bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA‐Based Microparticle Tension Sensors (μTS) for Measuring Cell Mechanics in Non‐planar Geometries and for High‐Throughput Quantification
Authors: Hu Yuesong , Ma Victor Pui‐Yan , Ma Rong , Chen Wenchun , Duan Yuxin , Glazier Roxanne , Petrich Brian G. , Li Renhao , Salaita Khalid
Published: May 2021

Mechanotransduction, the interplay between physical and chemical signaling, plays vital roles in many biological processes. The state‐of‐the‐art techniques to quantify cell forces employ deformable polymer films or molecular probes tethered to glass substrates. However, the applications of these assays in fundamental and clinical research are restricted by the planar geometry and low throughput of microscopy readout. Herein, we develop a DNA‐based microparticle tension sensor, which features a spherical surface and thus allows for investigation of mechanotransduction at curved interfaces. The micron‐scale of μTS enables flow cytometry readout, which is rapid and high throughput. We applied the method to map and measure T‐cell receptor forces and platelet integrin forces at 12 and 56 pN thresholds. Furthermore, we quantified the inhibition efficiency of two anti‐platelet drugs providing a proof‐of‐concept demonstration of μTS to screen drugs that modulate cellular mechanics.
Direct Immunodetection of Global A‐to‐I RNA Editing Activity with a Chemiluminescent Bioassay
Authors: Knutson Steve D. , Arthur Robert A. , Johnston H. Richard , Heemstra Jennifer M.
Published: May 2021

Adenosine‐to‐inosine (A‐to‐I) editing is a conserved eukaryotic RNA modification that contributes to development, immune response, and overall cellular function. Here, we utilize Endonuclease V (EndoV), which binds specifically to inosine in RNA, to develop an EndoV‐linked immunosorbency assay (EndoVLISA) as a rapid, plate‐based chemiluminescent method for measuring global A‐to‐I editing signatures in cellular RNA. We first optimize and validate our assay with chemically synthesized oligonucleotides. We then demonstrate rapid detection of inosine content in treated cell lines, demonstrating equivalent performance against current standard RNA‐seq approaches. Lastly, we deploy our EndoVLISA for profiling differential A‐to‐I RNA editing signatures in normal and diseased human tissue, illustrating the utility of our platform as a diagnostic bioassay. Together, the EndoVLISA method is cost‐effective, straightforward, and utilizes common laboratory equipment, offering a highly accessible new approach for studying A‐to‐I editing. Moreover, the multi‐well plate format makes this the first assay amenable for direct high‐throughput quantification of A‐to‐I editing for applications in disease detection and drug development.
Synthesis of Fluorinated Aminoalkylboronic Acids from Amphoteric α‐Boryl Aldehydes
Authors: Soor Harjeet S. , Diaz Diego B. , Burton Katherine I. , Yudin Andrei K.
Published: May 2021

Our ongoing search for underdeveloped functional group combinations has brought to light α‐fluorinated aminoalkylboronic acids, a new class of molecules featuring the B‐CF linkage. These compounds can now be generated from secondary amines and α‐boryl aldehydes through electrophilic fluorination of boryl enamines or enamides. Fluorinated β‐aminoalkylboronic acids show no signs of degradation under ambient conditions. We present evidence for the involvement of chair‐like motifs, favored over the acyclic forms by up to 1.7±0.1 kcal mol−1 in water and held together by an amine‐boronate hydrogen bond. Fluorinated β‐aminoalkylboronic acids are stable over a wide pH range and are characterized by a pKa of 3.4, which is the lowest of any alkylboronic acid.
Synthesis of Cyclic Anhydrides via Ligand‐Enabled C–H Carbonylation of Simple Aliphatic Acids
Authors: Zhuang Zhe , Herron Alastair N. , Yu Jin‐Quan
Published: May 2021

The development of C(sp3)–H functionalizations of free carboxylic acids has provided a wide range of versatile C−C and C−Y (Y=heteroatom) bond‐forming reactions. Additionally, C–H functionalizations have lent themselves to the one‐step preparation of a number of valuable synthetic motifs that are often difficult to prepare through conventional methods. Herein, we report a β‐ or γ‐C(sp3)–H carbonylation of free carboxylic acids using Mo(CO)6as a convenient solid CO source and enabled by a bidentate ligand, leading to convenient syntheses of cyclic anhydrides. Among these, the succinic anhydride products are versatile stepping stones for the mono‐selective introduction of various functional groups at the β position of the parent acids by decarboxylative functionalizations, thus providing a divergent strategy to synthesize a myriad of carboxylic acids inaccessible by previous β‐C–H activation reactions. The enantioselective carbonylation of free cyclopropanecarboxylic acids has also been achieved using a chiral bidentate thioether ligand
In Situ Formation of Ag2S Nanoparticles on a Paper‐Supported Wettable Microchip for High‐Throughput Photothermal Sensing of MicroRNA
Authors: Wu Tingting , Cao Yu , Chen Hanjun , Liu Zhihong
Published: May 2021

Photothermal biosensors have emerged as an attractive strategy for point‐of‐care testing (POCT). However, developing a photothermal biosensor with good accuracy to realize high‐throughput detection is still a big challenge. Herein, a photothermal biosensor comprised of a paper‐supported wettable microchip was proposed for sensitive, accuracy, high‐throughput detection of microRNA (miRNA). Hybridization chain reaction (HCR) products on the wettable paper induced by target miRNA were used as a template for in situ formation of Ag2S nanoparticles (NPs), which can translate miRNA concentration into temperature change. The developed photothermal biosensor with low sample volume exhibited high sensitivity with a detection limit of 49.7 pM. In addition, the biosensor showed excellent reproducibility and selectivity, and the miRNA content in cell lysates was successfully assayed. The proposed photothermal biosensor shows great potential in biomedical application and clinical diagnosis.
Mechanical properties and flame retardancy of PLA composites containing zinc oxide and chain extender
Authors: Chen Yajun , He Jingxiu , Xu Lifeng , Xu Bo , Qian Lijun
Published: May 2021

