bluuebunny/crossref_metadata_2025 huggingface dataset:
Atractylenolide I ameliorates cancer cachexia through inhibiting biogenesis of IL‐6 and tumour‐derived extracellular vesicles
Authors: Fan Meng , Gu Xiaofan , Zhang Wanli , Shen Qiang , Zhang Ruiqin , Fang Qiaoyu , Wang Yueping , Guo Xiaodong , Zhang Xiongwen , Liu Xuan
Published: September 2022

Background

Atractylenolide I (AI) is a natural sesquiterpene lactone isolated from Atractylodes macrocephala Koidz, known as Baizhu in traditional Chinese medicine. AI has been found to ameliorate cancer cachexia in clinic cancer patients and in tumour‐bearing mice. Here, we checked the influence of AI on biogenesis of IL‐6 and extracellular vesicles (EVs) in cancer cachexia mice and then focused on studying mechanisms of AI in inhibiting the production of tumour‐derived EVs, which contribute to the ameliorating effects of AI on cancer cachexia.

Methods

C26 tumour‐bearing BALB/c mice were applied as animal model to examine the effects of AI (25 mg/kg) in attenuating cachexia symptoms, serum IL‐6 and EVs levels. IL‐6 and EVs secretion of C26 tumour cells treated with AI (0.31–5 μM) was further observed in vitro. The in vitro cultured C2C12 myotubes and 3T3‐L1 mature adipocytes were used to check the potency of conditioned medium of C26 cells treated with AI (0.625–5 μM) in inducing muscle atrophy and lipolysis. The glycolysis potency of C26 cells under AI (0.31–5 μM) treatment was evaluated by measuring the extracellular acidification rate using Seahorse XFe96 Analyser. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms. STAT3 overexpression or knockout C26 cells were also used to confirm the effects of AI (5 μM).

Results

AI ameliorated cancer cachexia symptoms (P < 0.05), improved grip strength (P < 0.05) and decreased serum EVs (P < 0.05) and IL‐6 (P < 0.05) levels of C26 tumour‐bearing mice. AI directly inhibited EVs biogenesis (P < 0.001) and IL‐6 secretion (P < 0.01) of cultured C26 cells. The potency of C26 medium in inducing C2C12 myotube atrophy (+59.54%, P < 0.001) and 3T3‐L1 adipocyte lipolysis (+20.73%, P < 0.05) was significantly attenuated when C26 cells were treated with AI. AI treatment inhibited aerobic glycolysis and the pathway of STAT3/PKM2/SNAP23 in C26 cells. Furthermore, overexpression of STAT3 partly antagonized the effects of AI in suppressing STAT3/PKM2/SNAP23 pathway, EVs secretion, glycolysis and the potency of C26 medium in inducing muscle atrophy and lipolysis, whereas knockout of STAT3 enhanced the inhibitory effect of AI on these values. The inhibition of AI on STAT3/PKM2/SNAP23 pathway was also observed in C26 tumour tissues.

Conclusions

AI ameliorates cancer cachexia by decreasing the production of IL‐6 and EVs of tumour cells. The decreasing effects of AI on EVs biogenesis are based on its inhibition on STAT3/PKM2/SNAP23 pathway.
Optimization of the extraction of bioactive compounds from Muntingia calabura peels and cytotoxic and antiproliferative evaluation by the Allium cepa test
Authors: da Silva Luciana Alves , Aranha Ana Caroline Raimundini , dos Reis Marcela Funaki , Madrona Grasiele Scaramal , da Silva Scapim Monica Regina
Published: September 2022

Objective and Methods

The purpose of this article was to compare the extraction efficiency of bioactive compounds from Muntingia calabura peel using conventional methodology and ultrasound assistance, in addition, to verify the best extraction conditions, varying the drying temperature of the peels, time and solvents, and then to verify the cytotoxic and antiproliferative action of M. calabura extracts by Allium cepa.

Results and Conclusions

It was verified through the analysis of total phenolic compounds, 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) and iron reduction capacity that the best conditions were ultrasonic extraction, with a temperature of 50 °C, 50% aqueous ethanol solution and extraction time of 60 min. Regarding the quantification of total phenolic compounds (TPC), ABTS and ferric reducing antioxidant power (FRAP) in calabura peel, there was a variation of 571.33–1444.67 mg GAE (gallic acid equivalents) 100 g−1 dry peel for TPC, 19.36–115.74 mg Trolox 100 g−1 for ABTS and 306.73–1608.97 for FRAP. Regarding the cytotoxic effect on root growth of A. cepa, it was found that both conventional and ultrasound‐assisted extraction had an effect on onion root growth. In addition, together with the results of the analyzed cells and the literature, it can be verified that M. calabura peels also have an antiproliferative effect. This effect is due to the high concentration of phenolic compounds found in the analyzed extracts; such bioactive compounds are responsible for inhibiting cell division in meristematic cells. © 2022 Society of Chemical Industry (SCI).
The support influence of Au‐based catalysts in glycerin selective oxidation to glyceric acid
Authors: Shen Lingqin , Chen Xinyue , Chen Xiangjing , Qin Yanqin , Shao Shouyan , Zhu Guisheng , Yin Hengbo
Published: September 2022

Background

The sustainable conversion of biomass‐derived glycerin into high‐value‐added chemicals is a significant challenge in contemporary science. In this context, the selective oxidation of aqueous glycerin into glyceric acid was investigated in the presence of NaOH and atmospheric oxygen. It was demonstrated that the selective transformation of glycerin to glyceric acid involves a new chemical reaction path for commodity glyceric acid that is both abundant and economical.

