bluuebunny/crossref_metadata_2025 huggingface dataset:
MR Susceptibility Imaging for Detection of Tumor-Associated Macrophages in Glioblastoma
Authors: Nazem Amir , Guiry Samantha , Pourfathi Mehrdad , Ware Jeffrey B. , Anderson Hannah , Iyer Srikant Kamesh , Moon Brianna F , Fan Yi , Witschey Walter R. , Rizi Rahim , Bagley Stephen J. , Desai Arati , O’Rourke Donald M. , Brem Steven , Nasrallah MacLean , Nabavizadeh Ali
Published: November 2021

Purpose
Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, we investigated MRI to quantify iron as an imaging biomarker for TAMs in GBM patients.
Methods
21 adult patients with GBM underwent a 3D single echo gradient echo MRI sequence and quantitative susceptibility maps were generated. In 3 subjects, ex vivo imaging of surgical specimens was performed on a 9.4 Tesla MRI using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated. Each specimen was stained with hematoxylin and eosin, as well as CD68, CD86, CD206, and L-Ferritin.
Results
Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the L-ferritin positivity percent (r =0.56, p=0.018) and the combination of tumor’s enhancing zone and necrotic core and the L-Ferritin positivity percent (r=0.72; p=0.001). The mean susceptibility significantly correlated with positivity percent for CD68 (ρ = 0.52, p=0.034) and CD86 (r=0.7 p=0.001), but not for CD206 (ρ = 0.09; p=0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r =0.6, p=0.016). Similarly, mean R2* values significantly correlated with CD86 (r=0.54, p=0.03) but not with CD206 (r=0.15, p=0.5).
Conclusion
MR quantitative susceptibility mapping can quantify the iron content of GBM and provide a non-invasive method for TAM quantification and phenotyping.
Prognostic Factors For Intermediate-Risk Atypical Meningiomas Determining Early Postoperative Adjuvant Radiotherapy Versus Active Monitoring After Gross Total Resection
Authors: Gurses Muhammet Enes , Zengin Hatice Yagmur , Shıkhaliyeva Aysel , Askun Cengiz Savas , Mut Melike
Published: November 2021

Background

Atypical meningiomas (AMs) constitute 18% of meningiomas. Predictors of recurrence are still indeterminate, and the timing of RT whether to treat with radiation upfront or at initial recurrence remains controversial, especially after gross total resection (GTR).
Methods

A retrospective study of AMs with uni-and multivariate analyses was conducted with clinical, surgical, radiological, and histopathological parameters. The prognostic factors associated with increased risk of recurrence were elucidated in the whole series and in the subgroup with GTR only.
Results

Subtotal resection (STR), skullbase-tentorium localization, no adjuvant RT, and progesterone-negativity caused tumor recurrence in 37 patients with a median follow-up of 48 (2-120) months. Among subgroup of 23 patients GTR only, 30.8% showed recurrence in a median of 39.65 months. AMs with a preoperative volume ≥27.5 cm3 disclosed a significantly higher risk of recurrence (a 9.3 fold increase) than those with <27.5 cm3 (66.7% vs. 14.3%, respectively). Skullbase-tentorium localization and progesterone negativity tend to have higher recurrence rates after GTR.
Conclusions

Preoperative volume was found to be a prognostic factor for AMs with a cut-off value of 27.5 cm3 for the first time in the literature. Our results disclosed that RT could be delayed with active monitorization after GTR for AMs, which are smaller than 27.5 cm3, not localized in skullbase-tentorium and progesterone-positive. Otherwise, early postop RT would be a safer approach without waiting the recurrence for AMs.
Assessment of Mechanisms of HDO-AntimiR by Molecular Dynamics Simulation
Authors: Nishina Kazutaka , Hara Rintaro Iwata , Fukuhara Satoru , Yoshioka Kotaro , Yokota Takanori , Shibuta Yasushi
Published: November 2021

Recently, we found DNA/RNA heteroduplex oligonucleotide-based antimiR (HDO-antimiR) can more efficiently inhibit the target miRNA than conventional antimiR after its cellular uptake. But the mechanism of HDO-antimiR about the target-silencing is unknown. We here tried to elucidate the interaction mechanism of HDO-antimiR to miRNA using molecular dynamics (MD) simulation. When interaction of the conventional antimiR or HDO-antimiR and the target miRNA was simulated, they combined with each other in various forms. In the hydrogen bond analyses, base site of the antimiR formed hydrogen bond with miRNA. On the other hand, phosphate site of the HDO-antimiR formed hydrogen bond with miRNA. These results suggested that there were differences about the binding mechanisms between antimiR and HDO-antimiR to the target miRNA. In particular, there was a difference in the binding site between antimiR and HDO-antimiR. Additionally, it was found that guanine in the miRNA is mainly involved in the binding to the antimiR or HDO-antimiR. MD simulation method is useful in understanding the mechanism of oligonucleotide therapeutics.
UPLC-QTOF-MS-Based Untargeted Study of Metabolites Secreted by Sclerotinia Sclerotiorum Pathogen Under Axenic Condition
Authors: Gupta Navin Chandra , Arora Shaweta , Kundu Aditi , Sharma Pankaj , Rao Mahesh , Bhattacharya Ramcharan
Published: November 2021

