bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncovering ART adherence inconsistencies: An assessment of sustained adherence among adolescents in South Africa
Authors: Zhou Siyanai , Cluver Lucie , Shenderovich Yulia , Toska Elona
Published: October 2021

Introduction

Antiretroviral treatment (ART) adherence rates are lower among adolescents living with HIV (ALHIV) than among adults and children, but more evidence is needed on long‐term sustained ART adherence among ALHIV. This study assesses rates of sustained ART adherence in a cohort of adolescents in South Africa.

Methods

A prospective cohort of adolescents (10‐19 years) living with HIV (baseline sample N = 1 046, 55% female, mean age 13.6) in the Eastern Cape Province in South Africa were interviewed at baseline (2014‐15) and followed‐up twice (2015‐16, 2017–18). All adolescents ever initiated on treatment in 52 government health facilities were traced (with 90% uptake, 94% retention at Wave 2, and 97% retention at Wave 3, 3.4% mortality) and their clinic records were extracted where available. We investigate sustained ART adherence among adolescents interviewed at all three waves of data collection (N = 933). To quantify adherence at each study wave, we used self‐reported past‐week adherence (including weekdays and weekends). Self‐reported adherence was validated using HIV‐1 RNA viral load (>50 copies/mL cut‐off) reported in clinic records, in a random‐intercept logistic regression.

Results and discussion

At baseline, approximately 66% (N = 615) of adolescents reported past‐week ART adherence, and of these 45.3% reported adherence at both baseline and follow‐up. Only 37.1% of the sample reported sustained past‐week ART adherence over the three waves of the study. Most adolescents (N = 587, 62.9%) report inconsistent adherence across time (including 6.4% disengaged from care). Older (P = 0.007) and adolescents with horizontally acquired HIV (P = 0.002) were more likely to report inconsistent adherence across time. Controlling for socio‐demographic characteristics, past‐week adherence was associated with non‐detectable viral load (aOR 1.72, 95%CI 1.14‐2.59, P = 0.009). Overall, of the adolescents with viral load measurements at study Wave 1 and Wave 2, 50.6% maintained undetectable viral load for the preceding year.

Conclusions

Adolescents living with HIV reported very low rates of sustained ART adherence. Adherence reported at a single time may mask high rates of variability in adherence over time. These findings highlight the urgent need for enhanced and effective interventions to assist ALHIV with ART adherence through the challenging years of adolescence.
Characterizing winter season severity in the Midwest United States, Part I: Climatology and recent trends
Authors: Ford Trent W. , Budikova Dagmar , Wright Jefferson D.
Published: October 2021

Severe winter weather is a staple of Midwest United States (U.S.) climate and is an important natural hazard that has significant economic and environmental impacts. Winter season severity varies both spatially and temporally in the Midwest, and past studies have documented significant changes in Midwest winter characteristics, including increases in temperature and decreases in snow depth. In this study, we use the Accumulated Winter Season Severity Index (AWSSI) to characterize winter severity across the Midwest and assess its variability and change on various spatial and temporal scales during the 1951–2020 period. AWSSI is derived from daily records of snowfall (SF), snow depth (SD), maximum surface air temperature (TMAX), and minimum surface air temperature (TMIN) during the winter season. The daily total AWSSI index value reflects the sum of points accumulated from daily values of each of these four variables surpassing pre‐determined thresholds, and the total season sum reflects the overall winter season severity. We find AWSSI provides a unique perspective by which to describe climatological differences in winter season character in the Midwest. Namely, over three quarters of winter season days accumulate points in the northern Midwest, compared to just over half in the southern Midwest. Meanwhile, the relative contribution of extreme winter days to total winter severity is much larger in the southern Midwest than farther north. In addition, we find overall winter season severity has significantly decreased at only a quarter of stations and the frequency of extreme winter days has significantly decreased at only a fifth of stations, despite widespread increases in winter daily maximum and minimum temperature. The results suggest Midwest U.S. winter season severity as described by the AWSSI has not significantly changed over the past 70 years.
Risk of bias assessment in preclinical literature using natural language processing
Authors: Wang Qianying , Liao Jing , Lapata Mirella , Macleod Malcolm
Published: October 2021

We sought to apply natural language processing to the task of automatic risk of bias assessment in preclinical literature, which could speed the process of systematic review, provide information to guide research improvement activity, and support translation from preclinical to clinical research. We use 7840 full‐text publications describing animal experiments with yes/no annotations for five risk of bias items. We implement a series of models including baselines (support vector machine, logistic regression, random forest), neural models (convolutional neural network, recurrent neural network with attention, hierarchical neural network) and models using BERT with two strategies (document chunk pooling and sentence extraction). We tune hyperparameters to obtain the highest F1 scores for each risk of bias item on the validation set and compare evaluation results on the test set to our previous regular expression approach. The F1 scores of best models on test set are 82.0% for random allocation, 81.6% for blinded assessment of outcome, 82.6% for conflict of interests, 91.4% for compliance with animal welfare regulations and 46.6% for reporting animals excluded from analysis. Our models significantly outperform regular expressions for four risk of bias items. For random allocation, blinded assessment of outcome, conflict of interests and animal exclusions, neural models achieve good performance; for animal welfare regulations, BERT model with a sentence extraction strategy works better. Convolutional neural networks are the overall best models. The tool is publicly available which may contribute to the future monitoring of risk of bias reporting for research improvement activities.
Effects of almonds on ameliorating salt‐induced hypertension in dahl salt‐sensitive rats
Authors: Zeng Li , Liu Zerong , Zhou Luxin , Chen Meng , Zheng Xuewei , Yang Pengfei , Zhao Xinrui , Tian Zhongmin
Published: October 2021

BACKGROUND

Excessive dietary salt intake is related to an increased risk of hypertension. Dietary functional foods probably could help to improve salt‐induced hypertension. In this study, Dahl salt‐sensitive (DSS) rats were used to investigate their metabolic differences from those of salt‐resistant SS.13BN rats and determine whether dietary protein‐rich almonds could ameliorate salt‐induced elevation of blood pressure in DSS rats.

