bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence‐based use of scalable biomarkers to increase diagnostic efficiency and decrease the lifetime costs of autism
Authors: Frazier Thomas W. , Coury Daniel L. , Sohl Kristin , Wagner Kayla E. , Uhlig Richard , Hicks Steven D. , Middleton Frank A.
Published: March 2021

Challenges associated with the current screening and diagnostic process for autism spectrum disorder (ASD) in the US cause a significant delay in the initiation of evidence‐based interventions at an early age when treatments are most effective. The present study shows how implementing a second‐order diagnostic measure to high risk cases initially flagged positive from screening tools can further inform clinical judgment and substantially improve early identification. We use two example measures for the purposes of this demonstration; a saliva test and eye‐tracking technology, both scalable and easy‐to‐implement biomarkers recently introduced in ASD research. Results of the current cost‐savings analysis indicate that lifetime societal cost savings in special education, medical and residential care are estimated to be nearly $580,000 per ASD child, with annual cost savings in education exceeding $13.3 billion, and annual cost savings in medical and residential care exceeding $23.8 billion (of these, nearly $11.2 billion are attributable to Medicaid). These savings total more than $37 billion/year in societal savings in the US. Initiating appropriate interventions faster and reducing the number of unnecessary diagnostic evaluations can decrease the lifetime costs of ASD to society. We demonstrate the value of implementing a scalable highly accurate diagnostic in terms of cost savings to the US.

Lay Summary

This paper demonstrates how biomarkers with high accuracy for detecting autism spectrum disorder (ASD) could be used to increase the efficiency of early diagnosis. Results also show that, if more children with ASD are identified early and referred for early intervention services, the system would realize substantial costs savings across the lifespan.
Accuracy and uniformity of the nomenclature of biogenic amines and polyamines in metabolomics studies: A preliminary study
Authors: Akyol Omer , Tessier Kylie , Akyol Sumeyya
Published: March 2021

Metabolomics is one of the newest areas in biochemistry dedicated to investigating small biomolecules in biofluids, tissues, and cells. Cutting edge instruments used in metabolomics studies make it possible to identify thousands of biomolecules and determine their interactions with biological networks. This tremendous area has increased the significance of accurate chemical nomenclature of compounds. Therefore, the classification of the organic molecules has become one of the most important issues in the field. Biogenic amines are nitrogenous compounds of low molecular weight formed by the decarboxylation of amino acids or by the amination and the transamination of aldehydes and ketones during normal metabolic processes. This letter covers the topic of nomenclature with respect to the current usage of biogenic amines in scientific literature. We use metabolomics as an example of field reporting data on trace levels of molecules that may be miscategorized in primary literature. We suggest that the incorrect classification of molecules will influence science education adversely because resources used for teaching are drawn from primary literature references that may contain errors.
Phytochemical Investigations and In Vitro Bioactivity Screening on Melia azedarach L. Leaves Extract from Nepal
Authors: Shrestha Shyam Sharan , Ferrarese Irene , Sut Stefania , Zengin Gokhan , Grana Sara , Ak Gunes , Pant Deepak Raj , Dall'Acqua Stefano , Rajbhandary Sangeeta
Published: March 2021

Melia azedarach is a common tree used in the traditional medicine of Nepal. In this work, leaves were considered as source of bioactive constituents and composition of methanol extract was evaluated and compared with starting plant material. Flavonoid glycosides and limonoids were identified and quantified by HPLC‐DAD‐MSn approaches in dried leaves and methanolic extract, while HPLC‐APCI‐MSn and GC/MS analysis were used to study phytosterol and lipid compositions. β‐Sitosterol and rutin were the most abundant constituents. HPLC‐APCI‐MSn and HPLC‐DAD‐MSn analysis revealed high levels of phytosterols and flavonoids in methanolic extract accounting 9.6 and 7.5 % on the dried weight, respectively. On the other hand, HPLC/MSn data revealed that limonoid constituents were in minor amount in the extract <0.1 %, compared with leaves (0.7 %) indicating that degradation occurred during extraction or concentration procedures. The methanol extract was subjected to different bioassays, and antioxidant activity was evaluated. Limited inhibitory activity on acetyl and butyryl cholinesterase, as well as on amylase were detected. Moreover, tyrosinase inhibition was significant resulting in 131.57±0.51 mg kojic acid equivalents/g of dried methanol extract, suggesting possible use of this M. azedarach extract in skin hyperpigmentation conditions. Moderate cytotoxic activity, with IC50 of 26.4 μg/mL was observed against human ovarian cancer cell lines (2008 cells). Our findings indicate that the Nepalese M. azedarach leaves can be considered as valuable starting material for the extraction of phenolics and phytosterols, yielding extracts with possible cosmetic and pharmaceutical applications.
Effect of particle size and processing method on starch and protein digestibility of navy bean flour
Authors: Byars Jeffrey A. , Singh Mukti , Kenar James A. , Felker Frederick C. , Winkler‐Moser Jill K.
Published: March 2021

Background and objectives

Intact cotyledon cells in pulses are known to limit the access of digestive enzymes and to decrease starch digestibility. The objective of this study was to study the effect of the cells on starch and protein digestibility and raffinose family oligosaccharide (RFO) extraction. The in vitro starch and protein digestion and RFO extraction in 80% ethanol were studied for roasted, baked, and cooked navy bean flour fractions having large (297–500 µm), medium (74–297 µm), and small (<74 µm) particle sizes.

