bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of CT texture analysis to differentiate olfactory neuroblastoma from sinonasal squamous cell carcinoma
Authors: Ogawa Masaki , Osaga Satoshi , Shiraki Norio , Kawakita Daisuke , Hanai Nobuhiro , Tamaki Tsuneo , Tsukahara Satoshi , Kawaguchi Takatsune , Urano Misugi , Shibamoto Yuta
Published: February 2021

The purpose of this study was to examine differences in texture features between olfactory neuroblastoma (ONB) and sinonasal squamous cell carcinoma (SCC) on contrast-enhanced CT (CECT) images, and to evaluate the predictive accuracy of texture analysis compared to radiologists’ interpretations. Forty-three patients with pathologically-diagnosed primary nasal and paranasal tumor (17 ONB and 26 SCC) were included. We extracted 42 texture features from tumor regions on CECT images obtained before treatment. In univariate analysis, each texture features were compared, with adjustment for multiple comparisons. In multivariate analysis, the elastic net was used to select useful texture features and to construct a texture-based prediction model with leave-one-out cross-validation. The prediction accuracy was compared with two radiologists’ visual interpretations. In univariate analysis, significant differences were observed for 28 of 42 texture features between ONB and SCC, with areas under the receiver operating characteristic curve between 0.68 and 0.91 (median: 0.80). In multivariate analysis, the elastic net model selected 18 texture features that contributed to differentiation. It tended to show slightly higher predictive accuracy than radiologists’ interpretations (86% and 74%, respectively;P = 0.096). In conclusion, several texture features contributed to differentiation of ONB from SCC, and the texture-based prediction model was considered useful.
Structural insights into SARS-CoV-2 spike protein and its natural mutants found in Mexican population
Authors: Sixto-López Yudibeth , Correa-Basurto José , Bello Martiniano , Landeros-Rivera Bruno , Garzón-Tiznado Jose Antonio , Montaño Sarita
Published: February 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus responsible for coronavirus disease 2019 (COVID-19); it become a pandemic since March 2020. To date, there have been described three lineages of SARS-CoV-2 circulating worldwide, two of them are found among Mexican population, within these, we observed three mutations of spike (S) protein located at amino acids H49Y, D614G, and T573I. To understand if these mutations could affect the structural behavior of S protein of SARS-CoV-2, as well as the binding with S protein inhibitors (cepharanthine, nelfinavir, and hydroxychloroquine), molecular dynamic simulations and molecular docking were employed. It was found that these punctual mutations affect considerably the structural behavior of the S protein compared to wild type, which also affect the binding of its inhibitors into their respective binding site. Thus, further experimental studies are needed to explore if these affectations have an impact on drug-S protein binding and its possible clinical effect.
Experimental pilot study for augmented reality-enhanced elbow arthroscopy
Authors: Yamamoto Michiro , Oyama Shintaro , Otsuka Syuto , Murakami Yukimi , Yokota Hideo , Hirata Hitoshi
Published: February 2021

The purpose of this study was to develop and evaluate a novel elbow arthroscopy system with superimposed bone and nerve visualization using preoperative computed tomography (CT) and magnetic resonance imaging (MRI) data. We obtained bone and nerve segmentation data by CT and MRI, respectively, of the elbow of a healthy human volunteer and cadaveric Japanese monkey. A life size 3-dimensional (3D) model of human organs and frame was constructed using a stereo-lithographic 3D printer. Elbow arthroscopy was performed using the elbow of a cadaveric Japanese monkey. The augmented reality (AR) range of error during rotation of arthroscopy was examined at 20 mm scope–object distances. We successfully performed AR arthroscopy using the life-size 3D elbow model and the elbow of the cadaveric Japanese monkey by making anteromedial and posterior portals. The target registration error was 1.63 ± 0.49 mm (range 1–2.7 mm) with respect to the rotation angle of the lens cylinder from 40° to − 40°. We attained reasonable accuracy and demonstrated the operation of the designed system. Given the multiple applications of AR-enhanced arthroscopic visualization, it has the potential to be a next-generation technology for arthroscopy. This technique will contribute to the reduction of serious complications associated with elbow arthroscopy.
Association of changes of retinal vessels diameter with ocular blood flow in eyes with diabetic retinopathy
Authors: Ueno Yoshitaka , Iwase Takeshi , Goto Kensuke , Tomita Ryo , Ra Eimei , Yamamoto Kentaro , Terasaki Hiroko
Published: February 2021

We investigated morphological changes of retinal arteries to determine their association with the blood flow and systemic variables in type 2 diabetes patients. The patients included 47 non-diabetic retinopathy eyes, 36 mild or moderate nonproliferative diabetic retinopathy (M-NPDR) eyes, 22 severe NPDR (S-NPDR) eyes, 32 PDR eyes, and 24 normal eyes as controls. The mean wall to lumen ratio (WLR) measured by adaptive optics camera was significantly higher in the PDR groups than in all of the other groups (all P < 0.001). However, the external diameter of the retinal vessels was not significantly different among the groups. The mean blur rate (MBR)-vessel determined by laser speckle flowgraphy was significantly lower in the PDR group than in the other groups (P < 0.001). The WLR was correlated with MBR-vessel (r = − 0.337, P < 0.001), duration of disease (r = 0.191, P = 0.042), stage of DM (r = 0.643, P < 0.001), systolic blood pressure (r = 0.166, P < 0.037), and presence of systemic hypertension (r = 0.443, P < 0.001). Multiple regression analysis demonstrated that MBR-vessel (β = − 0.389, P < 0.001), presence of systemic hypertension (β = 0.334, P = 0.001), and LDL (β = 0.199, P = 0.045) were independent factors significantly associated with the WLR. The increased retinal vessel wall thickness led to a narrowing of lumen diameter and a decrease in the blood flow in the PDR group.
Coupling ITO3dE model and GIS for spatiotemporal evolution analysis of agricultural non-point source pollution risks in Chongqing in China
Authors: Zhu Kang-wen , Yang Zhi-min , Huang Lei , Chen Yu-cheng , Zhang Sheng , Xiong Hai-ling , Wu Sheng , Lei Bo
Published: February 2021