The stem rot disease has emerged globally as a major disease threat to the productivity and seed quality of oilseed Brassica. The generalist causal pathogen Sclerotinia sclerotiorum (Lib.) de Bary shows large variability in their aggressiveness and pathogenicity. Revealing the metabolic profile and signaling components of the pathogen in host-pathogen interaction are fundamental in understanding host resistance to the disease. In this study, the metabolites released by the pathogenic strains of S. sclerotiorum under the axenic culture have been identified using the untargeted high-resolution UPLC-QTOF-ESI-MS/MS. The analysis of the ethyl acetate extracts of the S. sclerotiorum culture revealed ten major secondary metabolites namely, sclerin, sclerotinin-B, sclerone, melanin, bostrycoidin, botcinin-D, botcinin-A, gliovirin, scleramide, and botcinic acid. The later six metabolites are being reported for the first time in the culture extract of the S. sclerotiorum pathogen. The phylogenetic analysis based on the overlapping and unique informative peaks in the chromatograms, the six S. sclerotiorum strains were grouped into three major clads. The clustering based on metabolic profiles does not substantiate the diversity based on morphology or virulence differences on the host. The findings of the study signified the metabolites secreted under the axenic conditions are varies based on their growth and developmental stages and may not necessarily be the determining factors for their differential aggressiveness and virulence over the host.
Covalent organic frameworks with high quantum efficiency in photocatalytic hydrogen evolution: mediating charge separation
Authors: Li Chunzhi , Liu Jiali , Li He , Wu Kaifeng , Wang Junhui , Yang Qihua
Published: November 2021

Compared with inorganic semiconductors, the difficulty of exciton dissociation is one of the main reasons for the lower photocatalytic activity of organic semiconductors. In this work, we report that the charge carrier lifetime is dramatically prolonged by incorporating a suitable donor-acceptor (β-ketene-CN) pair to a covalent organic framework nanosheet (CN-CON). CN-CON showed remarkably high apparent quantum efficiency up to 82.6% at 450 nm in photocatalytic H2 evolution, superior to all the COFs reported so far. The charge carrier kinetic analysis and femtosecond transient absorption spectroscopy characterizations verified that CN-CON had intrinsically lower exciton binding energies and hence longer-lived charge carriers than the corresponding CON without CN unit. This work provides an excellent model for gaining insight into the nature of ultrashort-lived active species in polymeric organic photocatalysts.
Diabetic Foot Disease Research in Aotearoa New Zealand: A Bibliometric Analysis (1970-2020)
Authors: Carroll Matthew , Al-Busaidi Ibrahim Saleh , Coppell Kirsten J , Garrett Michele , Ihaka Belinda , O'Shea Claire , Wu Justina , York Steve
Published: November 2021

Aim

The aim of this bibliometric study was to examine trends in the quality and quantity of published diabetic foot disease (DFD) research in Aotearoa/New Zealand (NZ) over the past five decades.
Method

In July 2021, the Scopus® database was searched for DFD-related publications (1970-2020) using predetermined search and inclusion criteria. Bibliometric data were extracted from Scopus® and Journal Citation Reports. Retrieved bibliographic indicators were analysed in Biblioshiny, an R Statistical Software interface and reported using descriptive statistics.
Results

Forty-seven DFD-related articles were identified. The annual number of publications showed a significant upward trend increasing from one in 1988 to 47 in 2020 (P < 0.001). The majority of identified articles (n = 31, 66%) were published in the last decade (2011-2020). Basic/clinical research accounted for 87% (n = 41) of publications and 14 (30%) investigated the screening and/or prevention of DFD. The average citation per article was 20.23 (range: 0-209) and the median impact factor was 4.31 (range, 1.82-79.32). Over a third of articles (36%) had an international authorship network. Funding was reported by 15 (32%) articles; 12 (26%) were supported by public national grants vs. three (6%) reporting industry-sponsorship.
Conclusion

DFD articles authored by NZ researchers have increased over the past five decades. Despite that NZ researchers increased their global impact through collaborative networks, most of the research was classified as low-level evidence, with limited focus on Indigenous Māori and limited financial support and funding. Increased funding for interventional research is required to enable a higher level of evidence-based and practice-changing research to occur. With rates of diabetes related amputations higher in Māori future research must focus on reducing inequalities in diabetes related outcomes for Māori by specifically targeting the prevention and screening of DFD in primary care settings in NZ.
Associations of self-repression with disordered eating and symptoms of other psychopathologies for men and women
Authors: Bachner-Melman Rachel , Watermann Yonatan , Lev-Ari Lilac , Zohar Ada H.
Published: November 2021