Findings

The starch digestibility and protein digestibility were highest for the smallest particle size flour. The digestibility was lowest for roasted flours and highest for cooked flours. Intact cotyledon cells did not affect RFO extraction.

Conclusions

The in vitro protein digestibility increased as the particle size of the navy bean flour decreased for the three fractions that had been roasted, baked, or cooked.

Significance and novelty

This is the first study showing that navy bean flours with different particle sizes have different in vitro protein digestibility. The effect on nutrient availability should be considered when selecting pulse flours for food applications.
Electrochemical Characterization of Fe(II) Complexation Reactions at an Electrified Micro Liquid‐Liquid Interface
Authors: Jiang Qi , Reader Heather E. , Stockmann Talia Jane
Published: March 2021

Phytoplankton growth in the open ocean is critical to carbon fixation and often limited by low iron concentrations. Owing to its low solubility, phytoplankton employ ligands for iron uptake; therefore, ligand binding characterization is important. Herein, a micro immiscible liquid/liquid interface was employed with four ligands through an electrochemically induced facilitated ion‐transfer process. Ligands 1,10‐phenathroline (phen), 1‐nitroso‐2‐naphthol (N2N), 2‐(2‐thiazolylazo)‐p‐cresol (TAC), and salicylaldoxime (SAL), where tested using established facilitated ion‐transfer thermodynamics combined with differential pulse voltammetry. Three metal ion/ligand binding stoichiometries were observed for Fe2+:phen, whereas only one was observed with Fe2+with SAL, N2N, and TAC. Overall binding constants were calculated such that binding strengths can be ranked highest to lowest as phen>N2N>TAC>SAL. Additionally, the formal ion transfer for Fe2+(0.66 V) for an aqueous/1,2‐dichloroethane interface was also determined.
Yellow nutsedge control with sequential applications of sulfentrazone and sulfentrazone pre‐mixtures within maintained turfgrass
Authors: de Castro Edicarlos B. , McCurdy James D.
Published: March 2021

Core Ideas

Field studies compared a sequential application of herbicides for yellow nutsedge control.

Halosulfuron, imazaquin, or sulfosulfuron controlled yellow nutsedge.

Sulfentrazone herbicide applied sequentially provided comparable yellow nutsedge control.
Beyond Pseudo‐natural Products: Sequential Ugi/Pictet‐Spengler Reactions Leading to Steroidal Pyrazinoisoquinolines That Trigger Caspase‐Independent Death in HepG2 Cells
Authors: Alonso Fernando , Galilea Agustín , Mañez Pau Arroyo , Acebedo Sofía L. , Cabrera Gabriela M. , Otero Marcelo , Barquero Andrea A. , Ramírez Javier A.
Published: March 2021

In this work, we describe how stereochemically complex polycyclic compounds can be generated by applying a synthetic sequence comprising an intramolecular Ugi reaction followed by a Pictet‐Spengler cyclization on steroid‐derived scaffolds. The resulting compounds, which combine a fragment derived from a natural product and a scaffold not found in nature. are both structurally distinct and globally similar to natural products at the same time, and interrogate an alternative region of the chemical space. One of the new compounds showed significant antiproliferative activity on HepG2 cells through a caspase‐independent cell‐death mechanism, an appealing feature when new antitumor compounds are searched.
Human attention‐inspired volume reconstruction method on serial section electron microscopy images
Authors: Zhou Fangxu , Shen Lijun , Chen Bohao , Chen Xi , Hua Han
Published: March 2021

The alignment of a 2D microscopic image stack to create a 3D image volume is an indispensable aspect of serial section electron microscopy (EM) technology, which could restore the original 3D integrity of biological tissues destroyed by chemical fixation and physical dissection. However, due to the similar texture intrasection and complex variations intersections of neural images, previous registration methods usually failed to yield reliable correspondences. And this also led to misalignment and impeded restoring the z‐axis anatomical continuity of the neuron volume. In this article, inspired by human behaviors in finding correspondences, which use the topological relationship of image contents, we developed a spatial attention‐based registration method for serial EM images to improve registration accuracy. Our approach combined the U‐Net framework with spatial transformer networks (STN) to regress corresponding transformation maps in an unsupervised training fashion. The spatial attention (SA) module was incorporated into the U‐Net architecture to increase the distinctiveness of image features by modeling its topological relationship. Experiments are conducted on both simulated and real data sets (MAS and RegCremi). Quantitative and qualitative comparisons demonstrate that our approach results in state of art accuracy (using the evaluation index of NCC, SSIM, Dice, Landmark error) and providing smooth and reliable transformation with less texture blur and unclear boundary than existing techniques. Our method is able to restore image stacks for visualization and quantitative analysis of EM image sequences.
Investigation of fabrication conditions for VO2 thin films by MOD using carbon thermal reduction
Authors: Fujishiro Yuhi , Kawahara Masami , Samura Tsuyoshi , Tachiki Takashi , Uchida Takashi
Published: March 2021

