bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic programming underpins B‐cell dysfunction in peanut and multi‐food allergy
Authors: Imran Samira , Neeland Melanie R , Koplin Jennifer , Dharmage Shyamali , Tang Mimi LK , Sawyer Susan , Dang Thanh , McWilliam Vicki , Peters Rachel , Perrett Kirsten P , Novakovic Boris , Saffery Richard
Published: August 2021

Objective

Rates of IgE‐mediated food allergy (FA) have increased over the last few decades, and mounting evidence implicates disruption of epigenetic profiles in various immune cell types in FA development. Recent data implicate B‐cell dysfunction in FA; however, few studies have examined epigenetic changes within these cells.

Methods

We assessed epigenetic and transcriptomic profiles in purified B cells from adolescents with FA, comparing single‐food‐allergic (peanut only), multi‐food‐allergic (peanut and ≥1 other food) and non‐allergic (control) individuals. Adolescents represent a phenotype of persistent and severe FA indicative of a common immune deviation.

Results

We identified 144 differentially methylated probes (DMPs) and 116 differentially expressed genes (DEGs) that distinguish B cells of individuals with FA from controls, including differential methylation of the PM20D1 promoter previously associated with allergic disorders. Subgroup comparisons found 729 DMPs specific to either single‐food‐ or multi‐food‐allergic individuals, suggesting epigenetic distinctions between allergy groups. This included two regions with increased methylation near three S100 genes in multi‐food‐allergic individuals. Ontology results of DEGs specific to multi‐food‐allergic individuals revealed enrichment of terms associated with myeloid cell activation. Motif enrichment analysis of promoters associated with DMPs and DEGs showed differential enrichment for motifs recognised by transcription factors regulating B‐ and T‐cell development, B‐cell lineage determination and TGF‐β signalling pathway between the multi‐food‐allergic and single‐food‐allergic groups.

Conclusion

Our data highlight epigenetic changes in B cells associated with peanut allergy, distinguishing features of the epigenome between single‐food‐ and multi‐food‐allergic individuals and revealing differential developmental pathways potentially underpinning these distinct phenotypes.
Oncogenic PAX6 elicits CDK4/6 inhibitor resistance by epigenetically inactivating the LATS2‐Hippo signaling pathway
Authors: Zhang Yi , He Long‐Jun , Huang Lin‐Lin , Yao Sheng , Lin Nan , Li Ping , Xu Hui‐Wen , Wu Xi‐Wen , Xu Jian‐Liang , Lu Yi , Li Yan‐Jie , Zhu Sen‐Lin
Published: August 2021

Intrinsic resistance to CDK4/6 inhibitors hinders their clinical utility in cancer treatment. Furthermore, the predictive markers of CDK4/6 inhibitors in gastric cancer (GC) remain incompletely described. Here, we found that PAX6 expression was negatively correlated with the response to palbociclib in vitro and in vivo in GC. We observed that the PAX6 expression level was negatively correlated with the overall survival of GC patients and further showed that PAX6 can promote GC cell proliferation and the cell cycle. The cell cycle is regulated by the interaction of cyclins with their partner serine/threonine cyclin‐dependent kinases (CDKs), and the G1/S‐phase transition is the main target of CDK4/6 inhibitors. Therefore, we tested whether PAX6 expression was correlated with the GC response to palbociclib. We found that PAX6 hypermethylates the promoter of LATS2 and inactivates the Hippo pathway, which upregulates cyclin D1 (CCND1) expression. This results in a suppressed response to palbociclib in GC. Furthermore, we found that the induction of the Hippo signaling pathway or treatment with a DNA methylation inhibitor could overcome PAX6‐induced palbociclib resistance in GC. These findings uncover a tumor promoter function of PAX6 in GC and establish overexpressed PAX6 as a mechanism of resistance to palbociclib.
Visibility of early gastric cancer in texture and color enhancement imaging
Authors: Abe Seiichiro , Yamazaki Takayuki , Hisada Izumi Tanimoto , Makiguchi Mai Ego , Yoshinaga Shigetaka , Sato Tomoya , Nonaka Satoru , Suzuki Haruhisa , Oda Ichiro , Saito Yutaka
Published: August 2021

Objective

There are little data regarding the efficacy of texture and color enhancement imaging (TXI) for early gastric cancer (EGC) diagnosis. This study aimed to compare the color difference and visibility of EGC between white light imaging (WLI) and TXI.

Methods

This study included 20 EGCs of 18 patients undergoing endoscopic submucosal dissection. Still images of EGC in WLI, TXI mode 1 (with color enhancement), and TXI mode 2 (without color enhancement), which were consistent in distance, angle, and air insufflation, were constructed by computer simulation. The center of the lesion, eight equal peripheral points 5 mm outside the lesion, and eight inner points two‐thirds of the distance from peripheral points to the EGC lesion center were annotated. Mean color differences (ΔE) of the area between peripheral and inner points per lesion in WLI, TXI mode 1, and TXI mode 2 were analyzed. In addition, four endoscopists independently scored the visibility of EGC images of TXI mode 1 and 2 compared with WLI.

