bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting SARS‐CoV‐2 with Chaga mushroom: An in silico study toward developing a natural antiviral compound
Authors: Eid Jehane Ibrahim , Das Biswadeep , Al‐Tuwaijri Majdah Mohamed , Basal Wesam Taha
Published: October 2021

The novel coronavirus (SARS‐CoV‐2) has caused large‐scale global outbreaks and mainly mediates host cell entry through the interaction of its spike (S) protein with the human angiotensin‐converting enzyme‐2 (ACE‐2) receptor. As there is no effective treatment for SARS‐CoV‐2 to date, it is imperative to explore the efficacy of new compounds that possess potential antiviral activity. In this study, we assessed the potential binding interaction of the beneficial components of Chaga mushroom, a natural anti‐inflammatory and immune booster with that of the SARS‐CoV‐2 receptor‐binding domain (RBD) using molecular docking, MD simulation, and phylogenetic analysis. Beta glycan, betulinic acid, and galactomannan constituents of Chaga mushroom exhibited strong binding interaction (−7.4 to −8.6 kcal/mol) forming multivalent hydrogen and non‐polar bonds with the viral S1‐carboxy‐terminal domain of the RBD. Specifically, the best interacting sites for beta glycan comprised ASN‐440, SER 373, TRP‐436, ASN‐343, and ARG 509 with average binding energy of −8.4 kcal/mol. The best interacting sites of galactomannan included ASN‐437, SER 373, TRP‐436, ASN‐343, and ALA 344 with a mean binding energy of −7.4 kcal/mol; and the best interacting sites of betulinic acid were ASN‐437, SER 373, TRP‐436, PHE 342, ARG 509, and ALA 344 that strongly interacted with the S‐protein (ΔG = −8.1 kcal/mol). The docking results were also compared with an S‐protein binding analog, NAG and depicted similar binding affinities compared with that of the ligands (−8.67 kcal/mol). In addition, phylogenetic analysis using global isolates depicted that the current SARS‐CoV‐2 isolates possessed a furin cleavage site (NSPRRA) in the RBD, which was absent in the previous isolates that indicated increased efficacy of the present virus for enhanced infection through increased interaction with ACE‐2. The results showed that Chaga could be an effective natural antiviral that can supplement the current anti‐SARS‐CoV‐2 drugs.
Macronutrient content and fatty acid composition and their positional distribution in human breast milk from Zhejiang Province, China in different lactation periods
Authors: He Guanghua , Li Guipu , Jiang Yanxi , Hua Jiacai , Chu Xiaojun , Xiong Lina , Gong Jinyan , Xiao Gongnian , Ye Xingqian
Published: October 2021

Lactational changes in macronutrient content, lipid profile, fatty acid composition, and positional distribution of human breast milk were investigated in this study. A total of 378 milk samples of six different lactation periods, including 0‒5, 6‒14, 15‒30, 31‒90, 91‒180, and 181‒360 days, were collected cross‐sectionally from healthy lactating women in Zhejiang, China. As lactation progressed from 0‒5 to 15‒30 days, the lipid content and the percentages of C10:0, C12:0, C14:0, C18:2n‐6, and C18:3n‐3 increased significantly, while the protein concentration and the proportions of phospholipids, cholesterols, C16:0, C18:1n‐9, C24:1n‐9, C20:4n‐6, C22:4n‐6, C22:5n‐3, and C22:6n‐3 decreased notably. When lactation was further extended to 181‒360 days, the protein content continued to decrease, and the percentages of C12:0 and C14:0 continued to increase, whereas the levels of other tested nutrients remained stable. Although the triacylglycerol positional distributions of some fatty acids underwent significant lactational variations, C14:0, C16:0, C24:1n‐9, C22:4n‐6, C22:5n‐3, and C22:6n‐3 were located mainly at the sn‐2 position, while C18:1n‐9, C18:2n‐6, and C18:3n‐3 were primarily distributed at the sn‐1,3 positions. Compared with human breast milk reported in Western countries, samples in our study demonstrated higher percentages of C18:2n‐6, C18:3n‐3, C20:4n‐6, and C22:6n‐3, but lower proportions of C12:0, C14:0, and C18:1n‐9. The results from this study indicated a nutritional composition different from that of the Western countries and may provide useful data for the development of infant formulas closer to Chinese breast milk in terms of the fatty acid composition and its specified positional distribution on triglyceride structure.
Fluid circulation in the South Tibetan Detachment System: Evidence from fluid inclusions and oxygen isotope data of quartz veins in the Ramba Dome, North Himalayan Gneiss Domes
Authors: Li Xiaorong , Zhang Bo , Cheng Feng , Zhang Jinjiang , Wang Yang , Chen Siyu , Liu Siqi , Zhang Lei , Huang Baoyou
Published: October 2021

Detachment faults are sites of intensive fluid–rock interactions. Here, we report fluid inclusion and oxygen isotope data for quartz veins in the Ramba Dome in the North Himalayan Gneiss Domes, with an aim to constrain the origin and circulation of crustal fluids associated with the South Tibetan Detachment System (STDS). Microthermometric data for fluid inclusions in quartz indicate that the fluids were aqueous and CO2 − H2O ± CH4 ± N2‐bearing with low to moderate salinities (0.60–11.80 wt% eq. NaCl). The entrapment conditions are 295–410°C and 98–135 Mpa, indicating a forming‐depth of 8–10 km. Oxygen isotopic compositions (δ18O) of quartz measured in situ by secondary ion mass spectrometry and bulk by the BrF5 method show limited variations in individual quartz veins, but δ18Oquartz values vary from 12.07 to 18.16‰ (V‐SMOW) among veins. The corresponding δ18Ofluid values range from 7.71 to 13.80‰, based on equilibrium temperatures obtained from fluid inclusions. From the footwall to the detachment zone, δ18Ofluid values exhibit a broadly decreasing trend and indicate that the STDS dominated the fluid flux pathway in the crust, with more contributions of meteoric water in the detachment zone. We further quantified the contribution of meteoric fluids to 8–27% using a binary end‐member mixing model. These data imply that the fluids were predominantly metamorphic/magmatic in origin, and were mixed with infiltrating, isotopically light, meteoric water during extensional detachment shearing of the STDS. The meteoric water can infiltrate from the surface to 8–10 km depth.
Community Socioeconomic Deprivation Predicts Nonalcoholic Steatohepatitis
Authors: Giammarino Alexa M. , Qiu He , Bulsara Kishen , Khan Sabrina , Jiang Yu , Da Ben L. , Bernstein David E. , Satapathy Sanjaya K.
Published: October 2021