RESULTS

After high‐salt intake, the systolic blood pressure and mean arterial pressure of the DSS rats increased dramatically. Metabolomics analysis indicated abnormal amino acid metabolism in their kidneys. Their renal nitric oxide (NO) content and nitric oxide synthase activity decreased significantly after high‐salt diet. Oxidative stress also occurred in DSS rats. After the DSS rats received almond supplementation, the levels of various amino acids in their kidney increased, and renal arginine and NO contents were upregulated. Their renal hydrogen peroxide and malonaldehyde levels decreased, whereas renal catalase, superoxide dismutase and glutathione peroxidase activities and glutathione levels increased.

CONCLUSION

The renal abnormal amino acid metabolism of DSS rats contributed to the impaired NO production in response to high‐salt intake. Together with salt‐induced oxidative stress, high‐salt diet intake ultimately led to an increase in the blood pressure of DSS rats. Protein‐rich almond supplementation might prevent the development of salt‐induced hypertension by restoring arginine and NO regeneration and alleviating salt‐induced oxidative stress. © 2021 Society of Chemical Industry.
High‐throughput bioanalysis of sitagliptin in plasma using direct analysis in real time mass spectrometry and its application in the pharmacokinetic study thereof
Authors: Liu Yingze , Meng Xiangjun , Zhang Yuyao , Zhang Linge , Shan Yuqin , Gu Jingkai , Sun Dong
Published: October 2021

Sitagliptin is a dipeptidyl peptidase‐IV inhibitor for the treatment of type 2 diabetes mellitus. In the present study, a sensitive and high‐throughput quantitative method based on the direct analysis in real time tandem mass spectrometry has been developed and validated for the bioanalysis of sitagliptin in rat plasma without chromatographic separation. Sitagliptin and its internal standard retagliptin were detected in positive ion mode by multiple reaction monitoring transitions at m/z 408.2→235.0 and 465.2→260.1, respectively. The method includes a simple solid‐phase extraction sample preparation procedure, through which appropriate and reproducible analytical results within the linear concentration range of 20–2000 ng/mL have been achieved. The intra‐ and interday precisions were <10.6% and the accuracies were ranging from −8.17 to 2.60%. This method has been successfully applied to the pharmacokinetic study of sitagliptin after single intravenous administration in rats. This approach shows considerable promise of direct analysis in real time tandem mass spectrometry method in the high‐throughput bioanalysis.
Otolaryngology Utilization in Patients With Achondroplasia: Results From the CLARITY Study
Authors: Tunkel David E. , Gough Ethan , Bober Michael B. , Hashmi S. Shahrukh , Hecht Jacqueline T. , Legare Janet M. , Little Mary Ellen , Modaff Peggy , Pauli Richard M. , Rodriguez‐Buritica David , Serna Maria Elena , Smid Cory J. , Hoover‐Fong Julie E.
Published: October 2021

Objectives/Hypothesis

To quantify otolaryngologic surgery utilization in patients with achondroplasia, and to identify any changes in utilization over the past four decades.

Study Design

Retrospective cohort study.

Methods

A retrospective cohort study of 1,374 patients with achondroplasia enrolled in the CLARITY retrospective cohort study at four centers of multi‐specialty care for patients with achondroplasia. Otolaryngologic surgeries are presented by birth cohort decade. The main outcomes were number of primary and additional otolaryngologic procedures; age at surgery; likelihood of repeated surgery; temporal trends in surgical utilization.

Results

In this cohort of 1,374 patients with achondroplasia, 620 (45.1%) had pharyngeal surgery at least once, 150 (10.9%) had pharyngeal surgery on more than one occasion, and patients who had adenoidectomy first were 2.68 times more likely to require a second pharyngeal surgery than those who had adenotonsillectomy. Seven hundred and seventy‐nine (56.7%) had tympanostomy tubes placed at least once, and 447 (32.5%) had tympanostomy tubes placed more than one time. Age at first pharyngeal surgery decreased by 1.2 years per birth cohort decade, and age at tympanostomy tube placement decreased by 1.1 years per decade.

Conclusions

Patients with achondroplasia often require otolaryngologic surgery, particularly adenoidectomy and/or tonsillectomy as well as tympanostomy tube placement. Such surgery is performed now more frequently and at younger ages than in earlier decades. While otolaryngologic disease associated with achondroplasia is now recognized earlier and treated more frequently, long‐term outcome studies are needed.

