bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID‐19 and multisystem inflammatory syndrome in children: A systematic review and meta‐analysis
Authors: Yasuhara Jun , Watanabe Kae , Takagi Hisato , Sumitomo Naokata , Kuno Toshiki
Published: January 2021

Background

Multisystem inflammatory syndrome in children (MIS‐C) associated with coronavirus disease 2019 has been increasingly recognized. However, the clinical features of MIS‐C and the differences from Kawasaki disease remain unknown. The study aims to investigate the epidemiology and clinical course of MIS‐C.

Methods

PubMed and EMBASE were searched through August 30, 2020. Observational studies describing MIS‐C were included. Data regarding demographic features, clinical symptoms, laboratory, echocardiography and radiology findings, treatments, and outcomes were extracted. Study‐specific estimates were combined using one‐group meta‐analysis in a random‐effects model.

Results

A total of 27 studies were identified including 917 MIS‐C patients. The mean age was 9.3 (95% confidence interval [CI], 8.4–10.1). The pooled proportions of Hispanic and Black cases were 34.6% (95% CI, 28.3–40.9) and 31.5% (95% CI, 24.8–38.1), respectively. The common manifestations were gastrointestinal symptoms (87.3%; 95% CI, 82.9–91.6) and cardiovascular involvement such as myocardial dysfunction (55.3%; 95% CI, 42.4–68.2), coronary artery aneurysms (21.7%; 95% CI, 12.8–30.1) and shock (65.8%; 95% CI, 51.1–80.4), with marked elevated inflammatory and cardiac markers. The majority of patients received intravenous immunoglobulin (81.0%; 95% CI, 75.0–86.9), aspirin (67.3%; 95% CI, 48.8–85.7), and corticosteroids (63.6%; 95% CI, 53.4–73.8) with a variety of anti‐inflammatory agents. Although myocardial dysfunction improved in 55.1% (95% CI, 33.4–76.8) at discharge, the rate of extracorporeal membrane oxygenation use was 6.3% (95% CI, 2.8–9.8) and the mortality was 1.9% (95% CI, 1.0–2.8).

Conclusion

Our findings suggest that MIS‐C leads to multiple organ failure, including gastrointestinal manifestations, myocardial dysfunction and coronary abnormalities, and has distinct features from Kawasaki disease.
Impact of obstructive sleep apnea on assisted ventilation in children with asthma exacerbation
Authors: Tsou Po‐Yang , Cielo Christopher , Xanthopoulos Melissa S. , Wang Yu‐Hsun , Kuo Pei‐Lun , Tapia Ignacio E.
Published: January 2021

Objective

To determine the impact of obstructive sleep apnea (OSA) on asthma exacerbation severity in children hospitalized for asthma exacerbation.

Hypothesis

OSA is associated with greater use of invasive mechanical ventilation (IMV) and noninvasive mechanical ventilation (NIMV) in children hospitalized for asthma exacerbation.

Study Design

A retrospective cohort study.

Patient–Subject Selection

Hospitalization records of children aged 2–18 years admitted for acute asthma exacerbation were obtained for 2000, 2003, 2006, 2009, and 2012 from the Kids’ Inpatient Database.

Methodology

The primary exposure was OSA, the primary outcome was IMV, and secondary outcomes were NIMV, length of hospital stay (LOS), and inflation‐adjusted cost of hospitalization. Multivariable logistic regression, negative binomial, and linear regression were conducted to ascertain the impact of OSA on primary and secondary outcomes. Exploratory analyses investigated the impact of obesity on primary and secondary outcomes.

Results

Among 564,467 hospitalizations for acute asthma exacerbation, 4209 (0.75%) had OSA. Multivariable regression indicated that OSA was associated with IMV (adjusted odds ratio [OR], 5.33 [95% confidence interval, CI: 4.35–6.54], p < .0001), NIMV (adjusted OR, 8.30 [95% CI: 6.56–10.51], p < .0001), longer LOS (adjusted incidence rate ratio, 1.34 [95% CI 1.28–1.43], p < .0001), and greater inflation‐adjusted cost of hospitalization (adjusted β, 0.38 [95% CI: 0.33–0.43], p < .0001). Obesity was also significantly associated IMV, NIMV, longer LOS, and greater inflation‐adjusted cost of hospitalization. There was no interaction between OSA and obesity.

Conclusion

OSA is an independent risk factor for IMV, NIMV, longer LOS, and elevated inflation‐adjusted costs of hospitalization in children hospitalized for asthma exacerbation.
Point of care diaphragm ultrasound in acute bronchiolitis: A measurable tool to predict the clinical, sonographic severity of the disease, and outcomes
Authors: Şık Nihan , Çitlenbik Hale , Öztürk Ali , Yılmaz Durgül , Duman Murat
Published: January 2021

Background

The aim of this study was to evaluate diaphragmatic parameters in bronchiolitis patients and identify correlations between clinical and sonographic severity scores and outcomes to develop a more objective and useful tool in the emergency department.

Methods

Children aged between 1 and 24 months and diagnosed with acute bronchiolitis were included in the study. The Modified Respiratory Distress Assessment Instrument (mRDAI) score was used to quantify the clinical severity of the disease. Lung ultrasound was performed and a bronchiolitis ultrasound score (BUS) was calculated. Diaphragm ultrasound was then performed and diaphragm thickness at the end of inspiration and expiration, thickening fraction, diaphragm excursion (EXC), inspiratory slope (IS), expiratory slope (ES), and total duration time of the respiratory cycle were measured.