A micro‐cross‐linked structure had been constructed by the addition of zinc oxide with nanometer‐scale particle size (nano ZnO) and chain extender (ADR) into intumescent flame retardant poly (lactic acid) (FRPLA). Flame retardant properties, mechanical properties and thermal stabilities were studied. Limited oxygen index of the FRPLA composite with 1% nano ZnO and 0.8% ADR (FRPLA/0.8ADR/1ZnO) was a maximum (39.4%).Tmaxand residue at 800°C of FRPLA/0.8ADR/1ZnO was the highest in air. Tensile strength, elongation at break and impact strength of FRPLA/0.8ADR/1ZnO was significantly higher than that which resulted with the addition of either individual filler, indicating that the synergistic effect between nano ZnO and ADR regulated the comprehensive performance of FRPLA. The synergetic effect between nano ZnO and ADR were further illustrated.
The information practices of law enforcement: Passive and active collaboration and its implication for sanctuary laws in Washington state
Authors: Tian Yubing , Gomez Ricardo , Cifor Marika , Wilson James , Morgan Henry
Published: May 2021

Although Washington state sanctuary policies of 2017 prohibit collaboration between local law enforcement and federal immigration enforcement in noncriminal cases, compliance with sanctuary policies has not been systematically studied. We explore information practices and collaboration between local law enforcement and federal immigration enforcement in Grant County, Washington, based on records from November 2017 to May 2019 obtained by the University of Washington Center for Human Rights through Public Records Act (PRA) requests. Qualitative analysis of over 8,000 pages reveals a baseline of passive and active information sharing and collaboration between local law enforcement and federal immigration agencies before Washington sanctuary laws went into effect in May 2019, a practice that needs to stop if agencies are to comply with the laws. We employ a systematic methodology to obtain (through PRA and other Access to Information requests) and analyze official records through qualitative content analysis, to monitor and hold local law enforcement accountable in their compliance with sanctuary laws. This method can be used to examine law enforcement information behaviors in other counties in Washington, and in other states that offer sanctuary protections, as a way to monitor compliance with sanctuary laws and strengthen the protection of immigrants' rights.
Interleukin‐9 deficiency affects lipopolysaccharide‐induced macrophage‐related oxidative stress and myocardial cell apoptosis via the Nrf2 pathway both in vivo and in vitro
Authors: Liang Zhishan , Pan Fuze , Yang Zicong , Wang Mengjie , Hu Changxing , Shi Lei , Ji Qingwei , Liu Ling
Published: May 2021

Previous studies showed that interleukin‐9 (IL‐9) is involved in cardiovascular diseases, including hypertension and cardiac fibrosis. This study aimed to investigate the role of IL‐9 in lipopolysaccharide (LPS)‐induced myocardial cell (MC) apoptosis. Mice were treated with LPS, and IL‐9 expression was measured and the results showed that compared with WT mice, LPS‐treated mice exhibited increased cardiac Mø‐derived IL‐9. Additionally, the effects of IL‐9 deficiency (IL‐9−/−) on macrophage (Mø)‐related oxidative stress and MC apoptosis were evaluated, the results showed that IL‐9 knockout significantly exacerbated cardiac dysfunction, inhibited Nrf2 nuclear transfer, promoted an imbalance in M1 and M2 Møs, and exacerbated oxidative stress and MC apoptosis in LPS‐treated mice. Treatment with ML385, a specific nuclear factor erythroid‐2 related factor 2 (Nrf2) pathway inhibitor significantly alleviated the above effects in LPS‐treated IL‐9−/− mice. Bone marrow‐derived Møs from wild‐type (WT) mice and IL‐9−/− mice were treated with LPS, and the differentiation and oxidative stress levels of Møs were measured. The effect of Mø differentiation on mouse MC apoptosis was also analyzed in vitro. The results showed that LPS‐induced M1 Mø/M2 Mø imbalance and Mø‐related oxidative stress were alleviated by IL‐9 knockout but were exacerbated by ML385 treatment. The protective effects of IL‐9 deficiency on the MC apoptosis mediated by LPS‐treated Møs were reversed by ML‐385. Our results suggest that deletion of IL‐9 decreased the nuclear translocation of Nrf2 in Møs, which further aggravated Mø‐related oxidative stress and MC apoptosis. IL‐9 may be a target for the prevention of LPS‐induced cardiac injury.
Electrostatic Perturbations from the Protein Affect C−H Bond Strengths of the Substrate and Enable Negative Catalysis in the TmpA Biosynthesis Enzyme
Authors: Lin Yen‐Ting , Ali Hafiz Saqib , de Visser Sam P.
Published: May 2021