Background: Disordered eating has been found to be associated with self-repression, specifically with selflessness, the tendency to relinquish one’s needs for others’, and concern for appropriateness, an alertness to information about social comparison and tendency to vary one’s behavior in different social situations. This study aimed to examine associations between these self-repression variables and symptoms of general psychopathology for women and men in a community sample. Methods: Two hundred and thirty-six participants (92 men) aged 18-76 (M=29.11+10.10) volunteered to complete measures of ED symptoms (EDE-Q), concern for appropriateness (CFA-CSV and CFA-ATSCI), selflessness (SS), and symptoms of depression (PHQ-9), anxiety (BSI-18 anx) and somatization (BSI-18 som) online. Structural equation models were built to assess pathways between the study variables for men and women separately. Results: A MANOVA 2*7 design showed that women scored significantly higher than men on the SS, EDE-Q and PHQ-9. For men, SS scores were positively and significantly associated only with PHQ-9 scores. CAS-CSV scores were positively associated with PHQ-9, BSI-18 som and BSI-18 anx scores. For women, SS scores were positively and significantly associated with PHQ-9, EDE-Q, BSI-18 som and BSI-18 anx scores. CAS-CSV scores were positively and significantly associated with PHQ-9, BSI-18 anx and BSI-18 som scores but not EDE-Q scores. CAS-ASCI scores were positively and significantly associated only with EDE-Q scores.Conclusions: Self-repression is a much more central path to psychopathology in women than in men. For men, self-suppression seems to play an important role in the development and maintenance of symptoms of internalizing disorders, but not disordered eating. Even for women, it appears that self-repression is not connected specifically with disordered eating, but with symptoms of psychopathology in general. Future research should explore why self-suppression plays such a central role in women’s psychopathology.
Soil Respiration Variations in Temperate Rhododendron (Rhododendronarboreum) Forest of Annapurna Conservation Area (ACA) in Nepal
Authors: Dhital Deepa , Manandhar Puruswattam , Gosain Bikash , Sijapati Jaishree
Published: November 2021

Background: Photosynthetic carbon released into the atmosphere in the form of carbon dioxide (CO2) which represented by soil respiration (SR), is considered the largest carbon (C) efflux of terrestrial ecosystem. Understanding the dynamics of SR is critical to coping with prevailing climate change from regional to global scale. Temperate forests are considered as most fragile hence need to recognize their vulnerability owing to continuous climatic changes and anthropogenic activities. Predicting the response of SR is essential, owing to the varying environmental factors that are most dominantly effective to become common determinants of forest carbon variability. This study aimed to assess SR by using closed chamber method in the natural Rhododendron arboretum forest in Annapurna Conservation Area (ACA) which is recognized as the world’s largest forest type located in a temperate region of Nepal. This research additionally aimed to evaluate the consequences of multiple ecological parameters mainly climatic and biotic factors on SR variations in consecutive two years measurement period in October 2016 and 2017.Results: Overall, SR in the forest well corresponded with the soil temperature (ST) variables. Within a short-range (2-3°C) of ST difference the variation in SR was recognized as highly significant (p<0.05) exponential curve (y=1.049e0.529x, 2016 and y = 26.34e0.284x, 2017). However, the effect of soil water content (SWC) on SR was scattered and clear effects of photosynthetic photon flux density (PPFD) were also not detected. Contrary to ST and SWC, seasonal trend of SR was compatible with the PPFD and litter input. The temporal, diurnal, and inter-annual variations of SR, ST, SWC and litter fall were accountable.Conclusions: Temperate forest could store the maximum amount of soil C with limited C emission through SR and become a larger sink of atmospheric CO2. SR is very sensitive to environmental changes and interactively affected by multiple ecological factors, even though it is often difficult to separate their interactions. This founding research is adequate measure in temperate Rhododendron forest; further study seeks understanding on how C emission responds to the regional climate warming, through changing precipitation and landuse, and integrates these feedbacks into global climate models and carbon budget.
Genetic Characterization of Fall Armyworm in Africa Indicates a Limited Capacity for Transcontinental Population Movements and Evidence of a Second Introduction
Authors: Nagoshi Rodney N. , Goergen Georg , Koffi Djima , Agboka Komi , Adjevi Anani Kossi Mawuko , Du Plessis Hannalene , Berg Johnnie Van den , Tepa-Yotto Ghislain T. , Winsou Jeannette K. , Meagher Robert L. , Brévault Thierry
Published: November 2021

The fall armyworm, Spodoptera frugiperda (J.E. Smith) is native to the Americas and a major pest of corn and several other crops of economic importance. The species has characteristics that make it of particular concern as an invasive pest, including broad host range, long-distance migration behavior, and a propensity for field-evolved pesticide resistance. The discovery of fall armyworm in western Africa in 2016 was followed by what was apparently a remarkably rapid spread throughout sub-Saharan Africa by 2018, causing economic damage estimated in the tens of billions USD and threatening the food security of the continent. Understanding the history of the fall armyworm invasion of Africa and the genetic composition of the African populations is critical to assessing the risk posed to different crop types, the development of effective mitigation strategies, and to make Africa less vulnerable to future invasions of migratory moth pests. This paper tested and expanded on previous studies by combining data from 22 sub-Saharan nations during the period from 2016-2019. The results support initial descriptions of the fall armyworm invasion, including the near absence of the strain that prefers rice, millet, and pasture grasses, while providing additional evidence that the magnitude and extent of FAW natural migration on the continent is more limited than expected. The results also show that a second entry of fall armyworm likely occurred in western Africa from a source different than that of the original introduction. These findings indicate that western Africa continues to be at high risk of future introductions of FAW, which could complicate mitigation efforts.
The estimated disease burden of acute COVID-19 in the Netherlands in 2020, in disability-adjusted life-years
Authors: McDonald Scott A. , Lagerweij Giske R. , de Boer Pieter , de Melker Hester E. , Pijnacker Roan , Gras Lapo Mughini , Kretzschmar Mirjam E. , Hartog Gerco den , Gageldonk-Lafeber Arianne B. van ,   RIVM COVID-19 surveillance and epidemiology team, Hof Susan van den , Wallinga Jacco
Published: November 2021