Results

There were 104 patients evaluated in this study. The mRDAI score and BUS had a significant positive correlation. There was a positive correlation between IS and respiratory rate at admission. As the clinical score increased, IS, ES, and EXC measurements rose and they were positively correlated. Values of IS, ES, and EXC were higher in the moderate‐severe group than the mild group for both mRDAI and BUS scores. Inspiratory slope values were correlated with the length of stay in the hospital.

Conclusion

Values of IS and ES were correlated with clinical and sonographic severity scores. Moreover, IS was a good predictor of outcome. Diaphragm ultrasound appears to be an objective and useful tool to help the physician make decisions regarding the evaluation and management of bronchiolitis.
Flash properties of Gaussia luciferase are the result of covalent inhibition after a limited number of cycles
Authors: Dijkema Fenne Marjolein , Nordentoft Matilde Knapkøien , Didriksen Anders Krøll , Corneliussen Anders Sværke , Willemoës Martin , Winther Jakob R.
Published: January 2021

Luciferases are widely used as reporters for gene expression and for sensitive detection systems. The luciferase (GLuc) from the marine copepod Gaussia princeps, has gained popularity, primarily because it is secreted and displays a very high light intensity. While firefly luciferase is characterized by kinetic behavior which is consistent with conventional steady‐state Michaelis–Menten kinetics, GLuc displays what has been termed “flash” kinetics, which signify a burst in light emission followed by a rapid decay. As the mechanistic background for this behavior was unclear, we decided to decipher this in more detail. We show that decay in light signal is not due to depletion of substrate, but rather is caused by the irreversible inactivation of the enzyme. Inactivation takes place after between 10 and 200 reaction cycles, depending on substrate concentration and can be described by the sum of two exponentials with associated rate constants. The dominant of these increases linearly with substrate concentration while the minor is substrate‐concentration independent. In terms of rate of initial luminescence reaction, this increases with the substrate concentration to the power of 1.5 and shows no signs of saturation up to 10 μM coelenterazine. Finally, we find that the inactivated form of the enzyme has a larger apparent size in both size exclusion chromatography and SDS‐PAGE analysis and shows a fluorescence peak at 410 nm when excited at 333 nm. These findings indicate that the “flash” kinetics in Gaussia luciferase are caused by an irreversible covalent binding to a substrate derivative during catalysis.
Duality and Higher Buscher Rules in p‐Form Gauge Theory and Linearized Gravity
Authors: Chatzistavrakidis Athanasios , Karagiannis Georgios , Ranjbar Arash
Published: January 2021

We perform an in‐depth analysis of the transformation rules under duality for couplings of theories containing multiple scalars, p‐form gauge fields, linearized gravitons or (p, 1) mixed symmetry tensors. Following a similar reasoning to the derivation of the Buscher rules for string background fields under T‐duality, we show that the couplings for all classes of aforementioned multi‐field theories transform according to one of two sets of duality rules. These sets comprise the ordinary Buscher rules and their higher counterpart; this is a generic feature of multi‐field theories in spacetime dimensions where the field strength and its dual are of the same degree. Our analysis takes into account topological theta terms and generalized B‐fields, whose behavior under duality is carefully tracked. For a 1‐form or a graviton in 4D, this reduces to the inversion of the complexified coupling or generalized metric under electric/magnetic duality. Moreover, we write down an action for linearized gravity in the presence of θ‐term from which we obtain previously suggested on‐shell duality and double duality relations. This also provides an explanation for the origin of theta in the gravitational duality relations as a specific additional sector of the linearized gravity action.
Prostatic ductal adenocarcinoma variant predicts worse pathological and oncological outcomes: Insight from over 1000 consecutive patients from a large prospective uro‐oncology registry
Authors: Tan Yu Guang , Khalid Farhan , Huang Hong Hong , Chen Kenneth , Tay Kae Jack , Lau Weber K. O. , Cheng Christopher W. S. , Ngo Nye Thane , Yuen John S. P.
Published: January 2021

Objective

To evaluate if prostatic ductal adenocarcinoma (PDA) independently predicts poorer pathological and oncological outcomes after radical prostatectomy (RP).

Methods and Materials

Utilizing a large prospective uro‐oncology registry, clinicopathological parameters of 1027 consecutive patients who underwent RP (2008–2017) were recorded. Oncological outcomes were determined by failure to achieve unrecordable PSA postoperatively and biochemical failure (BCF).

Results

PDA was present in 79 (7.7%) patients, whereas 948 (92.3%) patients had conventional prostatic acinar adenocarcinoma (PAA). Patients with PDA were older (mean 64.4 vs. 62.8‐years old; p = .045), had higher PSA at diagnosis (mean 12.53 vs. 10.80 ng/ml; p = .034), and a higher percentage of positive biopsy cores (mean 39.34 vs. 30.53%; p = .006). Compared to PAA, PDA exhibited a more aggressive tumor biology: (1) Grade groups 4 or 5 (26.6 vs. 9.4%, p < .001), (2) tumor multifocality (89.9 vs. 83.6%; p = .049), and (3) tumor size (mean 2.97 vs. 2.00 cm; p < .001). On multivariate analysis, PDA was independently associated with locally advanced disease (p = .002, hazard ratio [HR]: 2.786, 95% confidence interval [CI]: 1.473–5.263), with a trend towards positive surgical margins (p = .055) and nodal involvement (p = .061). Translating the poorer pathological features to oncological outcomes, presence of PDA independently predicted less likelihood of achieving unrecordable PSA (p = .019, HR: 2.368, 95% CI: 1.152–4.868, and higher BCF (p = .028, HR: 1.918, 95% CI: 1.074–3.423). Subgroup analysis demonstrated that a higher ductal component greater than 15% proportionally predicted worse oncological outcomes, with a shorter time to BCF of 14.3 months compared to 19.8 months in patients with ductal component lesser than 15% (p = .040, HR: 2.660, 95% CI: 1.046–6.757).

