evapotranspiration, normalized difference vegetation index during the growing season, multi‐year mean temperature, and clay content were the main environmental factors affecting the spatial distribution of SOCS. In the past 30 years, the SOCS of the northwestern arid zone has decreased by 585.50 Tg, with a mean decline of 19.52 Tg C yr−1. The changes in SOCS caused by land‐use conversion and reductions in SOCS were further shown to be attributable to grassland desertification and agricultural reclamation. These findings are valuable for exploring the carbon cycle in terrestrial ecosystems in the context of global climate change and for achieving China's goal of carbon neutrality.
Influence of Wood Husk and CaCO3 on the Mechanical Properties of Nitrile Butadiene Rubber
Authors: Krishna Ajay , Sabarinath S.B. , Abhishek P.S. , Chandran Greeshma U. , Hema S. , Sambhudevan Sreedha
Published: April 2022

Natural fiber reinforced composites have sparked a lot of research and engineering interest in recent decades because of their low density, high specific strength, low cost, lightweight, recyclability, and biodegradability, earning them the title of green composite. Nitrile rubber‐based composites are generally used as elastomers in many industries due to their applications such as O‐rings, gaskets, oil seals, synthetic leather, automotive transition belts, etc. In the present work, in order to enhance the mechanical properties of nitrile rubber, the fillers like CaCO3 and wood husk in five different proportions are added to the NBR matrix. The curing studies, mechanical measurements, and SEM (scanning electron microscopy) analysis are conducted and it is found that the tensile and tear strength of the mixture with the proportion of CaCO3 with 10% and wood husk with 50% is the best combination compared to nitrile rubber gum sample. The tensile strength of the matrix with proportion CaCO3 10% and wood husk 50% has increased around 86.15% and where the tear strength increased around 80.59% compared to the matrix without fillers. SEM analysis reveals the uniform distribution of fillers in the rubber matrix, which is in accordance with mechanical properties. This is a cost‐effective method that consumes less time and is non‐pollutant as if this study uses natural products such as wood husk as the fillers.
Properties of Seaweed Fiber Reinforced Polypropylene Composite: Effect of Alkaline Treatment
Authors: Abdullah Norshafika S. E. , Salim Nurjannah , Roslan Rasidi
Published: April 2022

Natural fibers are favored to use as raw resources in making reinforced polymer composite because they are abundant and inexpensive. However, natural fiber‐reinforced composites are suggested to be treated to improve their qualities before being employed in the production of composites. The seaweed fibers are treated with an alkaline medium in this study. Alkaline treatment of seaweed/polypropylene (SW/PP) composites is expected to increase their physical and mechanical qualities. Extrusion and hot‐pressing processes are used in the production of this composite. The results reveal that after being treated, the SW/PP composite has a low proportion of water absorption compared to the untreated SW/PP composite. Untreated SW/ PP composites have a higher melt flow resistance (MRF), which indicates the presence of waxy and cellulose constituents and makes the composites flow easier in the melt indexer. The tensile strength of composites is higher in treated SW/PP composites, with a value of 0.1944 MPa compared to 0.1311 MPa in untreated SW/PP composites. Furthermore, the impact strength of the untreated SW/PP composites is low, at 28.9910 J m–1, compared to the treated SW/PP composites, which has a higher energy value of 59.5800 J m–1. Alkaline treatment improves the properties of natural fibers in the composite, according to these findings.
Regulation of XPO5 phosphorylation by PP2A in hepatocellular carcinoma
Authors: Li Jiao , Zhou Jian‐Kang , Mu Xiaoyu , Shen Shu , Xu Xiaomin , Luo Yao , Luo Yuxin , Ming Yue , Wu Yuangang , Peng Yong
Published: April 2022

Exportin 5 (XPO5) is a shuttle protein that mediates precursor miRNA (pre‐miRNA) export from the nucleus to the cytoplasm, an important step in miRNA maturation. We previously demonstrated that XPO5 was phosphorylated by ERK kinase and subsequently underwent conformation change by the peptidyl‐prolyl isomerase Pin1, leading to the reduced miRNA expression in hepatocellular carcinoma (HCC). Protein phosphorylation modification serves as a reversible regulatory mechanism precisely governed by protein kinases and phosphatases. Here we identified that the phosphatase PP2A catalyzed XPO5 dephosphorylation. PP2A holoenzyme is a ternary complex composed of a catalytic subunit, a scaffold subunit, and a regulatory subunit that determines substrate specificity. In this study, we characterized the involvement of B55β subunit in XPO5 dephosphorylation that favored the distribution of XPO5 into the cytoplasm and promoted miRNA expression, leading to HCC inhibition in vitro and in vivo. Our study demonstrates the regulatory role of B55β‐containing PP2A in miRNA expression and may shed light on HCC pathogenesis.
A Randomized First‐in‐Human Study With UB‐312, a UBITh® α‐Synuclein Peptide Vaccine
Authors: Yu Hui Jing , Thijssen Eva , van Brummelen Emilie , van der Plas Johan L. , Radanovic Igor , Moerland Matthijs , Hsieh Eric , Groeneveld Geert Jan , Dodart Jean‐Cosme
Published: April 2022