In order to determine the relationship between socioeconomic deprivation and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), we retrospectively reviewed the electronic medical records of 1,430 patients in a large tertiary health care network in New York. These patients underwent liver biopsy over a 10‐year period and were included in our study if they had evidence of NAFLD/NASH on liver biopsy. Zip codes were used to obtain data necessary to derive the social deprivation index (SDI) from the US Bureau of the Census. The high‐SDI group was compared to the low‐SDI group. Univariate and multivariate logistic regressions were performed to assess association between socioeconomic factors and NAFLD parameters, including presence of NASH (NAFLD activity score >4), moderate to severe steatosis (>33%), and significant fibrosis (S2‐S4). We included 614 patients with NAFLD/NASH; the median SDI was 31.5. Hemoglobin A1c values were higher in the high‐SDI group compared to the low‐SDI group (6.46 vs. 6.12, P = 0.02). Socioeconomic factors, such as private versus public health care, percentage being foreign born, percentage without a car, percentage with higher needs (<5 years old and >65 years old), and percentage currently living in renter‐occupied and crowded housing units, showed statistically significant associations in predicting NASH. After adjusting for patient age, sex, race, body mass index, and diabetes, we saw a significant association between four or more socioeconomic parameters in predicting NASH (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.099‐2.856; P = 0.0190) and six or more socioeconomic parameters in predicting severe steatosis (OR, 1.498; 95% CI, 1.031‐2.176; P = 0.0338) but no significant correlation between the number of socioeconomic parameters and significant fibrosis. Conclusion: Greater number of socioeconomic determinants (four or more) are associated with greater severity of NASH. Awareness of NAFLD/NASH needs to be raised in communities with high socioeconomic deprivation.
Overlapping grid spectral collocation approach for electrical MHD bioconvection Darcy–Forchheimer flow of a Carreau–Yasuda nanoliquid over a periodically accelerating surface
Authors: Mkhatshwa M. P.
Published: October 2021

The focus of this study is on computational grid‐manipulation to enhance the accuracy, convergence, and computational efficiency of the multidomain bivariate spectral local linearization method (MD‐BSLLM). The improved method is used in the scrutiny of Darcy–Forchheimer bioconvection flow of Carreau–Yasuda nanofluid induced by an oscillatory moving surface with cross‐diffusion, activation energy with binary chemical reactive species, combined electrical and magnetohydrodynamic field effects. The proposed method is utilized in solving the nondimensional form of the flow equations. Sensitivity and error analyses are provided to aid an understanding of the efficiency, stability, convergence rate, and accuracy of the iterative scheme. The impact of different parameter values on fluid properties and transport phenomena is discussed. Numerical simulation has indicated that the overlapping grid MD‐BSLLM is computational efficacious, and produces stable and sufficiently accurate results using a few collocation nodes in each respective subinterval and the entire computational domain. Other findings include the fact that fluid properties are enhanced with injection while flow characteristics are improved with suction. Using the Darcy–Forchheimer model in the flow analysis improves the temperature of the nanofluid. The imposition of electric field augments nanofluid velocity, the amplitude of skin friction coefficient, rates of mass, and motile microorganisms transfer while reducing the rate of heat transfer. The considered flow analysis can contribute towards engineering solicitations in paper production, polymer solution, metal extrusion, and glass blowing.
Surface Pyroelectricity and Piezoelectricity of Centrosymmetric Crystals
Authors: Meirzadeh Elena , Dishon Shiri , Lubomirsky Igor , Ehre David
Published: October 2021

Properties of surfaces often define functionalities and applications of a large variety of materials, e. g., epitaxial growth of thin films, catalytic and optical properties. For this reason, advances in techniques for surface characterization are of great importance. Here we present an overview of the work conducted together with Prof. Meir Lahav over the last decade to detect and quantify near surface polar layers (NSPL). Though thin, these layers may accumulate considerable polarization and, thereby, affect surface properties. We demonstrated that pyroelectric measurement carried out with periodic temperature change protocol (modified Chynoweth) might be a primary tool to study NSPL. Two fundamentally different examples are considered. (i) NSPL in α‐glycine crystals develops as a result of solvent incorporation, e. g., water. This layer is maybe tens or even hundreds of micrometers thick, sometimes, thick enough to allow piezoelectric measurements. (ii) NSPL in SrTiO3 results from surface relaxation and it is only a few Angstroms thick. Nevertheless, NSPL in SrTiO3 has a polarization comparable with strongly ferroelectric materials, tens of μC/cm2.
Cancer of the cervix uteri: 2021 update
Authors: Bhatla Neerja , Aoki Daisuke , Sharma Daya Nand , Sankaranarayanan Rengaswamy
Published: October 2021