The nonheme iron dioxygenase 2‐(trimethylammonio)‐ethylphosphonate dioxygenase (TmpA) is an enzyme involved in the regio‐ and chemoselective hydroxylation at the C1‐position of the substrate as part of the biosynthesis of glycine betaine in bacteria and carnitine in humans. To understand how the enzyme avoids breaking the weak C2−H bond in favor of C1‐hydroxylation, we set up a cluster model of 242 atoms representing the first and second coordination sphere of the metal center and substrate binding pocket, and investigated possible reaction mechanisms of substrate activation by an iron(IV)‐oxo species by density functional theory methods. In agreement with experimental product distributions, the calculations predict a favorable C1‐hydroxylation pathway. The calculations show that the selectivity is guided through electrostatic perturbations inside the protein from charged residues, external electric fields and electric dipole moments. In particular, charged residues influence and perturb the homolytic bond strength of the C1−H and C2−H bonds of the substrate, and strongly strengthens the C2−H bond in the substrate‐bound orientation.
Slow Magnetic Relaxation in Mono‐ and Bimetallic Lanthanide Tetraimido‐Sulfate S(NtBu)42− Complexes
Authors: Jung Jochen , Benner Florian , Herbst‐Irmer Regine , Demir Selvan , Stalke Dietmar
Published: May 2021

Lanthanide ions are particularly well‐suited for the design of single‐molecule magnets owing to their large unquenched orbital angular momentum and strong spin‐orbit coupling that gives rise to high magnetic anisotropy. Such nanoscopic bar magnets can potentially revolutionize high‐density information storage and processing technologies, if blocking temperatures can be increased substantially. Exploring non‐classical ligand scaffolds with the aim to boost the barriers to spin‐relaxation are prerequisite. Here, the synthesis, crystallographic and magnetic characterization of a series of each isomorphous mono‐ and dinuclear lanthanide (Ln=Gd, Tb, Dy, Ho, Er) complexes comprising tetraimido sulfate ligands are presented. The dinuclear Dy complex [{(thf)2Li(NtBu)2S(tBuN)2DyCl2}2 ⋅ ClLi(thf)2] (1c) shows true signatures of single‐molecule magnet behavior in the absence of a dc field. In addition, the mononuclear Dy and Tb complexes [{(thf)2Li(NtBu)2S(tBuN)2LnCl2(thf)2] (2b,c) show slow magnetic relaxation under applied dc fields.
Stable and Storable N(CF3)2 Transfer Reagents
Authors: Schneider Leon N. , Tanzer Krauel Eva‐Maria , Deutsch Carl , Urbahns Klaus , Bischof Tobias , Maibom Kristina A. M. , Landmann Johannes , Keppner Fabian , Kerpen Christoph , Hailmann Michael , Zapf Ludwig , Knuplez Tanja , Bertermann Rüdiger , Ignat'ev Nikolai V. , Finze Maik
Published: May 2021

Fluorinated groups are essential for drug design, agrochemicals, and materials science. The bis(trifluoromethyl)amino group is an example of a stable group that has a high potential. While the number of molecules containing perfluoroalkyl, perfluoroalkoxy, and other fluorinated groups is steadily increasing, examples with the N(CF3)2 group are rare. One reason is that transfer reagents are scarce and metal‐based storable reagents are unknown. Herein, a set of CuI and AgI bis(trifluoromethyl)amido complexes stabilized by N‐ and P‐donor ligands with unprecedented stability are presented. The complexes are stable solids that can even be manipulated in air for a short time. They are bis(trifluoromethyl)amination reagents as shown by nucleophilic substitution and Sandmeyer reactions. In addition to a series of benzylbis(trifluoromethyl)amines, 2‐bis(trifluoromethyl)amino acetate was obtained, which, upon hydrolysis, gives the fluorinated amino acid N,N‐bis(trifluoromethyl)glycine.
A deep learning system to diagnose the malignant potential of urothelial carcinoma cells in cytology specimens
Authors: Nojima Satoshi , Terayama Kei , Shimoura Saeko , Hijiki Sachiko , Nonomura Norio , Morii Eiichi , Okuno Yasushi , Fujita Kazutoshi
Published: May 2021

Background

Although deep learning algorithms for clinical cytology have recently been developed, their application to practical assistance systems has not been achieved. In addition, whether deep learning systems (DLSs) can perform diagnoses that cannot be performed by pathologists has not been fully evaluated.

Methods

The authors initially obtained low‐power field cytology images from archived Papanicolaou‐stained urinary cytology glass slides from 232 patients. To aid in the development of a diagnosis support system that could identify suspicious atypical cells, the images were divided into high‐power field panel image sets for training and testing of the 16‐layer Visual Geometry Group convolutional neural network. The DLS was trained using linked information pertaining to whether urothelial carcinoma (UC) in the corresponding histology specimen was invasive or noninvasive, or high‐grade or low‐grade, followed by an evaluation of whether the DLS could diagnose these characteristics.

Results

The DLS achieved excellent performance (eg, an area under the curve [AUC] of 0.9890; F1 score, 0.9002) when trained on high‐power field images of malignant and benign cases. The DLS could diagnose whether the lesions were invasive UC (AUC, 0.8628; F1 score, 0.8239) or high‐grade UC (AUC, 0.8661; F1 score, 0.8218). Gradient‐weighted class activation mapping of these images indicated that the diagnoses were based on the color of tumor cell nuclei.

