bluuebunny/crossref_metadata_2025 huggingface dataset:
Mammographic density as marker of increased risk of breast cancer
Authors: Labazanova P. G. , Budanova M. V. , Burdina I. I. , Zapirova S. B. , Mazo M. L. , Mikushin S. Yu. , Prokopenko S. P. , Rozhkova N. I.
Published: August 2021

‘Mammographic density’ (MD) is a concept that has entered medical practice since 2017. as a marker of breast cancer risk factor (BC) according to the international classifiation of NCCN. The term reflcts the degree of severity of benign diffuse breast dysplasia in women of post-reproductive age. MD is determined by the ratio of stromal, epithelial, and adipose tissue. According to the literature, in young women, high MD limits the possibilities of X-ray mammography, reducing its effectiveness in oncomammoscreening, leading to the detection of advanced forms of breast cancer. Post-reproductive women with high MD are more likely to develop breast cancer than those with low MD. In this regard, MD is of particular interest for studying its role in oncogenesis. Recent molecular genetic studies of the differences between high and low MD explain the main biological reasons why post-reproductive women with dense breast structure are at a higher risk of developing breast cancer. The aim is to identify the factors that inflence the relationship of MD with the risk of developing breast cancer based on a comparative analysis of molecular genetic studies and radiological manifestations of MD of different severity and to identify the factors that contribute to the formation of MD variants.
Role of omega-3 fatty acids in parenteral nutrition of cancer patients
Authors: Gameeva E. V. , Shestopalov A. E.
Published: August 2021

Relevance. When selecting the components of parenteral nutrition (PN) for oncology patients, it is necessary to take into account not only the composition optimization but also its potential positive effect on the surgical treatment outcome. Therefore, the use of pharmaconutrients in PN, in particular, omega-3 fatty acids, is of great theoretical and practical interest and has determined the aim of this study.

The aim. To assess the effiacy of postoperative PN using the 3-in-1 system with omega-3 fatty acids (FA) (SMOFKabiven central and peripheral) in the treatment of metabolic disorders in patients undergoing gastrointestinal cancer surgery.

Materials and methods. A prospective, randomized, controlled, comparative study included the patients undergoing gastrointestinal cancer surgery. Group 1 (comparison group) consisted of 29 patients, postoperative PN was performed using a 3-in-1 system without omega-3 fatty acids.

Group 2 (main group) consisted of 20 patients treated with 3-in-1 system with omega-3 FA (SMOFKabiven central) and 9 patients recieved PN with omega-3 FA through peripheral vein access FA (SMOFKabiven peripheral).

Main results. A complete range of amino acids in SMOFKabiven (50 g/L) and an increased content of nitrogen (8 g/L) have a pronounced effect on protein metabolism and anabolic processes. The long-term PN showed that the liver enzyme (alanine transaminase [ALT], aspartate transaminase [AST], and total bilirubin) levels were signifiantly lower compared to the patients who received traditional lipid emulsions without fih oil. The analysis of the corrective effect of PN containing omega-3 fatty acids showed that at day 6–7 after surgery the group 2 patients had a signifiant decrease in the concentration of pro-inflmmatory cytokines: IL-6 down to 79.5±19.2 pg/mL, TNF-α down to 12.9±3.3 pg/mL (p < 0.05) compared to group 1. Clinical signs of gastrointestinal dysfunction were mainly resolved at day 4–5. Full recovery of the GIT functions was seen in more than 80 % of patients. The anti-inflmmatory properties of omega-3 fatty acids, as well as their effect on the cytokine balance recovery, have been confimed in our studies by signifiant reductions in the synthesis of IL-6, TNF.

Conclusion. The high content of omega-3 fatty acids in PN promotes early management of metabolic disorders after surgery, can have a signifiant effect on the ability to adequately tolerate the maintenance chemotherapy and radiation therapy, and can signifiantly improve the quality of life under the conditions of progressive disease.
Legislative Support for Expanding The Land Powers of Local Self-Government Bodies in Ukraine
Authors: Piddubnyi Oleksii Yu. , Rudenko Liudmyla D. , Hbur Liusia V. , Nezhevelo Valentyna V. , Oleksiuk Viktoriia P.
Published: August 2021

The relevance of this study is conditioned by the implementation of the reform in the context of the decentralisation of power in Ukraine, the aspirations of Ukraine for European integration and the movement for the creation of a "Europe of Regions". The purpose of the study is to comprehensively investigate the legislative support for expanding the land powers of local self-government bodies in Ukraine in the context of the movement for the creation of a "Europe of Regions" based on the analysis of scientific opinions, generalisation of the provisions of Ukrainian legislation and positive experience of other countries. Universal methods were used in the study: dialectical, empirical, and logical. The general scientific methods of cognition used in this study include analysis and synthesis, generalisation, modelling, etc. In addition, the study applied the following special legal methods: conceptual legal, comparative legal, formal legal, etc. The leading method in the study was the comparative legal method. It helped compare the specific features of the practice of other countries in the field of legislative support for the expansion of land powers of local self-government bodies, as well as identify how this issue is regulated in different countries of the continental model of the land management system. Information and knowledge from different countries can be used as a basis for the adoption, adaptation, and development of new relevant provisions in Ukraine. Based on the legislation on local self-government and land legislation, the study analysed the main powers of local self-government bodies in the management of land relations. The experience of the land management system in developed countries is studied considering the movement for the creation of a "Europe of Regions", focusing the research on the continental model of the land management system.
Determinants of the Innovative and Investment Development of Agriculture
Authors: Trusova Natalia V. , Hryvkivska Oksana V. , Kotvytska Nataliia M. , Nesterenko Svitlana A. , Yavorska Tetiana I. , Kotyk Olha V.
Published: August 2021