Conclusion

PDA is independently associated with adverse pathological and oncological outcomes after RP. A higher proportion of PDA supports a higher BCF rate with a shorter time interval. An aggressive extirpative approach with close monitoring of postoperative serum PSA levels is warranted for these patients.
Characterization and in planta validation of a CHI4 chitinase from Cajanus platycarpus (Benth.) Maesen for its efficacy against pod borer, Helicoverpa armigera (Hübner)
Authors: Rathinam Maniraj , Marimuthu Sathish Kumar , Tyagi Shaily , Kesiraju Karthik , Alagiamanavalan Lakshmi Prabha , Rao Uma , Sreevathsa Rohini
Published: January 2021

BACKGROUND

Pigeonpea, Cajanus cajan is one of the economically important legume food crops and a major source of dietary proteins. Management of pod borer, Helicoverpa armigera has been prominent among crop improvement programs. Lack of resistance sources in the cultivated germplasm and crossing incompatibility with pod borer‐resistant wild relatives have prompted biotechnological interventions. Identification and exploitation of genes from pigeonpea wild relatives in host plant resistance towards the pod borer assumes pertinence. Dynamic transcriptome analysis of the wild relative vis a vis cultivated pigeonpea identified a CHI4 chitinase as one of the putative insect resistance genes.

RESULTS

The study presents variations in important amino acids in CHI4 chitinases from C. cajan and its wild relative C. platycarpus. Comparative protein modeling and docking analysis of the two proteins demonstrated differences in substrate binding efficacy of the chitinase from C. platycarpus which resulted in a minimum binding energy of −8.7 kcal mol−1. Furthermore, we successfully evaluated the insecticidal activity of the chitinase from C. platycarpus against H. armigera challenge through heterologous expression in tobacco. Molecular characterization of transgenic plants confirmed that their efficacy against H. armigera was a result of the integration of CHI4 from C. platycarpus.

CONCLUSION

Docking analysis demonstrated effective substrate interaction as a possible reason for efficacy against pod borer in the chitinase from C. platycarpus. This was authenticated by successful overexpression and bioefficacy assessment against H. armigera in tobacco. The CHI4 gene from C. platycarpus can be useful in the mitigation of H. armegira in pigeonpea as well as in other crops. © 2021 Society of Chemical Industry
Six years of controlling the invasive species Vespa velutina in a Mediterranean island: The promising results of an eradication plan
Authors: Leza Mar , Herrera Cayetano , Picó Gabriela , Morro Toni , Colomar Victor
Published: January 2021

BACKGROUND

The yellow‐legged hornet, Vespa velutina nigrithorax, is an invasive alien species (IAS) which was accidentally introduced in Europe from Asia. This social insect preys primarily on honeybees but also on other pollinators and insects. Consequently, the establishment of this pest has a negative impact on biodiversity, pollination and economy. There is no clear coordination and uniformed methods for eradication measures between countries. Here we present the first field study of the strategy of eradication of the pest species V. velutina that has been conducted in the westernmost Mediterranean archipelago.

RESULTS

We investigated the combination of different eradication methods, such as trapping; the use of the citizen science data for detection of presence, the active search of nests and the removal of nests using mechanical methods. The progression of the number of secondary nests found was 1 (2015), 9 (2016) and 20 (2017), with zero during 2018, 2019 and 2020, and just one embryo nest in 2018. More than half of the nests (58%) were detected thanks to citizen science data. The people sent us adult detections, and we started the triangulation method to find the nests. The last hornet found in the traps was in June 2018.

CONCLUSION

Early detections of the IAS are crucial to minimise their effects, and citizen science may offer an important source of information to determine the presence and distribution of V. velutina. The findings we present here indicate successful management for this globally significant pest and could contribute to advance the ‘science of eradication’. © 2021 Society of Chemical Industry
Plant volatiles guide the new pest Dichelops furcatus to feed on corn seedlings
Authors: Jacobi Vanesa Gisela , Fernandez Patricia Carina , Barriga Lucía Guadalupe , Almeida‐Trapp Marilia , Mithöfer Axel , Zavala Jorge Alberto
Published: January 2021

BACKGROUND

Recently, in temperate and neotropical regions of South America the generalist stink bug Dichelops furcatus (Hemiptera: Pentatomidae) became a new pest of corn (Zea mays) seedlings. Implementation of no‐tillage cultivation system left organic matter covering the soil, which shelters adults of stink bugs during winter. In spring, corn is sowed under soybean stubble and D. furcatus adults start to feed on seedlings. To determine corn‐derived volatile organic compounds (VOCs) that attract this stink bug species, we evaluated stink bug preferences from two corn hybrids with contrast germplasm backgrounds, a temperate and a tropical hybrid.

RESULTS

Stink bugs preferred to feed on temperate seedlings rather than on the tropical ones. GC–MS and PCA analysis of VOCs suggested that hybrids emitted contrasting blends. Linalool represented 68% of total VOCs emitted from temperate corn, while in the tropical hybrid this compound represented 48%. Olfactometer experiments demonstrated that linalool was attractive to stink bugs. However, 2 h of D. furcatus attack induced emission of 14 additional VOCs in temperate seedlings, and olfactometer bioassay and blend of VOCs emission suggested that perceived volatiles by stink bugs induced feeding avoidance. The increment of VOCs emission was associated with the induction of JA, JA‐Ile, ABA, and IAA, and decreasing of SA concentrations.