Conclusions

The DLS could accurately screen UC cells and determine the malignant potential of tumors more accurately than classical cytology. The use of a DLS during cytopathology screening could help urologists plan therapeutic strategies, which, in turn, may be beneficial for patients.
Climate warming will increase chances of hybridization and introgression between two Takydromus lizards (Lacertidae)
Authors: Guo Kun , Zhong Jun , Xie Fan , Zhu Lin , Qu Yan‐Fu , Ji Xiang
Published: May 2021

Coexisting species may experience population and range changes alone or jointly in response to environmental change. Here, we used six climate variables and ten modeling algorithms to predict the distribution of two Takydromus species (T. septentrionalis and T. sexlineatus) in China. We identified the sympatric and allopatric areas by comparing projections between the two species based on habitat suitability under present and future climate scenarios. We constructed the hypervolumes of six climate variables for the two species and then evaluated overlaps between hypervolumes. From this study, we know the following. First, minimum temperature of coldest month contributes the most to the prediction of habitat suitability. Second, habitats suitable for the two species will shift northward in response to climate warming. Third, the range of T. sexlineatus will expand across the four future time intervals before 2,100, namely the 2021–2040, 2041–2060, 2061–2080, and 2081–2100 intervals, under both Shared socioeconomic pathway (SSP) 245 and SSP585 scenarios, and the range of T. septentrionalis will also expand in the future except at the 2081–2100 interval under the SSP585 scenario. Fourth, the sympatric areas will contract or expand under the SSP245 scenario and expand across the four future time intervals before 2,100 under the SSP585 scenario. Fifth, the niche hypervolumes of the two species partially overlapped, and the differences in niche centroid show some degree of niche differentiation between the two species. These results allow to conclude that climate warming will not only drive the northward drift of sympatric areas but also increase the size of these areas if nothing is done to limit the emission of greenhouse gases. Given the existence of hybridization and introgression between T. septentrionalis and T. sexlineatus in the field where they coexist, we also conclude that climate warming will increase chances of hybridization and introgression between the two species.
Prior disturbance legacy effects on plant recovery post‐high‐severity wildfire
Authors: Bowd Elle J. , Blair David P. , Lindenmayer David B.
Published: May 2021

Large, high‐severity wildfires are an important component of disturbance regimes around the world and can influence the structure and function of forest ecosystems. Climatic changes and anthropogenic disturbances have altered global disturbance patterns and increased the frequency of high‐severity wildfires worldwide. While the recovery of plant communities at different successional stages after fire is well known, the influence of prior disturbances and stand age is poorly understood. Despite this, high‐intensity wildfires can produce long‐lasting legacy effects, which can influence the resistance and resilience of ecosystems. Here, we quantified the influence of prior stand age and disturbance history on the recovery of plant communities in the Mountain Ash and Alpine Ash forests of south‐eastern Australia after high‐severity wildfire. Specifically, controlling for stand age, we compared the abundance (percent cover) of different plant life forms and reproductive strategies in forests that were, at the time of high‐severity wildfire in 2009, “young” (28–35 yr old and previously logged), “mixed” age (26, 70–83, >150 yr old), “mature” (70–83 yr old), and “old‐growth” (>150 yr old). We uncovered evidence that the legacy of prior disturbance and stand age at the time of high‐severity wildfire can influence the recovery of plant communities in early successional forests. Specifically, we found that “young” forests burnt in 2009 had a higher abundance of ruderal and graminoid species, but had a lower abundance of persistent, onsite seeders, includingAcaciaand eucalypt species, relative to “old‐growth” forests burnt in 2009. “Mature” aged forests burnt in 2009 also had a lower abundance ofAcacia, eucalypt, and shrub species, relative to “old‐growth forests” burnt in 2009. Our findings provide evidence of advanced recovery in forests that were older when burnt by high‐severity wildfire, relative to younger forests burnt by the same wildfire. Further, we also demonstrate the influence of different environmental conditions on plant communities. In a period of rapid, global, environmental change, our study provides insights into the recovery of plant communities post‐wildfire with implications for forest management. Further, our findings suggest that predicted increases in the frequency of high‐severity wildfires may have consequences for forest regeneration.
Pharmaceutical Contaminants in Shallow Groundwater and Their Implication for Poor Sanitation Facilities in Low-Income Countries
Authors: Do Quyen Thi Thuy , Otaki Masahiro , Otaki Yurina , Tushara Chaminda , Sanjeewa Ishara Wijesinghe
Published: May 2021

Rudimentary on-site sanitation systems (OSSs) are extensively used in low-income countries despite the risk of groundwater contamination. The present study investigated the potential impact of community soak pits on sandy shallow aquifers in a rural area in Sri Lanka. Thirty-two groundwater samples were collected and measured for the traditional indicators fecal bacteria Escherichia coli, total coliforms, nitrate, and chloride; 7 pharmaceuticals were added as wastewater indicators. Analysis showed that the local groundwater is infected by fecal bacteria, but it was unable to determine whether the source of fecal bacteria is the OSSs. Similarly, nitrate and chloride provided unclear evidence. Conversely, detection of 3 pharmaceuticals at trace levels in groundwater evidenced wastewater impact from OSSs. Caffeine was detected in 89% of the sample at a maximum concentration 7.9 ng/L, indicating fecal pollution. Carbamazepine was detected in 42% of the samples with a concentration of up to 6.9 ng/L, whereas sulfamethoxazole was detected in only 2 samples. The presence of carbamazepine and sulfamethoxazole was also consistent with recorded drug use of the residents. Escherichia coli showed a moderate positive correlation with caffeine concentration (Kendall's τ = 0.38, p = 0.017), indicating concurring short-lifetime fecal bacteria and labile wastewater organic compounds. Nitrate showed a significant correlation with carbamazepine concentration (τ = 0.39, p = 0.016). Fecal bacteria and nitrate can be used in screening for micropollutants in domestic wells impacted by OSSs. The present case study emphasizes the potential impact of poor sanitation on groundwater resources and the necessity of sanitation improvement in achieving Sustainable Development Goals in developing countries. Environ Toxicol Chem 2022;41:266–274. © 2021 SETAC

