bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of efficacious somatic cell genome editing strategies for recessive and polygenic diseases
Authors: Carlson-Stevemer Jared , Das Amritava , Abdeen Amr , Fiflis David , Grindel Benjamin , Akcan Tugce , Alam Tausif , Kletzien Heidi , Kohlenberg Lucille , Goedland Madelyn , Dombroe Micah , Saha Krishanu 
Published: October 2020

Abstract
Gene correction of multiple alleles for compound heterozygous recessive or polygenic diseases is a promising therapeutic strategy. However, the targeting of multiple alleles using genome editors in a single cell could lead to mixed genotypes and adverse events that amplify during tissue morphogenesis. Here we demonstrate that SpyCas9-based S1mplex genome editors can be designed and developed to correct two distinct mutant alleles within a single human cell precisely. Gene-corrected cells in a patient-derived, induced pluripotent stem cell (iPSC) model of Pompe disease robustly expressed the corrected transcript from both corrected alleles. The translated protein from the gene-corrected cells was properly processed after translation and was able to enzymatically cross-correct diseased cells at levels equivalent to standard-of-care, enzyme replacement therapy (ERT). Using a novel in silico model for the in vivo delivery of these and many other genome editors into a developing liver of a human infant, we identify progenitor cell targeting, delivery efficiencies, and suppression of imprecise editing outcomes at the on-target site as key design parameters controlling the potency and efficacy of in vivo somatic cell genome editing. Both single and double gene correction are efficacious for in vivo somatic cell editing strategies, while double gene correction is more effective than single-gene correction for autologous cell therapy with ex vivo gene-corrected cells. This work establishes that precise gene correction using genome editors to correct multiple distinct gene variants could be efficacious in the treatment of recessive and polygenic disorders.
Hypoalbuminemia&nbsp;in Severe COVID-19&nbsp;Post&nbsp;Recovery&nbsp;Patients
Authors: Ali Kameran Mohammed , Ali Ayad M. , Tawfeeq Hassan Mohammad , Grazziela Figueredo  , Rostam Hassan Muhammad 
Published: October 2020

Abstract
Pandemic Coronavirus disease 2019 (COVID-19) is a contagious disease affecting more than 200 countries, territories and regions. Thousands of studies have dealt with all aspects of the disease but little is known about post recovery status of the patients. Here, we examined ESR, CRP and serum albumin biomarkers in severe and mild-moderate COVID-19 post recovery patients. In severe group patients, serum albumin had a strong negative correlation with both ESR and CRP (R2= -0.861), (R2= -0.711) respectively. Also, there was a positive correlation between ESR and CRP (R2=0.85) in the same group. However, there was no correlation among mild-moderate group patients in those biomarkers. In addition, no correlation recorded between severe and mild-moderate groups. This finding concludes the sustained elevation of ESR and CRP with decreased serum albumin level in severe COVID-19 post recovery patients.
Covid-19 Therapy: What Have We Learned In 8 Months?
Authors: Adamczyk-Popławska Monika , Kwiatek Agnieszka 
Published: October 2020

Abstract
SARS-CoV-2, a novel pathogenic human coronavirus, emerged in December of 2019 in Wuhan (Hubei province, China). In most cases, the infection causes a mild to moderate respiratory illness. However, a undefined group of infected may develop a severe or critical illness: Coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS) and many other complications. Current efforts are focused on limiting the spread of the virus in the population. COVID-19 treatments are intensively evaluated, however, 8 months since the start of the pandemic and despite hundreds of clinical trials, our knowledge of effective treatments is still poor. In this review, we present the current status of drugs and treatments used during SARS-CoV-2 infection. Host-directed and virus-directed drugs, as well as new compounds specific for SARS-CoV-2 are presented.
1. Introduction. 2. Host-directed drugs. 2.1. Antiparasitic drugs with potential for repurposing. 2.2. Host proteases inhibitors. 2.3. Endocytosis inhibitors. 2.4. Immunomodulating drugs affecting host. 3. Virus-directed drugs. 3.1. Broad-range-antiviral drugs. 3.2. Inhibitors of viral S glycoprotein. 3.3. New potential virus-directed drugs against SARS-CoV-2. 4. Conclusions
TECHNOLOGICAL SCHEMES FOR THE PROCESSES OF PREPARATION AND MILLING BINARY GRAIN MIXTURES AND BIOCHEMICAL EVALUATION OF PRODUCED PRODUCTS
Authors: Pankratov G. N. , Meleshkina E. P. , Vitol I. S. , Kechkin I. A. , Nagainikova Ju. R. 
Published: October 2020