Level of Evidence

3 Laryngoscope, 132:1548–1554, 2022
Synthetic Triterpenoid RTA‐408: Limits Radiation Damage to Normal Tissue
Authors: Luginbuhl Adam J. , Hobelmann Kealan , Rodin Julianna , Shukla Sanket , Rodeck Ulrich , Linnenbach Alban
Published: October 2021

Objectives/Hypothesis

To assess the efficacy and mechanism of action of a novel approach to mitigate acute and chronic radiation toxicity in a validated animal model.

Study Design

Randomized, prospective study using an in vivo rat model.

Methods

Experimental animal study utilizing Sprague–Dawley rats divided into three cohorts: 1) radiation + dimethyl sulfoxide (DMSO) (inert vehicle); 2) radiation + RTA‐408 (therapeutic drug); and 3) no radiation + DMSO. All animals in the radiation cohorts underwent 40 Gy of radiation with subsequent inferior epigastric axial rotational flap 30 days later in all cohorts with percentage of flap necrosis and vascular density calculated by blinded observers. In a second experiment, an additional three cohorts, underwent serial punch biopsies of the abdominal skin before, during, and after radiation and drug/vehicle control treatment. Transcriptome analysis utilizing gene set enrichment analysis and digital polymerase chain reaction were performed at various time points.

Results

The first experiment revealed average flap necrosis of 20% (95% confidence interval [CI] 16–45) in the radiation control group, 3% (95% CI 0–11) in the nonirradiated control, and 3% (95% CI 0.2–10) in the radiation group treated with RTA‐408. Vascular density was preserved in the treatment group as compared to the radiated control. Nine rats were included in the second experiment, and transcriptome analyses in the treatment group revealed robust activation of antioxidant pathways with induced expression of genes associated with hypoxia and adipogenesis/angiogenesis.

Conclusions

Administration of RTA‐408 during radiation treatment in a rat model resulted in transcriptome changes which appear to mitigate the toxic effects of radiation, preserving capillary networks and improving flap survival and tissue healing after subsequent surgery.

Level of Evidence

Foundational Evidence, Animal Research Laryngoscope, 132:1196–1204, 2022
Increased petrogenic and biospheric organic carbon burial in sub‐Antarctic fjord sediments in response to recent glacier retreat
Authors: Berg Sonja , Jivcov Sandra , Kusch Stephanie , Kuhn Gerhard , White Duanne , Bohrmann Gerhard , Melles Martin , Rethemeyer Janet
Published: October 2021

Fjords are recognized as hotspots of organic carbon (OC) burial in the coastal ocean. In fjords with glaciated catchments, glacier discharge carries large amounts of suspended matter. This sedimentary load includes OC from bedrock and terrigenous sources (modern vegetation, peat, soil deposits), which is either buried in the fjord or remineralized during export, acting as a potential source of CO2 to the atmosphere. In sub‐Antarctic South Georgia, fjord‐terminating glaciers have been retreating during the past decades, likely as a response to changing climate conditions. We determine sources of OC in surface sediments of Cumberland Bay, South Georgia, using lipid biomarkers and the bulk 14C isotopic composition, and quantify OC burial at present and for the time period of documented glacier retreat (between 1958 and 2017). Petrogenic OC is the dominant type of OC in proximity to the present‐day calving fronts (60.4 ± 1.4% to 73.8 ± 2.6%) and decreases to 14.0 ± 2.7% outside the fjord, indicating that petrogenic OC is effectively buried in the fjord. Beside of marine OC, terrigenous OC comprises 2.7 ± 0.5% to 7.9 ± 5.9% and is mostly derived from modern plants and Holocene peat and soil deposits that are eroded along the flanks of the fjord, rather than released by the retreating fjord glaciers. We estimate that the retreat of tidewater glaciers between 1958 and 2017 led to an increase in petrogenic carbon accumulation of 22% in Cumberland West Bay and 6.5% in Cumberland East Bay, suggesting that successive glacier retreat does not only release petrogenic OC into the fjord, but also increases the capacity of OC burial.
Comprehensive analysis of chemical and biological problems associated with browning agents used in aquatic studies
Authors: Scharnweber Kristin , Peura Sari , Attermeyer Katrin , Bertilsson Stefan , Bolender Lucas , Buck Moritz , Einarsdóttir Karólína , Garcia Sarahi L. , Gollnisch Raphael , Grasset Charlotte , Groeneveld Marloes , Hawkes Jeffrey A. , Lindström Eva S. , Manthey Christin , Övergaard Robyn , Rengefors Karin , Sedano‐Núñez Vicente T. , Tranvik Lars J. , Székely Anna J.
Published: October 2021