Background. The impact of the COVID-19 pandemic on population health is recognised as being substantial, yet few studies have attempted to quantify to what extent infection causes mild or moderate symptoms only, requires hospital and/or intensive care unit (ICU) admission, results in prolonged and chronic illness, or leads to premature death. Our objectives were to quantify the total disease burden of acute COVID-19 in the Netherlands in 2020 using the disability-adjusted life-years (DALY) measure, and to investigate how disease burden varies between age-groups and occupation categories.Methods. Using standard methods and diverse data sources (registered COVID-19 deaths, hospital and ICU admissions, population-level seroprevalence, mandatory notifications, and the literature) , we estimated the total years of life lost (YLL), years lived with disability (YLD), DALY and DALY per 100,000 population due to COVID-19, excluding its post-acute sequelae, and additionally stratified by 5-year age-group and occupation.Results. The total disease burden in the Netherlands in 2020 due to acute COVID-19 was 273,500 (95% CI: 268,500–278,800) DALY, and the per-capita burden was 1570 (95% CI: 1540–1600) DALY/100,000, of which 99.4% consisted of YLL. The per-capita burden increased steeply with age, starting from the 60-64 years age-group. The per-capita burden by occupation category was highest for healthcare workers and lowest for the catering sector.Conclusions. SARS-CoV-2 infection and associated premature mortality was responsible for a considerable direct health burden in the Netherlands, despite extensive public health measures. Total DALY were much higher than for other high-burden infectious diseases, but lower than the estimated annual burden from coronary heart disease. These findings are valuable for informing public health decision-makers regarding the expected health burden due to COVID-19 among subgroups of the population, and the possible gains from targeted preventative interventions.
A Black Hole-Aided Deep-Helix Channel Model for DNA
Authors: Sarker Md. Abdul Latif , Kader Md. Fazlul , Sarker Md. Mostafa Kamal , Lee Moon Ho , Han Dong Seog
Published: November 2021

In this article, we present a black-hole-aided deep-helix (bh-dh) channel model to enhance information bound and mitigate a multiple-helix directional issue in Deoxyribonucleic acid (DNA) communications. The recent observations of DNA do not match with Shannon bound due to their multiple-helix directional issue. Hence, we propose a bh-dh channel model in this paper. The proposed bh-dh channel model follows a similar fashion of DNA and enriches the earlier DNA observations as well as achieving a composite like information bound. To do successfully the proposed bh-dh channel model, we first define a black-hole-aided Bernoulli-process and then consider a symmetric bh-dh channel model. After that, the geometric and graphical insight shows the resemblance of the proposed bh-dh channel model in DNA and Galaxy layout. In our exploration, the proposed bh-dh symmetric channel geometrically sketches a deep-pair-ellipse when a deep-pair information bit or digit is distributed in the proposed channel. Furthermore, the proposed channel graphically shapes as a beautiful circulant ring. The ring contains a central-hole, which looks like a central-black-hole of a Galaxy. The coordinates of the inner-ellipses denote a deep-double helix, and the coordinates of the outer-ellipses sketch a deep-parallel strand. Finally, the proposed bh-dh symmetric channel significantly outperforms the traditional binary-symmetric channel and is verified by computer simulations in terms of Shannon entropy and capacity bound.
Impact of metabolic indices of 18F-fluorodeoxyglucose positron emission tomography/computed tomography on post transplantation recurrence of hepatocellular carcinoma.
Authors: Bauschke Astrid , Altendorf-Hofmann Annelore , Brückner Lukas , Drescher Robert , Freesmeyer Martin , Settmacher Utz
Published: November 2021

Background
Tumor recurrence is the leading cause of death after liver transplantation in patients with hepatocellular carcinoma. There is an ongoing debate as to whether metabolic indices such as tumor to liver standardized uptake value ratio in 18 F-fluorodeoxyglucose positron emission tomography/computed tomography of the primary tumor can identify patients outside the Milan criteria with as low recurrence rates as patients inside Milan and thus should be added to the established prognostic factors.
Methods
This retrospective study analyzes 103 consecutive patients who underwent 18 F fluorodeoxyglucose positron emission tomography/computed tomography before liver transplantation for hepatocellular carcinoma using data of clinical tumor registry. Primary endpoints were overall survival and 10-year cumulative recurrence rates.
Results
Tumor to liver standardized uptake value ratio of the primary tumor was statistically significant higher in Milan out tumors, “up-to-seven” out tumors, grade 3 tumors, alpha-fetoprotein level >400 ng/ml and lesions upwarts 5cm in diameter. Factors with statistically significant influence on the 10-year overall survival in the univariate analysis were Milan, up-to-seven” criteria, number of lesions and pT-category. COX regression analysis did not show independently statistically significant factors for 10-year overall survival. Milan, “up-to-seven” criteria, grade, pV, number of lesions, size of lesion, pT-category, tumor to liver standardized uptake value ratio influenced 10-year cumulative recurrence rates statistically significantly. Tumor to liver standardized uptake value ratio, grade and pT-category proved to be independently statistically significant factors for 10-year cumulative recurrence rates.
Conclusions
Our study suggests that tumor to liver standardized uptake value standardized uptake value ratio in 18 F-fluorodeoxyglucose positron emission tomography/computed tomography is an independent prognostic factor in transplanted patients with hepatocellular carcinoma and might be helpful in estimating the risk of recurrence for patients scheduled for liver transplantation.
Maximum logq Likelihood Estimation for Parameters of Weibull Distribution and Properties: Monte Carlo Simulation
Authors: Cankaya Mehmet Niyazi , Vila Roberto
Published: November 2021