Results

The hydrotalcite‐supported Au nanoparticle catalyst (5%Au/HT) was found to be the most active for glycerin selective transformation to glyceric acid, showing 89.5% glycerin conversion with 61.2% glyceric acid selectivity under optimum experimental conditions. Furthermore, the 5%Au/HT catalyst was reused six times and maintained nearly the same activity in the catalytic recycle experiments.

Conclusion

In the Au‐based catalysts, there are strong electronic interactions between the different supports and Au nanoparticles (Au NPs). Besides, the basic sites of the catalysts participated in promotion of hydroxyl functional groups. © 2022 Society of Chemical Industry (SCI).
COVID‐19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity
Authors: Jiang Wei , Johnson Douglas , Adekunle Ruth , Heather Hughes , Xu Wanli , Cong Xiaomei , Wu Xueling , Fan Hongkuan , Andersson Lars‐Magnus , Robertson Josefina , Gisslén Magnus
Published: September 2022

Coronavirus disease 2019 (COVID‐19) is associated with autoimmune features and autoantibody production in a small subset of the population. Pre‐existing neutralizing antitype I interferons (IFNs) autoantibodies are related to the severity of COVID‐19. Plasma levels of IgG and IgM against 12 viral antigens and 103 self‐antigens were evaluated using an antibody protein array in patients with severe/critical or mild/moderate COVID‐19 disease and uninfected controls. Patients exhibited increased IgGs against Severe acute respiratory syndrome coronavirus‐2 proteins compared to controls, but no difference was observed in the two patient groups. 78% autoreactive IgGs and 93% autoreactive IgMs were increased in patients versus controls. There was no difference in the plasma levels of anti‐type I IFN autoantibodies or neutralizing anti‐type I IFN activity of plasma samples from the two patient groups. Increased anti‐type I IFN IgGs were correlated with higher lymphocyte accounts, suggesting a role of nonpathogenic autoantibodies. Notably, among the 115 antibodies tested, only plasma levels of IgGs against human coronavirus (HCOV)‐229E and HCOV‐NL63 spike proteins were associated with mild disease outcome. COVID‐19 was associated with a bystander polyclonal autoreactive B cell activation, but none of the autoantibody levels were linked to disease severity. Long‐term humoral immunity against HCOV‐22E and HCOV‐NL63 spike protein was associated with mild disease outcome. Understanding the mechanism of life‐threatening COVID‐19 is critical to reducing mortality and morbidity.
Zinc oxide nanoparticles impact the expression of the genes involved in toxin–antitoxin systems in multidrug‐resistant Acinetobacter baumannii
Authors: Shahbazi Shahla , Shivaee Ali , Nasiri Marzieh , Mirshekar Maryam , Sabzi Samira , sariani Omid K.
Published: September 2022

The aim of this study was to investigate the effect of zinc oxide nanoparticles (ZnO‐NPs) on the expression of genes involved in toxin–antitoxin (TA) systems in multidrug‐resistant (MDR) Acinetobacter baumannii. Seventy clinical isolates of A. baumannii were collected from variuos clinical samples. Antimicrobial susceptibility test was determined by disk diffusion. Type II TA system‐related genes including GNAT, XRE‐like, hipA, hipB, hicA, hicB were screened using polymerase chain reaction (PCR). ZnO‐NPs prepared and characterized by field emission scanning electron microscopy and X‐ray diffraction. MIC of ZnO‐NPs of A. baumannii isolates was performed using the microdilution method. The expression of type II TA systems‐related genes were assessed with and without exposure to ZnO‐NPs using real‐time PCR. The highest rate of resistance and sensitivity was observed against cefepime (77.14%), and ampicillin/sulbactam (42.85%), respectively. All A. baumannii isolates were considered as MDR. In this study, three TA loci were identified for A. baumannii including GNAT/XRE‐like, HicA/HicB, and HipA/HipB and their prevalence was 100%, 42%, and 27.1%, respectively. There was no significant relationship between the prevalence of these systems and the origin of A. baumannii. Our data showed significant correlations between the presence of HicA/HicB system and resistance to ceftazidime, meropenem, imipenem, and cefepime (p < 0.05), and the presence of HipA/HipB system and resistance to ceftazidime, meropenem, imipenem, and cefepime (p < 0.05). In presence of ZnO‐NPs, the expression of all studied genes decreased. GNAT and hicB showed the highest and lowest expression changes by 2.4 folds (p < 0.001) and 1.3 folds (p < 0.05), respectively. This study demonstrates the promising potential of nanoparticles to impact the expression of the genes involved in TA Systems. So, the application of ZnO‐NPs may be helpful to design target‐based strategies towards MDRs pathogens for empowered clinical applications by microbiologists and nanotechnologists.
Association between subclinical atherosclerosis and oral inflammation: A cross‐sectional study
Authors: Papi Piero , Pranno Nicola , Di Murro Bianca , Pompa Giorgio , Polimeni Antonella , Letizia Claudio , Petramala Luigi , Concistrè Antonio , Muñoz Aguilera Eva , Orlandi Marco , D'Aiuto Francesco
Published: September 2022

Background

The aim of this cross‐sectional study was to investigate the association between carotid intima‐media thickness (c‐IMT) values and periodontal and peri‐implant diseases in a sample of patients with hypertension.