Vanadium dioxide (VO2) thin films were fabricated by metal‐organic decomposition (MOD). To utilize a carbon thermal reduction for obtaining a VO2 composition, the precursor films were fabricated at the temperature Tp from 300°C to 380°C in a N2 atmosphere. From the measurement results of XRD, diffraction peaks indicating VO2 phase were observed with a wide range of firing temperatures from Tf = 560°C to 620°C. Furthermore, the peaks indicating VO2 phase were also observed with a wide range of firing time from tf = 15–45 min. Regarding the surface morphology of the films, the nanoparticles of 100–200 nm were densely packed although small spaces existed between the particles. The R‐T characteristics of the films indicated the phase transition with a rapid resistance change of about three orders of magnitude and hysteresis loop. From these experimental results, it was found that wide windows of firing conditions for fabricating VO2 thin film can be obtained in the MOD process using the carbon thermal reduction.
Low spatial autocorrelation in mountain biodiversity data and model residuals
Authors: Chevalier Mathieu , Mod Heidi , Broennimann Olivier , Di Cola Valeria , Schmid Sarah , Niculita‐Hirzel Hélène , Pradervand Jean‐Nicolas , Schmidt Benedikt R. , Ursenbacher Sylvain , Pellissier Loïc , Guisan Antoine
Published: March 2021

Spatial autocorrelation (SAC) is a common feature of ecological data where observations tend to be more similar at some geographic distance(s) than expected by chance. Despite the implications of SAC for data dependencies, its impact on the performance of species distribution models (SDMs) remains controversial, with reports of both strong and negligible impacts on inference. Yet, no study has comprehensively assessed the prevalence and the strength of SAC in the residuals of SDMs over entire geographic areas. Here, we used a large‐scale spatial inventory in the western Swiss Alps to provide a thorough assessment of the importance of SAC for (1) 850 species belonging to nine taxonomic groups, (2) six predictors commonly used for modeling species distributions, and (3) residuals obtained from SDMs fitted with two algorithms with the six predictors included as covariates. We used various statistical tools to evaluate (1) the global level of SAC, (2) the spatial pattern and spatial extent of SAC, and (3) whether local clusters of SAC can be detected. We further investigated the effect of the sampling design on SAC levels. Overall, while environmental predictors expectedly displayed high SAC levels, SAC in biodiversity data was rather low overall and vanished rapidly at a distance of ~5–10 km. We found low evidence for the existence of local clusters of SAC. Most importantly, model residuals were not spatially autocorrelated, suggesting that inferences derived from SDMs are unlikely to be affected by SAC. Further, our results suggest that the influence of SAC can be reduced by a careful sampling design. Overall, our results suggest that SAC is not a major concern for rugged mountain landscapes.
CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells
Authors: Sood Aditi , Lebel Marie‐Ève , Dong Mengqi , Fournier Marilaine , Vobecky Suzanne J. , Haddad Élie , Delisle Jean‐Sébastien , Mandl Judith N. , Vrisekoop Nienke , Melichar Heather J.
Published: March 2021

Studies in murine models show that subthreshold TCR interactions with self‐peptide are required for thymic development and peripheral survival of naïve T cells. Recently, differences in the strength of tonic TCR interactions with self‐peptide, as read‐out by cell surface levels of CD5, were associated with distinct effector potentials among sorted populations of T cells in mice. However, whether CD5 can also be used to parse functional heterogeneity among human T cells is less clear. Our study demonstrates that CD5 levels correlate with TCR signal strength in human naïve CD4+ T cells. Further, we describe a relationship between CD5 levels on naïve human CD4+ T cells and binding affinity to foreign peptide, in addition to a predominance of CD5hi T cells in the memory compartment. Differences in gene expression and biases in cytokine production potential between CD5lo and CD5hi naïve human CD4+ T cells are consistent with observations in mice. Together, these data validate the use of CD5 surface levels as a marker of heterogeneity among human naïve CD4+ T cells with important implications for the identification of functionally biased T‐ cell populations that can be exploited to improve the efficacy of adoptive cell therapies.
Rhodium‐Catalyzed [3+2]‐Annulation of ortho‐Diazoquinones with Enol Ethers: Diversity‐Oriented Total Synthesis of Aflatoxin B2
Authors: Paymode Dinesh J. , Sharma Indrajeet
Published: March 2021

A simple and efficient approach for synthesizing substituted and fused polycyclic 2,3‐dihydrobenzofurans has been developed through a Rh‐catalyzed [3+2]‐annulation of ortho‐diazoquinones with enol ethers. This methodology has a broad substrate scope and has been employed for the concise total synthesis of natural product aflatoxin B2.
Bioaccumulation, Metabolism, and Biomarker Responses in Hyriopsis cumingii Exposed to 4-Mono-Chlorinated Dibenzothiophene
Authors: Zhu Ziqing , Shi Jiaqi , Huang Xinxin , Zhang Xuesheng , Li Yucheng , Qin Li , Zhang Rui , Liu Bingxiang
Published: March 2021