Since the publication of the 2018 FIGO Cancer Report, giant strides have been made in the global effort to reduce the burden of cervical cancer, with the World Health Organization (WHO) rolling out a global strategy for cervical cancer elimination, aiming for implementation by 2030. In over 130 countries, including low‐ and middle‐income countries, HPV vaccination is now included in the national program. Screening has seen major advances with wider implementation of HPV testing. These interventions will take a few years to show their impact. Meanwhile, over half a million new cases are added each year. FIGO’s revised staging of cervical cancer (2018) has been widely implemented and retrospective analyses of data based on the new staging have been published. Minimally invasive surgery has been shown to be disadvantageous in women with cervical cancer. This chapter discusses the management of cervical cancer based on the stage of disease, including attention to palliation and quality of life issues.
Cancer of the vulva: 2021 update
Authors: Olawaiye Alexander B. , Cuello Mauricio A. , Rogers Linda J.
Published: October 2021

Vulvar cancer is an uncommon gynecological malignancy primarily affecting postmenopausal women. There is no specific screening and the most effective strategy to reduce vulvar cancer incidence is the opportune treatment of predisposing and preneoplastic lesions associated with its development. While vulvar cancer may be asymptomatic, most women present with vulvar pruritus or pain, or have noticed a lump or ulcer. Therefore, any suspicious vulvar lesion should be biopsied to exclude invasion. Once established, the most common subtype is squamous cell carcinoma. Treatment of vulvar cancer depends primarily on histology and surgical staging. Treatment is predominantly surgical, particularly for squamous cell carcinoma, although concurrent chemoradiation is an effective alternative, particularly for advanced tumors. Management should be individualized and carried out by a multidisciplinary team in a cancer center experienced in the treatment of these tumors.
Modelling the Darcy–Weisbach friction factor and the energy gradient of the lateral line*
Authors: Jardim Alexandre Maniçoba da Rosa Ferraz , Silva José Raliuson Inácio , Silva Marcos Vinícius da , Souza Luciana Sandra Bastos de , Araújo Júnior George do Nascimento , Alves Hygor Kristoph Muniz Nunes , Mesquita Márcio , Souza Paulo Jorge de Oliveira Ponte de , Teixeira Antônio Heriberto de Castro , Silva Thieres George Freire da
Published: October 2021

The objective was to adjust explicit mathematical models to determine the friction factor (f). Besides, an adaptation of the Blasius model is presented and an application of the Darcy–Weisbach equation to estimate the energy loss along the lateral line for four types of microsprinklers. f was determined by the model of Offor and Alabi and the model of Blasius for velocities between 0.5 to 3.0 m s−1 and internal pipe diameters of 0.0130, 0.0161, 0.0206, 0.0270, 0.0288, and 0.0368 m. The friction factor determined by Offor and Alabi was associated with the pipe diameters utilizing regression, and based on that an adaptation to the Blasius model was proposed. From the results of f, the energy and flow gradient along the lateral line for four NaanDanJain microsprinklers was simulated. The models of Offor and Alabi, Blasius, and Adapted Blasius showed excellent precision in determining f. The results of unit head loss, determined by the three mathematical models, showed dispersion close to zero among the pairs, showing a high correlation between the models (R2 = 0.99). The Blasius equation is the most suitable to be inserted into the Darcy–Weisbach model to determine the maximum length of the lateral line.
Global contributions of pharmacists during the COVID‐19 pandemic
Authors: Goff Debra A. , Ashiru‐Oredope Diane , Cairns Kelly A. , Eljaaly Khalid , Gauthier Timothy P. , Langford Bradley J. , Mahmoud Sara Fouad , Messina Angeliki P. , Michael Ubaka Chukwuemeka , Saad Thérèse , Schellack Natalie
Published: October 2021

Throughout the SARS‐CoV‐2 (COVID‐19) global pandemic, pharmacists were rarely mentioned as essential frontline health care providers by the news media, the public, or politicians. Around the world, pharmacists are working on the frontlines of health care every day providing essential health care services during the pandemic. Pharmacists are medication experts providing patient care in a variety of settings including hospitals, clinics, community pharmacies, long‐term care, physician offices, and national and public health. In this paper, we describe how pharmacists from high and low‐middle income countries contributed to essential patient care and well‐being of the public during the COVID‐19 pandemic. While the news media, the public, and politicians often overlooked pharmacists as essential frontline health care providers, we hope that this list of contributions by pharmacists from nine countries in this article can help to change this perspective.
Treatment of microvascular invasion in hepatocellular carcinoma with drug‐loaded nanocomposite platform under synergistic effect of magnetic field/near‐infrared light
Authors: Liu Daren , Wu Jinhong , Zhu Huanbing , Zhu Xiuliang , Jin Yun , Yu Yuanquan , Zhang Xiaoxiao
Published: October 2021

Despite progress in clinical treatment, microvascular invasion (MVI) remains a major factor for frequent recurrence and metastasis of hepatocellular carcinoma (HCC) after liver resection and surgery. Thus, this study constructed a target nanoplatform (αCD97‐USPIO‐Au‐DDP) with magnetic field/near‐infrared (NIR) light response using ultrasmall superparamagnetic iron oxide‐gold nanoporous spheres (USPIO‐Au) as multifunctional nanocarrier. Anticancer drug cisplatin (DDP) was loaded, and specifically expressed CD97 protein in MVI was taken as the therapeutic target. The αCD97‐USPIO‐Au‐DDP showed favorable photothermal and stable properties under the NIR light at 808 nm wavelength. As suggested by in vitro and in vivo research, this composite nanopreparation could effectively reduce damage to normal organs and showed good biocompatibility. Excellent magnetic targeting function of nanocarrier and modification of αCD97 strengthened accumulation of composite nanodrug in tumor to inhibit tumor growth. This system may have important ramifications for treatment of MVI in HCC.
Characteristics of Long-Term Femoral Neck Bone Loss in Postmenopausal Women: A 25-Year Follow-Up
Authors: Moilanen Anna , Kopra Juho , Kröger Heikki , Sund Reijo , Rikkonen Toni , Sirola Joonas
Published: October 2021