Methods

A total of 151 participants with presence of at least one dental implant in function for >5 years were recruited. Anthropometric measurements, 24‐h ambulatory blood pressure monitoring, ultrasound assessment of carotid arteries (c‐IMT and presence of plaque) were recorded and venous blood samples obtained. An oral examination was performed by calibrated examiners to ascertain prevalence and severity of periodontal and peri‐implant diseases. Binomial logistic regression was performed to investigate the potential association between various measures of exposure of dental diseases and predictors of cardiovascular risk (c‐IMT > 0.9 mm and presence of plaque or their combination).

Results

Diagnosis of periodontitis (OR 6.71, 95% CI: 2.68‐16.76, P < 0.001), cumulative mucosal/gingival inflammation (Periodontal Screening and Recording score) (OR 1.25, 95% CI:1.12‐1.41, P < 0.001), and mucositis (OR 3.34, 95% CI:1.13‐9.85, P < 0.05) were associated with c‐IMT > 0.9 mm and/or plaque presence independent of age, sex, smoking, 24 h systolic blood pressure and body mass index differences. No statistically significant results were noted for peri‐implantitis. Linear regression models confirmed a positive association of cumulative mucosal/gingival inflammation (β = 0.011, SE 0.002, P < 0.001), diagnosis of periodontitis (β = 0.114, SE 0.020, P < 0.001), and peri‐implant diseases (β = 0.011, SE 0.002, P < 0.001) with increased c‐IMT values.

Conclusions

This study confirms a positive association between mucosal/gingival inflammation and subclinical atherosclerosis assessed by c‐IMT values and the presence of carotid plaque in patients with hypertension, independent of traditional cardiovascular risk factors. Future studies are needed to further characterize this relationship.
Sulfur uptake and distribution, grain yield, and quality of hybrid and inbred winter wheat (Triticum aestivum L.) varieties under early and late waterlogging
Authors: Hussain Md Arif , Naeem Asif , Sulieman Saad , Pitann Britta , Mühling Karl H.
Published: September 2022

Background

Waterlogging at early and later growth stages could affect sulfur (S) uptake, distribution, yield, and quality of winter wheat. We hypothesized that the hybrid winter wheat variety (Hyvento), with a high degree of heterosis and genetic diversity, is likely to uptake and utilize S more efficiently and withstands waterlogging better than the inbred wheat variety (Kredo).

Aims

The objective of the present study was to investigate the effect of 2‐week waterlogging at the end of tillering stage (Feekes Stage 6) and/or ear emergence stage (Feekes Stage 10.1) on grain yield, yield components, S‐uptake and its partitioning, and composition of grain storage proteins (glutenins and gliadins) of hybrid (Hyvento) and inbred (Kredo) winter wheat varieties.

Methods

Plants were grown in large containers (120 L) in a semi‐controlled greenhouse and harvested three times immediately after each waterlogging treatment and at agronomic maturity. Grain yield, S concentration in different plant organs, total protein content, and patterns of gluten proteins (gliadin and glutenin) and their subunits (by sodium dodecyl sulfate–polyacrylamide gel electrophoresis) in grains were evaluated.

Results

Grain yield of the inbred variety was more negatively affected under early and late waterlogging than the hybrid variety and was associated with reduced grain size. The decline in grain yield was significantly higher under late waterlogging (30%–31%) than early waterlogging (17%–18%). Compared to the hybrid variety Hyvento, the waterlogging‐induced decline in S concentration in grains, husk, and straw was markedly lower in the inbred variety Kredo. While early waterlogging did not affect total grain protein content in either of the varieties, late waterlogging significantly reduced the total grain protein content (18%) in the inbred variety Kredo. Similarly, the grain gliadin content of the hybrid variety was not affected by both waterlogged conditions, whereas 32% and 23% reductions were recorded for the inbred variety under early and late waterlogging, respectively. Nevertheless, waterlogging significantly increased the proportion of S‐poor high‐molecular‐weight glutenin subunits and ω‐gliadin in the inbred variety.

Conclusion

It could be inferred from the present study that hybrid winter wheat variety is relatively resistant to waterlogging than the inbred wheat variety, and thereby produces higher grain yield. Efficient uptake and metabolism of S could be one of the mechanisms conferring waterlogging resistance in winter wheat.
The development of heat‐resistant and salt‐tolerant foam with betaine surfactants
Authors: Zhang Tianci , Ge Jijiang , Guo Hongbin , Li Longjie , Huang Lan , Wang Jianhai , Su Ziwei
Published: September 2022

A modified instrument was designed to evaluate foam properties under high temperature and pressure. The type and molar ratio of betaine surfactants were screened to develop the heat‐resistant and salt‐tolerant foam for Tahe oilfield (130°C, 220 g/L), and the effects of temperature and pressure on foam properties were also investigated. The synergism between surfactants and the enhanced oil recovery (EOR) mechanism of foam flooding in fractured‐vuggy reservoirs were studied. Experimental results showed the developed foam had excellent foaming ability and foam stability when the lauramidopropyl hydroxyl sulfobetaine (LHSB): erucic amide propyl betaine (EAB) molar ratio ranged from 1:1 to 1:2 (initial foam volume was 392 ml when the molar ratio was 1:1, drainage half‐time was 5.75 min and foam half‐time was 72 min when the molar ratio was 1:2 at 130°C and 2 MPa). The synergistic effect was found to reach its maximum when the LHSB:EAB molar ratio ranged from 1:1 to 1:2 according to interaction parameters, which agreed with the results of foam properties. Foam stability was found to considerably increase with increasing pressure, but decrease with increasing temperature. However, temperature and pressure were found to have consistent effects on foaming ability, that is, the foaming ability increased with increasing temperature and pressure. The flooding test showed foam flooding exhibited better sweep efficiency and higher recovery ratio in the fractured‐vuggy model than gas flooding and water flooding. This could be because injected foam did not channel through the top (or bottom) path due to its high viscosity and moderate density.
Cellular antioxidant mechanism of mannan‐oligosaccharides involving in enhancing flesh quality in grass carp (Ctenopharyngodon idella)
Authors: Lu Zhi‐Yuan , Jiang Wei‐Dan , Wu Pei , Liu Yang , Ren Hong‐Mei , Jin Xiao‐Wan , Kuang Sheng‐Yao , Li Shu‐Wei , Tang Ling , Zhang Lu , Mi Hai‐Feng , Zhou Xiao‐Qiu , Feng Lin
Published: September 2022