Polychlorinated dibenzothiophenes (PCDTs) are sulfur analogues of polychlorinated dibenzofurans with prevalent occurrence in aquatic environments and potential ecological risks. However, data on the behavior and toxicity of PCDTs in aquatic organisms remain scarce. In the present study, the bioaccumulation, metabolism, and oxidative damage of 4-mono-chlorinated dibenzothiophene (4-mono-CDT) in freshwater mussel (Hyriopsis cumingii) were investigated after exposure to 4-mono-CDT in semistatic water. The uptake rates, depuration rates, half-lives, and bioconcentration factors of 4-mono-CDT in hepatopancreas, gill, and muscle tissues ranged from 0.492 to 1.652 L d−1 g−1 dry weight, from 0.117 to 0.308 d−1, from 2.250 to 5.924 d, and from 2.903 to 8.045 × 103 L kg−1 dry weight, respectively. A dechlorinated metabolite (dibenzothiophene) was detected in hepatopancreas tissue, indicating that dechlorination was the main metabolic pathway of 4-mono-CDT. As the exposure time increased, the activities of superoxide dismutase, catalase, and glutathione peroxidase were induced or inhibited in the different experimental groups. The malondialdehyde content increased with increasing 4-mono-CDT dose and exposure time. A higher concentration of 4-mono-CDT corresponded to a greater integrated biomarker response in each tissue and greater oxidative damage. The antioxidant enzymes in hepatopancreas were more sensitive to 4-mono-CDT than those in gill. The results provide useful information on the behavior and ecotoxicity of PCDTs in freshwater mussels. Environ Toxicol Chem 2021;40:1871–1880. © 2021 SETAC

Abstract

4-mono-chlorinated dibenzothiophene accumulated in mussel and a dechlorinated metabolite was detected in mussel hepatopancreas. Moreover, it could trigger tissue oxidative damage. SOD = superoxide dismutase; CAT = catalase; GPx = glutathione peroxidase; MDA = malondialdehyde; IBR = integrated biomarker response.
Reproducing diabetic retinopathy features using newly developed human induced‐pluripotent stem cell‐derived retinal Müller glial cells
Authors: Couturier Aude , Blot Guillaume , Vignaud Lucile , Nanteau Céline , Slembrouck‐Brec Amélie , Fradot Valérie , Acar Niyazi , Sahel José‐Alain , Tadayoni Ramin , Thuret Gilles , Sennlaub Florian , Roger Jerome E , Goureau Olivier , Guillonneau Xavier , Reichman Sacha
Published: March 2021

Muller glial cells (MGCs) are responsible for the homeostatic and metabolic support of the retina. Despite the importance of MGCs in retinal disorders, reliable and accessible human cell sources to be used to model MGC‐associated diseases are lacking. Although primary human MGCs (pMGCs) can be purified from post‐mortem retinal tissues, the donor scarcity limits their use. To overcome this problem, we developed a protocol to generate and bank human induced pluripotent stem cell‐derived MGCs (hiMGCs). Using a transcriptome analysis, we showed that the three genetically independent hiMGCs generated were homogeneous and showed phenotypic characteristics and transcriptomic profile of pMGCs. These cells expressed key MGC markers, including Vimentin, CLU, DKK3, SOX9, SOX2, S100A16, ITGB1, and CD44 and could be cultured up to passage 8. Under our culture conditions, hiMGCs and pMGCs expressed low transcript levels of RLPB1, AQP4, KCNJ1, KCJN10, and SLC1A3. Using a disease modeling approach, we showed that hiMGCs could be used to model the features of diabetic retinopathy (DR)‐associated dyslipidemia. Indeed, palmitate, a major free fatty acid with elevated plasma levels in diabetic patients, induced the expression of inflammatory cytokines found in the ocular fluid of DR patients such as CXCL8 (IL‐8) and ANGPTL4. Moreover, the analysis of palmitate‐treated hiMGC secretome showed an upregulation of proangiogenic factors strongly related to DR, including ANG2, Endoglin, IL‐1β, CXCL8, MMP‐9, PDGF‐AA, and VEGF. Thus, hiMGCs could be an alternative to pMGCs and an extremely valuable tool to help to understand and model glial cell involvement in retinal disorders, including DR.
A Dynamic Aspartate‐to‐Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease
Authors: Åberg Fredrik , Danford Christopher J. , Thiele Maja , Talbäck Mats , Rasmussen Ditlev Nytoft , Jiang Z. Gordon , Hammar Niklas , Nasr Patrik , Ekstedt Mattias , But Anna , Puukka Pauli , Krag Aleksander , Sundvall Jouko , Erlund Iris , Salomaa Veikko , Stål Per , Kechagias Stergios , Hultcrantz Rolf , Lai Michelle , Afdhal Nezam , Jula Antti , Männistö Satu , Lundqvist Annamari , Perola Markus , Färkkilä Martti , Hagström Hannes
Published: March 2021

The aspartate‐to‐alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver‐related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population‐based health‐examination surveys (FINRISK, 2002‐2012; n = 18,067) with linked registry data for incident liver‐related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver‐related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol‐related liver disease (ALD). The dynamic AAR model predicted liver‐related outcomes both overall (optimism‐corrected C‐statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver‐related outcomes within 10 years. In independent cohorts, the C‐statistic for predicting liver‐related outcomes up to a 10‐year follow‐up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area‐under‐the‐curve (AUC) for detecting prevalent cirrhosis was 0.80‐0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C‐statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.
Modelling interannual variations in catchment evapotranspiration considering vegetation and climate seasonality using the Budyko framework
Authors: Wang Yaqin , Luo Yi , Shafeeque Muhammad , Zhou Meilin , Li Hongyu
Published: March 2021