Results

Clinicopathological characteristics were as follows: 0‐IIa/0‐IIb/0‐IIc/0‐IIa+IIc = 6/1/11/2, reddish/pale = 10/10, differentiated/undifferentiated = 18/2, median tumor size = 13.5 mm. Mean ΔE ± SD = WLI/TXI mode1/TXI mode2 = 10.3 ± 4.7, 15.5 ± 7.8, and 12.7 ± 6.1, respectively. Mean ΔE was significantly higher in TXI mode 1 than in WLI. Visibility (improved/no change/decreased) was 7/13/0 and 4/16/0 in TXI mode 1 and 2, respectively. The visibility was significantly more commonly improved in the macroscopic type 0‐IIc or 0‐IIb than in 0‐IIa or IIa+IIc in TXI mode 1.

Conclusions

TXI could improve the visibility of EGC compared with WLI.
Cobalt‐Catalyzed Asymmetric 1,4‐Reduction of β,β‐Dialkyl α,β‐Unsaturated Esters with PMHS
Authors: Lu Dongpo , Lu Peng , Lu Zhan
Published: August 2021

A cobalt‐catalyzed asymmetric reduction of β,β‐dialkyl α,β‐unsaturated esters with polymethylhydrosiloxane (PMHS) was reported to deliver the corresponding esters containing a chiral trialkyl carbon center at β‐position with up to 97 % yield and 98 % ee. The chiral tridentate ligand oxazoline iminopyridine (OIP) could perform well for the asymmetric reduction instead of chiral bidentate ligands. This operationally simple protocol shows a broad scope of substrates using one equivalent of readily available PMHS as a cheap and easy‐to‐handle reductive reagent.
Fuel flexibility of solid oxide fuel cells
Authors: Weber Andre
Published: August 2021

One of the major advantages of SOFCs is their high fuel flexibility. Next to natural gas and hydrogen, which are today's most common fuels for SOFC‐systems and cell‐/stack‐testing respectively, various other fuels are applicable as well. In the literature, a number of promising results show that available fuels as propane, butane, ammonia, gasoline, diesel etc. can be applied. Here, the performance of an anode supported cell operated in specialized single cell test benches with different gaseous and liquid fuels and reformates thereof is presented. Fuels as ammonia, dissolved urea (AddBlueTM), methane/steam and ethanol/water mixtures can directly be fed to the cell, whereas propane and diesel require external reforming. It is shown that in case of a stable fuel supply the cell performance with such fuels is similar to that of appropriate mixtures of H2, N2, CO, CO2, and steam, if the impact of endothermic reforming or decomposition reactions is considered. Even though a stable fuel cell operation with such fuels is possible in a single cell test bench, it should be pointed out that an appropriate fuel processing will be mandatory on the system level.
Differential interaction with TREM2 modulates microglial uptake of modified Aβ species
Authors: Joshi Pranav , Riffel Florian , Satoh Kanayo , Enomoto Masahiro , Qamar Seema , Scheiblich Hannah , Villacampa Nàdia , Kumar Sathish , Theil Sandra , Parhizkar Samira , Haass Christian , Heneka Michael T. , Fraser Paul E. , St George‐Hyslop Peter , Walter Jochen
Published: August 2021

Rare coding variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2) confer an increased risk for Alzheimer's disease (AD) characterized by the progressive accumulation of aggregated forms of amyloid β peptides (Aβ). Aβ peptides are generated by proteolytic processing of the amyloid precursor protein (APP). Heterogeneity in proteolytic cleavages and additional post‐translational modifications result in the production of several distinct Aβ variants that could differ in their aggregation behavior and toxic properties. Here, we sought to assess whether post‐translational modifications of Aβ affect the interaction with TREM2. Biophysical and biochemical methods revealed that TREM2 preferentially interacts with oligomeric Aβ, and that phosphorylation of Aβ increases this interaction. Phosphorylation of Aβ also affected the TREM2 dependent interaction and phagocytosis by primary microglia and in APP transgenic mouse models. Thus, TREM2 function is important for sensing phosphorylated Aβ variants in distinct aggregation states and reduces the accumulation and deposition of these toxic Aβ species in preclinical models of Alzheimer's disease.
RORα Enhances Lysosomal Acidification and Autophagic Flux in the Hepatocytes
Authors: Kim Hyeon‐Ji , Han Yong‐Hyun , Kim Ju‐Yeon , Lee Mi‐Ock
Published: August 2021

Lysosomes are intracellular acidic organelles with catabolic functions that contribute to the activation of autophagy. Although autophagy abnormality is associated with defects in lysosomal acidification during the progression of nonalcoholic fatty liver disease (NAFLD), the mechanisms of control of lysosomal acidification are not well understood at the molecular level. Thus, we aimed to elucidate the role of the orphan nuclear receptor retinoic acid–related orphan receptor α (RORα) in lysosomal acidification and autophagic flux, particularly in nutrition‐enriched hepatocytes. First, lysosomal acidity was much lower in the hepatocytes obtained from hepatocyte‐specific RORα‐deleted (RORα‐LKO) mice, whereas the infusion of an adenovirus encoding RORα in wild‐type hepatocytes increased lysosomal acidity, as determined by LysoSensor. Second, the lysosomal translocation of the mechanistic target of rapamycin was increased and immature cathepsin D was accumulated in the liver of RORα‐LKO mice. Third, the accumulation of LC3‐II, p62/sequestosome 1 (SQSTM1), and neighbor of BRCA1 gene 1 (NBR1) was increased in the livers of RORα‐LKO mice, indicating an impaired autophagic flux in the livers. Consistently, the number of autolysosomes containing mitochondria and lipid droplets was dramatically reduced in the RORα‐deleted hepatocytes. Finally, we found that RORα induced the transcription of genes involved in lysosomal function, such as Atp6v1g1, a vacuolar H+‐ATPase (v‐ATPase) subunit, which were largely down‐regulated in the livers of mice with high‐fat diet–induced NAFLD and patients with hepatitis. Conclusion: Targeting RORα may be a potential therapeutic strategy to restore lysosomal acidification, which inhibits the progression of NAFLD.
Foldable high‐strength electrode enabled by nanosheet subunits for advanced sodium‐ion batteries
Authors: Wang Hanwei , Fu Jinzhou , Wang Chao , Zhang Ruiwang , Li Yingying , Yang Yushan , Li Haobo , Sun Qingfeng , Li Huiqiao
Published: August 2021