The maximum logq likelihood estimation method is a generalization of the known maximum log likelihood method to overcome the problem for modeling non-identical observations ( inliers and outliers). The parameter $q$ is a tuning constant to manage the modeling capability. Weibull is a flexible and popular distribution for problems in engineering. In this study, this method is used to estimate the parameters of Weibull distribution when non-identical observations exist. Since the main idea is based on modeling capability of objective function p(x; ʘ) = logq [f(x; ʘ)], we observe that the finiteness of score functions cannot play a role in the robust estimation for inliers . The properties of Weibull distribution are examined. In the numerical experiment, the parameters of Weibull distribution are estimated by logq and its special form, log , likelihood methods if the different designs of contamination into underlying Weibull distribution are applied. The optimization is performed via genetic algorithm. The modeling competence of p(x; ʘ) and insensitiveness to non-identical observations are observed by Monte Carlo simulation. The value of $q$ can be chosen by use of the mean squared error in simulation and the $p$ -value of Kolmogorov - Smirnov test statistic used for evaluation of fitting competence. Thus, we can overcome the problem about determining of the value of $q$ for real data sets.
Effects of early home-based strength and sensory-motor training after total hip arthroplasty: study protocol for a randomized controlled trial
Authors: Mirt Pika Krištof , Strojnik Vojko , Kavčič Gregor , Trebše Rihard
Published: November 2021

BackgroundTotal hip arthroplasty (THA) is very effective in alleviating pain, but functional deficits persist up to a year following surgery. Regardless of standard physiotherapy programs, significant additional muscular atrophy and weakness occurs. Deficits in strength have serious adverse consequences for these patients with respect to physical function, the maintenance of independence and the requirement for revision surgery. Progressive resistance training in rehabilitation following THA has been shown to significantly enhance muscle strength and function. The fundamental principle is to progressively overload the exercised muscle as it becomes stronger. Different strength training protocols have been used at different times in the postoperative phase, in group or individual practices, with major differences being in center-based and home-based programs with or without supervision. The primary objectives of our study are to evaluate whether an early postoperative home-based strength training protocol is feasible for all elective THA patients, does not cause major adverse effects and can improve patient functional outcomes at 3 months and 1 year following surgery.Methods/DesignThis study is a prospective multicenter randomized clinical trial to be conducted in the orthopedic departments of two Slovenian hospitals. In each hospital, 124 patients aged 60 or older with unilateral osteoarthritis, an ASA score between 1 and 3, signed informed consent form, and no terminal illness disabling rehabilitation participation will be randomly assigned to the intervention or control group. THA with an anterior approach will be performed. All patients will receive current standard physiotherapy during hospitalization. Patients in the intervention group will also learn strength and sensory-motor training exercises. Upon discharge all will receive USB drives with exercise videos, written exercise instructions and a training diary. Physiotherapists will perform the assessments (physical tests and the maximal voluntary isometric contraction assessment), and patients will fill out outcome assessment questionnaires (the Harris Hip Score and 36-Item Short Form Health Survey) at baseline and 1, 3 and 12 months after surgery.DiscussionThe main purpose of our study is to design a new standardized rehabilitation protocol with videos that will be effective, safe and accessible to all Slovenian THA patients.Trial registrationClinicalTrials.gov ID: NCT04061993. Protocol ID: PRT_PhD. Record Verification April 2021. https://clinicaltrials.gov/ct2/show/NCT04061993
MCM7 Ubiquitination Regulates CMG Helicase Disassembly in Human
Authors: Sun Qianqian , Liu Kun , Li Fangzhou , Qiu Bingquan , Fu Zhisong , Mao Zebin , Tong Tanjun , Zhao Wenhui
Published: November 2021

BackgroundThe disassembly of the replisome plays an essential role in maintaining genome stability at the termination of DNA replication. However, the mechanism of replisome disassembly remains unknown in human. In this study, we screened E3 ligases and deubiquitinases (DUBs) for the ubiquitination of minichromosome maintenance protein (MCM) 7 and provided evidence of this process driving CMG helicase disassembly in human tumor cells. MethodsSILAC-MS/MS was analyzed to identify ubiquitinated proteins in HeLa cells. The ubiquitination/deubiquitylation assay in vitro and in vivo were detected by Western blot. Thymidine and HU were implied to synchronized cell cycle，and detect the role of ubiquitinated MCM7 in cell cycle. Cell fractionation assay was used to detect the function of ubiquitination of MCM7 in chromatin and non-chromatin. Aphidicolin、Etoposide、ICRF-193 and IR were applied to cause replication fork stalling. MG-132 and NMS-873 were used to inhibit the proteasome degradation and p97 segregase. Flow cytometer and FlowJo flow cytometry software were used to cell cycle analysis.ResultsIn our study, we found that the ubiquitin ligase RNF8 catalyzes the k63-linked poly-ubiquitination of MCM7 both in vivo and in vitro, and lysine 145 of MCM7 is the primary ubiquitination site. Moreover, the poly-ubiquitination of MCM7 mainly exists in the chromatin, which is dynamically regulated by the cell cycle, mainly occurs in the late S phase. And DNA damage can significantly reduce the poly-ubiquitylation of MCM7 in the late S phage. Furthermore, the proteasome, p97 segregase, USP29 and ATXN3 are required for the removal of MCM7 ubiquitination to promote the disassembly of CMG on chromatin. ConclusionsIn the late S phage of cell cycle, RNF8 catalyzes the poly-ubiquitination of MCM7, and then initiates the disassembly of CMG helicase from chromatin, which is mediated by p97, proteasome, USP29 and ATXN3 in human. We reveal the novel function of the poly-ubiquitylation of MCM7, which is a regulatory signal to control CMG complex unloading at replication termination sites.
Infarct Growth Precedes Cerebral Thrombosis Following Experimental Stroke in Mice
Authors: Göb Vanessa , Voll Maximilian G. , Zimmermann Lena , Hemmen Katherina , Stoll Guido , Nieswandt Bernhard , Schuhmann Michael K. , Heinze Katrin G. , Stegner David
Published: November 2021

