bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances of Ionic Liquids and Deep Eutectic Solvents in Green Processes of Biomass‐Derived 5‐Hydroxymethylfurfural
Authors: Chen Lifang , Xiong Yuhang , Qin Hao , Qi Zhiwen
Published: January 2022

5‐Hydroxymethylfurfural (HMF) is identified as an important bio‐based platform chemical to bridge petroleum‐based and biomass‐based resources. It can be obtained through dehydration of various carbohydrates as well as converted to value‐added fuels and chemicals. As designer solvents, ionic liquids (ILs) and deep eutectic solvents (DESs) have been widely used in catalytic transformation of biomass derivatives to various chemicals. This Review summarizes recent progress in experimental and theoretical studies on dehydration of carbohydrates such as fructose, glucose, sucrose, cellobiose, chitosan, cellulose, inulin, and even raw biomass to generate HMF using ILs and DESs as catalysts/cocatalysts and/or solvents/cosolvents. It also gives an overview of IL and DES‐involved catalytic transformation of HMF to downstream products via oxidation, reduction, esterification, decarboxylation, and so forth. Challenges and prospects of ILs and DESs are also proposed for further production of HMF and HMF derivatives from biomass in green and sustainable processes.
Disruption of the pentraxin 3/CD44 interaction as an efficient therapy for triple‐negative breast cancers
Authors: Hsiao Yu‐Wei , Chi Jhih‐Ying , Li Chien‐Feng , Chen Lei‐Yi , Chen Yi‐Ting , Liang Hsin‐Yin , Lo Yu‐Chih , Hong Jhen‐Yi , Chuu Chin‐Pin , Hung Liang‐Yi , Du Jyun‐Yi , Chang Wen‐Chang , Wang Ju‐Ming
Published: January 2022

Due to the heterogeneity and high frequency of genome mutations in cancer cells, targeting vital protumour factors found in stromal cells in the tumour microenvironment may represent an ideal strategy in cancer therapy. However, the regulation and mechanisms of potential targetable therapeutic candidates need to be investigated. An in vivo study demonstrated that loss of pentraxin 3 (PTX3) in stromal cells significantly decreased the metastasis and growth of cancer cells. Clinically, our results indicate that stromal PTX3 expression correlates with adverse prognostic features and is associated with worse survival outcomes in triple‐negative breast cancer (TNBC). We also found that transforming growth factor beta 1 (TGF‐β1) induces PTX3 expression by activating the transcription factor CCAAT/enhancer binding protein delta (CEBPD) in stromal fibroblasts. Following PTX3 stimulation, CD44, a PTX3 receptor, activates the downstream ERK1/2, AKT and NF‐κB pathways to specifically contribute to the metastasis/invasion and stemness of TNBC MDA‐MB‐231 cells. Two types of PTX3 inhibitors were developed to disrupt the PTX3/CD44 interaction and they showed a significant effect on attenuating growth and restricting the metastasis/invasion of MDA‐MB‐231 cells, suggesting that targeting the PTX3/CD44 interaction could be a new strategy for future TNBC therapies.
Diagnostics of Ne–Ar mixture plasma using a fine‐structure resolved collisional radiative model
Authors: Baghel Shubham S. , Gangwar Reetesh K. , Srivastava Rajesh
Published: January 2022

A collisional radiative (CR) model has been developed for the diagnostics of Ne–Ar mixture plasma. The 40 fine‐structure resolved energy levels of neon corresponding 2p53s, 2p53p, 2p53d, 2p54s, and 2p54p along with ground state (2p6) and ion state (2p5) have been considered. All the essential population and de‐population channels viz. electron impact excitation‐de‐excitation, ionization, two/three‐body recombination, radiative decay, self‐absorption correction, diffusion, etc., have been considered in the model. The quenching of relatively higher lifetime states 2p53s due to interaction with Ar atoms through associative and Penning ionization is also included in the model. The applicability of the CR model is demonstrated by performing the optical diagnostic of rf induced inductively coupled Ne–Ar mixture plasma. The plasma parameters viz. electron temperature, electron density, and population distribution of levels at various mixture conditions are extracted by coupling the present CR model predictions with emission and absorption measurements by Boffard et al. [J. Phys. D: Appl. Phys., 45, 382001 (2012) and private communication]. The results are also compared with earlier optical models and Langmuir probe measurements. The self‐absorption correction (escape) factors and electron impact excitation rates at various Ne–Ar mixture concentrations are also presented.
Effect of interferon regulatory factor 2 on inflammatory response and oxidative stress in lipopolysaccharide‐induced acute kidney injury
Authors: He Tianwei , Yang Lina , Wu Daoxu
Published: January 2022