Power sources with strong mechanical properties and high‐energy density are highly desirable for the next‐generation flexible electronics. However, the challenge arises from the current electrode structure design, which is unable to bring both satisfactory mechanical and electrochemical properties with high active materials content and mass. Herein, we reported novel flexible, high‐strength, and mechanically stable TiO2‐based film electrodes for advanced sodium‐ion batteries, achieving an ultrahigh strength (up to ≈60 MPa) and commercial‐level areal capacity (4.5 mAh cm−2). Highly‐dispersed TiO2 and interlaced carbon nanotube (CNT) networks are embedded in the sheet‐liked cellulose to form porous, high‐conductive, and high‐active TiO2‐C nanosheets that is basic building subunits of TiO2‐C films, allowing the films with structural robustness and origami‐level flexibility. This strategy reconciles the contradiction between mechanical properties and active material content in flexible electrodes, and the fabricated electrode with a high TiO2 content of >65% can be bent more than 11 000 times without breaking. Meanwhile, good capacity and excellent cycle stability (0.02‰ capacity‐decay rate over 9000 cycles) of TiO2‐C film under a higher active content (75%) has well satisfied the demands of flexible energy storage devices for electrochemical performances. This TiO2‐C subunit assembly methodology demonstrates enormous potential in high‐strength/toughness flexible electrode construction for flexible electronics.

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Automatic detection of basal cell carcinoma by hyperspectral imaging
Authors: Calin Mihaela Antonina , Parasca Sorin Viorel
Published: August 2021

The purpose of this study was to test the ability of hyperspectral imaging (HSI) combined with unsupervised anomaly detectors to automatically differentiate basal cell carcinoma (BCC) from normal skin. Hyperspectral images of the face of a female patient with a BCC of the lower lip were acquired using a visible/near‐infrared HSI system and two anomaly detection algorithms (Reed‐Xiaoli and Reed‐Xiaoli/Uniform Target hybrid anomaly detectors) were used to detect pathological tissue from normal skin. The results revealed that the receiver operating characteristic curve of the Reed‐Xiaoli/Uniform Target hybrid detector was higher than that of the Reed‐Xiaoli detector in the range of false positive rates between 0 and 0.8. The area under curve values were good (0.7074 and 0.8607, respectively) with Reed‐Xiaoli/Uniform Target hybrid detector performing better. In conclusion, HSI combined with either of two anomaly detectors can play a promising role in the automated screening of BCC.
Intracellular density is a novel indicator of differentiation stages of murine osteoblast lineage cells
Authors: Itoh Yuki , Itoh Shousaku , Naruse Haruna , Kagioka Takumi , Hue Mai Thi , Abe Makoto , Hayashi Mikako
Published: August 2021

Osteoblasts are primary bone‐making cells originating from mesenchymal stem cells (MSCs) in the bone marrow. The differentiation of MSCs to mature osteoblasts involves an intermediate stage called preosteoblasts, but the details of this process remain unclear. This study focused on the intracellular density of immature osteoblast lineage cells and hypothesized that the density might vary during differentiation and might be associated with the differentiation stages of osteoblast lineage cells. This study aimed to clarify the relationship between intracellular density and differentiation stages using density gradient centrifugation. Primary murine bone marrow stromal cell cultures were prepared in an osteogenic induction medium, and cells were separated into three fractions (low, intermediate, and high‐density). The high‐density fraction showed elevated expression of osteoblast differentiation markers (Sp7, Col1a1, Spp1, and Bglap) and low expression of MSC surface markers (Sca‐1, CD73, CD105, and CD106). In contrast, the low‐density fraction showed a high expression of MSC surface markers. These results indicated that intracellular density increased during differentiation from preosteoblasts to committed osteoblasts. Intracellular density may be a novel indicator for osteoblast differentiation stages. Density gradient centrifugation is a novel technique to study the process by which preosteoblasts transform into bone‐forming cells.
Two novel semiconducting B2CO monolayers with high carrier mobilities
Authors: Li Feng , Han Weibo , Cao Zhi , Ji Shilei , Wang Haiyun , Wang Lixia , Wu Hong , Zhu Yuping , Pu Yong
Published: August 2021