Inland waters receive and process large amounts of colored organic matter from the terrestrial surroundings. These inputs dramatically affect the chemical, physical, and biological properties of water bodies, as well as their roles as global carbon sinks and sources. However, manipulative studies, especially at ecosystem scale, require large amounts of dissolved organic matter with optical and chemical properties resembling indigenous organic matter. Here, we compared the impacts of two leonardite products (HuminFeed and SuperHume) and a freshly derived reverse osmosis concentrate of organic matter in a set of comprehensive mesocosm‐ and laboratory‐scale experiments and analyses. The chemical properties of the reverse osmosis concentrate and the leonardite products were very different, with leonardite products being low and the reverse osmosis concentrate being high in carboxylic functional groups. Light had a strong impact on the properties of leonardite products, including loss of color and increased particle formation. HuminFeed presented a substantial impact on microbial communities under light conditions, where bacterial production was stimulated and community composition modified, while in dark potential inhibition of bacterial processes was detected. While none of the browning agents inhibited the growth of the tested phytoplankton Gonyostomum semen, HuminFeed had detrimental effects on zooplankton abundance and Daphnia reproduction. We conclude that the effects of browning agents extracted from leonardite, particularly HuminFeed, are in sharp contrast to those originating from terrestrially derived dissolved organic matter. Hence, they should be used with great caution in experimental studies on the consequences of terrestrial carbon for aquatic systems.
3D‐Printed Porous Tantalum Coated with Antitubercular Drugs Achieving Antibacterial Properties and Good Biocompatibility
Authors: Hua Long , Qian Hu , Lei Ting , Zhang Yu , Lei Pengfei , Hu Yihe
Published: October 2021

Treatment of bone and joint tuberculosis remains a challenge. The development of tissue‐engineered drug‐loaded biomaterials has increased the therapeutic options. However, for the treatment of osteoarticular tuberculosis with severe local infection risks and high weight‐bearing requirements, it is still necessary to design materials consistent with bone biomechanics, cytocompatibility, and osteogenesis and to provide more effective antimicrobial functions. The antitubercular drugs isoniazid and rifampicin are loaded with gellan gum, and a 3D‐printed porous tantalum surface is treated with polydopamine to increase adhesion. The osteogenic induction and differentiation are tested using alkaline phosphatase, alizarin red staining, sirius red staining, and polymerase chain reaction testing. Bone regeneration in vivo is measured by X‐ray, micro‐computerized tomography, hard tissue sections, and fluorescence staining. The drug is released slowly in vitro and in vivo, increasing the duration of antibacterial action. The composite bio‐scaffolds inhibit Staphylococcus aureus growth, have good biocompatibility, and does not inhibit the induction of osteogenic differentiation of rat bone marrow mesenchymal stem cells. The composite bio‐scaffold can simultaneously achieve localized long‐term controlled drug release and bone regeneration and is a promising route for bone and joint tuberculosis treatment.
Five novel globin gene mutations identified in five Chinese families by next‐generation sequencing
Authors: Zhang Jie , Xie Meijuan , Peng Zhiyu , Zhou Xiaoyan , Zhao Tingting , Jin Chanchan , Yan Yuanlong , Zeng Xiaohong , Li Dongmei , Zhang Yangjia , Su Jie , Feng Na , He Jing , Yao Xiangmei , Lv Tao , Zhu Baosheng
Published: October 2021

Background

Thalassemia is one of the most common inherited diseases worldwide. This report presents three novel cases of α‐thalassemia and two novel cases of β‐thalassemia caused by five different mutations in the globin gene.

Methods

Next‐generation sequencing (NGS) was used to identify novel α‐ and β‐thalassemia in five individuals, which was confirmed by Sanger sequencing of the globin gene. Hematological parameters were determined by an automated cell counter, and hemoglobin electrophoresis was carried out by a capillary electrophoresis system, respectively. The isoelectric point (pI), molecular weight, and conservation for the mutations were described by the Internet software programs. The pathogenicity for globin mutations was analyzed by bioinformatics analysis and relative quantitative analysis.

Results

NGS revealed five novel cases of α‐ and β‐thalassemia: HBA2:c.245C>T, HBA2:c.95+11_95+34delCTCCCCTGCTCCGACCCGGGCTCC, HBA2:c.54delC, HBB:c.373C>A, and HBB:c.40G>A. The clinical implications of these mutations were described. Computational predictions were made for pI, amino acid conservation, and pathogenicity of the missense mutation. Relative quantitative data of the α‐globin mRNA were analyzed.

Conclusion

Five novel globin mutations were identified in the populations of China, and those mutations were analyzed to provide a mechanistic view for their pathogenicity. These analyzed results improve genetic diagnostics for thalassemia, which can improve screening programs for thalassemia and prenatal diagnosis for Chinese population.
Discovery of Inhibitors for Mycobacterium Tuberculosis Peptide Deformylase Based on Virtual Screening in Silico
Authors: Li Xinpeng , Jiang Qihua , Yang Xiaolan
Published: October 2021

Tuberculosis has been the serious disease threatening human health and public safety due to the emergence of MDR and XDR‐TB. Mycobacterium tuberculosis peptide deformylase (MtPDF) is a valuable target for antituberculotics. In order to discover new potential inhibitor candidates of MtPDF as leads for antituberculotics, Discovery Studio (DS) 2019 was used to perform molecular docking for virtual screening in silico with the bioactive compound library‐I (L1700) against MtPDF. Six compounds with high docking scores and favourable ligand‐protein interactions by LibDock and CDOCKER were selected for the evaluation of the inhibition potencies against MtPDF and Mycobacterium smegmatis. GST‐6×His tagged MtPDF was recombinant expressed and purified firstly by Glutathione Sepharose 4B, and secondly by Ni Sepharose 6 FF after the cleavage of human rhinovirus 3C protease. These compounds showed IC50 values from 0.5 μmol/L to 112 μmol/L against MtPDF, among which CUDC‐101 bearing hydroxamic acid exhibited IC50 of 0.5 μmol/L on MtPDF and MIC against Mycobacterium smegmatis of 32 μg/mL, and Ixazomib Citrate with IC50 of 63 μmol/L and MIC of 16 μg/mL. CUDC‐101 and Ixazomib Citrate are promising as the potential leads for antituberculotics.
Application of Molecular Docking, Homology Modeling, and Chemometric Approaches to Neonicotinoid Toxicity against Aphis craccivora
Authors: Crisan Luminita , Borota Ana , Bora Alina , Suzuki Takahiro , Funar‐Timofei Simona
Published: October 2021