Interferon regulatory factor (IRF) 2 plays an important role in lipopolysaccharide (LPS)‐induced acute kidney injury (AKI). In this study, we explored the effects of IRF2 on apoptosis, inflammation, and oxidative stress in AKI C57BL/6 male mouse model and HEK293 cells following LPS treatment. To determine the effect of IRF2, short hairpin RNAs in mice and small interfering RNAs in cells were used to knockdown IRF2 expression. IRF2 expression, apoptosis, and severity of inflammatory and oxidative stress in mice and cells were measured. IRF2 levels were upregulated in LPS‐treated mice and cells. IRF2 knockdown suppressed the levels of creatinine, blood urea nitrogen, and kidney injury molecule 1 and decreased the renal injury score in mice. Furthermore, IRF2 knockdown inhibited apoptosis and decreased the levels of inflammatory, reactive oxygen species (ROS), and malondialdehyde (MDA), but increased superoxide dismutase (SOD) levels in mice and cells. Furthermore, we found that the Janus kinase (JAK)/ signal transducer and activator of transcription pathway activated by LPS was inhibited by knockdown of IRF2, and enhanced by IRF2 overexpression. IRF2 overexpression increased cell apoptosis, inflammation, and ROS and MDA levels, and decreased SOD levels. However, the effect of IRF2 overexpression was reversed by the JAK inhibitor tofacitinib. Knockdown of IRF2 reduced LPS‐induced renal tissue injury in vivo and in vitro through anti‐inflammatory and antioxidant stress effects.
The regulatory role of nitric oxide in morphine‐induced analgesia in the descending path of pain from the dorsal hippocampus to the dorsolateral periaqueductal gray
Authors: Hashemi Mahboobeh , Karami Manizheh , Zarrindast Mohammadreza
Published: January 2022

Background

Nitric oxide (NO) levels in brain nuclei, such as the hippocampus and brainstem, are involved in morphine analgesia, but the relationship between the dorsal hippocampus (dH) and the dorsolateral periaqueductal gray matter (dlPAG) needs to be clarified, which is our goal.

Methods

Wistar rats were simultaneously equipped with a stereotaxic device with unilateral guide cannula at dH and dlPAG. After recovery, they were divided into control and experimental groups. Formalin (50 μl of 2.5%) was inoculated into the left hind paw of the rat. Morphine (6 mg/kg) was administered intraperitoneally (i.p.) 10 min before formalin injection. L‐Arginine (0.25, 0.5, 1 and 2 μg/rat), and L‐NAME (0.25, 0.5, 1 and 2 μg/rat), unrelatedly or with respect in the order of injection were used in the nuclei before morphine injection (i.p.). Activation of the neuronal NO synthase (nNOS) in the brains of all animals was measured using NADPH‐diaphorase, a selective biochemical marker of nNOS.

Results

Morphine reduced inflammatory pain in the early and late stages of the rat formalin test. The morphine response was attenuated before injection of single L‐arginine but not L‐NAME in the two target areas. However, the acute phase result was stopped due to L‐NAME pretreatment. When L‐NAME was injected into dlPAG before injecting L‐arginine at dH, the morphine response did not decrease at all, indicating a modulatory role of NO in dlPAG, which was confirmed by NADPH‐d staining.

Conclusions

High levels of NO in dlPAG may regulate the pain process in downward synaptic interactions.

Significance

Nitric oxide is involved in the dH and dlPAG in morphine‐induced analgesia in the rat formalin test. Morphine has analgesic effects in both phases of the rat formalin test. The morphine response is reduced in two stages by injection of the NO precursor L‐arginine but not the nNOS inhibitor L‐NAME in the dH and dlPAG. By injecting L‐NAME before L‐arginine in both nuclei, the morphine‐induced response returns in the early stages. Due to the initial injection of L‐NAME into dlPAG and the subsequent injection of L‐arginine at dH, morphine analgesia is not reduced at all, indicating NO modulation in the pain pathway from dH to dlPAG.
State‐of‐Health Prediction for Lithium‐Ion Batteries Based on Complete Ensemble Empirical Mode Decomposition with Adaptive Noise‐Gate Recurrent Unit Fusion Model
Authors: Xia Fei , Wang Kangan , Chen Jiajun
Published: January 2022

State‐of‐health (SOH) estimation is one of the most critical battery management system (BMS) tasks. A challenge remains for the SOH prediction due to the complicated battery aging mechanism. The most common health indicator is the capacity of the lithium‐ion battery. The fluctuation of capacity caused by the capacity regeneration phenomenon can seriously affect the prediction performance. A new complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and gate recurrent unit (GRU) based fusion prediction model for SOH estimation is proposed to solve the problem effectively. First, the CEEMDAN algorithm decomposes the original SOH into local fluctuations and global degradation trends. Then, the GRU network and autoregressive integrated moving average model are used to predict the above trends, respectively. Next, a sliding window is designed to calculate an average value of the global degradation trend prediction residuals. Then, the second GRU algorithm can be used to correct prediction residuals. Finally, the prediction results of the aforementioned parts are combined to obtain the final SOH estimation. The proposed method is verified by experimental battery data from NASA and CALCE datasets. The results show that the fusion method has both higher estimation accuracy and stronger robustness than other methods.
Evaluation of the Acute Effects of Arsenic on Adults of the Neotropical Native Fish Cnesterodon decemmaculatus Using a Set of Biomarkers
Authors: González Núñez Ayelén A. , Ferro Juan P. , Campos Liria B. , Eissa Bettina L. , Mastrángelo Martina M. , Ferrari Lucrecia , Ossana Natalia A.
Published: January 2022