The design of new two‐dimensional (2D) materials with moderate band gaps and high carrier mobility is an important aspiration for materials innovation. Recent studies have shown that boron and oxygen atoms can be integrated into the graphene lattice to form a stable B–C–O monolayer structure. To search for the most energetically stable configuration for 2D B–C–O, here, we theoretically propose two new 2D B–C–O crystal structures with a stoichiometric ratio of 2:1:1, namely monolayer (1 L) C3v‐ and C2v‐B2CO. Two configurations have 0.09 and 0.03 eV/unit cell lower energies than the reported 1 L Cs‐B2CO configuration (Nanoscale 2016, 8, 8910). This result is further confirmed by particle swarm optimization (PSO) calculations. According to the chemical bonding analysis, 1 L C3v‐B2CO with a quasi‐planar configuration has the lowest energy, which is consisted of three strong B′–O σ‐bonds, three B″–C σ‐bonds, and one B′–C σ‐bond. As a result, 2D B2CO has an ultra‐high mechanical strength of ~366 J m−2, comparable to graphene ~352 J m−2. In addition, 1 L C3v‐B2CO is a semiconductor with an HSE06 bandgap of 2.57 eV, and it has a high electron mobility of up to ~150 cm2 v−1 s−1. The high kinetic and thermodynamic stabilities of both 1 L C3v‐ and C2v‐B2CO were confirmed according to phonon dispersion and molecular dynamic simulation. Comparable to that of crystalline silicon, 1 L C3v‐B2CO also shows a high light absorption intensity in the 400–550 nm region. Therefore, 2D C3v‐B2CO will have promising applications in semiconductor devices and photodetectors.
Mirroring, monitoring, modelling, belonging, and distancing: Psychosocial processes in an online support group of breast cancer patients
Authors: Montali Lorenzo , Zulato Edoardo , Frigerio Alessandra , Frangi Elisa , Camussi Elisabetta
Published: August 2021

Breast cancer patients are primary users of Internet Health Forums, virtual self‐help communities where they find and share information, preoccupations, and support. Previous literature has mainly focused on analysing the contents and the outcomes of breast cancer forums' participation. In light of the Community of Practice theoretical model, our research investigated the psychosocial processes that build and shape patients' experience and participation in the forum. We conducted 16 semi‐structured email interviews with breast cancer patients recruited within a well‐established online community. Thematic analysis identified five processes—mirroring, monitoring, modelling, belonging, and distancing—that marked three phases of users' experience: initiation, participation, detachment. An interactive dynamic characterised the identified processes: the disease's experience was shaped by and, in turn, it crafted this virtual community. These community processes contributed to participants' empowerment at practical, informative, and emotional levels through the development of a shared repertoire of resources, stories, and ways of dealing with patients' recurring problems.
Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy
Authors: Morigny Pauline , Kaltenecker Doris , Zuber Julia , Machado Juliano , Mehr Lisa , Tsokanos Foivos‐Filippos , Kuzi Hanna , Hermann Chris D. , Voelkl Michael , Monogarov German , Springfeld Christoph , Laurent Victor , Engelmann Bernd , Friess Helmut , Zörnig Inka , Krüger Achim , Krijgsveld Jeroen , Prokopchuk Olga , Fisker Schmidt Søren , Rohm Maria , Herzig Stephan , Berriel Diaz Mauricio
Published: August 2021

Background

Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour‐derived and host‐derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities.

Methods

Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia‐inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and/or protein levels were measured in well‐established mouse models of CCx and in different cohorts of weight‐stable and weight‐losing cancer patients with different tumour entities. Genetic PLA2G7 knock‐down in tumours and pharmacological treatment using the well‐studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour‐bearing mice.

Results

High expression and secretion of PLA2G7 were hallmarks of cachexia‐inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock‐down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx.

Conclusions

Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre‐cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.
Maternal ethanol exposure induces behavioral deficits through oxidative stress and brain‐derived neurotrophic factor interrelation in rat offspring
Authors: Mahdinia Rahebeh , Goudarzi Iran , Lashkarbolouki Taghi , Elahdadi Salmani Mahmoud
Published: August 2021

Alcohol consumption during pregnancy damages the central nervous system of developing fetus and results in persistent physical and neurobehavioral abnormalities, including learning and memory disorders. The hippocampus which is involved in learning and memory is highly susceptible to the ethanol neurotoxic effects. Oxidative stress is one of the mechanisms in alcohol‐induced disorders. Ethanol also interferes with the brain‐derived neurotrophic factors (BDNF) expression. Using vitamin E as a potent antioxidant, we studied the possible interrelation between oxidative stress and BDNF on cognition. Ethanol (4 g/kg) and vitamin E (100, 200, and 400 mg/kg) were given to pregnant Wistar rats on first day of gestation (GD) until weaning (28 days). Oxidative stress marker, BDNF expression, and cyclic AMP‐response binding‐protein (CREB) expression levels were measured on postnatal days (PND) 28. Object location memory (OLM) was evaluated on PND 34. Our results demonstrated that ethanol exposure significantly reduced glutathione peroxidase (GPx) activity, reduced glutathione (GSH), reduced/oxidized glutathione (GSH/GSSG) ratio, and increased superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, and carbonyl protein content in the hippocampus. Total BDNF, BDNF mRNA, and CREB expression significantly reduced in the hippocampus by ethanol exposure. Also, ethanol significantly reduced the discrimination index (DI) in the OLM test. In addition, vitamin E administration could reduce oxidative stress, increase significantly BDNF and CREB levels, and improve cognitive dysfunction induced by ethanol exposure. Collectively, results suggest that probably oxidative stress can interrelate with the BDNF system for modulating cognitive function in the ethanol‐exposed rat.
Structural and histological observations on the male reproductive system of adult red poplar leaf beetle Chrysomela populi Linnaeus, 1758 (Coleoptera: Chrysomelidae)
Authors: Özyurt Koçakoğlu Nurcan
Published: August 2021