BACKGROUND

Deterioration of flesh quality has bad effects on consumer satisfaction. Therefore, effects of safe mannan‐oligosaccharides (MOS) on flesh quality of grass carp (Ctenopharyngodon idella) muscle were studied. A total of 540 healthy fish (215.85 ± 0.30 g) were randomly divided into six groups and fed six separate diets with graded levels of MOS (0, 200, 400, 600, 800 and 1000 mg kg−1) for 60 days. This study aimed at investigating the benefits of dietary MOS on flesh quality (fatty acids, amino acids and physicochemical properties) and the protection mechanism regarding antioxidant status.

RESULTS

Optimal MOS could improve tenderness (27.4%), pH (5.5%) while decreasing cooking loss (16.6%) to enhance flesh quality. Meanwhile, optimal MOS improved flavor inosine 5′‐monophosphate (IMP) of 11.8%, sweetness and umami‐associated amino acid, healthy unsaturated fatty acid (UFA) of 14.9% and n‐3 polyunsaturated fatty acids (n‐3 PUFAs) especially C20:5n‐3 (15.8%) and C22:6n‐3 (38.3%). Furthermore, the mechanism that MOS affected pH, tenderness and cooking loss could be partly explained by the reduced lactate, cathepsin and oxidation, respectively. The enhanced flesh quality was also associated with enhanced antioxidant ability concerning improving antioxidant enzymes activities and the corresponding transcriptional levels, which were regulated through NF‐E2‐related factor 2 (Nrf2) and target of rapamycin (TOR) signaling. Based on pH24h, cooking loss, shear force and DHA (docosahexaenoic acid, C22:6n‐3), optimal MOS levels for grass carp were estimated to be 442.75, 539.53, 594.73 and 539.53 mg kg−1, respectively.

CONCLUSION

Dietary MOS is a promising alternative strategy to improve flesh quality of fish muscle. © 2022 Society of Chemical Industry.
Application of definitive screening design to optimization of the protein extraction and functional properties of proteins in Auricularia auricula
Authors: Yang Mengdie , Qian Zheng , Zhan Qiping , Zhong Lei , Hu Qiuhui , Zhao Liyan
Published: September 2022

BACKGROUND

Auricularia auricula (A. auricula) is one of the most abundant sources of plant protein in edible fungi. Problems of low protein yield exist in traditional methods of protein extraction such as alkali extraction and ultrasonic‐assisted alkali after pretreatment with enzymes. Thus, the protein extraction process was investigated and optimized using a definitive screening design from A. auricula to improve the protein yield under practical operating conditions of temperature, the concentration of NaCl, meal/water ratio, extraction time and pH.

RESULTS

The yield of protein isolates of the isoelectric‐ammonium sulfate precipitation (9.34% w/w) was obtained almost three times and the protein content (55.23% w/w) was approximately 1.6 times that of the traditional extraction method of isoelectric precipitation. Next, the optimized method was successfully applied to the analysis of the functional properties of the protein. A. auricula protein isolate (AAPI) had better solubility, emulsification and foaming capacity than soy protein isolate (SPI) and pea protein isolate (PPI), and the oil holding capacity of AAPI exhibited extremely well, which was approximately five times that of SPI and six times that of PPI. The texture properties of AAPI gel were similar to those of PPI gels.

CONCLUSION

AAPI extracted by the optimized method had a satisfactory yield and had the potential to substitute plant‐originated proteins in food processing. © 2022 Society of Chemical Industry.
L‐Theanine regulates lipid metabolism by modulating gut microbiota and bile acid metabolism
Authors: Xu Wei , Kong Yingying , Zhang Tuo , Gong Zhihua , Xiao Wenjun
Published: September 2022

BACKGROUND

l‐Theanine (LTA) is a biologically active ingredient in tea that shows great potential for regulating lipid metabolism. Bile acids (BA), an important end‐product of cholesterol catabolism, participate in the regulation of lipid metabolism and gut microbiota. Here, we investigated the effect of LTA on lipid metabolism and the mechanism by which it regulates BA metabolism and gut microbiota. Male BALB/c mice were treated with LTA for 28 days.

RESULTS

Daily LTA doses of 100 and 300 mg kg−1 d−1 altered the gut microbiota in mice, predominantly by decreasing Lactobacillus, Streptococcus, Bacteroides, Clostridium and Enterorhabdus microbes associated with bile‐salt hydrolase (BSH) activity, thereby decreasing the activity of BSH and increasing the levels of ileum conjugated BA (such as glycocholic acid (GCA) and lithocholic acid), thereby inhibiting the intestinal farnesoid X receptor (FXR)‐fibroblast growth factor 15 (FGF15) signaling pathway. Inhibition of FXR‐FGF15 signaling was accompanied by upregulation of cholesterol 7α‐hydroxylase (CYP7A1) mRNA and protein expression and increased hepatic production of cholic acid, deoxycholic acid, GCA, glycine cholic acid and glycine ursodeoxycholic acid. Meanwhile, increasing hepatic unconjugated BA upregulated the mRNA and protein expression of liver 3‐hydroxy‐3‐methylglutaryl‐CoA reductase and downregulated the mRNA and protein expression of stearoyl‐CoA desaturase‐1, liver low‐density lipoprotein receptor and type B scavenger receptor. Therefore, the serum levels of cholesterol and triglycerides decreased.