The aim of this study was to monitor long-term changes in bone mineral density (BMD) after menopause and factors affecting BMD. The study population consisted of a random sample of 3222 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study, of which 62.1% were postmenopausal at the beginning of the study. This group of women underwent dual-energy X-ray absorptiometry (DXA) measurements at the femoral neck every 5 years from baseline (in 1989) up to 25-year follow-up. They also responded to risk-factor questionnaires at 5-year intervals. During the 25-year follow-up, the baseline cohort decreased to 686 women. The women were divided into quartiles based on their baseline BMD. Self-reported hormone replacement therapy (HRT) and corticosteroid use were divided into ever users and never users. Morbidity was assessed as the total number of self-reported diseases and BMD-affecting diseases. The mean 25-year BMD change was found to be −10.1%, p < 0.001. Higher baseline BMD was associated with higher bone loss rate; the reduction in the highest quartile BMD was 11.1% and in the lowest quartile 7.4% (p = 0.0031). Lower baseline body mass index (BMI) and a greater increase in BMI were found to protect against postmenopausal bone loss (p < 0.001). The lowest bone loss quartile included 15.2% more HRT users than the highest bone loss quartile (p = 0.004). The number of diseases/bone-affecting diseases, use of vitamin D/calcium supplementation, use of corticosteroids, smoking or alcohol use had no statistical significance for annual bone loss rate. This study presents hitherto the longest (25-year) BMD follow-up in postmenopausal women. The linear femoral neck bone loss of 10% was less than previously assumed. A 5-year BMD change appeared to predict long-term bone loss in postmenopausal women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Thymol ameliorates 5‐fluorouracil‐induced intestinal mucositis: Evidence of down‐regulatory effect on TGF‐β/MAPK pathways through NF‐κB
Authors: Al‐Khrashi Layla A. , Badr Amira M. , AL‐Amin Maha A. , Mahran Yasmen F.
Published: October 2021

5‐Fluorouracil (5‐FU) is a front‐line cytotoxic therapy. However, intestinal mucositis is a well‐known adverse event of 5‐FU, which limits its therapeutic use. Indeed, thymol, which is a monoterpene component of the essential oil derived from thymus, has a potential anti‐inflammatory and immunomodulatory activity. Therefore, this study aimed to investigate the potential chemoprotective effect of thymol against 5‐FU‐induced intestinal mucositis. Rats were either exposed to two doses of 5‐FU (150 mg/kg, ip) and/or treated with thymol (60 or 120 mg/kg). Oxidative stress and inflammatory markers, as well as pathological changes, were assessed. 5‐FU‐induced severe intestinal damages as were evidenced by histopathological changes as well as oxidative and inflammatory responses. Thymol pretreatment inhibited 5‐FU‐induced oxidative stress by reducing lipid peroxidation and increasing intestinal levels of antioxidant systems. Moreover, inflammatory response markers, such as interleukin‐6, prostaglandin E2, and COX‐2 were also improved. The immunoblotting analysis also showed that thymol significantly inhibited the 5‐FU‐induced expression of nuclear factor‐κB, tumor necrosis factor‐α, and transforming growth factor β‐1 (TGF‐β1), in addition to the suppression of p38 and phosphorylated c‐Jun N‐terminal kinases (p‐JNK) mitogen‐activated protein kinase proteins' expressions. Our study is the first to demonstrate the promising protective effect of thymol against 5‐FU‐induced intestinal mucositis through inhibition of oxidative, inflammatory pathways, and suppression of TGF‐β/p38/p‐JNK signaling.
Role of epigenetics in cellular reprogramming; from iPSCs to disease modeling and cell therapy
Authors: Li Yong , Darabi Radbod
Published: October 2021

Epigenetics play a fundamental role in induced pluripotent stem cell (iPSC) technology due to their effect on iPSC's reprogramming efficiency and their subsequent role in iPSC differentiation toward a specific lineage. Epigenetics can skew the differentiation course of iPSCs toward a specific lineage based on the epigenetic memory of the source cells, or even lead to acquisition of new cell phenotypes, due to its aberrations during reprogramming. This viewpoint discusses key features of the epigenetic process during iPSC reprogramming/differentiation and outlines important epigenetic factors that need to be considered for successful generation and differentiation of iPSCs for downstream applications.
Hsa_circ_0001806 promotes glycolysis and cell progression in hepatocellular carcinoma through miR‐125b/HK2
Authors: Chen Xueyi , She Pengyun , Wang Caihua , Shi Lina , Zhang Tieying , Wang Yanfei , Li Haixia , Qian Lu , Li Man
Published: October 2021

Objective

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours and a leading cause of cancer death. Circular RNA (circRNA) has been demonstrated to play an important role in regulating tumour development. The current study aims to explore the specific role of hsa_circ_0001806 during HCC progression.

Methods

The expression of hsa_circ_0001806 in HCC tissues and cells was measured through qRT‐PCR. Cell proliferation, apoptosis and migration were measured using CCK‐8 and Annexin V/PI staining kits, and Transwell assay. Bioinformatics prediction and dual‐luciferase reporter assay were adopted to explore the mechanism underlying the cell function of hsa_circ_0001806 in HCC cells. In addition, glycolysis was assessed by measuring the glucose uptake, lactate production and ATP level using a glucose assay kit, fluorometric lactate assay kit and ATP detection assay kit.