Neotropical fish Cnesterodon decemmaculatus were exposed to different sublethal concentrations (0.5, 1.0 and 5.0 mg As/L) of sodium arsenite (As III) to determine the median lethal concentration (LC50; 96 h) and to evaluate the response of a set of biomarkers (genotoxic, behavioral, biochemical, and metabolic). At the end of the exposure (96 h), fish were video-recorded for behavior assessment. We used the micronucleus and nuclear abnormality tests and the comet assay in peripheral blood as genotoxicity biomarkers. In regard to biochemical and metabolic biomarkers, we dissected the brain for acetylcholinesterase (AChE) activity; the liver for glutathione-S-transferase (GST) and catalase (CAT) activity and glutathione content (GSH); the gills for GSH content; and muscle for AChE, energy metabolism of lipids, carbohydrates, and proteins, and the electron transport system activity of the mitochondrial chain. We calculated an index using metabolic biomarkers, to determine the cellular energy allocation. The LC50 value was 7.32 mg As/L. The As affected some swimming parameters in females. No significant differences in micronucleus were found compared with the control, whereas nuclear aberrations increased significantly at 1.0 and 5.0 mg As/L. The genomic damage index and the percentage of cells with DNA damage (measured by the comet assay) showed a significant increase in the As-treated groups, and this technique was the most sensitive for detecting genotoxic damage. The As affected the antioxidant system (mainly GSH, CAT, and GST) and reduced the lipid content. A preliminary baseline was generated for the response of C. decemmaculatus exposed to sublethal concentrations of As, when it alters swimming behavior and the antioxidant system, has genotoxic effects, and reduces lipid content. Environ Toxicol Chem 2022;41:1246–1259. © 2022 SETAC
Persistent, Bioaccumulative, and Toxic Chemicals in Wild Alpine Insects: A Methodological Case Study
Authors: Hierlmeier Veronika Rosa , Struck Nils , Krapf Patrick , Kopf Timotheus , Hofinger Anna Malena , Leitner Viktoria , Stromberger Philipp Jakob Ernest , Freier Korbinian Peter , Steiner Florian Michael , Schlick-Steiner Birgit Christiane
Published: January 2022

With their high persistence in the environment and their potential for long-range atmospheric transport, persistent, bioaccumulative, and toxic chemicals (PBTs) may be among the numerous anthropogenic threats to insect populations worldwide. The effects of PBTs on insects have been investigated in the laboratory, but topical field studies are scarce. A reason might be the multiple challenges faced by PBT-related field studies on wild insects. We studied two species of bumblebees (Bombus spp.) and of ants (Formica spp.) in two high-elevation locations in the Austrian and German Alps to tackle two of these challenges. First, PBTs occur in minuscule concentrations compared with other substances in the environment. Therefore, the practicability of body burden data from pooled individuals was tested. Second, fitness proxies like fecundity, which typically are endpoints for chemical toxicity, are difficult to quantify in the field. Hence, fluctuating asymmetry of bumblebee wings and ant heads was tested as an alternative endpoint. To exclude the possibility that fluctuating asymmetry was caused by genetic stressors, inbreeding levels were estimated using population-genetic markers, and their relationships to fluctuating asymmetry in the same individuals were assessed. We successfully quantified polychlorinated biphenyls and Hg as PBTs using the pooled samples and found PBT data from pooled individuals useful, in that significant correlations to fluctuating asymmetry were identified in bumblebees and ants. This finding confirmed the potential of fluctuating asymmetry to indicate PBT effects in wild insects. Inbreeding did not interfere with PBT links to fluctuating asymmetry in any instance. Our findings contribute to the development of a quantitative methodological framework for investigating the effects of persistent environmental chemicals on wild insects. Environ Toxicol Chem 2022;41:1215–1227. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

The bioaccumulation of persistent, bioaccumulative, and toxic chemicals in wild alpine insects was proved via chemical analysis. The data showed some significant correlations with measured asymmetries of the body structures of the insects. Inbreeding, analyzed with genetic markers, did not interfere with these links.
LoRaWAN security issues and mitigation options by the example of agricultural IoT scenarios
Authors: Kuntke Franz , Romanenko Vladimir , Linsner Sebastian , Steinbrink Enno , Reuter Christian
Published: January 2022

The Internet of Things (IoT) is a major trend that is seen as a great opportunity to improve efficiency in many domains, including agriculture. This technology could transform the sector, improving the management and quality of agricultural operations, for example, crop farming. The most promising data transmission standard for this domain seems to beLong Range Wide Area Network (LoRaWAN), a popular representative of low power wide area network technologies today. LoRaWAN, like any wireless protocol, has properties that can be exploited by attackers, which has been a topic of multiple research papers in recent years. By conducting a systematic literature review, we build a recent list of attacks, as well as collect mitigation options. Taking a look at a concrete use case (IoT in agriculture) allows us to evaluate the practicality of both exploiting the vulnerabilities and implementing the countermeasures. We detected 16 attacks that we grouped into six attack types. Along with the attacks, we collect countermeasures for attack mitigation. Developers can use our findings to minimize the risks when developing applications based on LoRaWAN. These mostly theoretical security recommendations should encourage future works to evaluate the mitigations in practice.
Detection of sexually antagonistic transmission distortions in trio datasets
Authors: Lucotte Elise A. , Albiñana Clara , Laurent Romain , Bhérer Claude ,   Genome of the Netherland Consortium, Bataillon Thomas , Toupance Bruno
Published: January 2022