Neonicotinoids are known as effective pesticides against various insect species. They can harm useful insects including honeybees, with a relatively low threat to nontarget organisms and the environment. This paper presents combined methods to explore the insecticidal activity of neonicotinoids with diverse scaffolds, active against Aphis craccivora. Pharmacophore, molecular docking into the active site of nicotinic acetylcholine receptor homology model, and linear and non‐linear regression approaches were used to find new insecticide candidates. The potential toxic effects against honeybees were evaluated using the molecular docking in the active site of the new Aphis mellifera homology model. Four new untested compounds were assigned as insecticide candidates, active against Aphis craccivora with less potential toxic effects for honeybees. This approach may be an effective strategy to design environmentally friendly insecticides against the cowpea aphid.
Short‐Chain Fatty Acids Produced by Ruminococcaceae Mediate α‐Linolenic Acid Promote Intestinal Stem Cells Proliferation
Authors: Xie Jing , Li Ling‐fei , Dai Tian‐yi , Qi Xin , Wang Yan , Zheng Tiao‐zhen , Gao Xiao‐yu , Zhang Yun‐juan , Ai Yu , Ma Li , Chang Song‐lin , Luo Feng‐xian , Tian Yang , Sheng Jun
Published: October 2021

Scope: The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs; however, the regulation effect of α‐linolenic acid (ALA) has seldom been reported.

Methods and Results: After intervening mice with different doses of ALA for 30 days, it is found that ALA (0.5 g kg−1) promotes small intestinal and villus growth by activating the Wnt/β‐catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increases the abundance of the Ruminococcaceae and Prevotellaceae, and promotes the production of short‐chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrate that ALA on the proliferation of ISCs are gut microbiota dependent, among them, the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate shows a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigates 5‐fluorouracil‐induced intestinal mucosal damage by promoting ISCs proliferation.

Conclusion: These results indicate that SCFAs produced by Ruminococcaceae mediate ALA promote ISCs proliferation by activating the Wnt/β‐catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.
Allulose Attenuated Age‐Associated Sarcopenia via Regulating IGF‐1 and Myostatin in Aged Mice
Authors: Kim Ji‐Eun , Kwon Eun‐Young , Han Youngji
Published: October 2021

Scope

Allulose is shown to increase the muscle weight in diet‐induced obese mice. However, there are no studies on the effects of allulose in age‐associated sarcopenia. This study aims to elucidate the mechanisms of action for allulose in age associated by analyzing the transcriptional patterns in aged mice.

Methods and Results

The 48‐week‐old mice are fed with AIN‐93diet containing allulose for 12 weeks. Allulose supplementation increases the muscle mass and grip strength in aged mice. Allulose increases the insulin‐like growth factor 1 (IGF‐1) and its downstream factor expressions which 40 are related protein synthesis, while inhibits the myostatin expression related protein degradation. In mRNA‐seq analysis, allulose supplementation significantly decreases in Adiponectin, Adipsin, cell death inducing DFFA like effector (CIDEC), Haptoglobin, Neuroglobin, and stearoyl‐CoA desaturase‐1 (SCD1) and increases in cytokine‐inducible SH2‐containing protein (CISH) and ceramide synthase 1 (CerS1) that are regulate protein turn over in gastrocnemius. Also, allulose alleviates autophagy in muscle with regulated mammalian target of rapamycin (mTOR) signaling pathway and increases the anti‐oxidant enzyme activity.

Conclusion

These findings suggest that allulose improves the age‐associated sarcopenia with enhancing antioxidant properties by altering mRNA and protein expression.
Three‐dimensional simultaneous brain mapping of T1, T2, and magnetic susceptibility with MR Multitasking
Authors: Cao Tianle , Ma Sen , Wang Nan , Gharabaghi Sara , Xie Yibin , Fan Zhaoyang , Hogg Elliot , Wu Chaowei , Han Fei , Tagliati Michele , Haacke E. Mark , Christodoulou Anthony G. , Li Debiao
Published: October 2021

Purpose

To develop a new technique that enables simultaneous quantification of whole‐brain T1, T2, , as well as susceptibility and synthesis of six contrast‐weighted images in a single 9.1‐minute scan.

Methods

The technique uses hybrid T2‐prepared inversion‐recovery pulse modules and multi‐echo gradient‐echo readouts to collect k‐space data with various T1, T2, and weightings. The underlying image is represented as a six‐dimensional low‐rank tensor consisting of three spatial dimensions and three temporal dimensions corresponding to T1 recovery, T2 decay, and multi‐echo behaviors, respectively. Multiparametric maps were fitted from reconstructed image series. The proposed method was validated on phantoms and healthy volunteers, by comparing quantitative measurements against corresponding reference methods. The feasibility of generating six contrast‐weighted images was also examined.