The article considers the conditions for the formation of determinants of innovative-investment development of agriculture. A systematic approach to the development of agriculture in a single integration space of intersectoral cooperation and state support through the introduction of effective innovative and investment determinants, which form the criteria of investment attractiveness of economic entities and provide conditions for innovation in production and technological process, is implemented. The levels of innovative and investment development of agriculture are structured. Determinants of innovative and investment development of agriculture and indicators of its estimation are offered. A comprehensive methodological approach to financing innovative and investment projects with state guarantees to potential investors to obtain additional value from the introduction of scientific development in the technological cycle of agricultural production, taking into account economic, social, budgetary, environmental, resource, intellectual, scientific and technical components of innovative and investment processes proposed. It is recommended to evaluate the effectiveness of the introduction of innovations in agriculture by an integrated indicator with the ratio of effects (results) and costs by certain components. Scientific organizations by sectors of activity, which include development in innovative and investment development of agriculture of Ukraine, are analysed. An assessment of innovative and investment activity of Ukrainian producers with the distribution of the average number of employees in agriculture is carried out. The share of expenditures on research and development on agricultural development in the gross domestic product (GDP) of EU-28 countries and Ukraine is determined. The calculation of priority factors of external and internal environment of influence on the efficiency of innovative and investment development of the animal husbandry industry is carried out. The forecast values of functional risks and the level of efficiency of innovative and investment development of the animal husbandry industry of Ukraine are determined.
Research of Balance of Forces Affecting on the Grain Between Cylindrical Rolls of Small-Size Feed Mincing Unit
Authors: Mamadova Gulnara
Published: August 2021

The conducted research is devoted to the study of the balance of forces affecting on the grain between cylindrical rolls of the small-size feed mincing unit used in farming enterprises. It is established that substantiation of design and process parameters of the feed mincing units, plotting the analytical dependences and solution of process tasks are among the most important factors in manufacture of various versions of the unit. Using the obtained analytical solutions increase the efficiency of the works performed in this field. Recently, in the countries where the grain is harvested using the two-phase method, it is performed during the milk maturity period by pressing with special grinding machines immediately in the field, adding the conserving agent, preserving, packing into polyethylene bags, and then storing tight during winter. It is proven that the production costs for such nutritive grain feed reduce by 30% in contrast to the usual method. The grain stored in such a way is taken out of the grain bags and used directly for feeding the animals. The research work aimed at substantiation of design and process parameters of the small-size, low energy-intensive units for feed oakum production functioning on the basis of the grinding method in the conditions of farming enterprise is of great relevance. The work purpose is to study the balance of forces affecting on the grain between cylindrical rolls of the small-size feed mincing unit.
Relationship Between Economic Growth and Environmental Pressures (Legal Aspects)
Authors: Moroz Galyna V. , Grytsan Olga A. , Vivcharenko Oleh A. , Kobetska Nadiia R.
Published: August 2021

The problem of the impact of economic development of the world on the state of the environment is quite relevant today. Entrepreneurs usually defend their private interests and try to increase profits in every possible way, without caring about the state of the environment and the future. If in the economically developed countries of the world the government is trying hard to control compliance with environmental legislation and implement a green economy, Ukraine is hopelessly behind, and only in recent years is beginning to actively think about preserving the environment and develop mechanisms to achieve this goal. It is important to explore how the legal aspect can help address the balance between Ukraine's economic development and environmental quality, especially in terms of its impact on climate change, where air pollution, waste generation and energy security are key factors. The purpose of the study was to investigate the legal aspect of the interrelation between economic growth and environmental pressures. As a result, the world experience in finding ways of mutually beneficial activities for the economic development of countries and the preservation of the environment was analysed. The study examined the factors influencing climate change, waste generation and energy security in the projection of economic development. The main principles (strategy) of the state ecological policy of Ukraine for the period up to 2030 are analysed; regulations of Ukraine and the European Union, which regulate the preservation of the environment in terms of the legal effect on solving the problem of the interrelation between economic growth and pressure on the environment.
Features of the Organisation of Rooting Cuttings of Decorative Woody Plants Under Artificial Lighting with Led Equipment
Authors: Piatykh Andrei M. , Emelianov Mikhail A. , Akinchin Aleksandr V. , Partolin Ivan V. , Belyaeva Alla A.
Published: August 2021