Ischemic stroke is among the leading causes of disability and death worldwide. In acute ischemic stroke, successful recanalization of occluded vessels is the primary therapeutic aim, but even if it is achieved, not all patients benefit. Although blockade of platelet aggregation did not prevent infarct progression, cerebral thrombosis as cause of secondary infarct growth has remained a matter of debate. As cerebral thrombi are frequently observed after experimental stroke, a thrombus-induced impairment of the brain microcirculation is considered to contribute to tissue damage. Here, we combine the model of transient middle cerebral artery occlusion (tMCAO) with light sheet fluorescence microscopy and immunohistochemistry of brain slices to investigate the kinetics of thrombus formation and infarct progression. Our data reveal that tissue damage already peaks after 8 h of reperfusion following 60 min MCAO, while cerebral thrombi are only observed at later time points. Thus, cerebral thrombosis is not causative for secondary infarct growth during ischemic stroke.
Trends of CO and NO2 Pollutants Change in Iran during Covid-19 Pandemic using Time-Series Sentinel-5 Images in Google Earth Engine
Authors: Shami Siavash , Ranjgar Babak , Azar Mahdi Khoshlahjeh , Moghimi Armin , Sabetghadam Samaneh , Amani Meisam
Published: November 2021

The end of the Persian year (March 2020) coincided with its global pandemic, which led to quarantine and lockdown in Iran. Many studies have shown that with the spread of this disease and the decline of industrial activities, environmental pollutants were drastically reduced. Among these pollutants, Nitrogen Dioxide (NO2) and Carbon Monoxide (CO) are widely caused by anthropogenic and industrial activities. In this study, the changes of these pollutants in Iran and its four metropolises (i.e., Tehran, Mashhad, Isfahan, and Tabriz) in three time periods from March 11 to April 8 of 2019, 2020, and 2021 were investigated. To this end, time-series of the Sentinel-5P TROPOMI and in-situ data within the Google Earth Engine (GEE) cloud-based platform were employed. It was observed that the results obtained from the satellite data were in agreement with the in-situ data (average correlation coefficient =0.7). Moreover, the concentration of NO 2 and CO pollutants in 2020 was 5% lower than in 2019, indicating the observance of quarantine rules as well as people’s initial fear of the Coronavirus. Contrarily, these pollutants in 2021 were higher than those in 2020 by 5%, which could be due to high vehicle traffic and the lack of serious policy by the government to ban urban and interurban traffic. Furthermore, the increase of these pollutants in 2021 was followed by an increase in the deaths caused by Covid-19 and triggering the fourth peak in the Covid-19 cases, signifying a link between exposure to air pollution and Covid-19 mortality in Iran.
Multi-Center Evaluation of Artificial Intelligent Imaging and Clinical Models for Predicting Neoadjuvant Chemotherapy Response in Breast Cancer
Authors: Qi Tan Hong , Hian Ong Hiok , Kumaran Arjunan Muthu , Tan Tira J. , Cong Ryan Shea Tan Ying , Su-Xin Ghislaine Lee , Hsuen Elaine Lim , Hui Raymond Ng Chee , Chert Richard Yeo Ming , Tching Faye Lynette Lim Wei , Zewen Zhang , Hui Christina Yang Shi , Xin Wong Ru , Kai Gideon Ooi Su , Hao Lester Leong Chee , Ming Tan Su , Preetha Madhukumar , Yirong Sim , Mien Veronique Tan Kiak , Yeong Joe , Yong Wong Fuh , Yiyu Cai , Nei Wen Long , na JBCR ,   Ai3 na
Published: November 2021

Background:
Neoadjuvant chemotherapy (NAC) plays an important role in the management of locally advanced breast cancer. It allows for downstaging of tumours, potentially allowing for breast conservation. NAC also allows for in-vivo testing of the tumours’ response to chemotherapy and provides important prognostic information. There are currently no clearly defined clinical models that incorporate imaging with clinical data to predict response to NAC. Thus, the aim of this work is to develop a predictive AI model based on routine CT imaging and clinical parameters to predict response to NAC.
Methods:
The CT scans of 324 patients with NAC from multiple centers in Singapore were used in this study. Four different radiomics models were built for predicting pathological complete response (pCR): first two were based on textural features extracted from peri-tumoral and tumoral regions, the third model based on novel space-resolved radiomics which extract feature maps using voxel-based radiomics and the fourth model based on Deep Learning (DL). Clinical parameters were included to build a final prognostic model.
Results:
The best performing models were based on space-resolved and deep learning approaches. Space-resolved radiomics improves the clinical AUCs of pCR prediction from 0.743 (0.650 to 0.831) to 0.775 (0.685 to 0.860) and our DL model improved it from 0.743 (0.650 to 0.831) to 0.772 (0.685 to 0.853). The tumoral radiomics model performs the worst with no improvement of the AUC from the clinical model. The peri-tumoral combined model gives moderate performance with an AUC of 0.765 (0.671 to 0.855).
Conclusions:
Radiomics features extracted from diagnostic CT augments the predictive ability of pathological complete response when combined with clinical features. The novel space-resolved radiomics and deep learning radiomics approaches outperformed conventional radiomics techniques.
Spatio-Temporal Pollution Forecasting using Hybrid Networks
Authors: Nath Pritthijit , Saha Pratik , Middya Asif Iqbal , Roy Sarbani
Published: November 2021