This study described the anatomy and histology of the male reproductive system in Chrysomela populi, which is an economically important species belonging to the family Chrysomelidae. Therefore, reproductive biology has been studied to combat this insect. As well as, the characters associated with the reproductive tract have been potential to discuss aspects of the system and to better understand the reproductive dynamics. The male reproductive system of C. populi has a pair of testes, a pair of vas efferentia and deferentia, a pair of seminal vesicles, a pair of accessory glands, an ejaculatory bulb, an ejaculatory duct, and an aedeagus. The testis consists of two flower‐shaped lobes. Each testis has 20 sperm tubules (testicular follicles) containing cysts of germ cells at various developmental stages within the light orange peritoneal sheath. Testicular follicles are composed of three different (growth, maturation, and differentiation) zones. In the middle region of each testis joins with the vas efferens. The testis is attached to the seminal vesicle by a small stalk like vas efferens. In the lumen of the vas efferens, seminal vesicle, and vas deferens, sperms form clumps in the form of thin threads. The proximal end of the vas deferens is connected to the common ejaculatory duct. It joins with the ejaculatory bulb. Around the ejaculator bulb, there is a pair of convoluted, flat‐surface tubular structure accessory glands. Posterior ejaculatory duct joins with the aedeagus.
Jaundice in patients with COVID‐19
Authors: Bender Joshua M , Worman Howard J
Published: August 2021

Background and Aim

While many studies have reported on liver injury in patients with coronavirus disease 2019 (COVID‐19), none have specifically addressed the significance of hepatic jaundice. We aimed to determine the clinical consequences and etiologies of jaundice in patients with COVID‐19.

Methods

We retrospectively analyzed clinical features, laboratory abnormalities, and rates of survival and intensive care unit admission in 551 patients with COVID‐19, hospitalized between 1 March 2020, and 31 May 2020 at a tertiary care academic medical center. Hepatic jaundice was defined as a serum total bilirubin concentration >2.5 mg/dL and a direct bilirubin concentration >0.3 mg/dL that was >25% of the total. Liver injury was characterized as cholestatic, mixed, or hepatocellular at the time of peak serum total bilirubin concentration by calculating the R factor.

Results

Hepatic jaundice was present in 49 (8.9%) patients and associated with a mortality rate of 40.8% and intensive care unit admission rate of 69.4%, both significantly higher than for patients without jaundice. Jaundiced patients had an increased frequency of fever, leukopenia, leukocytosis, thrombocytopenia, hypotension, hypoxemia, elevated serum creatinine concentration, elevated serum procalcitonin concentration, and sepsis. Nine jaundiced patients had isolated hyperbilirubinemia. Of the 40 patients with abnormally elevated serum alanine aminotransferase or alkaline phosphatase activities, 62.5% had a cholestatic, 20.0% mixed, and 17.5% hepatocellular pattern of liver injury.

Conclusion

Hepatic jaundice in patients with COVID‐19 is associated with high mortality. The main etiologies of liver dysfunction leading to jaundice appear to be sepsis, severe systemic inflammation, and hypoxic/ischemic hepatitis.
The effectiveness of inactivated SARS‐CoV‐2 vaccine (CoronaVac) on antibody response in participants aged 65 years and older
Authors: Karamese Murat , Tutuncu Emin E.
Published: August 2021

In this study, it was aimed to determine the antibody responses after the two doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccinations in people who were above 65 years old and to evaluate the factors affecting this response. A total of 235 participants aged 65 years and older were included. Blood samples were taken and data about age, gender, comorbid diseases, and presence of side effects after vaccination were noted. Anti‐SARS‐CoV‐2 QuantiVac ELISA (IgG) test kit (catalogue number: EI‐2606‐9601‐10‐G, Euroimmun) was used. The mean age was 70.38 ± 4.76. Approximately 120 of 235 participants had at least one comorbid disease. The mean levels of anti‐SARS‐CoV‐2 IgG antibody after 4 weeks from the first and second doses of vaccine were 37.70 ± 57.08 IU/ml, and 194.61 ± 174.88 IU/ml, respectively. Additionally, 134 of 235 participants (57.02%) had under 25.6 IU/ml antibody level (negative) after 4 weeks from the first vaccine dose while this rate was 11.48% (n = 27) after 4 weeks from the second vaccine dose. The 19 (70.4%) participants who had under had 25.6 IU/ml antibody level after 4 weeks from the first dose of vaccine had at least one comorbid disease including diabetes mellitus, and 8 (29.6%) participants had no comorbid disease (F = 2.352, p = 0.006). Lower rates of antibody response were detected in participants aged 65 years and older and those with comorbidities both in our study and similar studies in the current literature. Further studies should evaluate whether the low antibody titers are really associated with age and comorbidities or not. Finally, prospective studies are needed to determine how long the immunity provided by SARS‐CoV‐2 vaccines will continue.
Humoral response to spike S1 and S2 and nucleocapsid proteins on microarray after SARS‐CoV‐2 infection
Authors: Portilho Amanda I. , Silva Valéria O. , Ahagon Cintia M. , Matsuda Elaine M. , de Oliveira Elaine L. , da Silveira Edilene P. R. , de Souza Lima Ana K. , Lindoso José A. L. , de Campos Ivana B. , Hong Marisa A. , De Gaspari Elizabeth , de Macedo Brígido Luís F.
Published: August 2021