Results

Hsa_circ_0001806 was up‐regulated in HCC tissues and cells and positively associated with the advanced TNM stage, metastasis and poor overall survival. The overexpression of hsa_circ_0001806 promoted HCC cell proliferation, migration and glycolysis and inhibited cell apoptosis, while the silence of hsa_circ_0001806 showed an opposite effect. Furthermore, hsa_circ_0001806 acted as a sponge of miR‐125b to up‐regulate hexokinase II (HK2) expression. In addition, the inhibition of miR‐125b and HK2 overexpression partly reversed the inhibitory effect of hsa_circ_0001806 silencing on HCC cell proliferation, migration and glycolysis.

Conclusion

The inhibition of hsa_circ_0001806 suppressed HCC cell proliferation, migration and glycolysis through mediating miR‐125b/HK2 axis.
Association between apolipoprotein E gene polymorphism and nonalcoholic fatty liver disease in Southern China: A case‐control study
Authors: Liu Sudong , Weng Ruiqiang , Gu Xiaodong , Li Lihai , Zhong Zhixiong
Published: October 2021

Background

Apolipoprotein E (ApoE) polymorphisms have been reported to be associated with nonalcoholic fatty liver disease (NAFLD), but the conclusions of studies are inconsistent in different regions. The present study aims to investigate the role of ApoE genotypes on NAFLD in southern China.

Methods

A total of 1064 subjects including 372 NAFLD patients and 692 controls who attended Meizhou People's Hospital located in southern China from March 1, 2016 to April 30, 2020 were enrolled in this study. The ApoE genotypes were detected and the laboratory parameters were examined.

Results

Significant differences were observed between NAFLD patients and controls in the prevalence of ε3/ε3 (p < 0.001) and ε3/ε4 (p = 0.004). NAFLD patients presented higher frequency of ε4 allele than controls (p = 0.013). Logistic regression analysis suggested that ε3/ε3 was an independent risk factor (OR: 1.435, 95% CI: 1.084–1.891, p = 0.010), while ε3/ε4 was an independent protective factor (OR: 0.578, 95% CI: 0.404–0.828, p = 0.003) for development of NAFLD. In addition, allele ε4 showed a protective effect on NAFLD with an adjusted OR of 0.588 (95% CI: 0.420–0.824, p = 0.002).

Conclusion

Our results suggested that ApoE genotype was associated with the development of NAFLD in the population of southern China. Individuals carrying ε3/ε3 were at higher risk of NAFLD, while those carrying ε3/ε4 were at lower risk of NAFLD.
Validation of the brief version of the Spence Children's Anxiety Scale for Spanish children (SCAS‐C‐8)
Authors: Rodríguez‐Menchón Miriam , Orgilés Mireia , Espada José P. , Morales Alexandra
Published: October 2021

Objective

This study aimed to validate the self‐reported brief version of the Spence Children's Anxiety Scale–Children (SCAS‐C‐8) in pre‐adolescent Spanish children.

Method

Participants were 824 children aged 8–12 from a community sample. The results revealed a good fit to the one‐factor structure, adequate internal consistency (α = 0.75), and evidence of test‐retest reliability (α = 0.77).

Results

The strong relationship between the SCAS‐C‐8 and emotional problems provided evidence of convergent validity. Also, the results showed factorial gender invariance.

Conclusion

The SCAS‐C‐8 is a suitable instrument for pre‐adolescent Spanish children. The brevity and simplicity of this scale may facilitate early detection and help to narrow the existent gap between the presence of anxiety problems and psychological assistance‐seeking.
Heat stress induced IPEC‐J2 cells barrier dysfunction through endoplasmic reticulum stress mediated apoptosis by p‐eif2α/CHOP pathway
Authors: Cui Yan‐jun , Chen Le‐yi , Zhou Xu , Tang Zhi‐ning , Wang Chong , Wang Hai‐feng
Published: October 2021

Heat stress (HS) induced by high ambient temperatures compromises intestinal epithelial cell. However, the underlying mechanisms by which HS causes intestinal barrier dysfunction remain unclear. In this study, we established an in vitro acute‐HS‐induced intestinal damage using porcine small intestinal epithelial cell (IPEC‐J2) that exposed to the high temperatures (43°C) for 2 h. The cell proliferation, apoptosis, tight junction (TJ) barrier integrity and transcriptomic profiles were measured. The results showed that HS decreased cell viability while increased proapoptotic signaling evidenced by Bax/bcl2 ratio, cytochrome C release to cytosol and active‐caspase 3 increases (p < 0.01). HS led to decreased transepithelial electrical resistance, increased cell permeability, and downregulated TJ proteins including ZO1, occludin, and claudin 3 (p < 0.05). Transcriptome sequencing and KEGG pathway analysis revealed HS‐induced cell cycle arrest and activation of endoplasmic reticulum stress (ERS) response mediated by a critical transcript eif2α and proapoptotic molecule DDIT3 (known as CHOP). Furthermore, inhibition of ERS by 4‐phenylbutyrate (4‐PBA) administration and knockdown of eif2α and CHOP significantly attenuated IPEC‐J2 cells apoptosis (p < 0.05). Transmission electron microscopy analysis suggested that 4‐PBA inhibited HS‐induced increase in ER lumen diameter, indicating ultrastructural sign of ERS. In addition, HS‐induced impairment of TJs was significantly attenuated by 4‐PBA (p < 0.05). Collectively, HS induces ERS and activates the p‐eif2α/CHOP signaling pathway to impair epithelial barrier integrity through triggering the intestinal epithelial cell apoptosis.
Liver‐humanized mice: A translational strategy to study metabolic disorders
Authors: Luo Yonghong , Lu Haocheng , Peng Daoquan , Ruan Xiangbo , Eugene Chen Yuqing , Guo Yanhong
Published: October 2021