Obtaining a technology for rooting cuttings and standard seedlings of decorative woody plants under artificial lighting conditions is relevant in connection with the need to increase the amount of planting material required for green building. Currently, cuttings are carried out mainly in greenhouses during the growing season. The development of technology for rooting cuttings using lamps with different lighting parameters opens up the possibility of creating installations that are effective in various conditions. In the course of the study, organisational and technological measures were taken to modernise the greenhouse and install equipment for growing planting material of decorative plants. In accordance with the plan to study the characteristics of various crops using the technology of dynamic regulation of the spectral composition and temporal characteristics of LED lighting in a greenhouse, an assortment of decorative tree species has been developed. Heated greenhouses are equipped with automatic irrigation hotbeds. Cutting of coniferous, deciduous, fast- and slow-growing species of decorative woody plants (7 species and 3 cultivars in total) was carried out. Rooting was carried out under illumination with batch-type LED installations. The success of rooting is studied when using LEDs of various production, with different spectral composition and varying illumination intensity during year-round cultivation. The findings are necessary not only for the development of a regional technology for the year-round production of rooted cuttings of decorative woody plants, but also for the development of the engineering specifics of lighting equipment.
Isolation, Identification, and Characterization of Polystyrene-Degrading Bacteria From the Gut of Galleria Mellonella (Lepidoptera: Pyralidae) Larvae
Authors: Jiang Shan , Su Tingting , Zhao Jingjing , Wang Zhanyong
Published: August 2021

Polystyrene (PS) is a widely used petroleum-based plastic, that pollutes the environment because it is difficult to degrade. In this study, a PS degrading bacterium identified as Massilia sp. FS1903 was successfully isolated from the gut of Galleria mellonella (Lepidoptera: Pyralidae) larvae that were fed with PS foam. Scanning electron microscopy and X-ray energy dispersive spectrometry showed that the structure and morphology of the PS film was destroyed by FS 1903, and that more oxygen appeared on the degraded PS film. A water contact angle assay verified the chemical change of the PS film from initially hydrophobic to hydrophilic after degradation. X-ray photoelectron spectroscopy further demonstrated that more oxygen-containing functional groups were generated during PS degradation. After 30 days of bacterial stain incubation with 0.15 g PS, 80 ml MSM, 30°C and PS of Mn 64400 and Mw 144400 Da, the weight of the PS film significantly decreased, with 12.97 ± 1.05% weight loss. This amount of degradation exceeds or is comparable to that previously reported for other species of bacteria reported to degrade PS. These results show that Massilia sp. FS1903 can potentially be used to degrade PS waste.
Comprehensive Analysis of RUNX and TGF-β Mediated Regulation of Immune Cell Infiltration in Breast Cancer
Authors: Gao Liang , Zhou Fangfang
Published: August 2021

Runt-related transcription factors (RUNXs) can serve as both transcription activators and repressors during biological development, including immune cell maturation. RUNX factors have both tumor-promoting and tumor-suppressive roles in carcinogenesis. Immune cell infiltration and the tumor immune microenvironment have been found to be key regulators in breast cancer progression, treatment response, and patient outcome. However, the relationship between the RUNX family and immune cell infiltration in breast cancer remains unclear. We performed a comprehensive analysis to reveal the role of RUNX factors in breast cancer. Analysis of patient data in the Oncomine database showed that the transcriptional levels of RUNX proteins in breast cancer were elevated. Kaplan–Meier plotter (KM plotter) analysis showed that breast cancer patients with higher expression of RUNX proteins had better survival outcomes. Through analysis of the UALCAN database, we found that the transcriptional levels of RUNX factors were significantly correlated with some breast cancer patient characteristics. cBio Cancer Genomics Portal (cBioPortal) analysis showed the proportions of different RUNX genomic alterations in various subclasses of breast cancer. We also performed gene ontology (GO) and pathway analyses for the significantly differentially expressed genes that were correlated with RUNX factors in breast cancer. TIMER database analysis showed that immune cell infiltration in breast cancer could be affected by the transcriptional level, mutation, and gene copy number of RUNX proteins. Using the Gene Set Cancer Analysis (GSCA) database, we analyzed the effects of RUNX gene methylation on the level of immune cell infiltration in breast cancer. We found that the methylation level changes of RUNX2 and RUNX3 had opposite effects on immune cell infiltration in breast cancer. We also analyzed the relationship between the methylation level of RUNX genes and the TGF-β signaling pathway using the TISIDB database. The results showed that the methylation levels of RUNX1 and RUNX3 were correlated with the expression of TGF-β1. In summary, our analysis found that the RUNX family members can influence the infiltration of various immune cells in breast cancer depending on their expression level, mutation, gene copy number, and methylation. The RUNX family is an important regulator of immune cell infiltration in breast cancer and may serve as a potential prognostic biomarker.
Heteroacene-Based Amphiphile as a Molecular Scaffold for Bioimaging Probes
Authors: Ranathunge Tharindu A. , Yaddehige Mahesh Loku , Varma Jordan H. , Smith Cameron , Nguyen Jay , Owolabi Iyanuoluwani , Kolodziejczyk Wojciech , Hammer Nathan I. , Hill Glake , Flynt Alex , Watkins Davita L.
Published: August 2021