The Budyko framework is an efficient tool for investigating catchment water balance, focusing on the effects of seasonal changes in climate (S) and vegetation cover (M) on catchment evapotranspiration (ET). However, the effects of vegetation seasonality on ET remain largely unknown. The present study explored these effects by modelling interannual variations in ET considering vegetation and climate seasonality using the Budyko framework. Reconstructed 15‐day GIMMS NDVI3g timeseries data from 1982 to 2015 were used to estimate M and extract the relative duration of the vegetation growing season (GL) in the Yellow River Basin (YRB). To characterize S, seasonal variations in precipitation and potential ET were extracted using a Gaussian algorithm. Analysis of the observed datasets for 19 catchments revealed that interannual variation in the catchment parameter ϖ (in Fuh's equation) was significantly and positively correlated with M and GL. Conversely, ϖ was significantly but negatively correlated with S. Furthermore, stepwise linear regression was used to calibrate the empirical formula of ϖ for these three dimensionless parameters. Following validation, based on observations in the remaining 11 catchments, ϖ was integrated into Fuh's equation to accurately estimate annual ET. Over 79% subcatchments showed an upward trend (0.9 mm yr−1), whereas fewer than 21% subcatchments showed a downward trend (−0.5 mm yr−1) across YRB. In the central region of the middle reach, ET increased with increased M, prolonged GL, and decreased S, whereas in the source region of YRB, ET decreased with decreased M and shortened GL. Our study provides an alternative method to estimate interannual ET in ungauged catchments and offers a novel perspective to investigate hydrological responses to vegetation and climate seasonality in the long‐term.
Mycorrhizal stress alleviation in Senecio bonariensis Hook & Arn growing in urban polluted soils
Authors: Bompadre María Josefina , Benavidez Matías , Colombo Roxana Paula , Silvani Vanesa Analía , Godeas Alicia Margarita , Scotti Adalgisa , Pardo Alejandro Guillermo , Fernández Bidondo Laura
Published: March 2021

Loss of biodiversity and accumulation of contaminants in urban soils and water bodies cause serious issues in metropolitan areas. The Matanza‐Riachuelo river basin (metropolitan area of Buenos Aires, Argentina) is one of the most environmentally degraded regions in the world. Senecio bonariensis Hook & Arn (Asteraceae) grows in the periodically flooded soils of this wetland. This plant concentrates potentially toxic trace elements (PTEs) in its tissues and establishes symbiosis with arbuscular mycorrhizal (AM) fungi that collaborate with PTE phytostabilization in soils. The objective of this work was to evaluate tolerance and stress alleviation of AM‐colonized S. bonariensis when transplanting and exposing to highly polluted environmental conditions of the river basin. Plants were initially inoculated with different AM strains and maintained in greenhouse conditions. After 6 mo, they were transplanted to the field. These plants showed a more equal distribution between shoot and root biomass production in comparison to field spontaneous S. bonaerensis plants. Plants in earlier contact with native soil inoculum showed positive correlation with phosphorus content and a significant increase of vesicle frequency. Plants belatedly contacted with native inoculum in the field (control) showed a higher catalase level that was positively correlated with the total colonization frequency and chlorophyll content. The ability to establish symbiosis with Rhizophagus intraradices (strain GC3), commonly used in the formulation of biofertilizers, was also analyzed. Plants inoculated with GC3 at the beginning of the assay showed lower colonization and were less efficient in the field. The preservation of spontaneous native plants with ornamental value and bioaugmentation of their associated microbiome can contribute to the stabilization of contaminants in soils.
Neutrophil-derived extracellular vesicles modulate the phenotype of naïve human neutrophils
Authors: Amjadi Maya F , Avner Benjamin S , Greenlee-Wacker Mallary C , Horswill Alexander R , Nauseef William M
Published: March 2021

Neutrophils (PMN) regulate inflammation in many ways, including communication with other immune cells via extracellular vesicles (EVs). EVs released by human neutrophils activated with N-formylmethionyl-leucyl-phenylalanine (fMLF) (PMN-fMLF EVs) had an outside-out orientation and contained functionally important neutrophil plasma membrane proteins, including flavocytochrome b558, and enzymatically active granule proteins, elastase, and myeloperoxidase. Treatment of naïve PMN with PMN-fMLF EVs primed fMLF-stimulated NADPH oxidase activity, increased surface expression of the complement receptors CD11b/CD18 and CD35, the specific granule membrane protein CD66, and flavocytochrome b558, and promoted phagocytosis of serum-opsonized Staphylococcus aureus. The primed oxidase activity reflected increased surface expression of flavocytochrome b558 and phosphorylation of SER345 in p47phox, two recognized mechanisms for oxidase priming. Taken together, these data demonstrate that stimulated PMN released EVs that altered the phenotype of naïve phagocytes by priming of the NADPH oxidase activity and augmenting phagocytosis, two responses that are integral to optimal PMN host defense.
Systematic inhibitor selectivity between PARP1 and PARP2 enzymes: Molecular implications for ovarian cancer personalized therapy
Authors: Zuo Xueqian , Zhao Haibo , Li Dan
Published: March 2021