The liver is the metabolic core of the whole body. Tools commonly used to study the human liver metabolism include hepatocyte cell lines, primary human hepatocytes, and pluripotent stem cells‐derived hepatocytes in vitro, and liver genetically humanized mouse model in vivo. However, none of these systems can mimic the human liver in physiological and pathological states satisfactorily. Liver‐humanized mice, which are established by reconstituting mouse liver with human hepatocytes, have emerged as an attractive animal model to study drug metabolism and evaluate the therapeutic effect in “human liver” in vivo because the humanized livers greatly replicate enzymatic features of human hepatocytes. The application of liver‐humanized mice in studying metabolic disorders is relatively less common due to the largely uncertain replication of metabolic profiles compared to humans. Here, we summarize the metabolic characteristics and current application of liver‐humanized mouse models in metabolic disorders that have been reported in the literature, trying to evaluate the pros and cons of using liver‐humanized mice as novel mouse models to study metabolic disorders.
OGT upregulates myogenic IL‐6 by mediating O‐GlcNAcylation of p65 in mouse skeletal muscle under cold exposure
Authors: Hu Yajie , Liu Yang , Yang Yuying , Lv Hongming , Lian Shuai , Xu Bin , Li Shize
Published: October 2021

Cold exposure is an unavoidable and severe challenge for people and animals residing in cold regions of the world, and may lead to hypothermia, drastic changes in systemic metabolism, and inhibition of protein synthesis. O‐linked‐N‐acetylglucoseaminylation (O‐GlcNAcylation) directly regulates the activity and function of target proteins involved in multiple biological processes by acting as a stress receptor and nutrient sensor. Therefore, our study aimed to examine whether O‐GlcNAcylation affected myogenic IL‐6 expression, regulation of energy metabolism, and promotion of survival in mouse skeletal muscle under acute cold exposure conditions. Total protein was extracted from C2C12 cells that had been cultured at 32°C for 3, 6, 9, and 12 h. Western blot analysis showed that mild hypothermia enhanced O‐GlcNAc transferase (OGT) and O‐GlcNAcase (OGA) expression. Furthermore, global OGT‐dependent glycosylation and interleukin‐6 (IL‐6) levels peaked 3 h after induction of mild hypothermia. Enhanced activation of the NF‐κB pathway was also observed in response to mild hypothermia. Alloxan and Thiamet G were used to reduce and increase global OGT glycosylation levels in C2C12 cells, respectively. Increased O‐GlcNAcylation was associated with significant upregulation of IL‐6 expression, as well as enhanced activity and nuclear translocation of p65, while decreased O‐GlcNAcylation had the opposite effect. In addition, increased O‐GlcNAcylation was associated with significantly increased glucose metabolism, and OGT‐mediated O‐GlcNAcylation of p65. We generated skeletal muscle‐specific OGT knockout mice and exposed them to cold at 4°C for 3 h per day for 1 week. OGT deficiency attenuated the O‐GlcNAcylation, activity, and nuclear translocation of p65, resulting in downregulation of IL‐6 in mouse skeletal muscle of mice exposed to cold conditions. Taken together, our data suggested that O‐GlcNAcylation of p65 enhanced p65 activity and nuclear translocation leading to the upregulation of IL‐6, which maintained energy homeostasis and promotes cell survival in mouse skeletal muscle during cold exposure.
Computed tomography‐defined low skeletal muscle index and density in cancer patients: observations from a systematic review
Authors: McGovern Josh , Dolan Ross D. , Horgan Paul G. , Laird Barry J. , McMillan Donald C.
Published: October 2021

Background

Computed tomography (CT) analysis of body composition has garnered interest as a potential prognostic tool in those with cancer. A range of pre‐defined thresholds currently exist within the literature to define low skeletal muscle mass and density. The aim of the present systematic review was to assess the prevalence of low skeletal muscle index (SMI) and density (SMD) within the literature, across a range of common solid tumours.

Methods

A systematic search of PubMed was carried out to identify studies reporting CT analysis of SMI and SMD in patients with colorectal, oesophageal, gastric, hepatobiliary, pancreatic, breast, and lung cancer. The type of cancer, whether curative or non‐curative disease, the anthropomorphic parameter studied, threshold used to define low SMI and SMD, and the prevalence of these anthropomorphic measurements within the population were recorded.

Results

Of the 160 studies included, 156 reported an assessment of SMI and 35 reported assessment of SMD. The median prevalence of low SMI was 43% (30.1–57.1) and low SMD 49.4% (31.7–58.5) across the entire cohort. There was little variation in the prevalence of low SMI and SMD when studies were divided into curative and non‐curative cohorts—40.7% (27.5–51.3) vs. 48.4% (30.9–60.1) and 37.8% (32.2–52.2) vs. 55.3% (38.5–64.7) respectively. When divided into colorectal, oesophageal, gastric, hepatobiliary, pancreatic, breast and lung cancers, similar prevalence of low SMI (46.0% %, 49.8%, 35.7%, 41.1%, 32.3%, 34%, and 49.5%) and low SMD were also observed (52.1%, 54.3%, 71.2%, 56.8%, 55.3%, and 52.6%). This was maintained when studies were stratified into cohorts by threshold used—low SMI (Martin 48.9%, Prado 49.9%, and Others 36.0%) and low SMD (Martin 52.4% and Others 48.6%).

Conclusions

Low SMI and SMD are endemic across a range of cancer types and disease stage, challenging pre‐existing dogma of the determinants of prevalence.
Transcranial color Doppler sonography as an alternative tool for evaluation of terminal internal carotid artery steno‐occlusion in moyamoya disease
Authors: Wang Jing‐Zhe , Zhang Sheng , Wei Xi , Zhang Dong , Zhao Ya‐Hui , Zhu Xun
Published: October 2021

Objective

To investigate color Doppler ultrasonography criteria and its value in assessing the steno‐occlusion of the terminal internal carotid artery in moyamoya disease.