The challenges faced with current fluorescence imaging agents have motivated us to study two nanostructures based on a hydrophobic dye, 6H-pyrrolo[3,2-b:4,5-b’]bis [1,4]benzothiazine (TRPZ). TRPZ is a heteroacene with a rigid, pi-conjugated structure, multiple reactive sites, and unique spectroscopic properties. Here we coupled TRPZ to a tert-butyl carbamate (BOC) protected 2,2-bis(hydroxymethyl)propanoic acid (bisMPA) dendron via azide-alkyne Huisgen cycloaddition. Deprotection of the protected amine groups on the dendron afforded a cationic terminated amphiphile, TRPZ-bisMPA. TRPZ-bisMPA was nanoprecipitated into water to obtain nanoparticles (NPs) with a hydrodynamic radius that was <150 nm. For comparison, TRPZ-PG was encapsulated in pluronic-F127 (Mw = 12 kD), a polymer surfactant to afford NPs almost twice as large as those formed by TRPZ-bisMPA. Size and stability studies confirm the suitability of the TRPZ-bisMPA NPs for biomedical applications. The photophysical properties of the TRPZ-bisMPA NPs show a quantum yield of 49%, a Stokes shift of 201 nm (0.72 eV) and a lifetime of 6.3 ns in water. Further evidence was provided by cell viability and cellular uptake studies confirming the low cytotoxicity of TRPZ-bisMPA NPs and their potential in bioimaging.
Antibiotic Resistance Pattern of Extended Spectrum Beta Lactamase Producing Escherichia coli Isolated From Patients With Urinary Tract Infection in Morocco
Authors: Kettani Halabi Mohamed , Lahlou Fatima Azzahra , Diawara Idrissa , El Adouzi Younes , Marnaoui Rabiaa , Benmessaoud Rachid , Smyej Imane
Published: August 2021

Extended-spectrum β-lactamases producing Escherichia coli (ESBL-EC) lend resistance to most β-lactam antibiotics. Because of limited treatment options, ESBL-EC infections are generally more difficult to treat, leading to higher hospital costs, reduced rates of microbiological and clinical responses, and a threat to the patient’s life. This study aimed to determine the antibiotic resistance pattern of ESBL-EC isolated from patients with urinary tract infection in Morocco. This retrospective laboratory-based study was conducted at Cheikh Khalifa International University Hospital, Casablanca, from January 2016 to June 2019. A total of 670 urine samples were collected from urinary tract infection patients and processed by standard microbiological methods. In vitro susceptibility testing to different antibiotics of all identified isolates of Escherichia coli (E. coli) was performed following Kirby–Bauer’s disc diffusion method on Mueller–Hinton Agar according to the EUCAST standards. The reviewing of ESBL-EC was confirmed by the appearance of a characteristically shaped zone referred to as a “champagne cork” using the Combined Disk Test. Among a total of 438 E. coli isolated from nonrepetitive urine samples, two hundred fifty-nine (59%) were ESBL-EC, of which 200 (77%) were isolated from adult patients (over the age of 50) and the majority were female. All ESBL-EC isolates were resistant to third-generation cephalosporin and quinolones and sensitive to carbapenem and fosfomycin. Knowledge of antimicrobial resistance patterns in ESBL-EC, the major pathogen associated with urinary tract infection, is indispensable as a guide in choosing empirical antimicrobial treatment.
Epistemic Perspectives and Communicative Acts
Authors: Benz Anton
Published: August 2021

Searle (Speech Acts, 1969) introduced his famous distinction between constitutive and regulative rules that together define felicity conditions of speech acts. Regulative rules are normative rules, whereas constitutive rules define what counts as a performance of a speech act. In this paper we demonstrate with the example of assertions and referential uses of definite description that simple regulative rules can be given to speech acts that hold only on a core of well-behaved utterance situations. From this core, extended uses can be derived based on epistemic paths that are defined by the epistemic perspectives of speaker and hearer. As the use of speech acts get extended to a wider class of utterance situations, conflicts with the constitutive rules can emerge. We show that the extended uses are nevertheless felicitous. We represent epistemic relations in a possible worlds framework, and take an interactional approach that considers speech acts as part of joint communicative acts.
COVID ISSUE: Visual Narratives About COVID-19 Improve Message Accessibility, Self-Efficacy, and Health Precautions
Authors: Jarreau Paige Brown , Su Leona Yi-Fan , Chiang Elfy Chun-Lin , Bennett Shauna M. , Zhang Jennifer Shiyue , Ferguson Matt , Algarra Doryan
Published: August 2021

Visual narratives are promising tools for science and health communication, especially for broad audiences in times of public health crisis, such as during the COVID-19 pandemic. In this study, we used the Lifeology illustrated “flashcard” course platform to construct visual narratives about COVID-19, and then assessed their impact on behavioral intentions. We conducted a survey experiment among 1,775 health app users. Participants viewed illustrated (sequential art) courses about: 1) sleep, 2) what COVID-19 is and how to protect oneself, 3) mechanisms of how the virus works in the body and risk factors for severe disease. Each participant viewed one of these courses and then answered questions about their understanding of the course, how much they learned, and their perceptions and behavioral intentions toward COVID-19. Participants generally evaluated “flashcard” courses as easy to understand. Viewing a COVID-19 “flashcard” course was also associated with improved self-efficacy and behavioral intentions toward COVID-19 disease prevention as compared to viewing a “flashcard” course about sleep science. Our findings support the use of visual narratives to improve health literacy and provide individuals with the capacity to act on health information that they may know of but find difficult to process or apply to their daily lives.
Upper Extremity Deep Vein Thrombosis and Asymptomatic Vein Occlusion in Patients With Transvenous Leads: A Systematic Review and Meta-Analysis
Authors: Duijzer Daniël , de Winter Maria A. , Nijkeuter Mathilde , Tuinenburg Anton E. , Westerink Jan
Published: August 2021

Aims: The presence of transvenous leads for cardiac device therapy may increase the risk of venous thromboembolisms. The epidemiology of these complications has not yet been determined systematically. Therefore, this study aims to determine (I) the incidence of symptomatic upper extremity deep vein thrombosis (UEDVT) and (II) the prevalence of asymptomatic upper extremity vein occlusion in patients with transvenous leads, both after the initial 2 months following lead implantation.