Many aspects of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), such as its role in protection after natural infection, are still unclear. We evaluated IgA and IgG response to spike subunits 1 and 2 (S1 and S2) and Nucleocapsid proteins of SARS‐COV‐2 in serum samples of 109 volunteers with viral RNA detected or seroconversion with different clinical evolution (asymptomatic, mild, moderate, and severe coronavirus disease 2019), using the ViraChip® Test Kit. We observed that the quantification of antibodies to all antigens had a positive correlation to disease severity, which was strongly associated with the presence of comorbidities. Seroreversion was not uncommon even during the short (median of 77 days) observation, occurring in 15% of mild‐asymptomatic cases at a median of 55 days for IgG and 46 days for IgA. The time to reach the maximal antibody response did not differ significantly among recovered and deceased volunteers. Our study illustrated the dynamic of anti‐S1, anti‐N, and anti‐S2 IgA and IgG antibodies, and suggests that high production of IgG and IgA does not guarantee protection to disease severity and that functional responses that have been studied by other groups, such as antibody avidity, need further attention.
Airway Ultrasound in Critically Ill Patients: A Narrative Review
Authors: Diaz‐Tormo Carmen , Rodriguez‐Martinez Enver , Galarza Laura
Published: August 2021

Airway assessment and management have a central role in critical care medicine. Airway ultrasound can help us evaluate the anatomy, facilitate interventions such as intubation in difficult airways and tracheostomy, prevent post‐extubation complications, and diagnose dysphagia. In this review, we will summarize the current use of ultrasound in airway assessment and management in critically ill patients.
Oscillatory chemical reaction as a sensor of Cu(II)–EDTA complex formation and ligand degradation in copper ion‐catalyzed oxidation of thiocyanate ions with hydrogen peroxide
Authors: Oliwa Przemysław , Orlik Marek
Published: August 2021

The complex dynamics of the homogeneous H2O2–NaSCN–CuSO4–NaOH oscillator is influenced by the addition of EDTA, which manifests itself in the modification or complete suppression of the oscillations. However, depending on EDTA concentration, this effect can be reversible or not. Potentiometric and spectroscopic studies of these phenomena, together with recent discoveries about possible chemical interactions and compound formation in the Cu(II)–H2O2–EDTA system, resulted in the development of a new kinetic mechanism of the complex interaction of EDTA with this oscillatory system. The model involves 13 intermediates and is an extension of our former, 10‐variable mechanism of the H2O2–NaSCN–CuSO4–NaOH oscillator. Reliability of the proposed reaction scheme has been confirmed by numerical calculations, enabling also the estimation of appropriate reaction rate constants. The work is an example of the application of the chemical oscillatory reaction to study qualitatively and quantitatively the interactions of foreign species with the components of positive and negative feedback loops of a chemical dynamical system.
High DNMT1 Is Associated With Worse Local Control in Early‐Stage Laryngeal Squamous Cell Carcinoma
Authors: Bruine de Bruin Leonie , Clausen Martijn J. A. M. , Slagter‐Menkema Lorian , de Bock Gertruida H , Langendijk Johannes A. , van der Vegt Bert , van der Laan Bernard F. A. M. , Schuuring Ed
Published: August 2021

Objectives/Hypothesis

Early‐stage laryngeal squamous cell carcinoma (LSCC) has yielded local control rates of 75% after radiotherapy. DNA methylation, in which DNA methyltransferases play an important role, has influence on tumorigenesis. In this study, we investigated the association between the expression of DNA methyltransferase 1 (DNMT1) and local control in early‐stage LSCC treated with radiotherapy.

Study Design

Retrospective cohort study.

Methods

We analyzed a well‐defined homogeneous series of 125 LSCC patients treated with radiotherapy with curative intent. The association of immunohistochemical expression of DNMT1 with local control was evaluated using Cox proportional hazard regression models.

Results

With a median follow‐up of 58 months, 29 local recurrences (23%) were observed. On univariate analysis, worse local control was associated with high DNMT1 expression (hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.10–6.01). Also, higher T‐stage (HR 2.48, 95% CI 1.06–5.80) and positive N‐status (HR 2.62, 95% CI 1.06–6.47) were associated with worse local control. Multivariate Cox regression demonstrated that high DNMT1 (HR 2.81; 95% CI 1.20–6.58) was independently associated with worse local control.

Conclusions

We found an association between high DNMT1 expression and worse local control in a homogeneous well‐defined cohort of early‐stage LSCC patients treated with definitive radiotherapy. The association between DNA methylation status as determined by DNMT1 expression and local control suggests that DNMT1 acts as a potential prognostic tumor marker in treatment decision‐making in early‐stage laryngeal carcinoma.

Level of evidence

NA Laryngoscope, 132:801–805, 2022
Factors Contributing to Missed Appointments in a Pediatric Otolaryngology Clinic
Authors: Agarwal Pratima , Nathan Ajay S. , Jaleel Zaroug , Levi Jessica R.
Published: August 2021

Objective

To understand why pediatric otolaryngology patients do not attend scheduled clinic appointments and identify factors correlated with no‐show status.

Study Design

Retrospective cohort study.

Methods

This is a retrospective cohort study that uses medical record data extraction of patients that was scheduled to attend new patient appointments at a pediatric otolaryngology clinic in 2018.