Results

High quality, co‐registered T1, T2, and susceptibility maps were generated that closely resembled the reference maps. Phantom measurements showed substantial consistency (R2 > 0.98) with the reference measurements. Despite the significant differences of T1 (p < .001), T2 (p = .002), and (p = 0.008) between our method and the references for in vivo studies, excellent agreement was achieved with all intraclass correlation coefficients greater than 0.75. No significant difference was found for susceptibility (p = .900). The framework is also capable of synthesizing six contrast‐weighted images.

Conclusion

The MR Multitasking–based 3D brain mapping of T1, T2, , and susceptibility agrees well with the reference and is a promising technique for multicontrast and quantitative imaging.
Simultaneous 3D‐TOF angiography and 4D‐flow MRI with enhanced flow signal using multiple overlapping thin slab acquisition and magnetization transfer
Authors: Kim Dahan , Eisenmenger Laura , Turski Patrick , Johnson Kevin M.
Published: October 2021

Purpose

To investigate the fusion of 3D time‐of‐flight principles into 4D‐flow MRI to enhance vessel contrast and signal without an exogenous contrast agent, enabling simultaneous in‐flow based angiograms.

Methods

A 4D‐flow MRI technique was developed consisting of multiple overlapping slabs with intermittent magnetization transfer preparation. The scan time penalty associated with multiple slab acquisitions was mitigated by using undersampled distributed spiral trajectories and compressed sensing reconstruction. A flow phantom was used to characterize in‐flow enhancement, velocity noise improvement, and flow rate measurements against the single‐slab 4D‐flow MRI. In a patient‐volunteer cohort (n = 15), magnitude‐based angiograms were radiologically evaluated against 3D time‐of‐flight, and velocity measurements were compared pixel‐wise against single‐slab and contrast‐enhanced 4D‐flow MRI.

Results

Multiple‐slab acquisitions, together with magnetization transfer preparation, substantially improved vessel signal, contrast, and vessel conspicuity in magnitude angiograms. Both clinical 3D time‐of‐flight and the proposed technique produced equivalent vessel depictions with no statistically significant difference (p < .1). Both techniques also produced clear depictions of brain aneurysms in all patients; however, very small vessels tended to show reduced conspicuity in the proposed technique. Velocity measurements agreed with contrast‐enhanced and single‐slab scans with high correlations (R2 = 0.941–0.974) and agreements (slopes = 0.994–1.071). Slab boundary and magnetization transfer‐related artifacts were not observed in velocity measurements, and velocity noise was reduced with in‐flow enhancement over single‐slab scans (phantom).

Conclusion

The vessel signal and contrast can be improved in 4D‐flow MRI without exogenous contrast agents by utilizing in‐flow enhancement, efficient sampling, and compressed sensing. The in‐flow enhancement also enables simultaneous 3D time‐of‐flight angiograms useful for flow quantification and diagnosis.
Highly efficient and stable perovskite solar cells based on E‐beam evaporated SnO2 and rational interface defects passivation
Authors: Li Mengjia , Zhu Lihua , Zhang Xian , Wang Chen , Gao Deyu , Han Jiaheng , Chen Chunlei , Song Hongwei , Xu Sai , Chen Cong
Published: October 2021

Owing to the significant roles in balancing carrier transport, bandgap alignment, and perovskite crystallization, realizing high‐quality electron transport layers (ETLs) and their effective electronic contact with the perovskite photoactive layer is crucial for future commercialization of perovskite solar cells (PSCs). Here, a high‐quality SnO2 ETL is firstly deposited at room temperature via the low‐cost electron beam evaporation (E‐beam) technology to help achieve an impressive PCE of 18.88% for rigid PSCs and a PCE of 15.73% for flexible devices. Then we introduced a novel passivating ligand molecule, 11 Maleimidoundecanoic acids (11MA), to help induce functional defects passivation at the interface of SnO2/Perovskite to coordinate with Pb2+ in perovskite and Sn4+ in SnO2 via the functional groups (‐C = O, ‐COOH). As a result, 11MA could help achieve the best PCE of 20.94% with negligible hysteresis for rigid devices. Also, doping 11MA in the perovskite photoactive layer further enhanced the PCE to 22.08% with much improved 2000 hours ambient stabilities. Finally, we fabricated different large‐area rigid devices (10, 40, 100, and 600 mm2) toward speeding up the commercialization of PSCs by industrial E‐beam technology and rational defects passivation strategies.
Paleodiet reconstruction of human and animal bones at the Dalujiao cemetery in Early Iron Age Xinjiang, China
Authors: Wang Xin , Shang Xue , Smith Colin , Wei Dong , Zhang Jie , Ruan Qiurong , Hu Yaowu
Published: October 2021