Methods: PubMed, EMBASE, and Cochrane Library were searched until March 31, 2020 to identify studies reporting incidence of UEDVT and prevalence of asymptomatic vein occlusion after the initial 2 months after implantation in adult patients with transvenous leads. Incidence per 100 patient years of follow-up (PY) and proportions (%) were calculated to derive pooled estimates of incidence and prevalence.

Results: Search and selection yielded 20 and 24 studies reporting on UEDVT and asymptomatic vein occlusion, respectively. The overall pooled incidence of UEDVT was 0.9 (95% CI 0.5–1.4) per 100PY after 2 months after lead implantation. High statistical heterogeneity was present among studies (I2 = 82.4%; P = < 0.001) and only three studies considered to be at low risk of bias. The overall pooled prevalence of asymptomatic upper extremity vein occlusion was 8.6% (95% CI 6.0–11.5) with high heterogeneity (I2 = 81.4%; P = <0.001). Meta-regression analysis showed more leads to be associated with a higher risk of UEDVT.

Conclusion: Transvenous leads are an important risk factor for symptomatic UEDVT, which may occur up to multiple years after initial lead implantation. Existing data on UEDVT after lead implantation is mostly of poor quality, which emphasizes the need for high quality prospective research. Asymptomatic vein occlusion is present in a substantial proportion of patients and may complicate any future lead addition.

Clinical Trial Registration: (URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020178136, Identifier: PROSPERO 2020 CRD42020178136).
Using Machine Learning and the National Health and Nutrition Examination Survey to Classify Individuals With Hearing Loss
Authors: Ellis Gregory M. , Souza Pamela E.
Published: August 2021

Even before the COVID-19 pandemic, there was mounting interest in remote testing solutions for audiology. The ultimate goal of such work was to improve access to hearing healthcare for individuals that might be unable or reluctant to seek audiological help in a clinic. In 2015, Diane Van Tasell patented a method for measuring an audiogram when the precise signal level was unknown (patent US 8,968,209 B2). In this method, the slope between pure-tone thresholds measured at 2 and 4 kHz is calculated and combined with questionnaire information in order to reconstruct the most likely audiograms from a database of options. An approach like the Van Tasell method is desirable because it is quick and feasible to do in a patient's home where exact stimulus levels are unknown. The goal of the present study was to use machine learning to assess the effectiveness of such audiogram-estimation methods. The National Health and Nutrition Examination Survey (NHANES), a database of audiologic and demographic information, was used to train and test several machine learning algorithms. Overall, 9,256 cases were analyzed. Audiometric data were classified using the Wisconsin Age-Related Hearing Impairment Classification Scale (WARHICS), a method that places hearing loss into one of eight categories. Of the algorithms tested, a random forest machine learning algorithm provided the best fit with only a few variables: the slope between 2 and 4 kHz; gender; age; military experience; and self-reported hearing ability. Using this method, 54.79% of the individuals were correctly classified, 34.40% were predicted to have a milder loss than measured, and 10.82% were predicted to have a more severe loss than measured. Although accuracy was low, it is unlikely audibility would be severely affected if classifications were used to apply gains. Based on audibility calculations, underamplification still provided sufficient gain to achieve ~95% correct (Speech Intelligibility Index ≥ 0.45) for sentence materials for 88% of individuals. Fewer than 1% of individuals were overamplified by 10 dB for any audiometric frequency. Given these results, this method presents a promising direction toward remote assessment; however, further refinement is needed before use in clinical fittings.
Case Report: Rare Presentation of Dentin Abnormalities in Loeys-Dietz Syndrome Type I
Authors: Jani Priyam , Duverger Olivier , Mishra Rashmi , Frischmeyer-Guerrerio Pamela A. , Lee Janice S.
Published: August 2021

Loeys-Dietz syndrome type 1 (LDS1) is caused by a mutation in the transforming growth factor-beta receptor 1 (TGFBR1) gene. We previously characterized the oral and dental anomalies in a cohort of individuals diagnosed with LDS and showed that LDS1 had a high frequency of oral manifestations, and most affected individuals had enamel defects. However, dentin anomalies were not apparent in most patients in the cohort. In this cohort, we had identified dentin anomalies in a patient with LDS1, harboring mutationTGFBR1c.1459C>T (p.Arg487Trp), and in this report, we present clinical and radiographic findings to confirm the dentin anomaly. The proband had gray-brown discoloration of most teeth typical for dentinogenesis imperfecta (DI). A radiographic exam revealed obliterated or very narrow pulp canals, with maxillary anterior teeth being affected more than the posterior teeth. The son of the proband, who also has the same mutation variant, had a history of DI affecting the primary teeth; however, his permanent teeth were normal in appearance at the time of exam.TGFBR1is expressed by odontoblasts throughout tooth development and deletion ofTGFBR1in mouse models is known to affect dentin development. In this report, we present a rare case of abnormal dentin in two individuals with LDS1. These dental anomalies may be the first obvious manifestation of a life-threatening systemic disease and demonstrate the variable and multi-organ phenotypic effects in rare diseases.
Paleoearthquakes Constrained by Stratigraphic Sequences of Different Drainages Since Late Pleistocene: A Case Study Along the Gulang Fault, NE Tibetan Plateau
Authors: Liang Shumin , Zheng Wenjun , Zhang Dongli , Chen Gan , Duan Lei , Yang Jingjun , Peng Hui , Sun Xin
Published: August 2021