CONCLUSION

This is the first time showing a complete profile of defensive phytohormones induced by stink bugs feeding on corn, and further demonstrating that a blend of corn seedling‐associated VOCs, mainly composed by linalool, modulates D. furcatus adults' behavior and feeding preferences. © 2021 Society of Chemical Industry
Relative efficiencies of experimental and conventional foliar sprayers and assessment of optimal LWA spray volumes in trellised wine grapes
Authors: Gil Emilio , Salcedo Ramón , Soler Agustí , Ortega Paula , Llop Jordi , Campos Javier , Oliva Jordi
Published: January 2021

BACKGROUND

Leaf wall area (LWA) has been proposed as an appropriate dose expression for field testing of plant protection products (PPPs) applied via

foliar spray in trellised grapes. However, its efficiency could change depending on the characteristics of the crop or the pesticide application equipment (PAE). Herein, three spray technologies were evaluated. A traditional air‐assisted tractor‐mounted sprayer was compared with two portable knapsack sprayers: a backpack mistblower and a backpack hydraulic sprayer. Trials were conducted in trellised wine grapes at three selected crop stages (BBCH 55, 65, 75) covering the main period of canopy development. In each canopy stage, leaf deposition and coverage were sampled for each technology. The tractor‐mounted sprayer was working at 200 L ha−1 of LWA spray volume for the earliest stage and 370 L ha−1 for the other two. Three higher volume rates were used for backpack sprayers up to 800 and 1250 L ha−1 for the mistblower and the hydraulic system, respectively.

RESULTS

Optimal LWA spray volumes differed among application devices in terms of efficiency and uniformity of deposition on the canopy. The efficiency of each spray application also was conditioned by the spray volume.

CONCLUSION

LWA is useful for defining optimal spray volumes in trellised grapes. However, both canopy density and spray technology should be considered to assist this process. Field testing of PPPs and subsequent label recommendations should consider the relative efficiencies of corresponding experimental and conventional spray technologies. © 2021 Society of Chemical Industry
A needle in a seedstack: an improved method for detection of rare alleles in bulk seed testing through KASP
Authors: Brusa Anthony , Patterson Eric L , Gaines Todd A , Dorn Kevin , Westra Philip , Sparks Crystal D , Wyse Don
Published: January 2021

BACKGROUND

Amaranthus palmeri is an aggressive and prolific weed species with major impact on agricultural yield and is a prohibited noxious weed across the Midwest. Morphological identification of A. palmeri from other Amaranthus species is extremely difficult in seeds, which has led to genetic testing for seed identification in commercial seed lots.

RESULTS

We created an inexpensive and reliable genetic test based on novel, species‐specific, single nucleotide polymorphisms (SNPs) from GBS (Genotyping by Sequencing) data. We report three SNP‐based genetic tests for identifying A. palmeri alone or in a mixed pool of Amaranthus spp. Sensitivity ranged from 99.8 to 100%, specificity from 99.59 to 100%. Accuracy for all three tests is > 99.7%. All three are capable of reliably detecting one A. palmeri seed in a pool of 200 Amaranthus spp. seeds. The test was validated across 20 populations of A. palmeri, along with eight other Amaranthus species, the largest and most genetically diverse panel of Amaranthus samples to date.

CONCLUSION

Our work represents a marked improvement over existing commercial assays resulting in an identification assay that is (i) accurate, (ii) robust, (iii) easy to interpret and (iv) applicable to both leaf tissue and pools of up to 200 seeds. Included is a data transformation method for calling of closely grouped competitive fluorescence assays. We also present a comprehensive GBS dataset from the largest geographic panel of Amaranthus populations sequenced. Our approach serves as a model for developing markers for other difficult to identify species. © 2021 Society of Chemical Industry
Film seeds coating with hexane extracts from Illicium verum Hook.f. and Syzygium aromaticum (L.) Merrill & Perry for controlling Callosobruchus maculatus (F.) and Callosobruchus chinensis L
Authors: Pumnuan Jarongsak , Sarapothong Kritima , Sikhao Potjana , Pattamadilok Chutichot , Insung Ammorn
Published: January 2021

BACKGROUND

The application of film seed coating with some plant extracts against stored insect pests was an alternative approach for insect protection instead of using chemical insecticides. The overuse of insecticides has contributed to both human health and environmental problems. The hexane extracts of Illicium verum (HS) and Syzygium aromaticum (HC) were evaluated against bruchid beetles (Callosobruchus maculatus and Callosobruchus chinensis). The insecticidal activities and enhancing seed germination after being coated by various concentrations of extracts, purified fraction (PF) of extracts, standard chemicals of PF, fipronil insecticide (FI), and coating agent groups were evaluated after stored.

RESULTS

Both HS and HC at 3% concentrations were more effective against C. maculatus than C. chinensis with LT50 values of 1.60–1.90 and 3.44–3.62 h, respectively. They could also kill those insects with a higher number than that of standards. The HS and HC could inhibit the progeny population of those insects over 95.6% with no significant difference compared to the FI group. The eugenol standard was the most effective and completely inhibited the emergence compared with trans‐anethol standard and PFs. The seed that was coated with 1% of HS and stored at 4 °C for 6 months showed no effect on seed germination with no significant difference between FI and control groups.