Human poly(ADP‐ribose) polymerases (PARPs) are a class of nuclear enzymes involved in the pathogenesis of diverse gynecologic tumors. The PARP1 and PARP2 are the two most documented members in PARP family, which have been approved as the druggable targets of ovarian and cervical cancers. Selective targeting of the two enzymes with small‐molecule inhibitors is a great challenge due to the high conservation in catalytic domain and active site. Here, we investigate the systematic selectivity profile of sophisticated PARP inhibitors between the two enzymes. Computational methods are used to model/optimize the complex structures of inhibitor ligands with PARP1/2 catalytic domains and then to estimate the theoretical Fenzymatic assays exhibit a good consistence with theoretical selectivity over six tested inhibitor samples (rc2 = 0.857). It is revealed that the inhibitor selectivity is conferred from the exquisite difference in the residue composition and structural architecture of both the local activity sites and the whole catalytic domains of the two enzymes. In particular, the TMZ50 and ME0328 show strong selectivity between PARP1 and PARP2, but only the former has a potent activity on the two enzymes, whereas the latter can only inhibit the enzymes moderately. These compounds can be considered as potential lead molecular entities to develop new specific PARP‐selective inhibitor drugs for personalized therapy combating gynecologic cancers.
Radiomics Models Based on Apparent Diffusion Coefficient Maps for the Prediction of High‐Grade Prostate Cancer at Radical Prostatectomy: Comparison With Preoperative Biopsy
Authors: Han Chao , Ma Shuai , Liu Xiang , Liu Yi , Li Changxin , Zhang Yaofeng , Zhang Xiaodong , Wang Xiaoying
Published: March 2021

Background

It is feasible to use magnetic resonance (MR)‐based radiomics to distinguish high‐grade from low‐grade prostate cancer (PCa), but radiomics model performance based on fully automated segmentation remains unknown.

Purpose

To develop and test radiomics models based on manually or automatically gained masks on apparent diffusion coefficient (ADC) maps to predict high‐grade (Gleason score ≥ 4 + 3) PCa at radical prostatectomy (RP).

Study Type

Retrospective.

Population

A total of 176 patients (94 high‐grade PCa and 82 low‐grade PCa) with complete RP, preoperative biopsy, and multiparametric magnetic resonance imaging (mpMRI) were retrospectively recruited and randomly divided into training (N = 123) and test (N = 53) cohorts.

Field Strength/Sequence

Using a 3.0‐T MR scanner, ADC maps were calculated from diffusion‐weighted imaging (b values = 0, 1400 s/mm2, echo planar imaging).

Assessment

Two radiologists segmented the whole prostate gland and the most index prostate lesion. Automatic segmentation of the prostate and the lesion were performed. Four radiomics models were constructed using four masks (manual/automatic prostate gland/PCa lesion segmentation). According to the standard reference of the RP histopathologic assessment, the performance of each radiomics models was compared with that of biopsy and Prostate Imaging Reporting and Data System version 2.1 (PI‐RADS) assessment.

Statistical Tests

A receiver operating characteristic curve analysis was employed to estimate the area under the curve (AUC) values of the models. The AUCs of the four models, biopsy, and PI‐RADS assessment were compared using the DeLong test.

Results

The four radiomics models yielded AUCs of 0.710, 0.731, 0.726, and 0.709 in the test cohort, respectively; biopsy and PI‐RADS assessment yielded AUCs of 0.793 and 0.680, respectively. No significant differences were found among model, biopsy, and PI‐RADS assessment comparisons (P = 0.132–0.988).

Data Conclusion

To distinguish high‐grade from low‐grade PCa, radiomics models based on automatic segmentation on ADC maps exhibit approximately the same diagnostic efficacy as manual segmentation and biopsy, highlighting the possibility of a fully automatic workflow combining automated segmentation with radiomics analysis.

Evidence Level

4

Technical Efficacy

Stage 2
Optimized protocol for high‐titer lentivirus production and transduction of primary fibroblasts
Authors: He Xiaoying , He Qin , Yu Wangshu , Huang Jiani , Yang Ming , Chen Wei , Han Wei
Published: March 2021

The lentivirus–short hairpin RNA (shRNA) system is a widely used tool for RNA interference. Multiple factors may affect the RNA interference efficiency during lentivirus production and transduction procedures. Thus, an optimized protocol is required to achieve high‐titer lentivirus and efficient gene delivery. In the present study, lentivirus was produced by transfecting lentiviral transfer and packaging plasmids into HEK 293T cells. The factors affecting lentiviral titer were assessed, including lentiviral plasmid ratio, lentiviral transfer plasmid type, serum type for cell culture, transfection reagent–plasmid mixture incubation time, and the inoculation density of 293T cells for transfection. The high‐titer lentivirus was achieved when plasmids were transfected at a molar ratio of 1:1:1:2, and the transfection reagent–plasmid mixture was replaced 6–8 h after transfection. The pLVX‐shRNA2 lentiviral transfer plasmid was associated with the highest lentiviral titer, while both pLVX‐shRNA2 and psi‐LVRU6GP plasmids were associated with efficient RNA interference in target cells. The serum type for 293T cell culture affected the lentiviral titer significantly, while the inoculation density of 293T cells showed no influence on transfection efficiency or lentiviral titer. Moreover, the human primary fibroblasts infected with lentivirus, using the centrifugation method, achieved higher transduction efficiency than those infected with the non‐centrifugation method. In conclusion, this study helped optimize lentiviral production and transduction procedures for more efficient gene delivery.
Clinical impact of the biology of synchronous axillary lymph node metastases in primary breast cancer on preoperative treatment strategy
Authors: Nakamura Rikiya , Hayama Shouko , Sonoda Itaru , Miyaki Toshiko , Itami Makiko , Yamamoto Naohito
Published: March 2021

Background and objectives

The purpose of this study was to assess the utility of determining the biological features of synchronous axillary lymph node (syLN) metastasis of breast cancer in evaluating the efficacy of preoperative systemic chemotherapy (PST).