CONCLUSION

Our findings indicate that LTA regulates lipid metabolism by modulating the gut microbiota and BA metabolism via the FXR‐FGF15‐CYP7A1 pathway. © 2022 Society of Chemical Industry.
Fifty years of bone tumors
Authors: Bartelstein Meredith K. , Boland Patrick J.
Published: September 2022

There have been enormous advances in the treatment of bone tumors over the past half‐century. The most notable of these has been the transition from amputation as the standard of care to limb salvage surgery. This transition is the result of advances in imaging techniques, accurate diagnosis, systemic therapies (including chemotherapy), and prosthetic design for the reconstruction of musculoskeletal defects. Advances have also been made in the management of benign and metastatic bone tumors.
Head and neck surgical oncology
Authors: Shah Jatin P. , Wong Richard J.
Published: September 2022

During the past five decades, major technological advances, including availability of imaging techniques such as computed tomography, magnetic resonance imaging, and positron emission tomography scans, have improved accurate assessment of tumors. Major advances in reconstructive surgery with development of microvascular free‐flap reconstruction have made one‐stage resection and reconstruction a reality, leading to a better quality of life. Multimodality treatments combining chemotherapy with radiation have led to development of organ preservation strategies and improved locoregional control of head and neck cancer.
Advances in the treatment of pediatric solid tumors: A 50‐year perspective
Authors: LaQuaglia Michael P. , Gerstle Justin T.
Published: September 2022

In the United States, more than 10 000 cancers occur annually in children aged 0–14 years, and more than 5000 in adolescents aged 15–19. In the last 50 years, significant advances have been made in imaging, molecular pathology, stage and risk assessment, surgical approach, multidisciplinary treatment, and survival for pediatric solid tumors (particularly neuroblastoma, Wilms tumor, rhabdomyosarcoma, and hepatoblastoma). Moreover, the molecular driver for fibrolamellar hepatocellular carcinoma, which occurs in adolescence and young adulthood, has been identified.
Fifty years of progress in surgical oncology: Melanoma
Authors: Coit Daniel G. , Ariyan Charlotte E.
Published: September 2022

This paper outlines the scientific and clinical advances in the treatment of melanoma over the past 50 years. Among the highlights of progress, the dominant themes include evidence‐based reduction in the extent and morbidity of surgical procedures in patients with local or regional melanoma without compromising end results, and the introduction of effective systemic therapy, specifically targeted therapy matched to patients based on specific tumor mutations, and immune checkpoint blockade. Management of advanced disease has also changed dramatically, due to improved understanding of the genomic variability of the disease as well as continuing improvements in imaging.
Hearing Loss in Exfoliation Syndrome: Systematic Review and Meta‐Analysis
Authors: Shih Michael C. , Gordis Tamar M. , Lambert Paul R. , Nguyen Shaun A. , Meyer Ted A.
Published: September 2022

Objective

To determine if exfoliation syndrome (XFS) is associated with hearing loss (HL) or vestibular dysfunction.

Data Sources

PubMed, Scopus, CINAHL, and Cochrane Library through April 1, 2022.

Review Methods

Two reviewers independently screened abstracts, selected articles for inclusion, and extracted data. Studies included for qualitative analysis conducted audiometric, tympanometric, or vestibular evaluations on all subjects.

Results

Twenty‐one publications (1148 patients with XFS and 1212 controls) were included in the systematic review, and 16 publications (968 patients with XFS and 1147 controls) in the meta‐analysis. Greater severity of HL was seen for patients with XFS compared to controls across all frequencies (odds ratio [OR] 8.8 [7.3–10.2]). Patients with XFS were more likely to have moderate to profound sensorineural HL (OR 1.8 [1.3–2.5]), and less likely to have none to mild HL (OR 0.34 [0.17–0.67]) or no HL (OR 0.37 [0.28–0.50]). Three studies found patients with XFS had lower tympanometric peaks. Two studies found that abnormal vestibular testing results could be more common for patients with XFS.

Conclusions

HL is associated with XFS. A sensorineural component to HL is confirmed, and mixed HL is possible. Given the high prevalence and infrequent diagnosis of XFS, the authors hypothesize that the current understandings of presbycusis might be improved by further investigation in XFS. Laryngoscope, 133:1025–1035, 2023
Prevalence of New‐Onset Tinnitus after COVID‐19 Vaccination with Comparison to Other Vaccinations
Authors: Dorney Ian , Bobak Lukas , Otteson Todd , Kaelber David C.
Published: September 2022

Objective

To investigate how often patients are diagnosed with new‐onset tinnitus within 21 days after COVID‐19 vaccination in comparison to after three other common vaccinations: influenza, Tdap (tetanus, diphtheria, and acellular pertussis), and polysaccharide pneumococcus.

Methods

The TriNetX Analytics Network, a federated health research network that aggregates the de‐identified electronic health record (EHR) data of over 78 million patients, was queried for patients receiving each vaccination. Instances of new‐onset tinnitus within 21 days of vaccination were recorded and reported.