To determine the risk state distribution, risk level, and risk evolution situation of agricultural non-point source pollution (AGNPS), we built an ‘Input-Translate-Output’ three-dimensional evaluation (ITO3dE) model that involved 12 factors under the support of GIS and analyzed the spatiotemporal evolution characteristics of AGNPS risks from 2005 to 2015 in Chongqing by using GIS space matrix, kernel density analysis, and Getis-Ord Gi* analysis. Land use changes during the 10 years had a certain influence on the AGNPS risk. The risk values in 2005, 2010, and 2015 were in the ranges of 0.40–2.28, 0.41–2.57, and 0.41–2.28, respectively, with the main distribution regions being the western regions of Chongqing (Dazu, Jiangjin, etc.) and other counties such as Dianjiang, Liangping, Kaizhou, Wanzhou, and Zhongxian. The spatiotemporal transition matrix could well exhibit the risk transition situation, and the risks generally showed no changes over time. The proportions of ‘no-risk no-change’, ‘low-risk no-change’, and ‘medium-risk no-change’ were 10.86%, 33.42%, and 17.25%, respectively, accounting for 61.53% of the coverage area of Chongqing. The proportions of risk increase, risk decline, and risk fluctuation were 13.45%, 17.66%, and 7.36%, respectively. Kernel density analysis was suitable to explore high-risk gathering areas. The peak values of kernel density in the three periods were around 1110, suggesting that the maximum gathering degree of medium-risk pattern spots basically showed no changes, but the spatial positions of high-risk gathering areas somehow changed. Getis-Ord Gi* analysis was suitable to explore the relationships between hot and cold spots. Counties with high pollution risks were Yongchuan, Shapingba, Dianjiang, Liangping, northwestern Fengdu, and Zhongxian, while counties with low risks were Chengkou, Wuxi, Wushan, Pengshui, and Rongchang. High-value hot spot zones gradually dominated in the northeast of Chongqing, while low-value cold spot zones gradually dominated in the Midwest. Our results provide a scientific base for the development of strategies to prevent and control AGNPS in Chongqing.
Persistent COUP-TFII expression underlies the myopathy and impaired muscle regeneration observed in resistance to thyroid hormone-alpha
Authors: Aguiari Paola , Liu Yan-Yun , Petrosyan Astgik , Cheng Sheue-yann , Brent Gregory A. , Perin Laura , Milanesi Anna
Published: February 2021

Thyroid hormone signaling plays an essential role in muscle development and function, in the maintenance of muscle mass, and in regeneration after injury, via activation of thyroid nuclear receptor alpha (THRA). A mouse model of resistance to thyroid hormone carrying a frame-shift mutation in the THRA gene (THRA-PV) is associated with accelerated skeletal muscle loss with aging and impaired regeneration after injury. The expression of nuclear orphan receptor chicken ovalbumin upstream promoter-factor II (COUP-TFII, or Nr2f2) persists during myogenic differentiation in THRA-PV myoblasts and skeletal muscle of aged THRA-PV mice and it is known to negatively regulate myogenesis. Here, we report that in murine myoblasts COUP-TFII interacts with THRA and modulates THRA binding to thyroid response elements (TREs). Silencing of COUP-TFII expression restores in vitro myogenic potential of THRA-PV myoblasts and shifts the mRNA expression profile closer to WT myoblasts. Moreover, COUP-TFII silencing reverses the transcriptomic profile of THRA-PV myoblasts and results in reactivation of pathways involved in muscle function and extracellular matrix remodeling/deposition. These findings indicate that the persistent COUP-TFII expression in THRA-PV mice is responsible for the abnormal muscle phenotype. In conclusion, COUP-TFII and THRA cooperate during post-natal myogenesis, and COUP-TFII is critical for the accelerated skeletal muscle loss with aging and impaired muscle regeneration after injury in THRA-PV mice.
A low power flexible dielectric barrier discharge disinfects surfaces and improves the action of hydrogen peroxide
Authors: Gershman Sophia , Harreguy Maria B. , Yatom Shurik , Raitses Yevgeny , Efthimion Phillip , Haspel Gal
Published: February 2021