Materials and Methods

The retrospective subjects initially comprised 59 patients (T1c‐4 N1‐3 M0) diagnosed with syLN metastasis via core needle biopsy who received PST. The hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status in each patient was assessed in primary breast tumor (pBT) and syLNs using immunohistochemistry, and the patients were classified into HR(+), HER2(+), and triple negative breast cancer (TN) subtypes.

Results

Subtype shift (SS) of pBT in syLNs was observed in 28% cases for HR(+), in 6% cases for the HER2(+), and in 16% cases for the TN. The pCR rate of the pBT and syLNs types were 45% and 36% in the HR(+), 45% and 39% in the TN, and 94% and 100% in the HER2(+), respectively. In SS cases, the pCR rate was significantly higher in 75% cases compared with 33% of the no‐SS cases.

Conclusion

A SS in syLNs was more frequent in HR(+) than in other types.
Association of preoperative and postoperative CA72‐4 with gastric cancer outcome
Authors: Wu Ting , Wang Chun‐Hua , Wang Wei , Liu Li‐Li , Yun Jing‐Ping , Zhou Zhi‐Wei
Published: March 2021

Background and Objectives

Carbohydrate antigen 72‐4 (CA72‐4) is widely used and has been associated with poor prognosis in gastric cancer (GC), but the prognostic significance of elevated preoperative CA72‐4 that normalizes after resection remains unknown.

Methods

This retrospective cohort analysis was conducted at the Sun Yat‐Sen University Cancer Center (SYSUCC). Consecutive patients (n = 1179) with GC who had undergone curative resection for stage Ⅰto Ⅲ gastric adenocarcinoma. The patients were grouped into three cohorts: normal preoperative CA72‐4 (C1), elevated preoperative but normalized postoperative CA72‐4 (C2), and elevated preoperative and postoperative CA72‐4 (C3).

Results

In total, 1179 patients were identified. Kaplan‐Meier analysis showed that patients with normal preoperative CA72‐4 had a longer overall survival (OS) (p < .001) and recurrence‐free survival (RFS) (p < .001) than those with elevated preoperative CA72‐4. Patients with C1 had a longer OS and RFS than those with C2 or C3. Moreover, patients with C3 had the lowest OS, but had similar RFS to patients with C2. Multivariate Cox regression analysis showed that elevated pre‐ or postoperative CA72‐4 was independently associated with shorter OS (hazard ratio [HR] = 1.273; 95% confidence interval [CI], 1.026–1.580; p = .029) and RFS (HR = 1.333; 95% CI, 1.064–1.668; p = .012).

Conclusions

Both elevated preoperative and postoperative CA72‐4 can well predict the poor prognosis of patients with GC. Therefore, routine measurement of both postoperative and preoperative CA72‐4 is warranted.
Informed consent and a risk‐based approach to oncologic surgery in a cancer center during the COVID‐19 pandemic
Authors: de Cássio Zequi Stênio , Franca Silva Ivan Leonardo Avelino , Duprat João Pedreira , Coimbra Felipe José Fernandez , Gross Jefferson L. , Vartanian Jose Guilherme , Makdissi Fabiana Baroni Alves , Leite Fernanda Perez M. , Costa Walter Henriques da , Yazbek Guilherme , Joaquim Eduardo Henrique Giroud , Bussolotti Raquel Marcondes , Caruso Pedro , de Ávila Lima Marcon Censoni , Nakagawa Suely Akiko , Aguiar Samuel , Baiocchi Glauco , Lopes Ademar , Kowalski Luiz Paulo
Published: March 2021

Background

Cancer patients configure a risk group for complications or death by COVID‐19. For many of them, postponing or replacing their surgical treatments is not recommended. During this pandemic, surgeons must discuss the risks and benefits of treatment, and patients should sign a specific comprehensive Informed consent (IC).

Objectives

To report an IC and an algorithm developed for oncologic surgery during the COVID‐19 outbreak.

Methods

We developed an IC and a process flowchart containing a preoperative symptoms questionnaire and a PCR SARS‐CoV‐2 test and described all perioperative steps of this program.

Results

Patients with negative questionnaires and tests go to surgery, those with positive ones must wait 21 days and undergo a second test before surgery is scheduled. The IC focused both on risks and benefits inherent each surgery and on the risks of perioperative SARS‐CoV‐2 infections or related complications. Also, the IC discusses the possibility of sudden replacement of medical staff member(s) due to the pandemic; the possibility of unexpected complications demanding emergency procedures that cannot be specifically discussed in advance is addressed.

Conclusions

During the pandemic, specific tools must be developed to ensure safe experiences for surgical patients and prevent them from having misunderstandings concerning their care.
Comparison of local therapy in patients with lung oligo‐recurrence of non‐small‐cell lung cancer
Authors: Sonoda Dai , Matsuura Yosuke , Kondo Yasuto , Ichinose Junji , Nakao Masayuki , Ninomiya Hironori , Nishio Makoto , Okumura Sakae , Satoh Yukitoshi , Mun Mingyon
Published: March 2021

Background and Objectives

The effectiveness of local therapy has been reported in non‐small‐cell lung cancer (NSCLC) patients with oligo‐recurrence. However, there is still no clear consensus on the choice of local therapy. We aimed to examine the choice of local therapy in NSCLC patients with lung oligo‐recurrence.

Methods

Among 1760 consecutive NSCLC patients who underwent complete resection between 1990 and 2008, 535 patients developed recurrence. Lung oligo‐recurrence was defined as 1–5 metachronous recurrences limited to the lungs only; such recurrence was found in 97 patients. We examined the differences in the prognosis of each therapy for these patients.