A study of the preparation and milling of a grain mixture containing 7% of flax seeds has been carried out in order to obtain a composite wheat-flax flour, in which the entire biopotential of flax seeds was preserved. It was revealed that the preparation of the components of the grain mixture should be carried out independently, in parallel flows. During the wheat grain preparation the cold conditioning was carried out, the modes of which were the following: humidity — 15.5%, dwell time in the water — 24 hours. The optimal conditions for milling the wheat-flax mixture have been determined, which are the following: yield (%) / ash content (%) in 3 break systems (in terms of the 1st break system — grain) for the first break system — 53.5 / 1.00; for the second break system. — 22.2 / 1.11; totally for the first and the second break systems — 75.7 / 1.035; totally for the first, the second and the third break systems — 81.0 / 1.1. The technological schemes have been developed and the new varieties of wheat-flax flour with predetermined technological properties and increased nutritional value have been formed. The approximate indices of yield and quality of the new wheat-flax flour varieties are the following: Flour A — yield 45–50%, lipids 3.6–4.0%, protein 13–13.5%, ash 0.55–0.70%, whiteness — 50 conventional units; Flour B — yield 20–25%, lipids 5.5–6.0%, protein 14–14.5%, ash 0.9–1.25%, whiteness — 22 conventional units; Flour C — yield 70–75%, lipids 4.5–5.0%, protein 13.6–14.0%, ash 0.75–0.90%, whiteness — 36 conventional units. It was indicated that the total lipids content in flour from two-component mixtures increases by about 4 times, and the total protein content in the studied samples increases by 1–2%. The content of linoleic acid (ɷ‑6) in wheat-flax flour samples is 1.6…3.3 times higher than in wheat flour; the content of linolenic acid (ɷ‑3) in wheat-flax flour samples is 36.8…57.2 times higher than in wheat flour (taking into account the total lipids content in the samples). The enrichment of wheat flour due to flax seeds allows to make up the deficiency of PUFA family in the diet of a modern person and to obtain products on a grain basis of a balanced composition.
PRODUCTION OF OLIGOFRUCTOSE SYRUP BY ENZYMATIC HYDROLYSIS FROM INULIN-CONTAINING CHICORY SYRUP
Authors: Puchkova T. S. , Pikhalo D. M. , Karasyova O. M. 
Published: October 2020

The purpose of the work is to study the enzymatic hydrolysis of inulin-containing syrups of various purification degrees from chicory chips in the production of oligofructose to be used in dietary, diabetic and health-preventive nutrition products. It has been determined that ion exchange purification of the syrup is necessary for hydrolysis. Individual stages of ion-exchange purification are specified using a two-stage scheme: К1-А1-К2-А2 and an additional stage on the “Macronet” sorbent MN200 to stabilize pH and remove bitterness taste. Requirements for the quality of syrup for hydrolysis have been developed: pH value — 4.5–5.0; chromaticity — not more than 0.5 units opt. den.; ash — not more than 0.2%; protein — 0.5%; no bitterness taste. Optimal conditions for hydrolysis of inulin-containing syrup have been established using Novozim 960 endoinulinase (Denmark): temperature — 55–58 °C; pH — 4.7–5.2; DS (dry substance) — 19%; preparation dosage — 0.4 units. INU/g of syrup DS; time 20–24 h. A sample of oligofructose syrup was obtained using the preparation “Novozim 960.” The carbohydrate composition of oligofructose after the inulin hydrolysis was determined: fructooligosaccharides (FOS) — 70.12%; oligofructosides — 24.79%; disaccharides — 2.11%; fructose — 2.98%. Requirements for carbohydrate composition of oligofructose obtained by enzymatic hydrolysis of inulin-containing syrup have been developed: sum total of FOS and oligosaccharides — not less than 93%, sum total of di- and monosaccharides — not more than 7%.
IMPACT OF ARTISANAL TECHNOLOGIES ON THE QUALITY INDICES OF THE COZONAC
Authors: Siminiuc R. , Țurcanu D. 
Published: October 2020

The research focused on studying the impact of sourdough with spontaneous flora (SSF) (obtained also from gluten-free flour) and artizanal technologies on the quality indices of cozonac — a traditional pastry product. Physico-chemical and microbiological indices were analyzed, as well as glycemic index (GI) of cozonac samples with different fermentation agents. The experimental results showed that the GI of the cozonac samples have similar values, being between GI = 68 and GI = 71. Respectively, cozonac with SSF samples can be classified in the category of foods with moderate GI, and cozonac with commercial yeast (CY) — in the category of foods with high GI. Digestibility indices for all samples reached values between 72% and 76%. The sensory profiles of baked cozonacs were analyzed descriptively by the panel members, and the results showed that all cozonac samples were characterized by slightly acid taste, with specific and pleasant flavors.However, it seems that a long fermentation of the dough, even if CY is used as a fermenting agent, leads to the formation of quality indices of the dough and cozonac, very close to the products obtained only with SSF. The use of SSF from sorghum flour would be an alternative in the development of gluten free bakery and pastry products using artisanal technologies.
Cooling Caramel in Ethyl Alcohol: Constructing a Mathematical Model
Authors: Khvostov Anatoly , Magomedov Gazibeg , Ryazhskikh Viktor , Plotnikova Inessa , Zhuravlev Aleksey , Magomedov Magomed 
Published: October 2020