There is an urgent need for disinfection and sterilization devices accessible to the public that can be fulfilled by innovative strategies for using cold atmospheric pressure plasmas. Here, we demonstrate a successful novel combination of a flexible printed circuit design of a dielectric barrier discharge (flex-DBD) with an environmentally safe chemical reagent for surface decontamination from bacterial contaminants. Flex-DBD operates in ambient air, atmospheric pressure, and room temperature without any additional gas flow at a power density not exceeding 0.5 W/cm2. The flex-DBD activation of a 3% hydrogen peroxide solution results in the reduction in the bacterial load of a surface contaminant of > 6log10 in 90 s, about 3log10 and 2log10 better than hydrogen peroxide alone or the flex-DBD alone, respectively, for the same treatment time. We propose that the synergy between plasma and hydrogen peroxide is based on the combined action of plasma-generated OH· radicals in the hydrogen peroxide solution and the reactive nitrogen species supplied by the plasma effluent. A scavenger method verified a significant increase in OH· concentration due to plasma treatment. Novel in-situ FTIR absorption spectra show the presence of O3, NO2, N2O, and other nitrogen species. Ozone dissolving in the H2O2 solution can effectively generate OH· through a peroxone process. The addition of the reactive nitrogen species increases the disinfection efficiency of the hydroxyl radicals and other oxygen species. Hence, plasma activation of a low concentration hydrogen peroxide solution, using a hand-held flexible DBD device results in a dramatic improvement in disinfection.
A case of retinitis pigmentosa homozygous for a rare CNGA1 causal variant
Authors: Saito Kohei , Gotoh Norimoto , Kang Inyeop , Shimada Toshio , Usui Takeshi , Terao Chikashi
Published: February 2021

Retinitis pigmentosa (RP) is a heterogenous hereditary disorder leading to blindness. Despite using next-generation sequencing technologies, causal variants in about 60% of RP cases remain unknown. The heterogeneous genetic inheritance pattern makes it difficult to pinpoint causal variants. Besides, rare penetrating variants are hardly observed in general case–control studies. Thus, a family-based analysis, specifically in a consanguineous family, is a clinically and genetically valuable approach for RP. We analyzed a Japanese consanguineous family with a member suffering from RP with a typical autosomal recessive pattern. We sequenced five direct descendants and spouse using Whole-exome sequencing (WES) and Whole-genome sequencing (WGS). We identified a homozygous pathogenic missense variant in CNGA1 (NM_000087.3, c.839G > A, p.Arg280His) in the proband, while we found no homozygous genotypes in the other family members. CNGA1 was previously reported to be associated with RP. We confirmed the genotypes by the Sanger sequencing. Additionally, we assessed the homozygous genotype in the proband for the possibility of a founder mutation using homozygosity analysis. Our results suggested the two copies of the variant derived from a founder mutation. In conclusion, we found the homozygotes for c.839G > A in CNGA1 as causal for RP.
Maximizing avertable doses with a minimum amount of waste for remediation of land areas around typical single family houses after radioactive fallout based on Monte Carlo simulations
Authors: Hinrichsen Yvonne , Finck Robert , Martinsson Johan , Rääf Christopher
Published: February 2021

The uncontrolled release of long-lived radioactive substances from nuclear accidents can contaminate inhabited land areas. The removal of topsoil is an important method for reducing future radiation exposure but can also generate a large amount of waste that needs safe disposal. To the best of our knowledge, previous studies have determined the optimal depth of topsoil removal but not the size of the area designated for this measure. For this purpose, this study performed Monte Carlo simulations of hypothetical 137Cs surface contamination on various ground areas in a typical northern European suburban area. The goal was to study the size of the areas needed and amount of waste generated to achieve a certain relative and absolute dose reduction. The results showed that removing the topsoil from areas larger than 3000 m2 around the houses in the study neighbourhood results in only marginal reduction in radiation exposure. If, on average, 5 cm of topsoil is removed over 3000 m2, then 150 m3 of waste would be generated. However, in this scenario adjacent properties benefit from each other’s decontamination, leading to a smaller amount of waste for a given reduction in future radiation exposure per inhabitant of these dwellings. Additionally, it was shown that topsoil removal over limited areas has a higher impact on the absolute dose reduction at an observation point inside or outside the houses with higher initial dose.
Bacterial-mediated RNAi and functional analysis of Natalisin in a moth
Authors: Wang Xia-Fei , Chen Zhe , Wang Xu-Bo , Xu Jin , Chen Peng , Ye Hui
Published: February 2021

The neuropeptide natalisin (NTL) has been determined to play essential roles in reproduction in two Diptera and one Coleoptera species. Whether NTL has similar or even different functions in Lepidoptera remains to be determined. Here, we cloned the NTL transcript in the common cutworm moth Spodoptera litura. This transcript encodes a 438-amino acid protein. Twelve putative Sl-NTL neuropeptides were defined by cleavage sites. These NTL peptides share a DDPFWxxRamide C-terminal motif. The expressions of Sl-NTL is low during the egg and larval stages, which increased to a higher level during the pupal stage, and then reached the maximum during the adult stage. Moreover, the expression pattern during the pupal stage is similar between sexes while during the adult stage, it is dimorphic. To explore the function of Sl-NTL and assess its potential as a target for pest control, we knocked down the expression of Sl-NTL in both sexes by using bacteria-mediated RNAi. This technique significantly down regulated (reduced up to 83%) the expression of Sl-NTL in both sexes. Knocking down Sl-NTL expression did not significantly affect its development, survival and morphology but significantly reduced adults’ reproductive behavior (including female calling, male courtship, mating and remating patterns and rates) and reproductive output (offspring gain reduced more than 70%).
Rimklb mutation causes male infertility in mice
Authors: Maekura Koji , Tsukamoto Satoshi , Hamada-Kanazawa Michiko , Takano Masaoki
Published: February 2021