Results

Factors associated with no‐shows included complex psychiatric history (OR (95% CI) 0.789 (0.71–0.88), P < .001), increased appointment lead time (OR (95% CI) 0.981 (0.976–0.987), P < .001), afternoon appointments (OR (95% CI) 0.783 (0.64–0.99), P = .038), and complex maternal medical history (OR (95% CI) 0.987 (0.979–0.996), P < .005). In contrast, factors associated with attendance included complex patients’ medical history (OR (95% CI) 1.058 (0.98–1.02), P < .001), primary care physician at the same hospital (OR (95% CI) 2.766 (2.25–3.39), P < .001), and primary language being Spanish (OR (95% CI) 2.536 (1.75–3.67) P < .001). The factors of distance from the hospital (OR (95% CI) 1.001 (0.99–1.01), P = .868), season of appointment (P = .997), race (P = .623), and ethnicity (P = .804) were not associated with attendance or no‐shows.

Conclusion

Patient and maternal medical problems, mental health history, primary care location, appointment lead time, hour of appointment, and primary language, all contribute to appointment attendance, while appointment timing, race, and ethnicity are not associated with attendance. Further work must be performed to overcome these barriers to minimize healthcare risks and improve patient outcomes.

Quality of Evidence

Level 3 Laryngoscope, 132:895–900, 2022
A nonlinear Klein–Gordon equation on a star graph
Authors: Goloshchapova Nataliia
Published: August 2021

We study local well‐posedness and orbital stability/instability of standing waves for a first order system associated with a nonlinear Klein–Gordon equation on a star graph. The proof of the well‐posedness uses a classical fixed point argument and the Hille–Yosida theorem. Stability study relies on the linearization approach and recent results for the NLS equation with the δ‐interaction on a star graph.
Efficiency of the synthetic self‐splicing RiboJ ribozyme is robust to cis‐ and trans‐changes in genetic background
Authors: Vlková Markéta , Morampalli Bhargava Reddy , Silander Olin K.
Published: August 2021

The expanding knowledge of the variety of synthetic genetic elements has enabled the construction of new and more efficient genetic circuits and yielded novel insights into molecular mechanisms. However, context dependence, in which interactions between cis‐ or trans‐genetic elements affect the behavior of these elements, can reduce their general applicability or predictability. Genetic insulators, which mitigate unintended context‐dependent cis‐interactions, have been used to address this issue. One of the most commonly used genetic insulators is a self‐splicing ribozyme called RiboJ, which can be used to decouple upstream 5′ UTR in mRNA from downstream sequences (e.g., open reading frames). Despite its general use as an insulator, there has been no systematic study quantifying the efficiency of RiboJ splicing or whether this autocatalytic activity is robust to trans‐ and cis‐genetic context. Here, we determine the robustness of RiboJ splicing in the genetic context of six widely divergent E. coli strains. We also check for possible cis‐effects by assessing two SNP versions close to the catalytic site of RiboJ. We show that mRNA molecules containing RiboJ are rapidly spliced even during rapid exponential growth and high levels of gene expression, with a mean efficiency of 98%. We also show that neither the cis‐ nor trans‐genetic context has a significant impact on RiboJ activity, suggesting this element is robust to both cis‐ and trans‐genetic changes.
Structure‐based Pharmacophore Screening Coupled with QSAR Analysis Identified Potent Natural‐product‐derived IRAK‐4 Inhibitors
Authors: Khanfar Mohammad A.
Published: August 2021

Interleukin‐1 Receptor‐Associated Kinase 4 (IRAK‐4) has crucial functions in inflammation, innate immunity, and malignancy. Structure‐based pharmacophore modeling integrated with validated QSAR analysis was implemented to discover structurally novel IRAK‐4 inhibitors from natural products database. The QSAR model combined molecular descriptors with structure‐based pharmacophore capable of explaining bioactivity variation of structurally diverse IRAK‐4 inhibitors. Manually built pharmacophore model, validated with receiver operating characteristic curve, and selected using the statistically optimum QSAR equation, was applied as a 3D‐search query to mine AnalytiCon Discovery database of natural products. Experimental in vitro testing of highest‐ranked hits identified uvaretin, saucerneol, and salvianolic acid B as active IRAK‐4 inhibitors with IC50 values in low micromolar range.
Some generalized fractional trapezoid and Ostrowski type inequalities for functions with bounded partial derivatives
Authors: Budak Hüseyin , Özçelik Kubilay
Published: August 2021

In this paper, we first prove three identities for twice partially differentiable functions. Then, by using these equalities, we obtain several trapezoid and Ostrowski type inequalities via generalized fractional integrals for functions with bounded partial derivatives. Moreover, we present some results for Riemann‐Liouville fractional integrals by special choice of main results.
An X‐band centrosymmetric microstrip bandpass filter with reflectionless range over 3.9–18.6 GHz and stopband up to 40 GHz
Authors: Zhang Awei , Xu Jinping , Liu Zhiqiang
Published: August 2021

In this letter, the design of a centrosymmetric absorptive bandpass filter (ABPF) with ultra‐wide reflectionless band at both input and output port and wide stopband is reported. It is based on a balanced‐circuit structure, consisting of a pair of 3‐dB couplers and two channels of conventional reflective bandpass filters (BPFs). The bandwidth of the 3‐dB couplers is maximized, which covers from C‐band up to beyond Ku‐band, to extend the reflectionless band of the ABPF. It is realized by introducing a cross‐fingered defected ground structure (DGS) into the classical coupled‐line coupler to strongly enhance the coupling effect while maintaining a compact size. To suppress the harmonics outside the passband, two C‐shaped DGSs are employed at the input and output ends of the coupled‐line‐based BPF which introduces extra transmission zeros in the stopband. A prototype of the proposed ABPF is fabricated and tested. Measured input/output return loss are better than 10 dB over 3.94–18.63 GHz, which is commonly viewed as the reflectionless band. Moreover, the upper stopband is extended up to 40 GHz with suppression higher than 23 dB. The presented ABPF features advantages in convenient integration, dual‐port ultra‐wide reflectionless band and broad stopband.
A Huygens’ surface approach to rapid characterization of peripheral nerve stimulation
Authors: Davids Mathias , Guerin Bastien , Wald Lawrence L.
Published: August 2021