Results

The 5‐year postrecurrence survival (PRS) rates in patients who underwent local therapy (n = 54) and those who did not (n = 43) were 55.6% and 31.1%, respectively; it was significantly higher in patients who underwent local therapy (p = 0.004). Among 47 patients who underwent resection or radiation therapy, the 5‐year PRS rates were 61.5% and 47.6% (p = 0.258), and the 5‐year postrecurrence progression‐free survival rates were 30.3% and 24.7% (p = 0.665), respectively, without any significant difference.

Conclusions

Patients with lung oligo‐recurrence should consider local therapy individually, depending on their general condition.
Compactness of the ∂¯‐Neumann operator on uniformly q‐convex intersections in ℂn
Authors: Khidr Shaban , Sambou Salomon
Published: March 2021

Compactness of the
‐Neumann operator Ns on uniformly q‐convex intersection in
is established. In fact, we prove the significantly stronger fact that the
‐Neumann operator satisfies a subelliptic gain of one half derivative in the L2‐Sobolev spaces, so that compactness of Ns follows immediately from Rellich's lemma. Applications for the Fredholm theory of Toeplitz operators are also provided.
Thickness/morphology of functional material patterned by topographical discontinuous dewetting
Authors: Corletto Alexander , Shapter Joseph G.
Published: March 2021

Topographical discontinuous dewetting (TDD) patterning is a nascent 2D printing technique explored for high‐throughput nanoscale patterning of functional material inks. However, variables affecting the z thickness and morphology of the deposited functional materials inside the patterned microchannels remain unexplored. We developed a theoretical model that can determine the thickness of the deposited functional material layers using the TDD patterning technique. We then confirmed the model with experimental data by depositing colloidal dispersions into microchannels using TDD patterning to systematically study the effects of different processing variables. The contribution of evaporation‐driven flow to the deposited layer thickness was significant, with the relationship of thickness to inking speed different to that previously determined for thin film blade coating of colloidal dispersions in the evaporative regime. Additionally, a viscosity dampening effect was observed, unique to TDD of microchannels, which slowed the evaporation‐driven flow due to local viscosity increase in the microchannels. Channel dimensions and ink dispersion concentration affected thickness as hypothesized. Internal flows in the microchannels normal to the sidewalls and perpendicular to the microchannel length (“coffee ring” effect capillary flow/Marangoni flow) were found to contribute significantly to the final morphology/thickness of the deposited layers for the systems/dispersions experimentally measured.
Carbonic anhydrase activity in the frontal lobe of human brain
Authors: Li Shizhe , An Li , Ferraris Araneta Maria , Victorino Milalynn , Johnson Christopher S. , Shen Jun
Published: March 2021

Carbonic anhydrase (CA) plays an important role in many biological processes. Recent technological advances have demonstrated the feasibility of measuring CA activity in the occipital lobe of human subjects in vivo. In this work we report, for the first time, in vivo measurement of CA activity in the frontal lobe of human brain, where structural and function abnormalities are strongly associated with symptoms of major psychiatric disorders. Despite the much larger magnetic field distortion in the frontal lobe, the pseudo first‐order bicarbonate dehydration rate constant was determined with high precision using in vivo 13C magnetic resonance magnetization transfer spectroscopy following oral administration of [U‐13C6]glucose. Nuclear Overhauser effect pulses were used to increase the signal‐to‐noise ratio; no proton decoupling was applied. The unidirectional dehydration rate constant of bicarbonate was found to be 0.26 ± 0.07 s−1, which is not statistically different from the dehydration rate constant in the occipital lobe determined in our previous study, indicating that CA activity in the two brain regions is essentially indistinguishable. These results demonstrate the feasibility of characterizing CA activity in the frontal lobe for future psychiatric studies.
Efficacy of a multimodal nursing intervention strategy in the process of becoming a mother: A randomized controlled trial
Authors: Vargas‐Porras Carolina , Roa‐Díaz Zayne M. , Hernández‐Hincapié Hernán G. , Ferré‐Grau Carme , de Molina‐Fernández María I.
Published: March 2021

The lack of knowledge and skills for transitioning to motherhood places first‐time mothers at greater risk of depression and stress, may lower their perceived self‐efficacy and satisfaction with the maternal role, and potentially affects the mother–infant bond. The purpose of this study was to test the efficacy of a multimodal nursing intervention (AMACOMPRI), based on Mercer's Becoming a Mother Theory, in supporting the process of becoming a mother in first‐time mothers of term infants. This study was a parallel‐group, double‐blind, randomized, controlled trial with a 4‐month postpartum follow‐up. The outcome measures were the process of becoming a mother, functional social support, mother–infant bond, and perceived maternal self‐efficacy. Sixty‐six first‐time mothers completed the study: 33 in the intervention group and 33 in the control group. The intervention was effective in supporting the process of becoming a mother, with a large effect size (Cohen's d = 1.50) and higher scores on the Becoming‐a‐Mother Scale in the intervention group compared with the control group (intergroup difference 13.04 points; 95% confidence interval: 8.72–17.34). Participants in the intervention group demonstrated higher scores in functional social support, perceived maternal self‐efficacy, and mother–infant bond. This study provides evidence for the efficacy of an innovative nursing intervention that supports the process of becoming a mother. Further testing of the intervention is required in different settings and first‐time mothers of low and high risk newborns.