Results

Out of 2,575,235 patients receiving a first dose of the mRNA COVID‐19 vaccine without any prior tinnitus diagnosis, 0.038% (95% CI: 0.036%–0.041%) of patients had a new diagnosis of tinnitus within 21 days. There was a higher risk of a new tinnitus diagnosis after the influenza vaccine (RR: 1.95, 95% CI: 1.72–2.21), Tdap vaccine (RR: 2.36, 95% CI: 1.93–2.89), and pneumococcal vaccine (RR: 1.97, 95% CI: 1.48–2.64) than after the first dose of the COVID‐19 vaccine. There was a lower risk of a new tinnitus diagnosis after the second dose of COVID‐19 than after the first dose (RR: 0.80, 95% CI: 0.71–0.91).

Conclusion

The rate of newly diagnosed tinnitus acutely after the first dose of the COVID‐19 vaccine is very low. There was a higher risk of newly diagnosed tinnitus after influenza, Tdap, and pneumococcal vaccinations than after the COVID‐19 vaccine. The present findings can help to address COVID‐19 vaccine hesitancy during the ongoing pandemic.

Level of Evidence

Level 3 Laryngoscope, 133:1722–1725, 2023
Construction of Degradable and Amphiphilic Triblock Polymer Carriers for Effective Delivery of siRNA
Authors: Yan Yunfeng , Zhu Fangtao , Su Huahui , Liu Xiaomin , Ren Qidi , Huang Fangqian , Ye Wenbo , Zhao Mengdan , Zhao Yunchun , Zhao Junpeng , Shuai Qi
Published: September 2022

The development of effective and safe delivery carriers is one of the prerequisites for the clinical translation of siRNA‐based therapeutics. In this study, a library of 144 functional triblock polymers using ring‐opening polymerization (ROP) and thiol‐ene click reaction is constructed. These triblock polymers are composed of hydrophilic poly (ethylene oxide) (PEO), hydrophobic poly (ε‐caprolactone) (PCL), and cationic amine blocks. Three effective carriers are discovered by high‐throughput screening of these polymers for siRNA delivery to HeLa‐Luc cells. In vitro evaluation shows that siLuc‐loaded nanoparticles (NPs) fabricated with leading polymer carriers exhibit sufficient knockdown of luciferase genes and relatively low cytotoxicity. The chemical structure of polymers significantly affects the physicochemical properties of the resulting siRNA‐loaded NPs, which leads to different cellular uptake of NPs and endosomal escape of loaded siRNA and thus the overall in vitro siRNA delivery efficacy. After systemic administration to mice with xenograft tumors, siRNA NPs based on P2‐4.5A8 are substantially accumulated at tumor sites, suggesting that PEO and PCL blocks are beneficial for improving blood circulation and biodistribution of siRNA NPs. This functional triblock polymer platform may have great potential in the development of siRNA‐based therapies for the treatment of cancers.
Metal Ion‐Directed Coordination Programming of Biomolecules to Bioinspired Nanoflowers
Authors: Butreddy Pravalika , Holden Hunter , Rathnayake Hemali
Published: September 2022

Bioinspired molecular and macromolecular systems could be a driver for new generation semiconductor‐synthetic biology (Semi‐Syn‐Bio) technologies, shifting the materials design paradigm by utilizing bioinspired and biological structures to design molecular and supramolecular architectures as bionanomaterials in the fabrication of devices and components. Herein, a simple and rapid self‐assembly approach of interfacial coordination programming of a biological amphiphile, a fatty acid, using a transition metal ion, copper cation (Cu2+) to direct the formation of nanoflowers of Cu2+‐conjugated supramolecular structures is demonstrated. The fatty acid molecules form complexes with the copper ions and then self‐assemble into microstructures with flower‐like petals, which are highly nanoporous thin sheets. The growth of microstructures is found to be independent from the precursors’ stoichiometric ratios, demonstrating a versatile interfacial coordination programming approach to make crystalline, uniquely shaped‐double peony flower‐like microstructures. It is anticipated that design principles and directed self‐assembly approaches for the interfacial coordination programming of biomolecules may advance the state‐of‐the‐art of biomaterials research, providing deeper understanding in the paradigm of design, synthesis, self‐assembly, and fabrication of Semi‐Syn‐Bio superstructure systems.
Cryo‐EM structure of G‐protein‐coupled receptor GPR17 in complex with inhibitory G protein
Authors: Ye Fang , Wong Thian‐Sze , Chen Geng , Zhang Zhiyi , Zhang Binghao , Gan Shiyi , Gao Wei , Li Jiancheng , Wu Zhangsong , Pan Xin , Du Yang
Published: September 2022

GPR17 is a class A orphan G protein‐coupled receptor (GPCR) expressed in neurons and oligodendrocyte progenitors of the central nervous system (CNS). The signalling of GPR17 occurs through the heterotrimeric Gi, but its activation mechanism is unclear. Here, we employed cryo‐electron microscopy (cryo‐EM) technology to elucidate the structure of activated GPR17‐Gi complex. The 3.02 Å resolution structure, together with mutagenesis studies, revealed that the extracellular loop2 of GPR17 occupied the orthosteric binding pocket to promote its self‐activation. The active GPR17 carried several typical microswitches like other class A GPCRs. Moreover, the Gi interacted with the key residues of transmembrane helix 3 (TM3), the amphipathic helix 8 (Helix8), and intracellular loops 3 (ICL3) in GPR17 to engage in the receptor core. In summary, our results highlight the activation mechanism of GPR17 from the structural basis. Elucidating the structural and activation mechanism of GPR17 may facilitate the pharmacological intervention for acute/chronic CNS injury.
Homozygous CADPS2 Mutations Cause Neurodegenerative Disease with Lewy Body‐like Pathology in Parrots
Authors: Lorenzo‐Betancor Oswaldo , Galosi Livio , Bonfili Laura , Eleuteri Anna Maria , Cecarini Valentina , Verin Ranieri , Dini Fabrizio , Attili Anna‐Rita , Berardi Sara , Biagini Lucia , Robino Patrizia , Stella Maria Cristina , Yearout Dora , Dorschner Michael O. , Tsuang Debby W. , Rossi Giacomo , Zabetian Cyrus P.
Published: September 2022