CONCLUSION

The application of 1% of HS incorporated in the film seed coating against bruchid beetles and did not affect seed germination quality after 6 months. © 2021 Society of Chemical Industry
Model‐Informed Pediatric Dose Selection for Dapagliflozin by Incorporating Developmental Changes
Authors: Jo Heeseung , Pilla Reddy Venkatesh , Parkinson Joanna , Boulton David W. , Tang Weifeng
Published: January 2021

This analysis reports a quantitative modeling and simulation approach for oral dapagliflozin, a primarily uridine diphosphate‐glucuronosyltransferase (UGT)–metabolized human sodium‐glucose cotransporter 2 selective inhibitor. A mechanistic dapagliflozin physiologically based pharmacokinetic (PBPK) model was developed using in vitro metabolism and clinical pharmacokinetic (PK) data and verified for context of use (e.g., exposure predictions in pediatric subjects aged 1 month to 18 years). Dapagliflozin exposure is challenging to predict in pediatric populations owing to differences in UGT1A9 ontogeny maturation and paucity of clinical PK data in younger age groups. Based on the exposure–response relationship of dapagliflozin, twofold acceptance criteria were applied between model‐predicted and observed drug exposures and PK parameters (area under the curve and maximum drug concentration) in various scenarios, including monotherapy in healthy adults (single/multiple dose), monotherapy in hepatically or renally impaired patients, and drug–drug interactions with UGT1A9 modulators, such as mefenamic acid and rifampin. The PBPK model captured the observed exposure within twofold of the observed monotherapy data in adults and adolescents and in special population. As a guide to determining dosing regimens in pediatric studies, the verified PBPK model, along with UGT enzyme ontogeny maturation understanding, was used for predictions of dapagliflozin monotherapy exposures in pediatric subjects aged 1 month to 18 years that best matched exposure in adult patients with a 10‐mg single dose of dapagliflozin.
Population pharmacokinetics of letermovir following oral and intravenous administration in healthy participants and allogeneic hematopoietic cell transplantation recipients
Authors: Prohn Marita , Viberg Anders , Zhang Da , Dykstra Kevin , Davis Casey , Macha Sreeraj , Sabato Philip , de Alwis Dinesh , Iwamoto Marian , Fancourt Craig , Cho Carolyn R.
Published: January 2021

Letermovir is indicated for prophylaxis of cytomegalovirus infection and disease in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Two‐stage population pharmacokinetic (PK) modeling of letermovir was conducted to support dose rationale and evaluate the impact of intrinsic/extrinsic factors. Data from healthy phase I study participants over a wide dose range were modeled to evaluate the effects of selected intrinsic factors, including pharmacogenomics; next, phase III HSCT‐recipient data at steady‐state following clinical doses were modeled. The model in HSCT recipients adequately described letermovir PK following both oral or i.v. administration, and was consistent with the healthy participant model at steady‐state clinical doses. Intrinsic factor effects were not clinically meaningful. These staged analyses indicate that letermovir PK in HSCT recipients and healthy participants differ only with respect to bioavailability and absorption rate. The HSCT recipient model was suitable for predicting exposure for exposure–response analysis supporting final dose selection.
Topological Defects in Nematic Liquid Crystals: Laboratory of Fundamental Physics
Authors: Kralj Mitja , Kralj Marko , Kralj Samo
Published: January 2021

Topological defects (TDs) appear in all branches of physics due to the simplicity of generic mechanisms: The necessary condition for their existence is spontaneous symmetry breaking in a relevant physical field. Nematic liquid crystals (NLCs) represent an ideal testbed for their study and they can display point, line, textures, and in favorable conditions also wall defects. TDs in NLCs can be relatively easily created, controlled, and experimentally observed. This enables a detailed and controlled analysis of their physical properties, leading to the cross‐fertilization of knowledge among different areas of physics, including condensed matter, particle physics, and cosmology. Furthermore, TDs in NLCs could be exploited in diverse applications. Herein, some salient features of most common TDs in NLCs, their generic mechanisms, their importance for fundamental science, and possible applications based on them are illustrated.
Dendrobium officinale flos increases neurotrophic factor expression in the hippocampus of chronic unpredictable mild stress‐exposed mice and in astrocyte primary culture and potentiates NGF‐induced neuronal differentiation in PC12 cells
Authors: Zhu Yue , Liu Mengqiu , Cao Cheng , Qu Suchen , Zheng Jiani , Zhu Ziqiang , Chen Zhichun , Wang Zhikang , Zhu Zhenhua , Huang Fei , Duan Jin‐ao
Published: January 2021

Dendrobium officinale flos (DOF) is the flower of Dendrobium officinale Kimura et Migo, which is usually regarded as a by‐product of Dendrobii Offcinalis Caulis. Based on its use as an alternative medicine, we evaluated the antidepressant‐like effect of DOF extracts on chronic, unpredictable, mild stress‐induced, depression‐like behaviour in mice and tested the effects of DOF on the regulation of neurotrophic factors in mouse astrocyte primary cultures and PC12 cell lines. Oral treatment with DOF ethanol extract (DOF‐E) could alleviate depression‐like behaviours in stress‐exposed mice, as evidenced by increased sucrose consumption and decreased immobile time in a forced swim test. In the hippocampus, DOF extracts increased the expression of NGF and BDNF, both at the transcriptional and protein levels. In astrocytes, DOF‐E increased the expression of NGF and BDNF via a cAMP‐dependent mechanism and regulated plasminogen and matrix metallopeptidase 9 (MMP‐9), which are related to the metabolic regulation of neurotrophic factors. In PC12 cells, DOF‐E induced the expression of neurofilaments and potentiated the induction of neurite outgrowth upon treatment with a low dose of NGF. Based on these findings, DOF might be used as a supplement for antidepressant therapy in patients with depression.
Poria cocos could ameliorate cognitive dysfunction in APP/PS1 mice by restoring imbalance of Aβ production and clearance and gut microbiota dysbiosis
Authors: Sun Yufei , Liu Zhiqiang , Pi Zifeng , Song Fengrui , Wu Jianlin , Liu Shu
Published: January 2021