Abstract

Fecal bacteria and pharmaceuticals detected in shallow groundwater samples indicated the impact from poor sanitation to groundwater resource in this study.
Dynamic changes of volatile compounds and bacterial diversity during fourth to seventh rounds of Chinese soy sauce aroma liquor
Authors: Wang Lingchang , Zhong Kai , Luo Aimin , Chen Jian , Shen Yi , Wang Xi , He Qiang , Gao Hong
Published: May 2021

Chinese soy sauce aroma liquor (CSSL) is a famous Baijiu. Multiple rounds of fermentation, the characteristic of CSSL processing, contributes to the differences in the quality of the liquor of different rounds. In this study, the grains on cooled, stacked, and fermented stages of 4th to 7th rounds were taken, of which the environmental factors, bacterial diversity, and volatile compounds were comprehensively analyzed. Lactobacillaceae, Bacillaceae, Thermoactinomycetaceae, and Enterobacteriaceae were the top four families, of which Lactobacillaceae dominated the fermented stage of each round. Principal component analysis (PCA) and principal coordinate analysis (PCoA) supported the popular view that the liquors of 3rd to 5th rounds possess the best quality. Lactobacillaceae is an extremely critical bacterium for CSSL fermentation. This study provides comprehensive understanding regarding the dynamic changes in fermented grains during the 4th to 7th rounds, which could help to improve the processing technology of CSSL.
International diversification, legitimacy, and corporate social performance of extractive industry multinationals
Authors: Williamson Peter J. , Symeou Pavlos C. , Zyglidopoulos Stelios
Published: May 2021

Research Summary

This article examines how different international diversification strategies impact the legitimacy challenges multinationals face and the way they manage their corporate and social responsibilities. Analyzing these questions in a sample of companies in extractive industries, we find that those who pursue resource‐seeking investments that involve locating extraction operations overseas respond with the largest improvement in their corporate‐level social performance (CSP). Those pursuing efficiency‐seeking by establishing processing subsidiaries abroad increase their CSP less, with the smallest increase for those pursuing market‐seeking through marketing and sales operations overseas. For each type of activity established overseas, the increase in CSP becomes greater the more developed the company's home country and the larger its international footprint, but is not dependent on the host country's level of development. These findings suggest that, in today's globalized world, the legitimacy challenges that result from subsidiaries' activities increasingly need to be managed at a global, corporate level.

Managerial Summary

This article investigates the relationships between different international diversification strategies, the different legitimacy challenges they create, and corporate‐level social performance (CSP) responses. For multinationals operating in the extractive industries, we find important legitimacy spillovers from different types of subsidiary activities on the corporation, but these also vary, leading it to respond with differential increases in global CSP. These increases are greatest for resource‐seeking diversification, involving the location of extractive activities abroad, moderate for efficiency‐seeking diversification, involving the location of processing activities and least for market‐seeking diversification, involving the location of marketing and sales activities. For each type of subsidiary activity, we also find that the increases in CSP are larger the more developed the company's home country and the larger its international footprint, but are not dependent on the host country's level of development. We show how these results extend existing theory and draw implications for management practice.
Causal structural covariance network revealing atrophy progression in Alzheimer's disease continuum
Authors: Qing Zhao , Chen Feng , Lu Jiaming , Lv Pin , Li Weiping , Liang Xue , Wang Maoxue , Wang Zhengge , Zhang Xin , Zhang Bing ,   For the Alzheimer's Disease Neuroimaging Initiative
Published: May 2021

The structural covariance network (SCN) has provided a perspective on the large‐scale brain organization impairment in the Alzheimer's Disease (AD) continuum. However, the successive structural impairment across brain regions, which may underlie the disrupted SCN in the AD continuum, is not well understood. In the current study, we enrolled 446 subjects with AD, mild cognitive impairment (MCI) or normal aging (NA) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The SCN as well as a casual SCN (CaSCN) based on Granger causality analysis were applied to the T1‐weighted structural magnetic resonance images of the subjects. Compared with that of the NAs, the SCN was disrupted in the MCI and AD subjects, with the hippocampus and left middle temporal lobe being the most impaired nodes, which is in line with previous studies. In contrast, according to the 194 subjects with records on CSF amyloid and Tau, the CaSCN revealed that during AD progression, the CaSCN was enhanced. Specifically, the hippocampus, thalamus, and precuneus/posterior cingulate cortex (PCC) were identified as the core regions in which atrophy originated and could predict atrophy in other brain regions. Taken together, these findings provide a comprehensive view of brain atrophy in the AD continuum and the relationships among the brain atrophy in different regions, which may provide novel insight into the progression of AD.
The first non‐radiographic axial spondyloarthrits with COVID‐19
Authors: Saikali Wassim , Gharib Suzanne
Published: May 2021

Background

Case report of a 21‐year‐old female developing non‐radiographic axialspondyloarthritis in the setting of a preceding severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. We felt this was a unique case as some cases of psoriatic arthropathy and reactive arthropathy but none, to our knowledge of non‐radiographic axial spondyloarthritis.

Case Presentation

Twenty one‐year‐old female presented in June 2020 with inflammatory symptoms with general work‐up per primary care provider being negative. Upon further work‐up per Rheumatology, felt to have inflammatory back pain with X‐rays of SI joints showing grade II sclerosis. Further work‐up including magnetic resonance imaging was positive demonstrating bone edema and erosions of SI joint. This prompted further investigation and she had had some vague symptoms of SARS‐CoV‐2 several months prior including loss of smell, fatigue, and malaise. SARS‐CoV‐2 semiquanitative antibodies where done that where high positive. She was treated with cetrolizumab and had prompt improvement over the course of the next week.