Long before the East–West “Silk Road” appeared, cultural communication as well as exchanges of materials and technologies had existed between different populations across the Eurasian Steppe. Xinjiang, located at a crossroads of the East and the West, is particularly important for exploring human interactions. The present paper contributes to this end from a stable isotopic perspective. Carbon and nitrogen stable isotope analysis were applied to 51 human and four animal bone remains collected from three types of tombs—namely, the earthen vertical tomb‐pit, earthen vertical tomb‐pit with second‐tier ledge, and earthen vertical tomb‐pit with side chamber—excavated from the Dalujiao cemetery, dated to the Early Iron Age (542 BCE–59 CE), in Xinjiang of northwest China. The δ13C (mean: −18.6 ‰) and δ15N (mean: 7.5‰) results of the faunal remains suggest that the two herbivore species (horse and sheep) were fed mainly by C3 terrestrial plants. By contrast, the human bone specimens differ in δ13C values (from −16.0‰ to −11.6‰, with a mean of −14.1‰ ± 1.1‰, n = 51). People buried in vertical tomb‐pits show a narrow range of δ13C values, an indication that they consumed quite stable sources of food. In contrast, those buried in vertical tomb‐pits with a second‐tier ledge or with a side chamber consumed more diverse foods and probably adopted different subsistence strategies. Taking into consideration both isotopic results and types of tombs, we propose that at least three groups of populations with diverse dietary and subsistence strategies are identifiable at the Dalujiao cemetery. Our study reveals not only human diets and subsistence patterns in the study area but also interactions among different populations prior to the rise of “Silk Road.”
Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation
Authors: Elgarten Caitlin W. , Tanes Ceylan , Lee Jung‐Jin , Danziger‐Isakov Lara A. , Grimley Michael S. , Green Michael , Michaels Marian G. , Barnum Jessie L. , Ardura Monica I. , Auletta Jeffery J. , Blumenstock Jesse , Seif Alix E. , Bittinger Kyle L. , Fisher Brian T.
Published: October 2021

Background

The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed.

Methods

We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted metabolic profiling on pretransplant stool samples. Samples were compared with normal age‐matched controls and by clinical characteristics. We then explored associations between stool microbiome measurements and metabolite concentrations.

Results

We profiled stool samples from 88 pediatric allogeneic HCT patients, a median of 4 days before transplant. Pretransplant stool samples differed from healthy controls based on indices of alpha diversity and in the proportional abundance of specific taxa and bacterial genes. Relative to stool from healthy patients, samples from HCT patients had decreased proportion of Bacteroides, Ruminococcaeae, and genes involved in butyrate production, but were enriched for gammaproteobacterial species. No systematic differences in stool microbiome or metabolomic profiles by age, transplant indication, or hospital were noted. Stool metabolites demonstrated strong correlations with microbiome composition.

Discussion

Stool samples from pediatric allogeneic HCT patients demonstrate substantial dysbiosis early in the transplant course. As microbiome disruptions associate with adverse transplant outcomes, pediatric‐specific analyses examining longitudinal microbiome and metabolome changes are imperative to identify causal associations and to inform rational design of interventions.
Carbon fiber reinforced areca/sisal hybrid composites for railway interior applications: Mechanical and morphological properties
Authors: Jagadeesh Praveenkumara , Puttegowda Madhu , Girijappa Yashas Gowda Thyavihalli , Rangappa Sanjay Mavinkere , Siengchin Suchart
Published: October 2021

The present experimental investigation focuses on the development of Areca/Sisal/Carbon reinforced epoxy hybrid composites under various stacking sequences and involves the assessment of their mechanical and morphological properties to evaluate their use in some railway interior applications. Nine different combinations of laminates were prepared by using the manual hand layup technique. Mechanical experiments such as tensile, flexural, impact, inter‐laminar shear strength and hardness tests were performed and the results envied the positive values which suggest the use of composites prepared in the study to be employed in some railway interior parts. The morphology of the composites was scrutinized using scanning electron microscopy and exposed the proper agglomeration of fibers in the matrix which in turn has influenced better mechanical properties. The experimental results convey that the hybridization of natural and synthetic fibers in polymer matrix would be an exciting prospect to be utilized in some railway interior applications.
Biocomposites based on starch with multi‐functionalized graphene oxide: Effect of graft composition and concentration
Authors: Cruz‐Benítez María Montserrat , Castro‐Rosas Javier , González‐Morones Pablo , Santos‐López Eva Maria , Villagómez‐Ibarra José Roberto , Tlahuextl‐Romero Angela Margarita , Fonseca‐Florido Heidi Andrea , Gómez‐Aldapa Carlos Alberto
Published: October 2021

The current global scenario has a great impact on the development of new bio‐based materials due to the vital advantages that are helpful in replacing synthetic and hazardous materials. In this study, biocomposites (BC) of cassava starch/grafts of multi‐functionalized graphene oxide were synthesized by solvent casting. To improve their interface compatibility, graphene oxide (GO) was grafted with fructose, microcellulose and/or starch. The multi‐functionalization of GO (grafts) was determined by Fourier transform infrared and Raman spectroscopy. The results confirm the covalent bond between GO and organic molecules, with a grafting average percentage of 45% by weight. Subsequently, the effects of the concentrations and composition of grafts on surface morphology (SEM) showed that the use of multi‐functionalized GO with organic molecules improves the compatibility and graft‐matrix interaction, preventing agglomeration, and it favors the formation of well‐dispersed BC. The thermogravimetric analysis (TGA) revealed significant improvement in the thermal stability of BC with grafts at 3%. The mechanical properties of BC showed tensile strength values were four (4) times higher as compared with those of CS matrix. The elongation at break values was also directly related to the concentration and type of grafts. The functionalization of GO with organic molecules allows to obtain BC with good thermomechanical properties, reducing the load of GO, which increases their applications. This knowledge can be used to the development of homogeneous and high‐quality BC through the modification of the GO structure as a fundamental step to improve graft‐matrix interactions.
General practitioner prescribing trends among pediatric patients in the United Kingdom: 1998–2018
Authors: Masarwa Reem , Lefebvre Claire , Platt Robert W. , Filion Kristian B.
Published: October 2021

Purpose

To describe the prescribing trends of 17 therapeutic drug categories and the specific drug classes of systemic antibiotics, analgesics, and antidepressants in children and adolescents in the United Kingdom between 1998 and 2018.