Rimklb is a mammalian homologue of the E. coli enzyme RimK, which catalyzes addition of glutamic acid to the ribosomal protein S6. To date, no previous studies have shown any physiological role for Rimklb in mammals. In this study, using Western blotting, we found that Rimklb is distributed and expressed in mouse testis and heart. Rimklb was subsequently localized to the testicular Leydig cells using immunohistochemistry with an anti-Rimklb antibody. We generated a Rimklb mutant mouse in which a three-base deletion results in deletion of Ala 29 and substitution of Leu 30 with Val, which we named the RimklbA29del, L30V mutant mouse. RimklbA29del, L30V mutant mice show a decrease in testicular size and weight, and in vitro fertilization demonstrates complete male infertility. Furthermore, we found that a key factor in the mammalian target of the rapamycin/ribosomal protein S6 transcriptional pathway is hyperphosphorylated in the seminiferous tubules of the mutant testis. We conclude that Rimklb has important roles that include spermatogenesis in seminiferous tubules. In summary, male RimklbA29del, L30V mice are infertile.
The rule of brain hematoma pressure gradient and its influence on hypertensive cerebral hemorrhage operation
Authors: Sun Guoqing , Fu Tingkai , Liu Zhaoyan , Zhang Yuhai , Chen Xiangtao , Jin Shigang , Chi Feng
Published: February 2021

To comparatively study the size of and variation in the ‘brain-haematoma’ pressure gradient for different surgical methods for hypertensive intracerebral haemorrhage (HICH) and analyse the gradient’s influence on surgical procedures and effects of the haemorrhage. Seventy-two patients with HICH treated from 1/2019 to 12/2019 were randomly divided into two groups, namely, the keyhole endoscopy and large trauma craniotomy groups, according to different operative methods. Intraoperative changes in intracranial pressure (ICP) were monitored to calculate intraoperative alterations in the ‘brain-haematoma’ pressure gradient. Intraoperative characteristics (operative time, bleeding volume, volume of blood transfusion, and haematoma clearance rate) and postoperative characteristics (oedema, postoperative activities of daily living (ADL) scores, mortality rate and rebleeding rate) were compared between the two groups. In the keyhole endoscopy group, ICP decreased slowly; the ‘brain-haematoma’ pressure gradient was large, averaging 251.1 ± 20.6 mmH2O, and slowly decreased. The mean operative time was 83.6 ± 4.3 min, the mean bleeding volume was 181.2 ± 13.6 ml, no blood transfusions were given, the average postoperative haematoma clearance rate was 95.6%, the rate of severe oedema was 10.9%, and the average postoperative ADL score was 85.2%. In the large trauma craniotomy group, ICP rapidly decreased after craniotomy. When the haematoma was removed, the ‘brain-haematoma’ pressure gradient was small, averaging 132.3 ± 10.5 mmH2O, and slowly decreased. The mean operative time was 232 ± 26.1 min, the mean bleeding volume was 412.6 ± 35.2 ml, the average volume of blood transfusion was 281.3 ± 13.6 ml, and the average postoperative haematoma clearance rate was 82.3%; moreover, the rate of severe oedema was 72.1%, and the average postoperative ADL score was 39.0%. These differences were statistically significant (P < 0.05). Neither the death rate (P > 0.05, 2.7% VS 2.8%) nor rebleeding rate (P > 0.05, 2.7% VS 2.8%) showed any obvious changes. The magnitude and variation in the ‘brain-haematoma’ pressure gradient for different surgical methods significantly influence surgical procedures and effects of HICH. During keyhole endoscopy surgery, this gradient was relatively large and slowly decreased; the haematoma was therefore easier to remove. Advantages of this approach include a high haematoma clearance rate, decreased bleeding volume, decreased operative time, reduced trauma, decreased postoperative brain oedema and improved postoperative recovery of neurological function.

Chinese Clinical Trial Register: ChiCTR1900020655 registration in 12/01/02,019 registration in 28/02/02,020 Number: NCOMMS-20–08,091.
Predicting exposure concentrations of chemicals with a wide range of volatility and hydrophobicity in different multi-well plate set-ups
Authors: Stadnicka-Michalak Julita , Bramaz Nadine , Schönenberger René , Schirmer Kristin
Published: February 2021

Quantification of chemical toxicity in small-scale bioassays is challenging owing to small volumes used and extensive analytical resource needs. Yet, relying on nominal concentrations for effect determination maybe erroneous because loss processes can significantly reduce the actual exposure. Mechanistic models for predicting exposure concentrations based on distribution coefficients exist but require further validation with experimental data. Here we developed a complementary empirical model framework to predict chemical medium concentrations using different well-plate formats (24/48-well), plate covers (plastic lid, or additionally aluminum foil or adhesive foil), exposure volumes, and biological entities (fish, algal cells), focusing on the chemicals’ volatility and hydrophobicity as determinants. The type of plate cover and medium volume were identified as important drivers of volatile chemical loss, which could accurately be predicted by the framework. The model focusing on adhesive foil as cover was exemplary cross-validated and extrapolated to other set-ups, specifically 6-well plates with fish cells and 24-well plates with zebrafish embryos. Two case study model applications further demonstrated the utility of the empirical model framework for toxicity predictions. Thus, our approach can significantly improve the applicability of small-scale systems by providing accurate chemical concentrations in exposure media without resource- and time-intensive analytical measurements.
Renal protective effect of sacubitril/valsartan in patients with heart failure
Authors: Hsieh Hui-Ling , Chen Chun-You , Chen Cheng-Hsien , Hsu Shih-Chang , Huang Wen-Cheng , Sue Yuh-Mou , Lin Feng-Yen , Shih Chun-Ming , Chang Yue-Cune , Huang Po-Hsun , Liu Chung-Te
Published: February 2021