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Amyloid beta‐protein (Aβ) plaques, which are the hallmark of AD, are formed from the imbalance of Aβ production and clearance accompanied by neuroinflammation, gut dysbiosis, and metabolite dysfunction. All of these processes give rise to neurochemical deficiencies and synaptic dysfunction, which ultimately contribute to recognition dysfunction. Poria cocos (PC), which contains multiple active ingredients, plays a significant role in the treatment of multiple‐pathogenesis senile diseases such as AD. Nevertheless, there are only very few investigations on the intricate action mechanism of PC for the treatment of AD. In this study, we evaluate the multi‐target cure effect of PC on APP/PS1 mice by behavioral, immunohistochemical (IHC), targeted metabolomics, and 16S rRNA sequencing experiments. Mice treated with PC showed significant improvements in cognitive function as evaluated by the behavioral experiment. IHC revealed that PC treatment relieved Aβ deposition by reducing the formation of Aβ and increasing its clearance. Moreover, PC treatment improved gut dysbiosis, which reversed the metabolite dysfunction of bile acid. These findings reveal that PC is a promising therapeutic agent, which might ameliorate the cognitive function of AD by restoring the imbalance of Aβ production and clearance and gut microbiota dysbiosis.
Herb–drug interactions between androgenic Chinese herbal medicines and androgen receptor antagonist on tumor growth: Studies on two xenograft prostate cancer animal models
Authors: Zhang Zhen‐Biao , Ip Siu‐Po , Cho William Chi Shing , Ng Anthony Chi Fai , Hu Zhen , Huang Yan‐Feng , Luo Dan‐Dan , Xian Yan‐Fang , Lin Zhi‐Xiu
Published: January 2021

Our previous study revealed that Epimedii Folium (EF) and Codonopsis Radix (CNR) significantly promoted tumor growth on a subcutaneous mouse model of prostate cancer (PCa) via enhancing the mRNA and protein expressions of androgen receptor (AR), while Astragali Radix (AGR) inhibited tumor growth via suppressing the protein expression of AR. In the present study, we aimed to investigate the potential interactions between EF, CNR or AGR and AR antagonist (abiraterone acetate [ABI]) on the tumor growth using subcutaneous and orthotopic PCa mouse models. EF, CNR, AGR and ABI were intragastrically given to mice once every 2 days for 4 weeks. The pharmacokinetics of ABI were evaluated in the plasma of rats when combined with EF, CNR, or AGR. Our results demonstrated that EF or CNR could weaken the anti‐tumor effects of ABI via increasing the AR expression involving activation of the PI3K/AKT and Rb/E2F pathways and decreasing the bioavailability of ABI, while AGR could enhance the anti‐tumor effects of ABI through suppressing the AR expression via inhibiting the activations of PI3K/AKT and Rb/E2F pathways and increasing the bioavailability of ABI. These findings imply that cautions should be exercised when prescribing EF and CNR for PCa patients.
Optimized workflow for unknown screening using gas chromatography high‐resolution mass spectrometry expands identification of contaminants in silicone personal passive samplers
Authors: Travis Steven C. , Kordas Katarzyna , Aga Diana S.
Published: January 2021

Rationale

Silicone wristbands have emerged as valuable passive samplers for monitoring of personal exposure to environmental contaminants in the rapidly developing field of exposomics. Once deployed, silicone wristbands collect and hold a wealth of chemical information that can be interrogated using high‐resolution mass spectrometry (HRMS) to provide a broad coverage of chemical mixtures.

Methods

Gas chromatography coupled to Orbitrap™ mass spectrometry (GC/Orbitrap™ MS) was used to simultaneously perform suspect screening (using in‐house database) and unknown screening (using vendor databases) of extracts from wristbands worn by volunteers. The goal of this study was to optimize a workflow that allows detection of low levels of priority pollutants, with high reliability. In this regard, a data processing workflow for GC/Orbitrap™ MS was developed using a mixture of 123 environmentally relevant standards consisting of pesticides, flame retardants, organophosphate esters, and polycyclic aromatic hydrocarbons as test compounds.

Results

The optimized unknown screening workflow using a search index threshold of 750 resulted in positive identification of 70 analytes in validation samples, and a reduction in the number of false positives by over 50%. An average of 26 compounds with high confidence identification, 7 level 1 compounds and 19 level 2 compounds, were observed in worn wristbands. The data were further analyzed via suspect screening and retrospective suspect screening to identify an additional 36 compounds.

Conclusions

This study provides three important findings: (1) a clear evidence of the importance of sample cleanup in addressing complex sample matrices for unknown analysis, (2) a valuable workflow for the identification of unknown contaminants in silicone wristband samplers using electron ionization HRMS data, and (3) a novel application of GC/Orbitrap™ MS for the unknown analysis of organic contaminants that can be used in exposomics studies.
Surgical outcomes of conventional laparoscopic and robotic‐assisted hysterectomy
Authors: Gitas Georgios , Alkatout Ibrahim , Proppe Louisa , Werner Nele , Rody Achim , Hanker Lars , Pados George , Freytag Damaris , Sommer Soteris , Baum Sascha
Published: January 2021

Introduction

The aim of the present study was to compare surgical outcomes of total laparoscopic hysterectomy with those of the robotic approach using the da Vinci Xi system.