Sexual dimorphisms are widespread in animals and plants, for morphological as well as physiological traits. Understanding the genetic basis of sexual dimorphism and its evolution is crucial for understanding biological differences between the sexes. Genetic variants with sex-antagonistic effects on fitness are expected to segregate in populations at the early phases of sexual dimorphism emergence. Detecting such variants is notoriously difficult, and the few genome-scan methods employed so far have limited power and little specificity. Here, we propose a new framework to detect a signature of sexually antagonistic (SA) selection. We rely on trio datasets where sex-biased transmission distortions can be directly tracked from parents to offspring, and identify signals of SA transmission distortions in genomic regions. We report the genomic location of six candidate regions detected in human populations as potentially under sexually antagonist selection. We find an enrichment of genes associated with embryonic development within these regions. Last, we highlight two candidate regions for SA selection in humans.
Deep Bayesian networks for uncertainty estimation and adversarial resistance of white matter hyperintensity segmentation
Authors: Mojiri Forooshani Parisa , Biparva Mahdi , Ntiri Emmanuel E. , Ramirez Joel , Boone Lyndon , Holmes Melissa F. , Adamo Sabrina , Gao Fuqiang , Ozzoude Miracle , Scott Christopher J. M. , Dowlatshahi Dar , Lawrence‐Dewar Jane M. , Kwan Donna , Lang Anthony E. , Marcotte Karine , Leonard Carol , Rochon Elizabeth , Heyn Chris , Bartha Robert , Strother Stephen , Tardif Jean‐Claude , Symons Sean , Masellis Mario , Swartz Richard H. , Moody Alan , Black Sandra E. , Goubran Maged
Published: January 2022

White matter hyperintensities (WMHs) are frequently observed on structural neuroimaging of elderly populations and are associated with cognitive decline and increased risk of dementia. Many existing WMH segmentation algorithms produce suboptimal results in populations with vascular lesions or brain atrophy, or require parameter tuning and are computationally expensive. Additionally, most algorithms do not generate a confidence estimate of segmentation quality, limiting their interpretation. MRI‐based segmentation methods are often sensitive to acquisition protocols, scanners, noise‐level, and image contrast, failing to generalize to other populations and out‐of‐distribution datasets. Given these concerns, we propose a novel Bayesian 3D convolutional neural network with a U‐Net architecture that automatically segments WMH, provides uncertainty estimates of the segmentation output for quality control, and is robust to changes in acquisition protocols. We also provide a second model to differentiate deep and periventricular WMH. Four hundred thirty‐two subjects were recruited to train the CNNs from four multisite imaging studies. A separate test set of 158 subjects was used for evaluation, including an unseen multisite study. We compared our model to two established state‐of‐the‐art techniques (BIANCA and DeepMedic), highlighting its accuracy and efficiency. Our Bayesian 3D U‐Net achieved the highest Dice similarity coefficient of 0.89 ± 0.08 and the lowest modified Hausdorff distance of 2.98 ± 4.40 mm. We further validated our models highlighting their robustness on “clinical adversarial cases” simulating data with low signal‐to‐noise ratio, low resolution, and different contrast (stemming from MRI sequences with different parameters). Our pipeline and models are available at: https://hypermapp3r.readthedocs.io.
Coping with complexity in the COVID pandemic: An exploratory study of intensive care units
Authors: Saurin Tarcisio Abreu , Wachs Priscila , Bueno Wagner Pietrobelli , de Souza Kuchenbecker Ricardo , Boniatti Márcio Manozzo , Zani Carolina Melecardi , Clay‐Williams Robyn
Published: January 2022

Although the COVID pandemic has challenged the resilience of health services in general, this impact has been most visible in intensive care units (ICUs). This paper presents an exploratory study of how ICUs in Brazil have coped with the complexity stemming from the pandemic. Five guidelines for coping with complexity were adopted as analytical framework. The guidelines were concerned with slack resources, diversity of perspectives, visibility, work‐as‐done, and unintended consequences. There were three main sources of data: (i) a survey with respondents from 33 ICUs, which indicated their agreement with 23 statements related to the use of the complexity guidelines; (ii) semistructured interviews with seven survey respondents and two public health officials; and (iii) 20 h of observations of the meetings of a municipal bed management committee. Seventy resilience practices were identified from these data sources. Most of these practices (n = 30) were related to the guideline on slack resources, which were commonly obtained from other hospital units. As for the survey data, the statement related to the availability of extra or standby human resources obtained the lowest score, reinforcing the key role of slack resources. Five lessons learned for coping with complexity in ICUs were drawn from our data; one lesson for each guideline. Furthermore, the survey questionnaire is a potential ICU assessment tool, which can be adapted to other health services.
Genetic syndromes, neuroconstuctivism and replicable research; challenges and future directions
Authors: Farran Emily K. , Scerif Gaia
Published: January 2022

With growing awareness of problems with replicability and reproducibility within the field of genetic syndrome research, we outline why and how, as a field, we can collectively reform our practice with the goal of research improvement. We advocate that our research is of most impact when researchers investigate how developmental pathways and phenotypic profiles unfold. However, this neuroconstructivist approach and more traditional approaches bring many challenges, not least the problem of statistical power. Here, we outline the challenges to research in our field, and suggest solutions. In recognition that solutions can require substantial resource, we have also included less resource‐intensive solutions where possible. The challenges and solutions discussed include sample size, individual differences, cross‐disorder comparisons, multi‐disciplinary expertise, measurement sensitivity and longitudinal data. Key recommendations include transparency and collaboration. For our field to produce rigorous, replicable research, researchers should strive to present protocols and data transparently (where possible) and collaborate to collect (multi‐disciplinary) data as a collective effort.
Lolium arundinaceum leaf and root developmental temperatures influence its allelopathic potency on Poa annua
Authors: Koo Daewon , Gonçalves Clebson G. , Askew Shawn D.
Published: January 2022