Sacubitril/valsartan is a combined neprilysin inhibitor/angiotensin II receptor blocker designed for treatment of heart failure (HF). Nonetheless, its renal protective effect remained an issue of debate. This retrospective cohort study investigated the renal protective effect of sacubitril/valsartan in HF patients. HF patients on sacubitril/valsartan or valsartan for > 30 days were matched for gender, age, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF) to be enrolled into analysis. The follow-up period was 18 months. The outcomes included end eGFR, renal function decline defined as 20% reduction of eGFR, mortality, and HF-related hospitalization. Each group had 137 patients after matching. The mean age was 72.7 years and 65.7% were male. Mean eGFR was 70.9 mL/min/1.73 m2 and LVEF was 54.0% at baseline. Overall, the eGFR of sacubitril/valsartan groups was significantly higher than valsartan group at the end (P < 0.01). Subgroup analysis showed that the difference in eGFR was significant in subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2. Multivariate Cox regression model showed that sacubitril/valsartan group had significantly reduced risk for renal function decline (hazard ratio: 0.5, 95% confidence interval: 0.3–0.9). Kaplan–Meier curve showed no difference in the risk for cardiovascular mortality, all-cause mortality or HF-related hospitalization. We showed renal protective effect of neprilysin inhibition in HF patients and specified that subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2 were sensitive to this effect, suggesting an optimal subgroup of this treatment.
The impact of the COVID-19 pandemic on wellbeing and cognitive functioning of older adults
Authors: De Pue Sarah , Gillebert Céline , Dierckx Eva , Vanderhasselt Marie-Anne , De Raedt Rudi , Van den Bussche Eva
Published: February 2021

COVID-19 took a heavy toll on older adults. In Belgium, by the end of August, 93% of deaths due to COVID-19 were aged 65 or older. Similar trends were observed in other countries. As a consequence, older adults were identified as a group at risk, and strict governmental restrictions were imposed on them. This has caused concerns about their mental health. Using an online survey, this study established the impact of the COVID-19 pandemic on adults aged 65 years or older, and which factors moderate this impact. Participants reported a significant decrease in activity level, sleep quality and wellbeing during the COVID-19 pandemic. Depression was strongly related to reported declines in activity level, sleep quality, wellbeing and cognitive functioning. Our study shows that the COVID-19 pandemic had a severe impact on the mental health of older adults. This implies that this group at risk requires attention of governments and healthcare.
Association of mitochondrial DNA copy number with prevalent and incident type 2 diabetes in women: A population-based follow-up study
Authors: Memon Ashfaque A. , Sundquist Jan , Hedelius Anna , Palmér Karolina , Wang Xiao , Sundquist Kristina
Published: February 2021

Mitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50–59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.
Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells
Authors: Wigner Paulina , Zielinski Krzysztof , Labieniec-Watala Magdalena , Marczak Agnieszka , Szwed Marzena
Published: February 2021

Doxorubicin (DOX) is considered one of the most powerful chemotherapeutic agents but its clinical use has several limitations, including cardiomyopathy and cellular resistance to the drug. By using transferrin (Tf) as a drug carrier, however, the adverse effects of doxorubicin as well as drug resistance can be reduced. The main objective of this study was to determine the exact nature and extent to which mitochondrial function is influenced by DOX–Tf conjugate treatment, specifically in human breast adenocarcinoma cells. We assessed the potential of DOX–Tf conjugate as a drug delivery system, monitoring its cytotoxicity using the MTT assay and ATP measurements. Moreover, we measured the alterations of mitochondrial function and oxidative stress markers. The effect of DOX–Tf was the most pronounced in MDA-MB-231, triple-negative breast cancer cells, whereas non-cancer endothelial HUVEC-ST cells were more resistant to DOX–Tf conjugate than to free DOX treatment. A different sensitivity of two investigate breast cancer cell lines corresponded to the functionality of their cellular antioxidant systems and expression of estrogen receptors. Our data also revealed that conjugate treatment mediated free radical generation and altered the mitochondrial bioenergetics in breast cancer cells.
Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration
Authors: Staley Christopher , Halaweish Hossam , Graiziger Carolyn , Hamilton Matthew J. , Kabage Amanda J. , Galdys Alison L. , Vaughn Byron P. , Vantanasiri Kornpong , Suryanarayanan Raj , Sadowsky Michael J. , Khoruts Alexander
Published: February 2021

Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is ~ 80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potential of freeze-dried microbiota without the complexity of variables associated with oral administration. We compared engraftment of identical preparations and doses of freeze-dried microbiota following colonoscopic (9 patients) versus oral administration (18 patients). Microbiota were characterized by sequencing of the 16S rRNA gene, and engraftment was determined using the SourceTracker algorithm. Oligotyping analysis was done to provide high-resolution patterns of microbiota engraftment. Colonoscopic FMT was associated with greater levels of donor engraftment within days following the procedure (ANOVA P = 0.035) and specific increases in the relative abundances of donor Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae (P ≤ 0.033). Lower relative abundances of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae families were associated with clinical failures. These results suggest that further optimization of oral capsule FMT may improve its engraftment efficiency and clinical efficacy.
Improved adulticidal activity against Aedes aegypti (L.) and Aedes albopictus (Skuse) from synergy between Cinnamomum spp. essential oils
Authors: Aungtikun Jirapon , Soonwera Mayura
Published: February 2021

Improved natural adulticidal agents against mosquito vectors are in urgent need, and essential oils from Cinnamomum plants can assume this role quite readily.Cinnamomum verum,C.cassia, andC.loureiroiessential oils (EOs) were extracted from the barks and evaluated for their chemical composition by GC–MS. The major constituent of the three EOs was cinnamaldehyde. WHO susceptibility tests on individual and combined EOs as well as cinnamaldehyde were conducted against female adults ofAedes aegyptiandAedes albopictus.All EO combinations exhibited a synergistic effect, manifesting a higher toxicity, with a synergistic value ranging from 2.9 to 6.7. Their increasing mortality value was improved between 16.0 to 41.7%. The highest synergistic effect was achieved by an EO combination of 0.5%C.cassia + 0.5%C.loureiroi, while the highest insecticidal activity was achieved by 2.5%C.verum + 2.5%C.cassiaand 1% cinnamaldehyde, with a knockdown and mortality rate of 100% and a KT50between 0.7 and 2.1 min. This combination was more toxic to both mosquito species than 1% w/v cypermethrin. These findings demonstrate that cinnamaldehyde and synergistic combinations ofC.verum + C.cassiaEOs andC.cassia + C.loureiroiEOs have a high insecticidal efficacy againstAedespopulations.
Basement membrane proteins modulate cell migration on bovine pericardium extracellular matrix scaffold
Authors: Xing Qi , Parvizi Mojtaba , Lopera Higuita Manuela , Griffiths Leigh G.
Published: February 2021

Native bovine pericardium (BP) exhibits anisotropy of its surface ECM niches, with the serous surface (i.e., parietal pericardium) containing basement membrane components (e.g., Laminin, Col IV) and the fibrous surface (i.e., mediastinal side) being composed primarily of type I collagen (Col I). Native BP surface ECM niche anisotropy is preserved in antigen removed BP (AR-BP) extracellular matrix (ECM) scaffolds. By exploiting sideness (serous or fibrous surface) of AR-BP scaffolds, this study aims to determine the mechanism by which ECM niche influences human mesenchymal stem cells (hMSCs) migration. Human mesenchymal stem cells (hMSC) seeding on serous surface promoted more rapid cell migration than fibrous surface seeding. Gene analysis revealed that expression of integrin α3 and α11 were increased in cells cultured on serous surface compared to those on the fibrous side. Monoclonal antibody blockade of α3β1 (i.e., laminin binding) inhibited early (i.e. ≤ 6 h) hMSC migration following serous seeding, while having no effect on migration of cells on the fibrous side. Blockade of α3β1 resulted in decreased expression of integrin α3 by cells on serous surface. Monoclonal antibody blockade of α11β1 (i.e., Col IV binding) inhibited serous side migration at later time points (i.e., 6–24 h). These results confirmed the role of integrin α3β1 binding to laminin in mediating early rapid hMSCs migration and α11β1 binding to Col IV in mediating later hMSCs migration on the serous side of AR-BP, which has critical implications for rate of cellular monolayer formation and use of AR-BP as blood contacting material for clinical applications.
Power law behaviour in the saturation regime of fatality curves of the COVID-19 pandemic
Authors: Vasconcelos Giovani L. , Macêdo Antônio M. S. , Duarte-Filho Gerson C. , Brum Arthur A. , Ospina Raydonal , Almeida Francisco A. G.
Published: February 2021

We apply a versatile growth model, whose growth rate is given by a generalised beta distribution, to describe the complex behaviour of the fatality curves of the COVID-19 disease for several countries in Europe and North America. We show that the COVID-19 epidemic curves not only may present a subexponential early growth but can also exhibit a similar subexponential (power-law) behaviour in the saturation regime. We argue that the power-law exponent of the latter regime, which measures how quickly the curve approaches the plateau, is directly related to control measures, in the sense that the less strict the control, the smaller the exponent and hence the slower the diseases progresses to its end. The power-law saturation uncovered here is an important result, because it signals to policymakers and health authorities that it is important to keep control measures for as long as possible, so as to avoid a slow, power-law ending of the disease. The slower the approach to the plateau, the longer the virus lingers on in the population, and the greater not only the final death toll but also the risk of a resurgence of infections.
Correlation between circulating interleukin-18 level and systemic lupus erythematosus: a meta-analysis
Authors: Xiang Mengmeng , Feng Yang , Wang Yilun , Wang Jie , Zhang Zhixiong , Liang Jun , Xu Jinhua
Published: February 2021