Paleoearthquake data obtained from fault trenching are essential for rebuilding the rupture history and understanding the rupture behavior of active faults. However, due to the lack of attention to stratigraphic sequences, the usual multiple trench constraining method may result in uncertainties of paleoearthquake sequences. In this study, we proposed an improved constraining method to generate stratigraphic sequences from multiple trenches of different drainages to obtain a paleoearthquake sequence of the Gulang fault. Single-trench stratigraphic sequences were built up by nineteen trenches excavated along the fault. Based on stratigraphic characteristics, we found the strata sedimented around the fault were derived from five drainages. The single-trench sequences were divided into five drainages to establish the composite sequence of multiple trenches through the correlation of stratigraphic units. Meanwhile, we used high-quality event indicators to pick out very likely earthquakes. Coupled with the dating samples, the events were used to determine the earthquake horizons in the composite sequence and to constrain the numbers and ages of events in each drainage. After combining the event sequences, six paleoearthquakes were determined along the Gulang fault since the late Pleistocene. Their occurrence timings are 13,700–10,400, 10,400–10,200, 8,560–7,295, 5,825–4,810, 4,285–3,200, and 2,615–2,240 a B.P. And their different rupture scenarios indicate that the fault might be composed of two rupture segments.
Effects of Rhodotorula mucilaginosa on the Immune Function and Gut Microbiota of Mice
Authors: Ge Ye , Huang Kaisen , Xie Weitian , Xu Chunhou , Yao Qiucheng , Liu Ying
Published: August 2021

As a dominant species among marine yeasts, Rhodotorula benthica accounts for ~50% of all marine yeasts. Rhodotorula is rich in a variety of bioactive substances and commonly used in the production of carotenoids by microbial fermentation and is worth developing. Therefore, the present study used a strain of Rhodotorula mucilaginosa isolated from the coastal waters of the South China Sea as the target yeast to investigate its impact on the immune function and gut microbiota of mice. A total of 200 mice were randomly divided into gavage groups and control group and garaged for 30 consecutive days at different concentration. Samples were collected on day 15 and day 30 of gavage administration. The results showed that R. mucilaginosa ZTHY2 could increase the thymus and spleen indices of mice, and its effect on the thymus index was more significant after long-term gavage administration. Short-term (15 days) gavage administration of R. mucilaginosa suspension enhanced delayed hypersensitivity in mice, increased serum IgG, IgA, and IL-2. Long-term (30 days) gavage administration of R. mucilaginosa suspension significantly enhanced the phagocytosis of macrophages in mice and significantly increased serum TNF-α and INF-γ. R. mucilaginosa ZTHY2 altered the structure of the gut microbiota of mice at the phylum and genus levels, leading to an increased relative abundance of Firmicutes and Lactobacillus and a decreased relative abundance of Bacteroidetes. This strain increased the beneficial intestinal bacteria and reduced the harmful intestinal bacteria in mice. This study provides experimental evidence and lays the foundation for the future development and application of this strain as a microecological source of carotenoids.
Gene Signatures and Prognostic Values of N6-Methyladenosine Related Genes in Ovarian Cancer
Authors: Na Zhijing , Fan Ling , Wang Xiuxia
Published: August 2021

N6-Methyladenosine (m6A) is one of the most prominent modification regulating RNA processing and metabolism. Increasing studies have illuminated the vital role of m6A methylation in carcinogenesis. However, little is known about the interaction between m6A-related genes and survival of ovarian cancer (OC) patients. The purpose of this study was to obtain more reliable m6A-related genes that could be used as prognostic markers of OC using bioinformatics analysis performed on the RNA-seq data of OC. Gene expression datasets of all m6A-related genes as well as corresponding clinical data were obtained from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. We detected differential expressed m6A-related candidate genes as well as their relationship and interaction. m6A RNA methylation regulator ALKBH5 and 35 m6A-related genes are dysregulated in OC. A gene set that could be used as a potential independent prognostic risk feature was further screened including NEBL, PDGFRA, WDR91, and ZBTB4. The results of mRNA expression analysis by PCR were consistent with those of bioinformatics analysis. We applied consensus clustering analysis on the expression of the four prognostic genes and obtained four OC subgroups TM1-TM4. There were significant differences in age, stage and grade among the subgroups, and the overall survival (OS) as well as Disease-free survival (DFS) of TM2 group were shorter than those of the other three groups. Further GO and KEGG enrichment analysis indicated that these differential genes were closely related to biological processes and key signaling pathways involved in OC. In summary, our study has indicated that m6A-related genes are key factors in the progression of OC and have potential effects on the prognostic stratification of OC and the development of treatment strategies.
Total Demand, Use and Unmet Need for Modern Contraceptives Among Women Living in Informal Settlements in Kira Municipality, Wakiso District, Uganda. Implications for Urban Health
Authors: Tetui Moses , Baroudi Mazen , Ssekamatte Tonny , Birabwa Catherine , Kibira Simon Peter , Atuyambe Lynn , Delamou Alexandre , Makumbi Fredrick Edward
Published: August 2021