Methods

According to the digital subtraction angiography findings, patients were divided into three groups: occlusion of the terminal internal carotid artery, >50% stenosis, and ≤50% stenosis. We measured the terminal and proximal internal carotid artery parameters of each group using transcranial and cervical color Doppler sonography.

Results

Blood flow signals in 12 terminal internal carotid arteries were absent, which were verified as occlusion by digital subtraction angiography. Parameters were obtained in the remaining 159 terminal/proximal internal carotid arteries to predict cutoffs for >50% stenosis and occlusion. For >50% stenosis, mean flow velocity >88.50 cm/s in the terminal internal carotid artery could achieved the highest receiver operating characteristic curve area of 0.776 with 62.50% sensitivity, 88.15% specificity, 48.39% positive predictive values, 92.97% negative predictive value, and 84.27% overall accuracy. For the occlusion, mean flow velocity <49.50 cm/s in the terminal internal carotid artery achieve the highest receiver operating characteristic curve area of 0.734 with 55.56% sensitivity, 83.81% specificity, 63.83% positive predictive values, 78.57% negative predictive value, and 74.21% overall accuracy. The area under receiver operating characteristic curve cutoffs for other parameters were less than 0.7.

Conclusion

Mean flow velocity of terminal internal carotid artery provides useful diagnostic information for detecting steno‐occlusion in moyamoya disease. It may be used as an alternative tool to evaluate steno‐occlusion of the terminal internal carotid artery in moyamoya disease.
Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe‐host‐communication in vivo
Authors: Bittel Miriam , Reichert Patrick , Sarfati Ilann , Dressel Anja , Leikam Stefanie , Uderhardt Stefan , Stolzer Iris , Phu Tuan Anh , Ng Martin , Vu Ngan K. , Tenzer Stefan , Distler Ute , Wirtz Stefan , Rothhammer Veit , Neurath Markus F. , Raffai Robert L. , Günther Claudia , Momma Stefan
Published: October 2021

The intestinal microbiota influences mammalian host physiology in health and disease locally in the gut but also in organs devoid of direct contact with bacteria such as the liver and brain. Extracellular vesicles (EVs) or outer membrane vesicles (OMVs) released by microbes are increasingly recognized for their potential role as biological shuttle systems for inter‐kingdom communication. However, physiologically relevant evidence for the transfer of functional biomolecules from the intestinal microbiota to individual host cells by OMVs in vivo is scarce. By introducing Escherichia coli engineered to express Cre‐recombinase (E. coliCre) into mice with a Rosa26.tdTomato‐reporter background, we leveraged the Cre‐LoxP system to report the transfer of bacterial OMVs to recipient cells in vivo. Colonizing the intestine of these mice with E. coliCre, resulted in Cre‐recombinase induced fluorescent reporter gene‐expression in cells along the intestinal epithelium, including intestinal stem cells as well as mucosal immune cells such as macrophages. Furthermore, even far beyond the gut, bacterial‐derived Cre induced extended marker gene expression in a wide range of host tissues, including the heart, liver, kidney, spleen, and brain. Together, our findings provide a method and proof of principle that OMVs can serve as a biological shuttle system for the horizontal transfer of functional biomolecules between bacteria and mammalian host cells.
Acute toxicity and patient‐reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer
Authors: Iizumi Takashi , Ishikawa Hitoshi , Sekino Yuta , Tanaka Keiichi , Takizawa Daichi , Makishima Hirokazu , Numajiri Haruko , Mizumoto Masashi , Nakai Kei , Okumura Toshiyuki , Sakurai Hideyuki
Published: October 2021

Introduction

To confirm the feasibility of hypofractionated proton beam therapy (PBT), we compared the acute adverse event rates and International Prostate Symptom Score (IPSS) in prostate cancer patients treated with hypofractionated versus conventionally fractionated (2.0 Gy relative biological effectiveness (RBE)/fraction) PBT.

Methods

We reviewed 289 patients with prostate cancer, of whom 73, 100, and 116 patients were treated with 2.0, 2.5, and 3.0 Gy (RBE)/fraction, respectively. The endpoints were acute genitourinary and gastrointestinal toxicities and the IPSS, evaluated up to 6 months after PBT initiation.

Results

No significant differences were found in acute toxicity rates or the IPSS among the fractionation schedules. Diabetes mellitus, age, and androgen deprivation therapy were not identified as factors associated with the IPSS.

Conclusion

There were no significant differences in adverse events or quality of life among the three fractionation schedules early after PBT.
Long COVID syndrome‐associated brain fog
Authors: Asadi‐Pooya Ali A. , Akbari Ali , Emami Amir , Lotfi Mehrzad , Rostamihosseinkhani Mahtab , Nemati Hamid , Barzegar Zohreh , Kabiri Maryam , Zeraatpisheh Zahra , Farjoud‐Kouhanjani Mohsen , Jafari Anahita , Sasannia Sarvin , Ashrafi Shayan , Nazeri Masoume , Nasiri Sara , Shahisavandi Mina
Published: October 2021