This study is a meta-analysis aimed at pooling reported data and clarifying the association between circulating level of interleukin-18 and systemic lupus erythematosus (SLE). We searched medical databases including Medline/Pubmed, Embase, Scopus, The Cochrane Library, and Web of Science thoroughly to obtain all related articles published before July 15th, 2020. We pooled computed standardized mean difference (SMD) and its 95% confidence interval using STATA 13.0 and exhibited in the form of forest graph. Meta-regression and subgroup analysis were also performed to explore the source of heterogeneity. Publication bias was first evaluated by the symmetry of the funnel plot and then Egger’s linear regression test. Thirty eligible studies from eighteen regions were finally included and the relevant data from these studies were pooled. The analysis results displayed that SLE patients showed a significantly higher level of circulating IL-18 level in comparison with healthy controls (SMD = 1.56, 95% CI [1.20–1.93]; I2 = 94.9%,p < 0.01). The conclusion was equally applicable in subgroups divided based on sample type, mean age, disease duration, and testing method. Patients with SLEDAI score higher than five, or who were Asian, White, Arab, or mixed ethnicity had an elevated level of IL-18, while the others didn’t. This meta-analysis has elucidated that compared with healthy people, the circulating level of IL-18 is considerably higher in SLE patients, which indicates the underlying role of IL-18 in SLE pathogenesis.
Effects of different proportions of soft rock additions on organic carbon pool and bacterial community structure of sandy soil
Authors: Li Wan-ying , Guo Zhen , Li Juan , Han Ji-chang
Published: February 2021

The sandy soil leaks water and fertilizer, and the ecological degradation is serious. The structural characteristics of soft rock and sandy soil are complementary, and the improvement of sandy soil by adding soft rock is of great significance to improve soil fertility, restore biodiversity, and maintain sustainable development of the Mu Us sandy land region. In this study, total organic carbon (TOC), particulate organic carbon (POC), dissolved organic carbon (DOC), easily oxidized organic carbon (ROC), microbial biomass carbon (SMBC), bacterial community structure and crop yield were examined using soft rock:sand volume ratios of 0:1 (CK), 1:5 (C1), 1:2 (C2) and 1:1 (C3). Our results indicated that, compared with the CK treatment, TOC (9.66–22.34%), POC (85.65–120.41%) and ROC (114.12–192.31%) noticeably increased in C1, C2 and C3 treatments; SMBC in treatment C3 increased by 42.77%. The three dominant bacteria in the soil (Proteobacteria, Actinobacteria and Chloroflexi), as well as Proteobacteria abundance, greatly declined in the treatments with the addition of soft rock. Pseudarthrobacter was the dominant Genus in all treatments, having an abundance between 11.83 and 19.33%. Bacterial diversity, richness and evenness indices all recorded an increase under the treatments. POC, TOC and SMBC recorded the most significant effects on the bacterial community structure. The largest increases in wheat and corn yields were recorded in the C2 treatment (16.05% and 16.30%), followed by the C1 treatment (8.28% and 8.20%, respectively). Our findings indicate that a soft rock:sand ratio between 1:5 and 1:2 recorded the most improvement in the sandy soil environment.
Association between KCNJ11 rs5219 variant and alcohol consumption on the effect of insulin secretion in a community-based Korean cohort: a 12-year follow-up study
Authors: Yun Ji Ho , Yoo Min-Gyu , Park Ji Young , Lee Hye-Ja , Park Sang Ick
Published: February 2021

Chronic alcohol consumption is known to be associated with type 2 diabetes (T2D), which is developed by two underlying mechanisms, β-cell dysfunction and insulin resistance. Identification of genetic variants in association with the development of T2D may help explain the genetic risk factors of T2D. In this study, we tried to find out some genetic variations, which interact with alcohol consumption and also are associated with β-cell function through 12 year’s follow-up study in Korean population. We performed a genotype association study using the community-based Ansung-Ansan Cohort data (baseline n = 3120; follow-up n = 433). Genotype association analyses of the baseline data showed that alcohol consumption is associated with the decreases of blood insulin levels and insulin secretion in participants with the KCNJ11 rs5219 risk allele. Moreover, multivariate logistic regression analyses revealed that the risk allele group is vulnerable to impairment of β-cell function in response to alcohol consumption (OR 1.450; 95% CI 1.061–1.982). Furthermore, 12-year’ follow-up results showed that alcohol consumption synergistically decreases insulin secretion in participants with KCNJ11 rs5219 risk alleles. Our findings demonstrate that the KCNJ11 rs5219 risk allele in combination with alcohol consumption could be a potential risk factor of β-cell dysfunction. We hope that this new findings could be helpful to further understand the development of T2D depending on individual genetic background in association with alcohol consumption.
Cannabinoids modulate food preference and consumption in Drosophila melanogaster
Authors: He Jianzheng , Tan Alice Mei Xien , Ng Si Yun , Rui Menglong , Yu Fengwei
Published: February 2021