Methods

A population‐based retrospective cohort study including children and adolescents aged 018 years. Overall and annual prescription rates per 10 000 person‐years and corresponding 95% confidence intervals (CIs) were calculated. Rate ratios and 95% CIs were calculated to assess changes in prescription rates during the study period using Poisson regression.

Results

Among 4 075 527 children and adolescents during the study period from 1998 to 2018, the prescribing rates increased by 15% for attention deficit hyperactivity disorder drugs (rate ratio: 1.15, 95% CI: 1.12–1.18), 14% for anxiolytics and hypnotics (rate ratio: 1.14, 95% CI: 1.13–1.16), and 8% for drugs for gastroesophageal reflux disease (GERD) (rate ratio: 1.08, 95% CI: 1.07–1.09). Prescribing rates decreased by 6% for cough preparations (rate ratio: 0.94, 95% CI: 0.92–0.95) and by 3% for analgesics (rate ratio: 0.97, 95% CI: 0.96–0.99). No meaningful changes were observed for systemic antibiotics (rate ratio: 1.02, 95% CI: 0.99–1.04). Among specific drug classes, prescribing rates decreased for broad‐spectrum penicillins and cephalosporins, and they increased for selective serotonin reuptake inhibitors, opioids, and drugs for migraine.

Conclusions

Between 1998 and 2018, the prescribing of centrally acting drugs and drugs for GERD increased among pediatric patients, whereas prescribing of cough preparations and analgesics declined in this population.
Improving processability for in‐mold coating formulations
Authors: Cai Kaiyu , Zhang Dan , Straus Elliott J. , Villarreal Maria G. , Castro Jose M.
Published: October 2021

In‐mold coating (IMC) being 100% solids upon polymerization is an environmentally friendly alternative to traditional painting/coating. The standard commercial IMC formulation contains 2.8 wt% carbon black (CB) to achieve the electrical conductivity needed for maximum transfer efficiency during electrostatic painting. This formulation, however, makes the primed surface deep black and significantly increases the viscosity. To address this issue, our previous research evaluated the use of single‐wall carbon nanotubes as an alternative to CB. It was found that IMC with 0.15 wt% SWCNT provides the same level of conductivity as the standard IMC, but a much clear coating. However, the processability of this new formulation was adversely affected. In this research, other carbon‐based materials, that is, carbon nanofiber (CNF), multi‐wall carbon nanotube (MWCNT), and industrial graphene (grapheneblack [G]), were evaluated. Results indicate that the same level of conductivity can be reached by adding 1.6 wt% CNF, 1.8 wt% MWCNT, or 11.3 wt% G. Results also suggest that IMC with 1.8 wt% MWCNT has the best curing process, IMC with 11.3 wt% G has the highest flowability, and all three new formulations have a slightly better greyscale reading than the standard IMC.
Identifying blood‐brain barrier peptides by using amino acids physicochemical properties and features fusion method
Authors: Zou Hongliang
Published: October 2021

Blood‐brain barrier peptides (BBPs) play a promising role in current drug study of central nervous system diseases. Hence, it is an urgent need to rapidly and accurately discriminating BBPs from non‐BBPs. Experimental approaches are the first choice, however, these methods are expensive and take a lot of time. Thus, more and more researchers focused their attention on computational models. In current work, we developed a support vector machine (SVM) based model to identify BBPs. First, amino acids physicochemical properties were employed to represent peptide sequences, and Pearson's correlation coefficient (PCC) and maximal information coefficient (MIC) were applied to extract useful information. Then, similarity network fusion algorithm was utilized to integrate these two different kinds of features. Next, Fisher algorithm was used to pick out the discriminative features. Finally, these selected features were input into SVM for distinguishing BBPs from non‐BBPs. The proposed model achieved 100.00% and 89.47% classification accuracies on training and independent datasets, respectively. Additionally, we found that pK2 (NH3) property of amino acid plays a key role in discriminating BBPs from non‐BBPs. The results showed that our proposed method is effective, and achieved a significantly improvement in identifying BBPs, as compared with the state‐of‐the‐art approach. The Matlab codes and datasets are freely available at https://figshare.com/articles/online_resource/iBBPs_zip/14723766.
Statin withdrawal and treating COVID‐19 patients
Authors: Fedson David S.
Published: October 2021

Most but not all observational studies of statin treatment of COVID‐19 patients suggest that treatment improves outcomes. However, almost all of these studies fail to consider that withdrawing statins after hospital admission may have detrimental effects, a finding which cardiovascular investigators have known for 15–20 years. Continuing or starting statin treatment after hospital admission consistently improves cardiovascular outcomes. Similarly, inpatient statin treatment of COVID‐19 improves survival. For this reason, observational studies of the effectiveness of outpatient‐documented statin treatment of COVID‐19 patients must consider the negative consequences of statin withdrawal after hospital admission.