We investigated the frequency of brain fog in a large cohort of patients with documented coronavirus disease‐2019 (COVID‐19) who have survived the illness. We also scrutinized the potential risk factors associated with the development of brain fog. Adult patients (18–55 years of age), who were referred to the healthcare facilities anywhere in Fars province from February 19, 2020 to November 20, 2020 were included. All patients had a confirmed COVID‐19 diagnosis. In a phone call, at least 3 months after their discharge from the hospital, we obtained their current information. A questionnaire was specifically designed for data collection. In total, 2696 patients had the inclusion criteria; 1680 (62.3%) people reported long COVID syndrome (LCS). LCS‐associated brain fog was reported by 194 (7.2%) patients. Female sex (odds ratio [OR]: 1.4), respiratory problems at the onset (OR: 1.9), and intensive care unit (ICU) admission (OR: 1.7) were significantly associated with reporting chronic post‐COVID “brain fog” by the patients. In this large population‐based study, we report that chronic post‐COVID “brain fog” has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness (ICU admission).
Concerns on the multiple nomenclature systems for SARS‐CoV‐2
Authors: Li Xingguang
Published: October 2021

The multiple nomenclature systems of SARS‐CoV‐2 are confusing and have several issues. The emergence of variants of concern and variants of interest has posed an increased risk to global health. To assist with public discussion and communication with nonscientific audiences about significant mutations, and ultimately to inform the ongoing response to the COVID‐19 pandemic, we scientists need to develop easy‐to‐pronounce and nonstigmatizing labels for significant mutations.
Natural spring water gargle samples as an alternative to nasopharyngeal swabs for SARS‐CoV‐2 detection using a laboratory‐developed test
Authors: Gobeille Paré Sarah , Bestman‐Smith Julie , Fafard Judith , Doualla‐Bell Florence , Jacob‐Wagner Mariève , Lavallée Christian , Charest Hugues , Beauchemin Stéphanie , Coutlée François , Dumaresq Jeannot , Busque Lambert , St‐Hilaire Manon , Lépine Guylaine , Boucher Valérie , Desforges Marc , Goupil‐Sormany Isabelle , Labbé Annie‐Claude ,   G‐SPIT study group
Published: October 2021

The objective of this study was to validate the use of spring water gargle (SWG) as an alternative to oral and nasopharyngeal swab (ONPS) for SARS‐CoV‐2 detection with a laboratory‐developed test. Healthcare workers and adults from the general population, presenting to one of two COVID‐19 screening clinics in Montréal and Québec City, were prospectively recruited to provide a gargle sample in addition to the standard ONPS. The paired specimens were analyzed using thermal lysis followed by a laboratory‐developed nucleic acid amplification test (LD‐NAAT) to detect SARS‐CoV‐2, and comparative performance analysis was performed. An individual was considered infected if a positive result was obtained on either sample. A total of 1297 adult participants were recruited. Invalid results (n = 18) were excluded from the analysis. SARS‐CoV‐2 was detected in 144/1279 (11.3%) participants: 126 from both samples, 15 only from ONPS, and 3 only from SWG. Overall, the sensitivity was 97.9% (95% CI: 93.7–99.3) for ONPS and 89.6% (95% CI: 83.4–93.6; p = 0.005) for SWG. The mean ONPS cycle threshold (Ct) value was significantly lower for the concordant paired samples as compared to discordant ones (22.9 vs. 32.1; p < 0.001). In conclusion, using an LD‐NAAT with thermal lysis, SWG is a less sensitive sampling method than the ONPS. However, the higher acceptability of SWG might enable a higher rate of detection from a population‐based perspective. Nonetheless, in patients with a high clinical suspicion of COVID‐19, a repeated analysis with ONPS should be considered. The sensitivity of SWG using NAAT preceded by chemical extraction should be evaluated.
Influence of the El Niño–Southern Oscillation and the sypnotic systems on the rainfall variability over the Brazilian Cerrado via Climate Hazard Group InfraRed Precipitation with Station data
Authors: Correia Filho Washington Luiz Félix , de Oliveira‐Júnior José Francisco , da Silva Junior Carlos Antonio , Santiago Dimas de Barros
Published: October 2021

The rainfall is essential to Brazil's hydrological cycle, agricultural development, and power generation, mainly Cerrado biome. Thus, the study assessed the influence of the El Niño–Southern Oscillation (ENSO) and synoptic systems on rainfall variability over the Brazilian Cerrado. To evaluate this variability, it used monthly rainfall data from the second version of the Climate Hazard Group InfraRed Precipitation with Station (CHIRPS) database (1981–2020), based on the annual densidrograms and thematic maps. In Annual terms, the average climatological was 1,417 mm·year−1. The highest precipitation values (>1,500 mm·year−1) occurred at the boundaries between Cerrado and Amazon, mainly in the states of the Maranhão, Mato Grosso, and Tocantins due to physiography (<500 m). The seasonal rainfall was more frequent in summer (on average, 48% of the annual total) distributed over the biome due to the South American monsoon system and South Atlantic convergence zone. The climatological dry period occurred between November and March (on average, 8% of the annual total) due to the Atmospheric Blocking called as Bolivia High that inhibit the passage of synoptic system transients in Central Brazil. In monthly terms, January (July) is the wetter month with 18% (drier month with 1%) of the annual total. The annual densidrograms appointed the following wetter (drier) years: 1985, 1989, and 2009 (1990, 1993, and 2012), influenced by ENSO events. The year 1985 appointed an increase of 19% in the mean annual rainfall, but in 1990 showed a reduction of 18% in climatology (1981–2020). In terms of seasonal anomalies, the summer of 1985 (1990) appointed an increase of 26% above (2.5% below) mean seasonal climatological, verified in the states of Maranhão, Piauí, and Tocantins (states of Mato Grosso). The La Niña (El Niño) events influenced positively (negatively) the annual rainfall anomalous pattern in Cerrado.

Highlights

The rainiest period occurs during September and April months (>200 mm·month−1).

The driest period occurs during May and August months (<200 mm·month−1).

1985 (1990) year presents the most significant (smallest) annual rainfall average.

The border zone between Amazon and Cerrado presents the highest annual rainfall.