Background: Update and utilization of modern contraceptives has public health benefits including reduction of unintended pregnancies, unsafe abortions, and related maternal mortality. However, paucity of evidence on key indicators of family planning in the informal settlements abounds. Data are usually collapsed within the larger urban communities that tend to mask peculiarities of informal settlements. This study determined the proportion of women using modern contraceptives, the unmet need for modern contraceptives and the total demand in informal settlements of an urban municipality.

Methods: A cross-sectional study conducted among 626 women in the reproductive age (15–49 years) in the informal settlements of Kira municipality (part of metropolitan Kampala). Multi-stage sampling was applied in the selection of the respondents. Descriptive and log-binomial regression analysis were conducted to determine percentage of women using modern contraceptives, unmet need, and total demand with their associated factors. All analyses were conducted using STATA version 15.0.

Results: The total demand for modern contraceptives was 84.9%, modern contraceptive prevalence was 47.4% nearly meeting the national target of 50%, however the unmet need was 37.3%, which much higher than the national target of 10%. Lower total demand for contraceptives was associated with higher women's education status and preference to have another child, while higher total demand was associated with having at least one living child. Higher modern contraceptives use was associated with older age, having at least one living child and high decision-making power, while lower modern contraceptives use was associated with higher education and undetermined fertility preference. Lower unmet need for modern contraceptives was associated with older age (PR 0.68, 95% CI: 0.48–0.97) and high decision-making power (PR 0.64, 95% CI: 0.50–0.81), while higher unmet need was found among those who having at least one living child (PR 1.40, 95% CI: 1.01–1.93) and undetermined fertility preference (PR 1.70, 95% CI: 1.24–2.34).

Conclusions: Total demand and contraceptive use were found to be higher in the informal settlements of Kira municipality, however, the unmet need was much higher among this population as compared to the national urban estimates. This indicates a much higher demand for contraceptives and the need to consider the diverse socio-demographic characteristics of urban spaces. Development of Interventions need to critically consider the diverse urban space, associated explanatory variables and a collaborative systems lens to achieve sustained improvements.
A Novel Radioimmune 99mTc-Labeled Tracer for Imaging Sphingosine 1-Phosphate Receptor 1 in Tumor Xenografts: An In Vitro and In Vivo Study
Authors: Ye Min , Gai Yongkang , Ji Hao , Jiang Yaqun , Qiao Pengxin , Wang Wenxia , Zhang Yongxue , Xia Xiaotian , Lan Xiaoli
Published: August 2021

Sphingosine-1-phosphate (S1P) is a phospholipid that regulates pleiotropic biological activities and exerts extracellular functions by binding to five specific G-protein-coupled receptors, S1P receptors (S1PR) 1–5. When activated by S1P, S1PR promote the proliferation and invasion of tumor cells by inducing the formation of new blood vessels. We developed and assessed a new monoclonal antibody imaging probe 99mTc-HYNIC-S1PR1mAb, to explore the feasibility of targeting the S1PR1 in vitro and in vivo. S1PR1mAb was prepared and followed by technetium-99m labeling with succinimidyl 6-hydraziniumnicotinate hydrochloride. Cell uptake and blocking studies were performed to investigate the binding specificity of 99mTc-HYNIC-S1PR1mAb in vitro. 99mTc-HYNIC-S1P1mAb was also tested in vivo in mice xenografted with SK-HEP-1 (high-expression of S1PR1) and MCF-7 (low-expression of S1PR1) using single-photon emission-computed tomography (SPECT). Ex vivo gamma counting of tissues from tumor-bearing mice was used to evaluate 99mTc-HYNIC-S1PR1mAb biodistribution. The biodistribution study results showed significantly higher uptake in SK-HEP-1 tumors than in MCF-7 tumors (P < 0.001). Reduced uptake of 99mTc-HYNIC-S1PR1mAb in SK-HEP-1 was observed in tumor-bearing nude mice pretreated with fingolimod, which binds competitively to the receptors, especially S1PR1. 99mTc-HYNIC-S1PR1mAb can be synthesized and specifically targeted to S1PR1 in vitro and in vivo, allowing S1PR1 expression assessment with SPECT imaging.
Immunity, Sex Hormones, and Environmental Factors as Determinants of COVID-19 Disparity in Women
Authors: Rehman Suriya , Ravinayagam Vijaya , Nahvi Insha , Aldossary Hanan , Al-Shammari Maha , Amiri Mai Saad Al , Kishore Uday , Al-Suhaimi Ebtesam A.
Published: August 2021