Allelopathy is a commonly recognized but not fully understood method that could be utilized for weed management. Controlled environment studies in a growth chamber were conducted at Virginia Tech's Glade Road Research Facility in Blacksburg, VA, to determine whether aqueous leaf or root extracts from two Lolium arundinaceum (Schreb) Darbysh (tall fescue) cultivars grown under different growing temperature conditions affected the seed germination and growth of Poa annua L. (annual bluegrass). Two cultivars (‘Falcon III’ and ‘Kentucky 31’) of L. arundinaceum were maintained at cold (day/night 4.4:–1.1°C) or warm (day/night 32.2:26.7°C) conditions for 20 d. Leaf and root extracts were collected via destructive methods and applied to P. annua seed placed in petri dishes. The results indicated that aqueous leaf extracts of L. arundinaceum could inhibit P. annua seed germination, though there was no significant germination reduction with the root extract of L. arundinaceum. The results suggest that temperature may interact with other factors, such as L. arundinaceum cultivar, to influence its allelopathic potency on P. annua seed germination. These results further demonstrate that different cultivars of L. arundinaceum might have different allelopathic effects on P. annua germination.
Strong coloring 2‐regular graphs: Cycle restrictions and partial colorings
Authors: McDonald Jessica , Puleo Gregory J.
Published: January 2022

Let be a graph with , and let be obtained from by gluing in vertex‐disjoint copies of . We prove that if contains at most one odd cycle of length exceeding 3, or if contains at most three triangles, then . This proves the Strong Coloring Conjecture for such graphs . For graphs with that are not covered by our theorem, we prove an approximation result towards the conjecture.
Maximum spectral radius of outerplanar 3‐uniform hypergraphs
Authors: Ellingham M. N. , Lu Linyuan , Wang Zhiyu
Published: January 2022

In this paper, we study the maximum spectral radius of outerplanar 3‐uniform hypergraphs. Given a hypergraph , the shadow of is a graph with and . A graph is outerplanar if it can be embedded in the plane such that all its vertices lie on the outer face. A 3‐uniform hypergraph is called outerplanar if its shadow has an outerplanar embedding such that every hyperedge of is the vertex set of an interior triangular face of the shadow. Cvetković and Rowlinson conjectured in 1990 that among all outerplanar graphs on vertices, the graph attains the maximum spectral radius. We show a hypergraph analogue of the Cvetković–Rowlinson conjecture. In particular, we show that for sufficiently large , the ‐vertex outerplanar 3‐uniform hypergraph of maximum spectral radius is the unique 3‐uniform hypergraph whose shadow is .
Titling and the value of land in Tanzania
Authors: Aikaeli Jehovaness , Markussen Thomas
Published: January 2022

We use household survey data to investigate the relationship between formal, private property rights to agricultural land and agricultural investment, land valuation and access to credit in Tanzania. Results show that landownership documents are associated with substantial increases in the market value of land (more than 25%). One reason appears to be that well‐documented private property rights facilitate the use of land as collateral for loans and therefore ease access to credit. The findings suggest that there are potentially significant, economic returns to systematic land titling in Tanzania and other countries.
CAR NK-92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo
Authors: Liu Manting , Huang Wensou , Guo Yongjian , Zhou Yubo , Zhi Cheng , Chen Jingwu , Li Junping , He Jinping , Lian Hui , Zhou Jingwen , Ye Xiaodie , Hu Yuling , Hu Hong , Liu Zhaoyuan , Huang Jingjun , Lin Liteng , Cai Mingyue , Wang Xiaobin , Huang Jingzhen , Zhang Zhenfeng , Zhu Kangshun , Zhao Qi , Cao Bihui
Published: January 2022

Small cell lung cancer (SCLC) is characterized by a high relapse rate, drug tolerance, and limited treatment choices. Chimeric antigen receptor (CAR)-modified NK cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential applications have not been explored in SCLC. Delta-like ligand 3 (DLL3) has been reported to be overexpressed in SCLC and may be a rational target for CAR NK immunotherapy. In this study, we developed DLL3-specific NK-92 cells and explored their potential in the treatment of SCLC. A coculture of DLL3+ SCLC cell lines with DLL3-CAR NK-92 cells exhibited significant in vitro cytotoxicity and cytokine production. DLL3-CAR NK-92 cells induced tumor regression in an H446-derived pulmonary metastasis tumor model under a good safety threshold. The potent antitumor activities of DLL3-CAR NK-92 cells were observed in subcutaneous tumor models of SCLC. Moreover, obvious tumor-infiltrated DLL3-CAR NK-92 cells were detected in DLL3+ SCLC xenografts. These findings indicate that DLL3-CAR NK-92 cells might be a potential strategy for the treatment of SCLC.
The impact of neutralizing monoclonal antibodies on the outcomes of COVID‐19 outpatients: A systematic review and meta‐analysis of randomized controlled trials
Authors: Lin Wei‐Ting , Hung Shun‐Hsing , Lai Chih‐Cheng , Wang Cheng‐Yi , Chen Chao‐Hsien
Published: January 2022