Rising real estate prices along with expensive maintenance costs, and lack of spares during times of instrument failure have become major issues for statutory bodies when dealing with real-time pollution monitoring stations. As a possible solution to these problems, a novel class of hybrid spatio-temporal pollution forecasting networks which are a combination of various widely used temporal forecasting methods and spatial interpolation methods have been proposed in this paper. In addition, a novel multi-site Multi Layer Perception based Ensemble method, capable of improving accuracy by taking exogenous variables into account, has also been proposed. Experimental results based on the multi-site air pollution data of Beijing demonstrate that the proposed class of hybrid networks have been effective in predicting the pollution of unknown locations with great levels of accuracy. Moreover, the proposed novel MLP Ensemble method for spatial interpolation has also been empirically shown to perform equivalently in comparison to commonly used spatial interpolation methods.
Knowledge and Social Beliefs of Malaria and Prevention Strategies Among Itinerant Nomadic Arabs, Fulanis and Dagazada groups in Chad: A Mixed Method Study
Authors: Moukénet Azoukalné , Beakgoubé Honoré , Smith Helen , Moundine Kebfene , Djonkamla Wang-Mbe , Richardson Sol , Dormbaye Makido , Ngarasta Ngarkodje , Seck Ibrahima
Published: November 2021

Background: Nomadic populations in Chad are at increased risk of contracting malaria because of their lifestyle. Being highly mobile they are often excluded from disease control programs, and access to preventive measures and treatment is more difficult. Effective malaria control interventions take account of local modes of transmission, patterns of care-seeking behavior and community perceptions of cause and prevention practices. There is currently little information about malaria knowledge and perceptions among nomadic groups in Chad, or their awareness of malaria control interventions and this study sought to address this knowledge gap. Methods: A mixed methods study, including a cross-sectional survey with men and women (n = 78) to determine the level of knowledge and use of malaria prevention strategies among Arabs, Peuls and Dagazada nomadic groups. Three focus group discussions were conducted with women to explore their representation of malaria and knowledge of preventive methods. Key informant interviews were held with leaders of nomadic groups (n = 6) to understand perception of malaria risk among itinerant communities.Results: nomads are aware of the risk of malaria, recognize the symptoms and have local explanations for the disease. Reported use of preventive interventions such as Seasonal Malaria Chemoprophylaxis (SMC) for children and Intermittent Preventive Treatment (IPT) of malaria in pregnancy was very low. However, 42.3% of respondents reported owning at least one LLIN and 60% said they slept under an LLIN the night before the survey. In case of a malaria episode, nomads seek clinicians, informal drug sellers in the street or market for self-medication, or traditional medicine depending on their financial means. Interviews with nomad leaders and discussions with women provide key themes on: (i) social representation of malaria risk and (ii) social representation of malaria and (iii) perspectives on malaria prevention and (iv) malaria treatment practices.Conclusion: The nomadic groups included in this study are aware of risk of malaria and their level of exposure. Local interpretations of the cause of malaria could be addressed through tailored and appropriate health education. Except for LLINs, malaria prevention interventions are not well known or used. Financial barriers lowered access to both mosquito nets and malaria treatment. Reducing the barriers highlighted in this study will improve access to the healthcare system for nomadic groups, and increase the opportunity to create awareness of and improve uptake of SMC and IPT among women and children.
“Characterization, Cytotoxicity, and Genotoxicity Properties of Novel Biomediated Nanosized-Silver By Egyptian Streptomyces Roseolus For Safe Antimicrobial Applications”
Authors: Nadi Asmaa El , Sorour Noha Mohamed , Abbas Rateb
Published: November 2021