Cannabinoids have an important role in regulating feeding behaviors via cannabinoid receptors in mammals. Cannabinoids also exhibit potential therapeutic functions in Drosophila melanogaster, or fruit fly that lacks cannabinoid receptors. However, it remains unclear whether cannabinoids affect food consumption and metabolism in a cannabinoid receptors-independent manner in flies. In this study, we systematically investigated pharmacological functions of various cannabinoids in modulating food preference and consumption in flies. We show that flies display preferences for consuming cannabinoids, independent of two important sensory regulators Poxn and Orco. Interestingly, phyto- and endo- cannabinoids exhibit an inhibitory effect on food intake. Unexpectedly, the non-selective CB1 receptor antagonist AM251 attenuates the suppression of food intake by endocannabinoids. Moreover, the endocannabinoid anandamide (AEA) and its metabolite inhibit food intake and promote resistance to starvation, possibly through reduced lipid metabolism. Thus, this study has provided insights into a pharmacological role of cannabinoids in feeding behaviors using an adult Drosophila model.
Antisense oligonucleotide development for the selective modulation of CYP3A5 in renal disease
Authors: Lidberg Kevin A. , Annalora Andrew J. , Jozic Marija , Elson Daniel J. , Wang Lu , Bammler Theo K. , Ramm Susanne , Monteiro Maria Beatriz , Himmelfarb Jonathan , Marcus Craig B. , Iversen Patrick L. , Kelly Edward J.
Published: February 2021

CYP3A5 is the primary CYP3A subfamily enzyme expressed in the human kidney and its aberrant expression may contribute to a broad spectrum of renal disorders. Pharmacogenetic studies have reported inconsistent linkages between CYP3A5 expression and hypertension, however, most investigators have considered CYP3A5*1 as active and CYP3A5*3 as an inactive allele. Observations of gender specific differences in CYP3A5*3/*3 protein expression suggest additional complexity in gene regulation that may underpin an environmentally responsive role for CYP3A5 in renal function. Reconciliation of the molecular mechanism driving conditional restoration of functional CYP3A5*3 expression from alternatively spliced transcripts, and validation of a morpholino-based approach for selectively suppressing renal CYP3A5 expression, is the focus of this work. Morpholinos targeting a cryptic splice acceptor created by the CYP3A5*3 mutation in intron 3 rescued functional CYP3A5 expression in vitro, and salt-sensitive cellular mechanisms regulating splicing and conditional expression of CYP3A5*3 transcripts are reported. The potential for a G-quadruplex (G4) in intron 3 to mediate restored splicing to exon 4 in CYP3A5*3 transcripts was also investigated. Finally, a proximal tubule microphysiological system (PT-MPS) was used to evaluate the safety profile of morpholinos in proximal tubule epithelial cells, highlighting their potential as a therapeutic platform for the treatment of renal disease.
Assessment of the choroidal structure in pregnant women in the first trimester
Authors: Azuma Keiko , Okubo Atsushi , Suzuki Takafumi , Igarashi Nozomi , Nomura Yoko , Soga Hirotsugu , Murata Hiroshi , Fujino Ryosuke , Ogawa Asako , Matsui Haruka , Nagamatsu Takeshi , Iriyama Takayuki , Asaoka Ryo , Inoue Tatsuya , Maruyama-Inoue Maiko , Kadonosono Kazuaki , Obata Ryo
Published: February 2021

We investigated the anatomical differences in the choroidal structure between pregnant women in the first trimester of pregnancy and age-matched healthy nonpregnant women using enhanced depth imaging optical coherence tomography (EDI-OCT) and choroidal binarization analysis. The main parameters measured in the two study groups, namely, pregnant women in the first trimester and healthy nonpregnant women, were choroidal thickness and the choroidal luminal area. Binarization of the EDI-OCT images from each patient was performed, and the choroidal vascularity index (CVI) was calculated. The correlations between the baseline characteristics of the subjects and the CVI were investigated using linear mixed model analysis. As a result, there was no statistically significant difference in the mean age, best-corrected visual acuity, axial length, central retinal thickness, subfoveal choroidal thickness, systolic blood pressure (BP), or diastolic BP between the two study groups. Conversely, a significant difference was observed in the CVI (P = 0.012) between the two groups. The multivariate analysis identified a significant correlation between the CVI and the systolic BP (P = 0.0044, linear mixed test). Taken together, a larger choroidal luminal area was associated with a higher systolic BP, especially in the first trimester of pregnancy. Our findings may provide further insight into the choroidal changes that occur during pregnancy.
Seasonal distribution and environmental parameters associated with Brugia pahangi and Dirofilaria immitis in naturally infected dogs in Bangkok and vicinity, Thailand
Authors: Jitsamai Wanarit , Piromkij Pimsiri , Kamkong Patchana , Chungpivat Sudchit , Taweethavonsawat Piyanan
Published: February 2021

Dirofilaria immitis and Brugia pahangi are vector-borne parasites found in dogs and cats, including Thailand. In order to evaluate the effects of season and environmental parameters on the prevalence of these parasites, this retrospective study was conducted in 2019. A total of 79,506 canine blood samples were examined. B. pahangi was found in 0.55% of samples (438/79,506; 95% CI 0.50–0.61) while D. immitis was detected in 0.43% (345/79,506; 95% CI 0.39–0.48). One-way ANOVA found no effect of seasonal conditions on prevalence. For B. pahangi, the parameters rainfall, relative humidity and sunshine hours showed associations with p ≤ 0.20 and were included in multiple logistic regressions resulting in adjusted odds ratios of 0.53, 1.31 and 0.55, respectively. For D. immitis, only average temperature showed p ≤ 0.20, resulting in an odds ratio of 0.42. In conclusion, Thailand has environmental parameters that do not change very much during the year, so they might not affect the prevalence of two filarial nematodes. However, the threat of B. pahangi and D. immitis should not be ignored, especially in subtropical regions where their vectors are abundant. Both owners and veterinarians should be concerned about filarial prevention and control of D. immitis and B. pahangi.