Methods

Patients who underwent hysterectomy with da Vinci Xi for early endometrial cancer or benign indications from 2018 to 2019 were selected. The control group consisted of patients who underwent conventional laparoscopy.

Results

A total of 300 patients were included in the study. The mean duration of surgery differed significantly (p = 0.025) between those who underwent laparoscopy (125.01 ± 76.168) and robotic‐assisted surgery (142.96 ± 82.657 min). Blood loss, median hospital stay, intraoperative and postoperative complications were similar in both groups. No statistical difference was observed in the subgroups with a body mass index of more than 30 kg/m2 or more than 40 kg/m2 concerning the duration of surgery or the surgical outcome.

Conclusion

The da Vinci Xi did not improve surgical outcomes in patients who underwent hysterectomy by trained laparoscopists and takes more time than conventional laparoscopy when performed in patients of normal weight.
Altered gut microbial metabolites could mediate the effects of risk factors in Covid‐19
Authors: Chen Jiezhong , Hall Sean , Vitetta Luis
Published: January 2021

Coronavirus disease 2019 (Covid‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, is now pandemic. While most Covid‐19 patients will experience mild symptoms, a small proportion will develop severe disease, which could be fatal. Clinically, Covid‐19 patients manifest fever with dry cough, fatigue and dyspnoea, and in severe cases develop into acute respiratory distress syndrome (ARDS), sepsis and multi‐organ failure. These severe patients are characterized by hyperinflammation with highly increased pro‐inflammatory cytokines including IL‐6, IL‐17 and TNF‐alpha as well as C‐reactive protein, which are accompanied by decreased lymphocyte counts. Clinical evidence supports that gut microbiota dysregulation is common in Covid‐19 and plays a key role in the pathogenesis of Covid‐19. In this narrative review, we summarize the roles of intestinal dysbiosis in Covid‐19 pathogenesis and posit that the associated mechanisms are being mediated by gut bacterial metabolites. Based on this premise, we propose possible clinical implications. Various risk factors could be causal for severe Covid‐19, and these include advanced age, concomitant chronic disease, SARS‐CoV‐2 infection of enterocytes, use of antibiotics and psychological distress. Gut dysbiosis is associated with risk factors and severe Covid‐19 due to decreased commensal microbial metabolites, which cause reduced anti‐inflammatory mechanisms and chronic low‐grade inflammation. The preconditioned immune dysregulation enables SARS‐CoV‐2 infection to progress to an uncontrolled hyperinflammatory response. Thus, a pre‐existing gut microbiota that is diverse and abundant could be beneficial for the prevention of severe Covid‐19, and supplementation with commensal microbial metabolites may facilitate and augment the treatment of severe Covid‐19.
Unified tracking control under full‐state constraints imposed irregularly
Authors: Cui Qian , Wang Yujuan , Song Yongduan
Published: January 2021

It is nontrivial to address the control problem of nonlinear systems with irregular constraining conditions (where the constraints, possibly time‐varying, asymmetric and alternating positively and negatively, would occur or disappear in the middle of system operation). In this work, we present a control design framework for uncertain pure‐feedback systems under the aforementioned constraining conditions. By making use of auxiliary constraining boundaries, we analytically extend the originally imposed constraints over the entire time interval of system operation, with which we introduce a useful state transformation with unique features. It is such transformation that allows for the development of the control scheme capable of uniformly addressing a variety of constraints formed dynamically and imposed irregularly. It is shown that, for the scenarios where the constraints are partially or fully imposed or removed at any time instant during system operation, one only needs to reset the corresponding extended constraining boundaries in the control scheme instead of altering its structure. Both theoretical analysis and numerical simulation authenticate the effectiveness of the proposed method.
Guaranteed cost control of rigid‐body attitude systems under control saturation
Authors: Wang Hui , Yang Jianan , Liang Ye , Zhu Yanzheng , Zhang Lixian
Published: January 2021

This article investigates the guaranteed cost control (GCC) problem of nonlinear rigid‐body attitude systems subject to control saturation. A novel methodology is proposed, by which the nonlinearities inherent in the attitude dynamics are effectively accounted for and thereby the existence of the proposed controller is cast into linear/bilinear matrix inequality conditions without resorting to model linearization techniques. As a result, the underlying closed‐loop attitude system can be asymptotically stabilized by limited control effort and the defined cost function has an upper bound, by which four optimal GCC methods are further formed to minimize the cost index. Simulation results are provided that fully highlight the properties of the developed methodology in terms of cost guaranteeing and control effort limiting.
XPS characterization of cobalt impregnated SiO2 and γ‐Al2O3
Authors: Cañón Jhonn , Teplyakov Andrew V.
Published: January 2021

SiO2 and γ‐Al2O3 impregnation with nominal 10 and 20% of cobalt was examined using wet impregnation method starting with Co(NO3)2·6H2O. The samples were dried and analyzed by XPS prior to calcination to study the surface species in the solids and the role of the support in the processing of supported cobalt catalysts. The results showed that cobalt introduction alters the few top nanometers of the support materials as there are significant changes recorded in the XPS spectra. Most importantly, there is a remarkable similarity between the O 1s XPS signal of SiO2 and γ‐Al2O3 following Co 20% impregnation, which suggests that these materials could have similar properties in terms of the oxidation ability and the general redox behavior. The shift of Al 2p peaks to higher binding energy (BE) in the XPS investigations and the shift of Si 2p peaks to lower BE were observed for high nominal cobalt loading. These results suggest that the choice of the support in cobalt‐based catalysts would tune the chemical characteristics of cobalt in the final materials.
Scale mixture of skew‐normal linear mixed models with within‐subject serial dependence
Authors: Schumacher Fernanda L. , Lachos Victor H. , Matos Larissa A.
Published: January 2021