To assess the clinical efficacy and safety of neutralizing monoclonal antibodies (mABs) for outpatients with coronavirus disease 2019 (COVID‐19). PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) databases were searched from inception to July 19, 2021. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of neutralizing mABs in the treatment of COVID‐19 outpatients were included. The Cochrane risk‐of‐bias tool was used to assess the quality of the included RCTs. The primary outcome was the risk of COVID‐19‐related hospitalization or emergency department (ED) visits. The secondary outcomes were the risk of death and adverse events (AEs). Five articles were included, in which 3309 patients received neutralizing mAB and 2397 patients received a placebo. A significantly lower rate of hospitalization or ED visits was observed among patients who received neutralizing mABs than those who received a placebo (1.7% vs. 6.5%, odds ratios (OR): 0.26; 95% confidence interval (CI): 0.19–0.36; I2 = 0%). In addition, the rate of hospitalization was significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.24; 95% CI: 0.17−0.34; I2 = 0%). The mortality rate was also significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.16; 95% CI: 0.05−0.58; I2 = 3%). Neutralizing mABs were associated with a similar risk of any AE (OR: 0.81; 95% CI: 0.64–1.01; I2 = 52%) and a lower risk of serious AEs (OR: 0.37; 97% CI: 0.19–0.72; I2 = 45%) compared with a placebo. Neutralizing mABs can help reduce the risk of hospitalization or ED visits in COVID‐19 outpatients. For these patients, neutralizing mABs are safe and not associated with a higher risk of AEs than a placebo.
“Line care governs our entire world”: Understanding the experience of caregivers of children with intestinal failure receiving long‐term parenteral nutrition
Authors: Belza Christina , Patterson Catherine , Ghent Emily , Avitzur Yaron , Ungar Wendy J. , Fehlings Darcy , Stremler Robyn , Wales Paul W.
Published: January 2022

Background

Children with intestinal failure (IF) receiving long‐term parenteral nutrition (PN) require significant medical care, including high‐risk procedures such as accessing a central venous catheter, with the majority provided by family caregivers in the home. This study sought to understand the experiences of family caregivers.

Methods

This was a qualitative study of family caregivers of children with IF. Participants were recruited from an intestinal rehabilitation program to participate in virtual focus groups, which were recorded and transcribed. Thematic analysis was used to capture and describe experiences.

Results

Thirteen caregivers providing care to 11 children participated in three virtual focus groups held between May and June 2020. Data analysis revealed five primary themes: (1) caregiving as a 24/7 commitment, (2) facing constant risk of death, (3) chronic illness creates difficult feelings and emotions, (4) effects on all aspects of family life, and (5) adapting and functioning as a family. The findings of this study pair well with the biopsychosocial model highlighting the need for multifaceted assessment and supports.

Conclusion

The impact of caring for a child with IF receiving long‐term PN is significant for caregivers and their families and has implications for all aspects of their lives. A better understanding of the impact on caregivers and their coping strategies lays the groundwork for the optimization of quality of life for caregivers and their family.
Surfactants produced from carbohydrate derivatives: A review of the biobased building blocks used in their synthesis
Authors: Ortiz Maria Soledad , Alvarado Jose Gregorio , Zambrano Franklin , Marquez Ronald
Published: January 2022

This work reviews the use of carbohydrates and their derivatives as renewable raw materials in the production of surfactants. Methods to attain state‐of‐the‐art carbohydrate‐derived surfactants are described. This includes surfactants widely used nowadays and others that have not yet transcended beyond the academic field. Given the abundance of hydroxyl groups in carbohydrates and the considerable quantity of different surfactant structures that can be generated during their synthesis, selectively obtaining a target product represents a challenge. Therefore, this work focuses on the platform chemicals available to synthesize biobased surfactants. The first part of the review comprises a brief introduction of simple and complex carbohydrates to better understand their chemistry. Then, a description of the processes to obtain biobased building blocks derived from carbohydrates according to the National Renewable Energy Laboratory (NREL, USA), and their usefulness in synthesizing surfactants is presented. This provides an organized inventory of the knowledge around the synthesis–production of surfactants from carbohydrate derivatives, emphasizing raw materials that could be inserted into the circular bioeconomy concept. Finally, the current industry trends and the potential role of biobased surfactants around new dioxane regulations are discussed.
Toxicity effects of aged refuse on Tagetes patula and rhizosphere microbes
Authors: Hou Fen , Du Junjie , Bi Xu , Yuan Ye , Wu Xihui
Published: January 2022