Discussion and Conclusion

Mechanism of SARS‐CoV‐2 triggering autoimmunity is still unknown at this time. However, it is important that insights be gained into the type of disease that can be triggered by this infection. As the pandemic continues to rage on, Rheumatologist need to be increasing aware that patients presenting with various forms of inflammatory arthritis may be triggered by an antecedent SARS‐CoV‐2 infection. Following these cases may help to determine how they differ from other forms of inflammatory arthropathy.
COVID‐19 infection in CVID patients: What we know so far
Authors: Weifenbach Niels , Jung Alisha , Lötters Stefan
Published: May 2021

Introduction

In patients with common variable immunodeficiency (CVID), immunological response is compromised. Knowledge about COVID‐19 in CVID patients is sparse. We, here, synthesize current research addressing the level of threat COVID‐19 poses to CVID patients and the best‐known treatments.

Method

Review of 14 publications.

Results

The number of CVID patients with moderate to severe (~29%) and critical infection courses (~10%), and the number of fatal cases (~13%), are increased compared to the general picture of COVID‐19 infection. However, this might be an overestimate. Systematic cohort‐wide studies are lacking, and asymptomatic or mild cases among CVID patients occur that can easily remain unnoticed. Regular immunoglobulin replacement therapy was administered in almost all patients, potentially explaining why the numbers of critical and fatal cases were not higher. In addition, the application of convalescent plasma was demonstrated to have positive effects.

Conclusions

COVID‐19 poses an elevated threat to CVID patients. However, only systematic studies can provide robust information on the extent of this threat. Regular immunoglobulin replacement therapy is beneficial to combat COVID‐19 in CVID patients, and best treatment after infection includes the use of convalescent plasma in addition to common medication.
Group cohesiveness in children free‐play activity: A social network analysis
Authors: Lira Paula , Moretti Christina , Guimarães Danilo , Resende Briseida
Published: May 2021

Despite the ethnic diversity and presence of Amerindian communities in all Brazilian states, the indigenous population suffers from a long process of invisibility and stereotyping. Aiming to increase interethnic associations, together with Mbya‐Guarani leaders we promoted interventions in which indigenous and non‐indigenous children shared free playtime. We hypothesised that free play activity would stimulate group cohesiveness, mitigating ethnic group avoidance in children's playgroups. Twenty‐one Mbya‐Guarani and 61 non‐indigenous children participated in two “Encounters for Play.” We recorded children's social interactions during the free playtimes. We selected the first and last 10 minutes of each encounter and performed scans every 30s registering spatial proximity (children who were up to 1 m of each other) and play. Then, we applied Social Network Analysis to explore the children's association pattern at the beginning and end of playtime in each encounter. Our results show free play activity was effective in stimulating group cohesiveness. Children' proximity association pattern and playgroup configuration changed between clips, and there was a significant correlation between both categories' associations. We conclude that the encounters have potential applicability as an intervention to mitigate ethnic group avoidance in children.
The Convergence of Struggles! Reusability Assessment of Inner‐Source Components for Product Lines
Authors: Froment Thomas , de Lohéac Guillaume Angier
Published: May 2021

Inner source is establishing open source‐like collaborations within an organization. Product Line Engineering (PLE) is the approach for engineering a related product portfolio in an efficient manner, taking advantage of products’ similarities while managing their differences. These two well‐documented approaches propose smart techniques for reuse, but they use different terminology. A language characteristic is to be polysemic and polymorphic. Indeed, PLE and inner source do not use the same words to refer to equivalent concepts. This could badly affect project performance when evolving in a multi‐domain context. What if there was a way to better integrate PLE, inner source, modeling, data management, hardware and software engineering, and integration, verification, validation, and qualification (IVVQ) through the similarity concept?

This paper shows it is possible to build a common way to assess the components (also called building blocks) contributing to a product line, thanks to a process to determine the component maturity levels using the similarity approach. After detailing the commonalities between the inner source and PLE domains, we present the Inner Sourcing Process Maturity Level (ISPML) as a key engineering practice. Why is it important for engineering? If engineers reuse components defined by their engineering assets, it is important to have a formalized, common way to do this across the company to integrate reusable multi‐domain assets with a certain confidence level. This paper introduces a simple method for multi‐domain organizations to better determine whether sharing an engineering asset is favorable or not.
Morpho‐taxonomic identification of algal diversity of district Lahore based on light microscopic techniques
Authors: Mukhtar Anser , Jaffer Mehwish , Shaheen Shabnum , Ullah Nadeem , Rehman Shafiq ur
Published: May 2021