For biosafety purposes, the genotoxicity of biosynthesized silver nanoparticles (Ag-NPs) was assessed using comet assay for the first time on Blood Lymphocytes, with zero tail migration and 100% head intensity indicating non-genotoxic effect. Ag-NPs have been projected as a new generation of antimicrobial agents because of its antimicrobial property. Ag-NPs were biomediated by Egyptian Streptomyces roseolus for the first time, that was molecularly identified using 16S rRNA sequencing under accession no. MT071505. Biosynthesized Ag-NPs were characterized using UV-Vis spectroscopy, XRD, TEM, FTIR, and DLS. FTIR confirmed the presence of different bioactive functional groups, such as, O-H, N-H, C-H, C-O-C, C-NH2, and C=O acting as reducing-stabilizing agents for biosynthesized Ag-NPs. Biosynthesized Ag-NPs exhibited antimicrobial activity against some multi-drug resistant Gram-positive and Gram-negative pathogens. MBC of biosynthesized Ag-NPs against Listeria monocytogenes and Klebsiella pneumonia were 0.195 and 0.048 mg/mL, respectively, with tolerance level of 2 confirming its biocidal effect. SEM imaging of Ag-NPs-treated L. monocytogenes and K. pneumonia showed shrunk destroyed cells after 6h. Biosynthesized Ag-NPs exhibited IC50 of <0.3 and 8.21 mg/mL, respectively, on normal Human Skin Fibroblast, and Blood Lymphocytes. IC50 values were significantly higher than its MBC values, with no harmful cytotoxic-effect, thus can be safely applied at its biocidal concentration. An ecofriendly biomediated synthesis of Ag-NPs was described with easy scale-up, non-toxic by-products, so, it can be recommended as powerful-safe antimicrobial agent.
Global Myocardial Work in Coronary Artery Disease Patients Without Regional Wall Motion Abnormality: Correlation With Gensini Score
Authors: Li Miao , Wang Yuhao , Li Lin , Wu Wenfang , Zhang Pingyang
Published: November 2021

PurposeThis study aimed to investigate global myocardial work (GMW), derived from non-invasive left ventricular (LV) pressure-strain loops (PSLs) in coronary artery disease (CAD) patients without regional wall motion abnormality (RWMA), and explored the relationship between GMW and severity of CAD using Gensini score (GS) . Methods120 patients prepared for coronary angiography (CAG) who had left ventricular ejection fraction≥55%, no resting RWMA in two-dimensional echocardiography were enrolled. Global longitudinal strain (GLS), GMW parameters (including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW) and global myocardial work efficiency (GWE)) were quantified. The severity of coronary lesions was evaluated by GS system based on CAG findings. We divided CAG-confirmed CAD patients into three subgroups according to the tertiles of GS: low 0<GS 16, mid 1638. ResultsCAD patients showed a significantly reduced GLS and GWE, but an increased GWW. GLS, GWE, GWI and GCW were significantly decreased in the high-GS group while GWW was increased. GLS, GWE, GWI and GCW was negatively correlated with the GS, GWW was positively correlated with GS. Multivariate regression analysis showed that GWE was the independent factor of predicting coronary stenosis. ROC analysis demonstrated that GWE was the most powerful predictor of high-GS and was superior to GLS. GWE under 91% had the optimal sensitivity and specificity for identifying high-GS. ConclusionThe proposed GWE, which outperformed the GLS, showed the optimal performance and could be considered as a potential predictive indicator to detect severe coronary disease in non-RWMA CAD patients.
Irinotecan Loaded Lipomers: Development, And Characterization For Proof of Concept To Combat Colon Cancer
Authors: Giram Prabhanjan S , Garnaik Baijayantimala
Published: November 2021

PLGA Poly (lactide-co-Glycolide) is a biocompatible and biodegradable copolymer gained popularity for tissue engineering, drug delivery, biosensing, and biomedical applications. In the present study PLGA of (Mw =13,900) has synthesized by ring opening polymerization with zinc proline initiator. Irinotecan (Ir) loaded Lipomers (LPs) formulated with PLGA, DSPE-PEG (2000) (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000) and soya lecithin excipients by nanoprecipitation method. These formulated LPs further validated by physicochemical and biological potential for colon delivery applications. The potential of LPs for delivery of Irinotecan (Ir), a poorly water-soluble chemotherapeutic drug used for the treatment of colon cancer was studied. LPs of controlled size (80-120 nm), surface charge (~ -35 mV), sustained release potential and significant cytotoxicity against CT-26 (colon) cancer cells, were successfully prepared. In-vivo biodistribution and tumor site retention in CT-26 xenografts tumor bearing Balb/C mice showed promising result for tumor uptake and retention for prolong time period. Unlike P-DSPE-Ir, PEG coated P-DSPE-PEG-Ir LPs exhibit significant tumor growth delay compared to untreated and blank formulation treated groups in the CT-26 subcutaneous tumor model, after 4 treatments of 10 mg Ir/kg dose. The biocompatibility, safety of LPs confirmed by acute toxicity study of optimized formulation. Overall, this proof-of-concept study demonstrates that the LPs improved efficacy, bioavailability and decreases neutropenia of Ir to combat colon cancer.
Feasibility of Adding Twitter Data to Aid Drought Depiction: Case Study in Colorado
Authors: Mukherjee Sarbajit , Wang Shih-Yu , Hirschfeld Daniella , Lisonbee Joel , Deng Liping , Gillies Robert
Published: November 2021

The use of social media, such as Twitter, has changed the information landscape for citizens participation in crisis response and recovery activities. Given that drought progression is slow and also spatially extensive, an interesting set of questions arise: How the usage of Twitter by a large population may change during the development of a major drought alongside how changing usage promotes drought detection? For this reason, by investigating contemporary procedures, this paper scrutinizes the potential to advance drought depiction. Hence, an analysis of how social media data, in conjunction with meteorological records, was conducted towards improvement in the detection of drought and furthermore, its progression. The research utilized machine learning techniques applied over satellite-derived drought conditions in Colorado. Specifically, 3 different machine learning techniques were examined: the generalized linear model, support vector machines and deep learning, each applied to test the integration of Twitter data with meteorological records as a predictor of drought development. It is maintained that the data integration of resources is viable given that the Twitter-based model outperformed the control run which did not include social media input. Furthermore the Twitter-based model was superior in predicting drought severity.