Background

Several genetic models that recapitulate neurodegenerative features of Parkinson's disease (PD) exist, which have been largely based on genes discovered in monogenic PD families. However, spontaneous genetic mutations have not been linked to the pathological hallmarks of PD in non‐human vertebrates.

Objective

To describe the genetic and pathological findings of three Yellow‐crowned parrot (Amazona ochrocepahala) siblings with a severe and rapidly progressive neurological phenotype.

Methods

The phenotype of the three parrots included severe ataxia, rigidity, and tremor, while their parents were phenotypically normal. Tests to identify avian viral infections and brain imaging studies were all negative. Due to their severe impairment, they were all euthanized at age 3 months and their brains underwent neuropathological examination and proteasome activity assays. Whole genome sequencing (WGS) was performed on the three affected parrots and their parents.

Results

The brains of affected parrots exhibited neuronal loss, spongiosis, and widespread Lewy body‐like inclusions in many regions including the midbrain, basal ganglia, and neocortex. Proteasome activity was significantly reduced in these animals compared to a control (P < 0.05). WGS identified a single homozygous missense mutation (p.V559L) in a highly conserved amino acid within the pleckstrin homology (PH) domain of the calcium‐dependent secretion activator 2 (CADPS2) gene.

Conclusions

Our data suggest that a homozygous mutation in the CADPS2 gene causes a severe neurodegenerative phenotype with Lewy body‐like pathology in parrots. Although CADPS2 variants have not been reported to cause PD, further investigation of the gene might provide important insights into the pathophysiology of Lewy body disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
A review of causal discovery methods for molecular network analysis
Authors: Kelly Jack , Berzuini Carlo , Keavney Bernard , Tomaszewski Maciej , Guo Hui
Published: September 2022

Background

With the increasing availability and size of multi‐omics datasets, investigating the casual relationships between molecular phenotypes has become an important aspect of exploring underlying biology andgenetics. There are an increasing number of methodlogies that have been developed and applied to moleular networks to investigate these causal interactions.

Methods

We have introduced and reviewed the available methods for building large‐scale causal molecular networks that have been developed and applied in the past decade.

Results

In this review we have identified and summarized the existing methods for infering causality in large‐scale causal molecular networks, and discussed important factors that will need to be considered in future research in this area.

Conclusion

Existing methods to infering causal molecular networks have their own strengths and limitations so there is no one best approach, and it is instead down to the discretion of the researcher. This review also to discusses some of the current limitations to biological interpretation of these networks, and important factors to consider for future studies on molecular networks.
Resurfacing of lower extremities: Versatility of thigh flap as pedicle extension graft with consecutive thoracodorsal artery perforator‐based flap
Authors: Choi Ji Seon , Seo Hyun Joon , Park Ji Ah , Kim Youn Hwan , Shim Hyung‐Sup
Published: September 2022

Background

For successful microsurgical reconstruction using free tissue transfer, healthy recipient vessels must be obtained from outside the zone of injury. Securing an appropriate length pedicle length is also essential, and various techniques for lengthening a vascular pedicle have been developed. Herein, we present our experience using the descending branch (DB) of the lateral circumflex femoral vessels (LCFVs) with a thigh flap as an extender graft for consecutive second flap.

Methods

We reconstructed the complex and vessel‐depleted defects of nine patients. The mean age was 47.6 years. The defects were located in the lower leg in four patients, in the perineum in two patients and in the forearm in three patients. The two patients who suffered from Fournier's gangrene underwent a pedicled anteromedial thigh (pAMT) flap with the DB of the LCFVs and seven patients, five who suffered high‐energy trauma and two who had scar contracture, underwent a free anterolateral thigh (ALT) flap with the distal run‐off DB of the LCFVs. In all patients, second consecutive free latissimus dorsi or thoracodorsal artery perforator flaps were prepared and the thoracodorsal vessels of the second flap were anastomosed to the distal DB of the LCFVs.

Results

The total length of the thigh flap pedicles measured from both ends of the DB of the LCFVs varied from 15 to 20 cm, which was sufficient for use as a vascular conduit. Of the 18 flaps, 17 survived completely without any complications and 1 pAMT flap showed partial necrosis, which was covered with a perineal perforator‐based island flap. The mean follow‐up period was 16.7 months. Unfortunately, one patient, who suffered a total amputation below the knee and had replantation surgery, underwent amputation due to venous congestion in the distal leg. However, the previous two flaps survived and were used for coverage of the stump.