Background

α‐Synuclein (αSyn) is believed to play a central role in Parkinson's disease (PD) neuropathology and is considered a target for disease modification. UB‐312 is a synthetic αSyn peptide conjugated to a T helper peptide and is expected to induce antibodies specifically against oligomeric and fibrillar αSyn, making UB‐312 a potential immunotherapeutic for synucleopathies.

Objective

To investigate the safety, tolerability, and immunogenicity of UB‐312 vaccination in healthy participants and to determine a safe and immunologically optimal dose for the first‐in‐patient study.

Methods

Fifty eligible healthy participants were enrolled in a 44‐week, randomized, placebo‐controlled, double‐blind study. Participants in seven cohorts were randomized to three intramuscular UB‐312 or placebo injections at weeks 1, 5, and 13 (doses ranging between 40 and 2000 μg). Safety and tolerability were assessed by adverse events, clinical laboratory, vital signs, electrocardiograms, and neurological and physical examinations. Immunogenicity was assessed by measuring serum and cerebrospinal fluid (CSF) anti‐αSyn antibody concentrations.

Results

Twenty‐three participants received all three vaccinations of UB‐312. Most adverse events were mild, transient, and self‐resolving. Common treatment‐emergent adverse events included headache, nasopharyngitis, vaccination‐site pain, lumbar puncture‐site pain, and fatigue. UB‐312 induced dose‐ and time‐dependent antibody production. Antibodies were detectable in serum and CSF of all participants receiving the 300/300/300 μg UB‐312 dose regimen. The average CSF/serum ratio was 0.2%.

Conclusions

UB‐312 was generally safe, well tolerated, and induced anti‐αSyn antibodies in serum and CSF of healthy participants. The 100 and 300 μg doses are selected for further evaluation in participants with PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Somatic TEK variant with intraarticular venous malformation and knee hemarthrosis treated with rapamycin
Authors: Adham Salma , Revencu Nicole , Mestre Sandrine , Nou‐Howaldt Monira , Vernhet‐Kovacsik Hélène , Quéré Isabelle
Published: April 2022

Background

Venous malformations (VMs) are the most common vascular anomalies and have been associated with somatic variants in TEK. Current treatment of VM joint component might be challenging due to the size or location of some lesions or ineffective with recurrence of malformed veins. Targeted molecular therapies after identification of genetic defects might be an alternative.

Methods

We report a case with intraarticular bleeding due to VM with a TEK pathogenic somatic variant treated with rapamycin.

Results

A 26‐year‐old female patient was evaluated for right calf pain secondary to venous malformation of the right inferior limb with an intraarticular component in the right knee. Hemarthrosis and degenerative chondropathy of the knee were evidenced at MRA. Molecular diagnosis evidenced a pathogenic somatic TEK variant. Rapamycin was introduced to stop bleeding, with good tolerance and efficacy.

Conclusion

The TEK receptor signals through the PI3K/AKT/mTOR pathway and TEK mutations have been linked to AKT activation. As rapamycin acts against angiogenesis and reduces phosphorylated‐AKT levels, targeted molecular therapy should be discussed as first‐line therapy in patients with proven molecular diagnosis and diffuse VM inaccessible to conventional treatment.
High gain Vivaldi antenna from 26 up to 40 GHz for 5G applications
Authors: Dam Thi‐Hong‐Le , Houzet Gregory , Lacrevaz Thierry , Vuong Tan‐Phu
Published: April 2022

We propose a directive broadband and high gain Vivaldi antenna in the Ka‐band (26–40 GHz) for 5G applications. To increase the gain of this antenna, we use a substrate lens and the quasi‐substrate integrated waveguide structure with the aim of reducing reflected waves and emphasizing the traveling waves. With this method, the gain is increased by 4.5 dBi in average and 7.5 dBi in the peak. The antenna has a good impedance matching in the whole band.
Towards free breathing 3D ASL imaging of the human liver using prospective motion correction
Authors: Huber Jörn , Günther Matthias , Channaveerappa Meghashree , Hoinkiss Daniel Christopher
Published: April 2022

Purpose

Measurements of liver perfusion yield valuable information about certain diseases like carcinomas and cirrhosis. To assess perfusion, noninvasive arterial spin labeling (ASL) MRI has the potential to become an important alternative to contrast agent–based methods. Unfortunately, ASL perfusion‐weighted images are highly susceptible to breathing motion. This work presents a prospective motion‐compensation technique, tackling breathing motion during ASL experiments of the human liver.