Total 23 algal species belonging to 14 genera were reported from different sites of district Lahore. They were collected from freshwater of some areas of Lahore city during October 2017 to March 2018. All were taxonomically investigated up to specie level using light microscopy (LM). Following species were identified: Achanthes hungarica (Grunow) Grunow in Cleve et Grunow 1880, Achnanthes minutissima (Kützing) Cleve, Anabaena affinis Lemmermann, Aphanothece endophytica G.M. Smith, Aphanothece nidulans P. Richter, Calothrix fusca (Kützing) Bornet & Flahault, Chroococcus limenticus var. distans G.M. Smith, Chroococcus minor (Kützing) Lemmermann, Cyclotella operculata (C.A. Agardh) Brebisson, Cymbella ehrengbergii Kützing, Cymbella turgida, Lyngbya arboricola Bruhlet Bruh, Lyngbya tylorii Drouet & Strickland, Navicula confervacea (Kützing) Grun. var. confervacea, Navicula knsnesis Meister, Oedogonium behemicum Hirn, Oscillatoria amoena (Kützing) Gomont, Oscillatoria amphibia C. Agardh ex Gomont, Oscillatoria subbrevis Schmidle, Pinuularia interrupta W. Smith, Spirulina subsala (Oersted) ex Gomont, Ulothrix aequalis Kützing, Ulothrix tenuissima Kützing.
CD9 inhibition reveals a functional connection of extracellular vesicle secretion with mitophagy in melanoma cells
Authors: Suárez Henar , Andreu Zoraida , Mazzeo Carla , Toribio Víctor , Pérez‐Rivera Aldo Emmanuel , López‐Martín Soraya , García‐Silva Susana , Hurtado Begoña , Morato Esperanza , Peláez Laura , Arribas Egoitz Astigarraga , Tolentino‐Cortez Tarson , Barreda‐Gómez Gabriel , Marina Ana Isabel , Peinado Héctor , Yáñez‐Mó María
Published: May 2021

Tetraspanins are often used as Extracellular Vesicle (EV) detection markers because of their abundance on these secreted vesicles. However, data on their function on EV biogenesis are controversial and compensatory mechanisms often occur upon gene deletion. To overcome this handicap, we have compared the effects of tetraspanin CD9 gene deletion with those elicited by cytopermeable peptides with blocking properties against tetraspanin CD9. Both CD9 peptide or gene deletion reduced the number of early endosomes. CD9 peptide induced an increase in lysosome numbers, while CD9 deletion augmented the number of MVB and EV secretion, probably because of compensatory CD63 expression upregulation. In vivo, CD9 peptide delayed primary tumour cell growth and reduced metastasis size. These effects on cell proliferation were shown to be concomitant with an impairment in mitochondrial quality control. CD9 KO cells were able to compensate the mitochondrial malfunction by increasing total mitochondrial mass reducing mitophagy. Our data thus provide the first evidence for a functional connection of tetraspanin CD9 with mitophagy in melanoma cells.
Emerging methods in biomarker identification for extracellular vesicle‐based liquid biopsy
Authors: Liang Yaxuan , Lehrich Brandon M. , Zheng Siyang , Lu Mengrou
Published: May 2021

Extracellular vesicles (EVs) are released by many cell types and distributed within various biofluids. EVs have a lipid membrane‐confined structure that allows for carrying unique molecular information originating from their parent cells. The species and quantity of EV cargo molecules, including nucleic acids, proteins, lipids, and metabolites, may vary largely owing to their parent cell types and the pathophysiologic status. Such heterogeneity in EV populations provides immense challenges to researchers, yet allows for the possibility to prognosticate the pathogenesis of a particular tissue from unique molecular signatures of dispersing EVs within biofluids. However, the inherent nature of EV's small size requires advanced methods for EV purification and evaluation from the complex biofluid. Recently, the interdisciplinary significance of EV research has attracted growing interests, and the EV analytical platforms for their diagnostic prospect have markedly progressed. This review summarizes the recent advances in these EV detection techniques and methods with the intention of translating an EV‐based liquid biopsy into clinical practice. This article aims to present an overview of current EV assessment techniques, with a focus on their progress and limitations, as well as an outlook on the clinical translation of an EV‐based liquid biopsy that may augment current paradigms for the diagnosis, prognosis, and monitoring the response to therapy in a variety of disease settings.
On the infinite Lucchesi–Younger conjecture I
Authors: Gollin J. Pascal , Heuer Karl
Published: May 2021

A dicut in a directed graph is a cut for which all of its edges are directed to a common side of the cut. A famous theorem of Lucchesi and Younger states that in every finite digraph the least size of an edge set meeting every dicut equals the maximum number of disjoint dicuts in that digraph. In this first paper out of a series of two papers, we conjecture a version of this theorem using a more structural description of this min‐max property for finite dicuts in infinite digraphs. We show that this conjecture can be reduced to countable digraphs where the underlying undirected graph is 2‐connected, and we prove several special cases of the conjecture.
Edge‐colored complete graphs without properly colored even cycles: A full characterization
Authors: Li Ruonan , Broersma Hajo , Yokota Maho , Yoshimoto Kiyoshi
Published: May 2021

The structure of edge‐colored complete graphs containing no properly colored triangles has been characterized by Gallai back in the 1960s. More recently, Cǎda et al. and Fujita et al. independently determined the structure of edge‐colored complete bipartite graphs containing no properly colored . We characterize the structure of edge‐colored complete graphs containing no properly colored even cycles, or equivalently, without a properly colored or . In particular, we first deal with the simple case of 2‐edge‐colored complete graphs, using a result of Yeo. Next, for , we define four classes of ‐edge‐colored complete graphs without properly colored even cycles and prove that any ‐edge‐colored complete graph without a properly colored even cycle belongs to one of these four classes.
Prediction of High‐Risk Cytogenetic Status in Multiple Myeloma Based on Magnetic Resonance Imaging: Utility of Radiomics and Comparison of Machine Learning Methods
Authors: Liu Jianfang , Zeng Piaoe , Guo Wei , Wang Chunjie , Geng Yayuan , Lang Ning , Yuan Huishu
Published: May 2021

Background

Radiomics has shown promising results in the diagnosis, efficacy, and prognostic assessments of multiple myeloma (MM). However, little evidence exists on the utility of radiomics in predicting a high‐risk cytogenetic (HRC) status in MM.

Purpose

To develop and test a magnetic resonance imaging (MRI)‐based radiomics model for predicting an HRC status in MM patients.

Study Type

Retrospective.