Conclusions

Using a thigh flap as a vascular extender graft for second flap may be an alternative option in vessel‐depleted reconstructions.
Analysis the dispersive nature of Love wave in fibre‐reinforced composite materials plate: A Green's function approach
Authors: Kumar Dharmendra , Kumhar Raju , Kundu Santimoy , Gupta Shishir
Published: September 2022

The research article mainly focuses on investigating the dispersive behaviour of Love waves influenced by an impulsive point source in a fibre‐reinforced magnetoelastic (FRME) plate placed on functionally graded fibre‐reinforced visco‐elastic (FGFRVE) semi‐infinite stratum. The materials of the considered structure have been assumed under the influence of magnetic field and functionally graded. The functionally graded in the lower semi‐infinite space is caused by consideration of quadratic variation in the shear moduli and mass density. Maxwell's equation and generalised Ohm's law have been employed to calculate the Laurentz force in the fibre‐reinforced magnetoelastic (FRME) plate. For solving the coupled field equations, three‐dimensional Green's function and Fourier transform are applied; consequently, the closed‐form of the Love wave's dispersion relation is obtained. The obtained dispersion curve is plotted and compared in the numerical results and discussions by taking the different magnitude of materials quantities such as reinforcement parameter, magnetoelastic coupling parameter, functionally graded parameter, and visco‐elastic parameter. In some particular cases, the deduced dispersion equation is found to be identical to the classical Love wave equation for uniform homogeneous isotropic cases, indicating that the assumed structures are valid. The obtained results from the entire study can be utilised to better understand the dispersive nature of Love wave propagation in the considered systems containing fibre‐reinforced, magnetoelastic, viscoelastic, and point sources.
Limit analysis of masonry walls using discontinuity layout optimization and homogenization
Authors: Valentino John , Gilbert Matthew , Gueguin Maxime , Smith Colin C.
Published: September 2022

A numerical limit analysis model for masonry walls subject to in‐plane loading is posed as a discontinuity layout optimization (DLO) problem, with the masonry conveniently modeled using a smeared continuum (“macromodeling”) approach and a homogenized yield surface. Unlike finite element limit analysis, DLO is formulated entirely in terms of discontinuities and can produce accurate solutions for problems involving singularities naturally, without the need for mesh refinement. In the homogenized model presented, masonry joints are reduced to interfaces, with sliding governed by an associative friction flow rule and blocks are assumed to be infinitely resistant. The model takes account of the interlock ratio of the masonry blocks, their aspect ratio and the cohesion and coefficient of friction of interfaces in both the vertical and horizontal directions. Results from the proposed model are compared with those from the literature, showing that complex failure mechanisms can be identified and that safe estimates of load carrying capacity can be obtained. Finally, to demonstrate the utility of the proposed modeling approach, it is applied to more complex problems involving interactions with other elements, such as voussoir arches and weak underlying soil layers.
Ballistic impact response and failure mechanism of aluminum/ultrahigh molecular weight polyethylene fiber laminates with different adhesive quantity
Authors: Ge Fei , Zhang Zhongwei , Sun Minqian , Lin Yuan , Wu Jianan , Xiong Ziming , Wang Mingyang
Published: September 2022

The aim of this study is to investigate the effects of metal‐composite interface (MCI) adhesive quantity on the energy absorption and failure behavior of fiber metal laminates (FMLs) under ballistic impact. The dynamic shear and ballistic impact tests were systematically conducted, and CT scan was employed to quantitatively investigate the damage and failure mechanisms of the FMLs. The results reveal that the dynamic shear strength of MCI initially increases and then remains constant with the increase in the adhesive quantity at a constant strain rate. Moreover, the MCI adhesive quantity has a certain influence on the impact energy absorption of FMLs, and the degree of influence is related to the impact velocity. At an impact velocity of 360 m/s, the difference of energy absorption is maximal, approximately 14.7%. The distribution of total debonding area changes with increase in the adhesive quantity. When the impact velocity is 212 m/s, compared to FMLs with the lowest adhesive quantity, the total debonding area of FMLs with the highest adhesive quantity decreases by 774.57 mm2 (9.20%), otherwise the debonding area near the rear aluminum alloy sheet increases by 595.94 mm2 (58.99%).
Brain cancer patients' levels of distress and supportive care needs over time
Authors: Halkett Georgia K. B. , Lobb Elizabeth , Spilsbury Katrina , Dhillon Haryana , Nowak Anna K.
Published: September 2022

Purpose

This study aimed to describe patient self‐reported distress over time and how this was associated with wellbeing, and supportive care needs over a 6‐month period from commencing chemoradiotherapy for high grade glioma (HGG).

Methods

In this prospective cohort study, participants completed surveys at three time points: before chemoradiotherapy, at 3 and 6 months. These included Distress Thermometer, Functional Assessment of Cancer/Brain Cancer Treatment‐general (Fact‐G/FACT‐BR), Supportive Care Needs Scale (SF‐34) and Brain Tumour Specific subscale. Patient survival time was also collected. Group‐based trajectory modelling was performed. Multinominal logistic regression assessed variables associated with different distress trajectory groups.

Results

One hundred and sixteen participants completed assessments at baseline, 89 participants at 3 and 64 at 6 months. Four distress trajectory groups were identified; consistent low distress (18%), low to high distress (38%), high‐to low distress (24%) and consistent high distress (19%). Younger participants tended to report decreased distress over time, whereas older participants reported consistently high distress. High distress trajectory participants had less education, lower physical wellbeing, more unmet needs, but higher functional wellbeing compared to the low to high distress trajectory. The number of unmet needs paralleled the patterns of distress over time. The highest unmet needs in people with HGG and high distress were disease specific changes in mental ability and physical side effects.

Conclusion

This study demonstrates people with HGG experience ongoing distress and highlights a need for continuous distress and unmet needs screening and referrals.