Purpose

Peripheral nerve stimulation (PNS) modeling has a potential role in designing and operating MRI gradient coils but requires computationally demanding simulations of electromagnetic fields and neural responses. We demonstrate compression of an electromagnetic and neurodynamic model into a single versatile PNS matrix (P‐matrix) defined on an intermediary Huygens’ surface to allow fast PNS characterization of arbitrary coil geometries and body positions.

Methods

The Huygens’ surface approach divides PNS prediction into an extensive pre‐computation phase of the electromagnetic and neurodynamic responses, which is independent of coil geometry and patient position, and a fast coil‐specific linear projection step connecting this information to a specific coil geometry. We validate the Huygens’ approach by performing PNS characterizations for 21 body and head gradients and comparing them with full electromagnetic‐neurodynamic modeling. We demonstrate the value of Huygens’ surface‐based PNS modeling by characterizing PNS‐optimized coil windings for a wide range of patient positions and poses in two body models.

Results

The PNS prediction using the Huygens’ P‐matrix takes less than a minute (instead of hours to days) without compromising numerical accuracy (error ≤ 0.1%) compared to the full simulation. Using this tool, we demonstrate that coils optimized for PNS at the brain landmark using a male model can also improve PNS for other imaging applications (cardiac, abdominal, pelvic, and knee imaging) in both male and female models.

Conclusion

Representing PNS information on a Huygens’ surface extended the approach’s ability to assess PNS across body positions and models and test the robustness of PNS optimization in gradient design.
Cytotoxicity of Amino‐BODIPY Modulated via Conjugation with 2‐Phenyl‐3‐Hydroxy‐4(1H)‐Quinolinones
Authors: Porubský Martin , Vychodilová Kristýna , Milićević David , Buděšinský Miloš , Stanková Jarmila , Džubák Petr , Hajdúch Marián , Hlaváč Jan
Published: August 2021

The combination of cytotoxic amino‐BODIPY dye and 2‐phenyl‐3‐hydroxy‐4(1H)‐quinolinone (3‐HQ) derivatives into one molecule gave rise to selective activity against lymphoblastic or myeloid leukemia and the simultaneous disappearance of the cytotoxicity against normal cells. Both species′ conjugation can be realized via a disulfide linker cleavable in the presence of glutathione characteristic for cancer cells. The cleavage liberating the free amino‐BODIPY dye and 3‐HQ derivative can be monitored by ratiometric fluorescence or by the OFF‐ON effect of the amino‐BODIPY dye. A similar cytotoxic activity is observed when the amino‐BODIPY dye and 3‐HQ derivative are connected through a non‐cleavable maleimide linker. The work reports the synthesis of several conjugates, the study of their cleavage inside cells, and cytotoxic screening.
Associations of physical activity and sedentary behavior with appetite sensations and eating regulation behaviors before and during the initial year following bariatric surgery
Authors: Bond Dale S. , Smith Kathryn E. , Schumacher Leah M. , Vithiananthan Sivamainthan , Jones Daniel B. , Webster Jennifer , Thomas J. Graham
Published: August 2021

Background

Bariatric surgery produces weight loss in part by impacting appetite and eating behavior. Research suggests physical activity (PA) assists with regulation of appetite and eating during non‐surgical weight loss, although whether PA carries similar benefits in the context of bariatric surgery is unknown.

Objective

Evaluate associations of moderate‐to‐vigorous intensity PA (MVPA) and sedentary time (ST) with appetite sensations (hunger [homeostatic/hedonic], satiety) and eating regulation behaviors (restraint, disinhibition) before and during the initial year following bariatric surgery.

Method

Adult bariatric patients received an accelerometer to measure MVPA/ST and a smartphone to complete appetite/eating ratings at four semi‐random times daily for 10 days at pre‐ and 3‐, 6‐, and 12‐months post‐surgery. Data were analyzed using generalized linear mixed models.

Results

Higher MVPA levels related to more satiety across time (p = 0.045) and more restraint at 3‐months post‐surgery (p < 0.001). At pre‐surgery, higher MVPA levels also related to more disinhibition (p's < 0.01), although participants reported more disinhibition on days they performed less MVPA than usual (p = 0.017). MVPA did not relate to hunger. Lower ST levels related to more hedonic hunger (p = 0.003), especially at 12‐months post‐surgery (p < 0.001), and participants reported more homeostatic hunger on days they accumulated more ST than usual (p = 0.044). Additionally, higher ST levels related to more disinhibition at 3‐months post‐surgery (p's < 0.01) and lower restraint at pre‐surgery (p's < 0.05). ST did not relate to satiety.

Conclusions

This study is the first to show that MVPA and ST each associate with appetite and eating regulation in daily life before and during post‐surgical weight loss. Results, while preliminary and requiring experimental confirmation, highlight potential for targeting bariatric patients' activity behaviors to enhance modulation of appetite, control of food intake, and resistance to overeating.