Methods

Feasibility of 3D pseudo‐continuous ASL imaging under free breathing is investigated by using a prospective motion‐compensation technique with fat signal in additional 2D‐EPI navigators. The proposed technique is compatible with strong signal suppression, occurring in background‐suppressed pseudo‐continuous ASL imaging. An additional retrospective 2D elastic registration algorithm is proposed to correct for residual elastic deformations. The technique is validated in 8 healthy volunteers.

Results

The prospective technique allowed a significant reduction of the cranial–caudal liver shifts during free breathing pseudo‐continuous ASL experiments. Additional 2D elastic image registration allowed reduction of cranial–caudal liver motion to levels of timed breathing protocols. Artifacts in perfusion‐weighted images could be reduced when compared with free‐breathing ASL images without motion correction.

Conclusion

The proposed technique is suitable for prospective compensation of liver motion in background‐suppressed 3D pseudo‐continuous ASL imaging. Future work focuses on further improving the quality of perfusion‐weighted images.
Delivering multidisciplinary neuromuscular care for children via telehealth
Authors: Carroll Kate , Adams Justine , de Valle Katy , Forbes Robin , Kennedy Rachel A. , Kornberg Andrew J. , Vandeleur Moya , Villano Daniella , Woodcock Ian R. , Yiu Eppie M. , Ryan Monique M. , Davidson Zoe
Published: April 2022

Introduction/Aims

In response to coronavirus disease 2019 (COVID‐19) pandemic restrictions int 2020, our face‐to‐face (F2F) multidisciplinary neuromuscular clinic (NMC) transitioned to widespread use of telehealth (TH). This study aimed to (1) understand parent/guardian, child, and clinician perceptions of TH; (2) examine TH‐related changes in clinical activity; and (3) use these findings to inform a future model of care for the NMC.

Methods

A clinical audit was undertaken to examine clinical activity throughout 2018–2020. Online surveys were distributed to clinicians and parents of children attending the NMC via TH in 2020. A working group of clinicians created a checklist to guide a future hybrid model of TH and F2F care.

Results

Total clinical activity in 2020 was maintained from previous years; 62.8% of all appointments occurred via TH, and 82.3% of patients attended NMC by TH at least once. Ninety‐nine parents (30.6% response rate), 52 children, and 17 clinicians (77% response rate) responded to the survey. All groups reported better interaction when F2F compared to TH. Eighty percent of parents identified advantages of TH and reported lower levels of stress. A lack of “hands‐on” physical assessment was identified by parents and clinicians as a TH limitation. Most families (68.1% of parents; 58.8% of children) and all clinicians indicated a preference for a mix of TH and F2F NMC appointments in the future.

Discussion

This study has informed a checklist to guide future TH use in a new hybrid model of care. Further investigation is required to assess health impacts of TH use in pediatric neuromuscular care.
Exploring faunal conservation in carbon projects through Map of Life: A case study
Authors: Miles Danielle Christine
Published: April 2022

With the onset of global change, forest species diversity has declined in recent decades as pristine habitat in biological hotspots rapidly diminishes. Many carbon mitigation efforts directed at decreasing emissions from forest degradation and destruction assume that faunal biodiversity will benefit from such efforts. Yet, conservation of faunal biodiversity is rarely considered in carbon mitigation plans. Despite this, forest preservation and reforestation through greenhouse gas frameworks such as Reducing Emissions from Deforestation and Forest Degradation may provide means to conserve and enhance species richness while also sequestering carbon stocks simply through the establishment of large forest preserves. In this case study, students assess the disparities and synergies between management priorities focused on carbon sequestration and faunal conservation of amphibians, birds, and mammals. Future conservation practitioners need to gain experience balancing multiple, potentially competing, project goals especially within the context of climate change and habitat loss. Students using this case study examine the application of species data from Map of Life and the International Union for Conservation of Nature Red List to assess real differences between 86 Verified Carbon Standard carbon mitigation projects based on location, certifications for additional priorities, and size of forest preserve.
Taming an articulated laser
Authors: Aharon Oren
Published: April 2022

Articulated arms are a well‐established method for laser beam delivery, with superior characteristics for diversified spectral wavelengths. Recent innovative applications, especially in the dentistry industry, benefit from improved performance, including user‐friendly beam delivery directly to the treatment position. The preferred technology relies on mounting mirrors in hollow members, rotating with respect to each other. The beam is delivered by a train of mirrors to the end point.
Pachyrhynchus Weevils Use 3D Photonic Crystals with Varying Degrees of Order to Create Diverse and Brilliant Displays
Authors: Parisotto Alessandro , Steiner Ullrich , Cabras Analyn Anzano , Van Dam Matthew H. , Wilts Bodo D.
Published: April 2022