Population

Eighty‐nine MM patients (HRC [n: 37] and non‐HRC [n: 52]).

Field Strength/Sequence

A 3.0 T; fast spin‐echo (FSE): T1‐weighted image (T1WI) and fat‐suppression T2WI (FS‐T2WI).

Assessment

Overall, 1409 radiomics features were extracted from each volume of interest drawn by radiologists. Three sequential feature selection steps—variance threshold, SelectKBest, and least absolute shrinkage selection operator—were repeated 10 times with 5‐fold cross‐validation. Radiomics models were constructed with the top three frequency features of T1WI/T2WI/two‐sequence MRI (T1WI and FS‐T2WI). Radiomics models, clinical data (age and visually assessed MRI pattern), or radiomics combined with clinical data were used with six classifiers to distinguish between HRC and non‐HRC statuses. Six classifiers used were support vector machine, random forest, logistic regression (LR), decision tree, k‐nearest neighbor, and XGBoost. Model performance was evaluated with area under the curve (AUC) values.

Statistical Tests

Mann–Whitney U‐test, Chi‐squared test, Z test, and DeLong method.

Results

The LR classifier performed better than the other classifiers based on different data (AUC: 0.65–0.82; P < 0.05). The two‐sequence MRI models performed better than the other data models using different classifiers (AUC: 0.68–0.82; P < 0.05). Thus, the LR two‐sequence model yielded the best performance (AUC: 0.82 ± 0.02; sensitivity: 84.1%; specificity: 68.1%; accuracy: 74.7%; P < 0.05).

Conclusion

The LR‐based machine learning method appears superior to other classifier methods for assessing HRC in MM. Radiomics features based on two‐sequence MRI showed good performance in differentiating HRC and non‐HRC statuses in MM.

Evidence Level

3

Technical Efficacy

Stage 2
FDG‐PET for preoperative evaluation of tumor invasion in ampullary cancer: A retrospective analysis
Authors: Watanabe Akira , Harimoto Norifumi , Araki Kenichiro , Kubo Norio , Igarashi Takamichi , Tsukagoshi Mariko , Ishii Norihiro , Hirai Keitaro , Tanaka Hiroshi , Mochida Yasushi , Kogure Norimichi , Higuchi Tetsuya , Shirabe Ken
Published: May 2021

Background

Tumor invasion is the most significant prognostic factor in ampullary cancer and is thus a crucial factor in decision making for treatment. Endoscopic ultrasound can be performed to evaluate tumor invasion, but its diagnostic accuracy varies depending on the endoscopist. This study aimed to assess the usefulness of fluorodeoxyglucose positron emission tomography (FDG‐PET) for preoperatively predicting tumor invasion in ampullary cancer.

Methods

We retrospectively evaluated 44 patients with ampullary cancer (adenoma, n = 6; adenocarcinoma, n = 38) who underwent surgical resection. The SUVmax of the ampullary tumor site was assessed using FDG‐PET, and the correlation among tumor invasion, lymph node metastasis, and other clinicopathological factors was evaluated.

Results

The SUVmax of the ampullary tumor site gradually increased depending on the extent of tumor invasion (p = 0.0075). Moreover, the SUVmax was significantly different between ≤T1a and ≥T1b, which is an indication for endoscopic papillectomy or surgical resection (p = 0.0015). The SUVmax of the ampullary section was significantly correlated with lymph node metastasis (p = 0.035).

Conclusion

The SUVmax of the ampullary tumor site is correlated with tumor invasion and lymph node metastasis in ampullary cancer. Thus, FDG‐PET can be a useful modality for preoperative staging and treatment strategy.
Success rates in restoring hearing loss in patients with chronic otitis media: A systematic review
Authors: Lewis Aaran , Vanaelst Barbara , Hua Håkan , Yoon Choi Byung , Jaramillo Rafael , Kong Kelvin , Ray Jaydip , Thakar Alok , Järbrink Krister , Hol Myrthe K. S.
Published: May 2021

Objective

To assess the effectiveness of tympanoplasty in treating chronic otitis media‐related hearing loss, published literature was systematically reviewed to determine the clinical success rate of tympanoplasty at restoring hearing in chronic otitis media patients at a minimum follow‐up period of 12‐months.

Data Sources

PubMed, Embase and the Cochrane Library.

Methods

Two independent reviewers performed literature searches. Publications reporting long‐term (≥12‐month) hearing outcomes and complications data on adult and pediatric patients with chronic otitis media were included and assessed for risk of bias and strength of evidence. To assess how tympanoplasty influences long‐term hearing outcomes, data on pure tone audiometry (air‐bone gap) and complications were extracted and synthesized.

Results

Thirty‐nine studies met the inclusion criteria. Data from 3162 patients indicated that 14.0% of patients encountered postoperative complications. In adult patients, mean weighted air‐bone gap data show closure from 26.5 dB hearing level (HL) (preoperatively) to 16.1 dB HL (postoperatively). In studies that presented combined adult and pediatric data, the mean preoperative air‐bone gap of 26.7 dB HL was closed to 15.4 dB HL. In 1370 patients with synthesizable data, 70.7% of patients had a postoperative air‐bone gap ˂ 20 dB HL at long‐term follow‐up. Finally, subgroup analysis identified that mean improvement in ABG closure for patients with and without cholesteatoma was 10.0 dB HL and 12.4 dB HL, respectively.

Conclusion

In patients with chronic otitis media, tympanoplasty successfully closed the air‐bone gap to within 20 dB HL in 7/10 cases and had an overall complication rate of 14.0%.

Level of Evidence

2a.