In longitudinal studies, repeated measures are collected over time and hence they tend to be serially correlated. These studies are commonly analyzed using linear mixed models (LMMs), and in this article we consider an extension of the skew‐normal/independent LMM, where the error term has a dependence structure, such as damped exponential correlation or autoregressive correlation of orderp. The proposed model provides flexibility in capturing the effects of skewness and heavy tails simultaneously when continuous repeated measures are serially correlated. For this robust model, we present an efficient EM‐type algorithm for parameters estimation via maximum likelihood and the observed information matrix is derived analytically to account for standard errors. The methodology is illustrated through an application to schizophrenia data and some simulation studies. The proposed algorithm and methods are implemented in the newRpackageskewlmm.
Solvent‐Controlled Regioselectivity in Nucleophilic Substitution Reactions of 1‐X‐2,4‐Difluorobenzenes with Morpholine Using Deep Eutectic Solvents
Authors: Valvi Arun , Tiwari Shraeddha
Published: January 2021

Regioselectivity in aromatic nucleophilic substitution (SNAr) reactions of activated substrates is critical but challenging to control. The use of reaction media to achieve the desired regioselectivity is a promising approach, given the sensitivity of nucleophilic substitutions to solute‐solvent interactions. The present report exploits the sensitivity of SNAr reactions to medium effects by using varying compositions of deep eutectic solvents (DES) to achieve excellent regioselectivity. Substitution reactions of 2,4‐difluoroacetophenone (1), 2,4‐diflurobenzonitrile (3) and 2,4‐difluoronitrobenzene (5) with morpholine (2) were carried out in 15 DES mixtures using the “zero VOC” strategy. The regioselectivity was determined using NMR spectra and was observed to change drastically with the substrate and nature of the eutectic mixture. Substitution reaction (1+2) was the most sensitive to reaction medium. The regioselectivity for (1+2) changed from para‐selective (85 : 15 para:ortho ratio) to ortho‐selective (24 : 76 selectivity ratio) by merely changing the DES medium. The results demonstrate that eutectic mixtures could be effectively used as reaction media to control the desired stereochemical outcome.
Thermal Stability, Kinetic Degradation and Lifetime Prediction of Chitosan Schiff Bases Derived from Aromatic Aldehydes
Authors: El Hamdaoui Lahcen , El Marouani Maryam , El Bouchti Mehdi , Kifani‐Sahban Fatima , El Moussaouiti Mohammed
Published: January 2021

This study intends to synthesis chitosan‐aromatic aldehyde Schiff bases (ChSB) to investigate their thermal stability and kinetics degradation. All samples were characterized by FTIR, XRD and SEM techniques. Chitosan and chitosan derivatives were subjected to thermo‐gravimetric analysis, at four multiple heating rates 5, 10, 15 and 20 °C.min−1. Calculations using two isoconversional integral methods, Flynn Wall Ozawa and Kissinger were performed. The changes in Entropy, Enthalpy, Gibbs free energy, and lifetime have been estimated. Thus, chitosan modification with aromatic aldehydes would have an accelerating effect on thermal decomposition. In addition, chitosan p‐chlorobenzaldehyde were found to have the relative highest activation energy and the highest lifetime to thermally decompose amongst the other examined biopolymers. The kinetic process for the degradation of pure chitosan, chitosan‐N,N‐dimethylaminobenzaldehyde and chitosan‐p‐chlorobenzaldehyde was most probably described by an exponential function E1.While for chitosan‐p‐methoxybenzoaldehyde the function D12 corresponding to a mechanism coupling “transfer and diffusion” seems to describe the degradation.
Impedimetric Microfluidic Sensor‐in‐a‐Tube for Label‐Free Immune Cell Analysis
Authors: Egunov Aleksandr I. , Dou Zehua , Karnaushenko Dmitriy D. , Hebenstreit Franziska , Kretschmann Nicole , Akgün Katja , Ziemssen Tjalf , Karnaushenko Daniil , Medina‐Sánchez Mariana , Schmidt Oliver G.
Published: January 2021

Analytical platforms based on impedance spectroscopy are promising for non‐invasive and label‐free analysis of single cells as well as of their extracellular matrix, being essential to understand cell function in the presence of certain diseases. Here, an innovative rolled‐up impedimetric microfulidic sensor, called sensor‐in‐a‐tube, is introduced for the simultaneous analysis of single human monocytes CD14+ and their extracellular medium upon liposaccharides (LPS)‐mediated activation. In particular, rolled‐up platinum microelectrodes are integrated within for the static and dynamic (in‐flow) detection of cells and their surrounding medium (containing expressed cytokines) over an excitation frequency range from 102 to 5 × 106 Hz. The correspondence between cell activation stages and the electrical properties of the cell surrounding medium have been detected by electrical impedance spectroscopy in dynamic mode without employing electrode surface functionalization or labeling. The designed sensor‐in‐a‐tube platform is shown as a sensitive and reliable tool for precise single cell analysis toward immune‐deficient diseases diagnosis.