Aged refuse, also named mineralized refuse, refers to garbage that has been buried in landfills for many years, has basically stabilized and can be mined and utilized. In this study, we examined the effects of different mass ratios of aged refuse on Tagetes patula and rhizosphere microbes. Compared to growth in ordinary soil, growth in aged refuse or mixed soil with aged refuse significantly increased chlorophyll content, activities of superoxide dismutase, catalase, and peroxidase, while it decreased malondialdehyde levels and protein carbonyl content in leaf tissue of Tagetes patula. Aged refuse was found to be enriched in a variety of rhizosphere microbes that contribute to pollutant degradation, although microbial diversity was found to be relatively low. Bacterial genera such as Ferruginibacter, Hymenobacter, unclassified_Gemmataceae, Longimicrobium, Tychonema CCAP 1459‐11B, Gemmatirosa, and Rubellimicrobium were depleted in soil: aged refuse groups compared with ordinary soil. Correspondingly, bacterial genera such as Emticicia, Caedibacter, Anaerosalibacter, Tumebacillus, Patulibacter, Oceanotoga, Dyadobacter, Chloroflexus, and Acidobacteria bacterium SCN 69–37, Polycyclovorans, were enriched in soil: aged refuse groups compared with ordinary soil. Furthermore, rhizosphere microbe functions changed markedly following the addition of aged refuse. These findings indicate that aged refuse may represent a source of environmental stress for plants and modifies the dominant bacterial composition of rhizosphere microbes. There were underlying close associations among pollutants, plant physiological stress responses, and rhizosphere microbial community composition. With respect to identifying potential approaches to recycling aged refuse, it will be necessary to focus on selecting optimal mass ratios of aged refuse and ordinary soil to control contaminant exposure.
The Impact of Interfacial Interactions on Structural, Electronic, and Sensing Properties of Poly(3‐methylthiophene) in Core‐Shell Nanocomposites. Application for Chemical Warfare Agent Simulants Detection
Authors: Ogurtsov Nikolay A. , Mamykin Andrii V. , Kukla Oleksandr L. , Pavluchenko Alexey S. , Borysenko Mykola V. , Piryatinski Yuri P. , Wojkiewicz Jean‐Luc , Pud Alexander A.
Published: January 2022

In this paper, structural, electronic, and sensing properties of the poly(3‐methylthiophene) (P3MT) in two types of its core–shell nanocomposites with multiwall carbon nanotubes (MWCNTs) and poly(vinylidene fluoride) with different contents of the P3MT component (shell) are explored and are compared. The results indicate specific changes in the P3MT properties appear due to its interfacial interactions with the MWCNTs and PVDF components. In the case of the doped P3MT, charge transfer from MWCNT to P3MT leads to partial dedoping of the latter. The evidence of intermolecular charge transfer complex formation between undoped P3MT (donor) and MWCNTs (acceptor) is obtained. Changes in the properties of P3MT in nanocomposites are used to detect and to reliably recognize some chemical warfare agent's simulants of nerve agents and mustard gas. The sensitivity dependences of the nanocomposites on their work functions, Hansen solubility parameters and analytes electronegativity are studied. It is shown that the sensor response is controlled by a partial charge transfer if the difference between the work function of the sensing material and the electronegativity of the analyte molecules does not exceed a certain value (in the case herein ≈0.3 eV).
California pilots targeting vulnerable overcame obstacles early in pandemic
Authors: Enos Gary
Published: January 2022

Pilot efforts to improve care coordination for California Medi‐Cal beneficiaries with historically poor health outcomes, including many individuals with serious mental illness, appear to have weathered the initial challenges associated with the COVID‐19 pandemic. A report released this month by the UCLA Center for Health Policy Research states that by the end of 2020, specialty and primary care services for these populations had returned to pre‐pandemic levels.
Technical note: Toward implementation of MR‐guided radiation therapy for laryngeal cancer with healthy volunteer imaging and a custom MR‐CT larynx phantom
Authors: Huynh Elizabeth , Boyle Sara , Campbell Jennifer , Penney Jessica , Mak Raymond H. , Schoenfeld Jonathan D. , Leeman Jonathan E. , Williams Christopher L.
Published: January 2022

Purpose

Internal motion of the larynx can cause normal tissue toxicity and/or tumor underdosage during radiotherapy. MR‐guided radiation therapy (MRgRT) provides improved soft‐tissue contrast for patient setup and real‐time gating of radiation based on cine imaging of tumor motion, potentially making it an advantageous modality for laryngeal treatments. However, there are potential concerns regarding the small target size, proximity to heterogeneous tissue interfaces in the airway that may cause dosimetric errors in the presence of the magnetic field, and uncertainty about the ability of MR‐linear accelerator (MR‐Linac) systems to visualize and track laryngeal motion. To date, there have been no reports of the use of MRgRT for laryngeal treatments.

Methods

A healthy volunteer was imaged on a ViewRay MRIdian MR‐Linac. Organs‐at‐risk and a laryngeal pseudo target were contoured and used to generate a stereotactic body radiotherapy plan. A custom phantom was created using 3D‐printing based on structures delineated on the volunteer images to construct an enclosure containing the target and airway anatomy, with a gap for radiochromic film, and filled with gelatin . The treatment plan was mapped onto the phantom and delivered dose assessed on radiochromic film with global normalization and a 10% dose threshold. A cine MR of the volunteer was acquired to assess the magnitude of larynx motion with speaking and swallowing, and system's ability to gate radiation.

Results

A clinically acceptable laryngeal treatment plan and larynx phantom that was MR and computed tomography‐visible were successfully created. The delivered dose had good agreement with the treatment plan with a gamma passing rate of 96.5% (3%/2 mm). The MR‐Linac was able to visualize, track, and gate larynx motion.