The brilliant appearance of Easter Egg weevils, genus Pachyrhynchus (Coleoptera, Curculionidae), originates from complex dielectric nanostructures within their elytral scales and elytra. Previous work, investigating singular members of the Pachyrhynchus showed the presence of either quasi‐ordered or ordered 3D photonic crystals based on the single diamond () symmetry in their scales. However, little is known about the diversity of the structural coloration mechanisms within the family. Here, the optical properties within Pachyrhynchus are investigated by systematically identifying their spectral and structural characteristics. Four principal traits that vary their appearance are identified and the evolutionary history of these traits to identify ecological trends are reconstructed. The results indicate that the coloration mechanisms across the Easter Egg weevils are diverse and highly plastic across closely related species with features appearing at multiple independent times across their phylogeny. This work lays a foundation for a better understanding of the various forms of quasi‐ordered and ordered diamond photonic crystal within arthropods.
Charge Separation Efficiency in WO3/BiVO4 Photoanodes with CoFe Prussian Blue Catalyst Studied by Wavelength‐Dependent Intensity‐Modulated Photocurrent Spectroscopy
Authors: Vecchi Pierpaolo , Piccioni Alberto , Mazzaro Raffaello , Mazzanti Michele , Cristino Vito , Caramori Stefano , Pasquini Luca
Published: April 2022

The understanding of charge carrier dynamics in complex heterojunctions is of the utmost importance for the performance optimization of photoelectrochemical cells, especially in operando. Intensity‐modulated photocurrent spectroscopy (IMPS) is a powerful tool to this aim, but the information content provided by this technique can be further enhanced by selectively probing each layer of complex heterojunctions by means of multiple excitation sources. Herein, the charge carrier dynamics of a WO3/BiVO4/CoFe–PB heterojunction, used in a conventional three electrode cell for water splitting, is studied using wavelength‐dependent IMPS (WD‐IMPS). The proposed data analysis allows us to identify the occurrence of interface recombination processes affecting the semiconductor junction, as well as the positive contribution of the inorganic complex catalyst on the charge separation efficiency of the BiVO4 layer. The deep understanding of the fate of charge carriers in the studied photoanode validates WD‐IMPS as a straightforward method to widen the understanding of such structures.
Vaginal prolapse in ewes
Authors: Christodoulopoulos Georgios
Published: April 2022

In 2019 and 2020, an annual vaginal prolapse incidence of 13% was recorded among hoggets in a dairy sheep farm in Greece, whereas in mature ewes the annual incidence was 0.7%. During our farm visit, we noticed that the feeders were particularly elevated both in hoggets and mature ewes barn, which forced the animals to take a highly inclined position to reach their feed. We identified the feeders’ elevation as a possible cause of vaginal prolapse and advised their replacement. In December 2020, in the hoggets’ barn, the raised feeders were replaced with lower ones, resolving the problem. These findings provide strong circumstantial evidence that hoggets are particularly prone to vaginal prolapse when forced to maintain an inclined position for long periods, whereas mature ewes appear less susceptible.
Successful medical management of an acute case of pentobarbital toxicosis in a wild bald eagle (Haliaeetus leucocephalus)
Authors: Gonzalez‐Jassi Hugo A. , Jakobek Benjamin , Ebbott Austin , de Bie Fiep , Cusack Lara
Published: April 2022

A bald eagle (Haliaeetus leucocephalus) presented in a comatose state, with clinical signs consistent with an acute toxicosis of unknown aetiology. After 24 hours of aggressive supportive care, the eagle mildly improved, but was still unable to move or perch. Radiographs revealed severe upper gastrointestinal distention consistent with food remnants, and blood chemistry values were suggestive of an acute pharmacological induced toxicosis. An upper gastric lavage was performed and 36 hours after the procedure, the eagle was responsive and displayed normal behaviour. The eagle was released back to the wild following 6 days of supportive care, with complete resolution of the presenting clinical signs. Gastric content and crop fluid retrieved were frozen and then analysed using gas chromatography/mass spectrometry. Both samples were positive for sodium pentobarbital, due to a presumed ingestion of an inadequately disposed carcase from a euthanased animal.
Correction to: An Authoring Tool to Engage Younger Audiences in the Development of Nature Preservation Games: The G4N Toolkit to Game Design
Authors: Beça Pedro , Aresta Mónica , Santos Rita , Veloso Ana Isabel
Published: April 2022

Chapter “An Authoring Tool to Engage Younger Audiences in the Development of Nature Preservation Games: The G4N Toolkit to Game Design” was previously published non-open access. It has now been changed to open access under a CC BY 4.0 license and the copyright holder updated to ‘The Author(s)’. The book has also been updated with this change.