The current coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has resulted in a major global pandemic, causing extreme morbidity and mortality. Few studies appear to suggest a significant impact of gender in morbidity and mortality, where men are reported at a higher risk than women. The infectivity, transmissibility, and varying degree of disease manifestation (mild, modest, and severe) in population studies reinforce the importance of a number of genetic and epigenetic factors, in the context of immune response and gender. The present review dwells on several contributing factors such as a stronger innate immune response, estrogen, angiotensin-converting enzyme 2 gene, and microbiota, which impart greater resistance to the SARS-CoV-2 infection and disease progression in women. In addition, the underlying importance of associated microbiota and certain environmental factors in gender-based disparity pertaining to the mortality and morbidity due to COVID-19 in women has also been addressed.
Low-Density Granulocyte Contamination From Peripheral Blood Mononuclear Cells of Patients With Sepsis and How to Remove It – A Technical Report
Authors: Schenz Judith , Obermaier Manuel , Uhle Sandra , Weigand Markus Alexander , Uhle Florian
Published: August 2021

Elucidating the mechanisms contributing to the dysregulated host response to infection as part of the syndrome is a current challenge in sepsis research. Peripheral blood mononuclear cells are widely used in immunological studies. Density gradient centrifugation, a common method, is of limited use for blood drawn from patients with sepsis. A significant number of low-density granulocytes co-purify contributing to low purity of isolated peripheral blood mononuclear cells. Whole blood anticoagulated with lithium heparin was drawn from patients with sepsis (n=14) and healthy volunteers (n=11). Immediately after drawing, the plasma fraction was removed and PBMC were isolated from the cellular fraction by density gradient centrifugation. Samples derived from patients with sepsis were subsequently incubated with cluster of differentiation 15 MicroBeads and granulocytes were depleted using magnetic-activated cell sorting. Core cellular functions as antigen presentation and cytokine secretion were analyzed in cells isolated from healthy volunteers (n=3) before and after depletion to confirm consistent functionality. We report here that depleting CD15+ cells after density gradient centrifugation is a feasible way to get rid of the low-density granulocyte contamination. Afterwards, the purity of isolated, functionally intact peripheral blood mononuclear cells is comparable to healthy volunteers. Information on the isolation purity and identification of the containing cell types are necessary for good comparability between different studies. Depletion of CD15+ cells after density gradient centrifugation is an easy but highly efficient way to gain a higher quality and more reliability in studies using peripheral blood mononuclear cells from septic patients without affecting the functionality of the cells.
Bleomycin-Induced Lung Injury Increases Resistance to Influenza Virus Infection in a Type I Interferon-Dependent Manner
Authors: Seo Sang-Uk , Jeong Jae-Hyeon , Baek Bum-Seo , Choi Je-Min , Choi Youn Soo , Ko Hyun-Jeong , Kweon Mi-Na
Published: August 2021

Acute lung injury (ALI) results in acute respiratory disease that causes fatal respiratory diseases; however, little is known about the incidence of influenza infection in ALI. Using a ALI-mouse model, we investigated the pro-inflammatory cytokine response to ALI and influenza infection. Mice treated with bleomycin (BLM), which induces ALI, were more resistant to influenza virus infection and exhibited higher levels of type I interferon (IFN-I) transcription during the early infection period than that in PBS-treated control mice. BLM-treated mice also exhibited a lower viral burden, reduced pro-inflammatory cytokine production, and neutrophil levels. In contrast, BLM-treated IFN-I receptor 1 (IFNAR1)-knockout mice failed to show this attenuated phenotype, indicating that IFN-I is key to the antiviral response in ALI-induced mice. The STING/TBK1/IRF3 pathway was found to be involved in IFN-I production and the establishment of an antiviral environment in the lung. The depletion of plasmacytoid dendritic cells (pDCs) reduced the effect of BLM treatment against influenza virus infection, suggesting that pDCs are the major source of IFN-I and are crucial for defense against viral infection in BLM-induced lung injury. Overall, this study showed that BLM-mediated ALI in mice induced the release of double-stranded DNA, which in turn potentiated IFN-I-dependent pulmonary viral resistance by activating the STING/TBK1/IRF3 pathway in association with pDCs.
CD8+ Regulatory T Cell – A Mystery to Be Revealed
Authors: Mishra Shruti , Srinivasan Saranya , Ma Chaoyu , Zhang Nu
Published: August 2021

Regulatory T cells (Treg) are essential to maintain immune homeostasis and prevent autoimmune disorders. While the function and molecular regulation of Foxp3+CD4+ Tregs are well established, much of CD8+ Treg biology remains to be revealed. Here, we will review the heterogenous subsets of CD8+ T cells have been named “CD8+ Treg” and mainly focus on CD122hiLy49+CD8+ Tregs present in naïve mice. CD122hiLy49+CD8+ Tregs, which depends on transcription factor Helios and homeostatic cytokine IL-15, have been established as a non-redundant regulator of germinal center (GC) reaction. Recently, we have demonstrated that TGF-β (Transforming growth factor-β) and transcription factor Eomes (Eomesodermin) are essential for the function and homeostasis of CD8+ Tregs. In addition, we will discuss several open questions regarding the differentiation, function and true identity of CD8+ Tregs as well as a brief comparison between two regulatory T cell subsets critical to control GC reaction, namely CD4+ TFR (follicular regulatory T cells) and CD8+ Tregs.