Conclusions

The MRgRT workflow for laryngeal treatments was assessed and performed in preparation for clinical implementation on the MR‐Linac, demonstrating that it is feasible to treat laryngeal cancer patients on the MR‐Linac.
Metabolite selection for machine learning in childhood brain tumour classification
Authors: Zhao Dadi , Grist James T. , Rose Heather E.L. , Davies Nigel P. , Wilson Martin , MacPherson Lesley , Abernethy Laurence J. , Avula Shivaram , Pizer Barry , Gutierrez Daniel R. , Jaspan Tim , Morgan Paul S. , Mitra Dipayan , Bailey Simon , Sawlani Vijay , Arvanitis Theodoros N. , Sun Yu , Peet Andrew C.
Published: January 2022

MRS can provide high accuracy in the diagnosis of childhood brain tumours when combined with machine learning. A feature selection method such as principal component analysis is commonly used to reduce the dimensionality of metabolite profiles prior to classification. However, an alternative approach of identifying the optimal set of metabolites has not been fully evaluated, possibly due to the challenges of defining this for a multi‐class problem. This study aims to investigate metabolite selection from in vivo MRS for childhood brain tumour classification. Multi‐site 1.5 T and 3 T cohorts of patients with a brain tumour and histological diagnosis of ependymoma, medulloblastoma and pilocytic astrocytoma were retrospectively evaluated. Dimensionality reduction was undertaken by selecting metabolite concentrations through multi‐class receiver operating characteristics and compared with principal component analysis. Classification accuracy was determined through leave‐one‐out and k‐fold cross‐validation. Metabolites identified as crucial in tumour classification include myo‐inositol (P < 0.05,
), total lipids and macromolecules at 0.9 ppm (P < 0.05,
) and total creatine (P < 0.05,
) for the 1.5 T cohort, and glycine (P < 0.05,
), total N‐acetylaspartate (P < 0.05,
) and total choline (P < 0.05,
) for the 3 T cohort. Compared with the principal components, the selected metabolites were able to provide significantly improved discrimination between the tumours through most classifiers (P < 0.05). The highest balanced classification accuracy determined through leave‐one‐out cross‐validation was 85% for 1.5 T 1H‐MRS through support vector machine and 75% for 3 T 1H‐MRS through linear discriminant analysis after oversampling the minority. The study suggests that a group of crucial metabolites helps to achieve better discrimination between childhood brain tumours.
National childhood obesity‐related intervention systems and intervention programs in China in 1949 to 2020: A narrative review
Authors: Ma Lu , Wen Xiaozhong , Xue Hong , Zhao Li , Ding Yixin , Xu Fei , Ruan Guorui , Li Yixuan , Chang Suying , Wang Youfa
Published: January 2022

Objective

This review examines main government and nongovernmental institutions for childhood obesity prevention and control in China, as well as major national interventions for childhood obesity.

Methods

PubMed, China National Knowledge Infrastructure (CNKI), Wanfang, official websites of national governments and professional institutions/associations, Baidu.com, and Google.com were systematically searched in March 2020 to April 2020. A total of 20 international and national experts on childhood obesity were surveyed.

Results

“Government‐led multisector cooperation” obesity‐related intervention systems have been formed. National‐level interventions were mainly implemented by the Chinese State Council and its administrative departments, along with national professional institutions/associations. Provincial, municipal, and county governments and their subordinate departments coordinated local works. Actions taken by these sectors to fight childhood obesity included developing and implementing regulations and laws, health standards and practice guidelines, surveillance for obesity and related determinants, governmental budget and research funds, and interventions. A total of 14 major national childhood obesity‐related interventions were found: comprehensive interventions (e.g., “Healthy Lifestyle for All campaign,” 2007), diet and nutrition (e.g., “Chinese Rural Compulsory Education Student Nutrition Improvement Program,” since 2011), and physical activity (e.g., “Happy 10 Minutes Program,” 2006).

Conclusions

Although obesity‐related intervention systems and national interventions were implemented, more efforts and stronger government leadership and commitment are needed.
Metabolic adaptation delays time to reach weight loss goals
Authors: Martins Catia , Gower Barbara A. , Hunter Gary R.
Published: January 2022

Objective

The aim of this study was to determine whether metabolic adaptation, at the level of resting metabolic rate, was associated with time to reach weight loss goals, after adjusting for confounders.

Methods

A total of 65 premenopausal women with overweight (BMI: 28.6 ± 1.5 kg/m2; age: 36.4 ± 5.9 years; 36 were White, and 29 were Black) followed an 800‐kcal/d diet until BMI ≤25 kg/m2. Body weight and composition were measured at baseline and after weight loss. Dietary adherence was calculated from total energy expenditure, determined by double labeled water, and body composition changes. Metabolic adaptation was defined as a significantly lower measured versus predicted resting metabolic rate (from own regression model). A regression model to predict time to reach weight loss goals was developed including target weight loss, energy deficit, dietary adherence, and metabolic adaptation as predictors.

Results

Participants lost on average 12.5 ± 3.1 kg (16.1% ± 3.4%) over 155.1 ± 49.2 days. Average dietary adherence was 63.6% ± 31.0%. There was significant metabolic adaptation after weight loss (−46 ± 113 kcal/d, p = 0.002) and this variable was a significant predictor of time to reach weight loss goals (β = −0.1, p = 0.041), even after adjusting for confounders (R2 adjusted = 0.63, p < 0.001).

Conclusion

In premenopausal women with overweight, metabolic adaptation after a 16% weight loss increases the length of time necessary to achieve weight loss goals.