Introduction. The process of air-cooling caramel remains one of the most complicated issues of contemporary food industry, since it is time-consuming and requires multi-level cooling units. Therefore, the development of an innovative method of cooling caramel in “cold” potable ethanol is an urgent task the modern food science has to solve. The method op-timizes and intensifies the technological process, as it reduces production areas by eliminating some technological stages and complex units of metal-intensive and energyintensive equipment. It gives caramel antiseptic properties and a perfectly smooth, shiny, and dry surface.
Study objects and methods. The research objective was to develop a fundamentally new and promising caramel technology. The experimental studies on the production and cooling were performed in a mixing and forming multi-unit with a high-performance cooling chamber. The chamber had functions of automatic measurements and control of the main parameters of the cooling process. The research used “cold” potable ethanol.
Results and discussion. The paper introduces a mathematical model of the process of cooling caramel in ethanol. It includes heat transfer processes in alcohol, in the caramel mass, and on their border. The model was based on equations of transient heat conduction in a sphere. The process of heat exchange with the environment, i.e. alcohol, was characterized by the coefficient of heat transfer from the sphere. The model parameters included dynamic viscosity, density, thermal conductivity coefficient, and specific heat capacity. Based on the experimental data, the parameters were ap-proximated as a function of temperature by a cubic polynomial.
Conclusion. The developed mathematical model made it possible to estimate the radial temperature distribution of caramel in the form of a sphere during its convective cooling in ethanol. The model also predicted the change in the average volume temperature of the caramel and energy costs depending on the cooling period, the flow speed of the ethanol, the thermophysical properties of the caramel and the cooling agent. The proposed mathematical model can be used to calculate the required consumption of ethanol for cooling and backwater of the caramel production line.
Готовность студентов технических вузов к инновационной деятельности
Authors: Буравлева Наталья А. , Богомаз Сергей А. 
Published: October 2020

Introduction. Nowadays innovations determine the success of breakthrough transformations in the country. This article examines readiness for innovative activities among student youth studying at technical universities. Methods. The study used the following techniques: (a) the techniques by Sh. Schwartz and R. Inglehart to measure individual values; (b) the questionnaires for assessing activity self-organization and styles of responding to changes; (c) the scales for self-assessing innovative personality traits, needs for autonomy, competence and relatedness, life satisfaction, and academic motivation; (d) ‘openness’ scale of the Big Five questionnaire; and (e) the index of personal readiness for activities. Factor analysis and regression analysis of diagnostic results were carried out. The sample comprised 160 students of Tomsk Technical Universities. Results. The findings identified the most significant factors influencing the manifestation of students’ innovative characteristics. These include, first of all, personality values, styles of responding to changes, and openness to experience. The study of values as a significant predictor of innovative activities showed the heterogeneity of the value system of students studying at technical universities. The simultaneous manifestation of traditional values, values of survival, and the values of openness to change, self-transcendence, and self-determination is characteristic of them. Regression analysis showed that the innovative style of responding to changes is not characteristic of students. Discussion. This study represents the first attempt to measure the main psychological characteristics that affect the manifestation of innovativeness among students of technical universities, and also the parameters of their personal readiness for innovative activities. In the context of readiness for innovative activities personal characteristics of young people are contradictory. However, there are positive tendencies towards self-development and professional improvement. The findings speak in favour of the transitivity of social reality in society and indicate the need to create the educational environment focused on personal development and innovative competencies of students.
Оценка пандемии COVID-19 россиянами с разным уровнем жизнестойкости
Authors: Одинцова Мария А. , Радчикова Наталия П. , Степанова Лариса В. 
Published: October 2020

Introduction. The COVID-19 pandemic provides an opportunity to examine the impact of psychological characteristics on human adaptation under uncertainty. Hardiness, which is still controversial for its role in maintaining human mental, physical, and social health, is such a psychological characteristic. Methods. To test the hypothesis that individuals with different levels of hardiness have different attitudes towards the current COVID-19 pandemic, the present study used the Hardiness Survey by S. Maddi (modified by E. N. Osin and E. I. Rasskazova) and a special questionnaire to assess various aspects of the pandemic situation, including its characteristics and impact on various spheres of life, fears, and possibilities for coping (using a 11-point Likert scale). The study was conducted during self-isolation using the Google Form (N = 421; age 18–78 years, mean age = 40.3 ± 12.6 years; 81 % females). Results. Most Russians perceived the pandemic situation as a challenge to their capabilities. The high-risk group comprised 17 % of respondents, which indicates the need for targeted psychological assistance aimed at psychological education. High hardy Russians recognize the uncertainty and complexity of the pandemic situation, and consider it controllable. For the low hardiness group, this situation is highly uncertain, complex, unpredictable, and uncontrollable, affecting physical activity and the quality of social contacts. Besides fears for their loved ones, fear of the future is pronounced among respondents of this group. Discussion. The findings from this study are in agreement with the idea of hardiness as the ability to withstand stressful situations, while maintaining internal balance without reducing performance in activities, which indicates the predictive value of this construct.
Evaluating the Need for Routine COVID-19 Testing of Emergency Department Staff: Quantitative Analysis
Authors: Zhang Yuemei , Cheng Sheng-Ru 
Published: October 2020

BackgroundAs the number of COVID-19 cases in the US continues to increase and hospitals experience shortage of personal protective equipment (PPE), health care workers have been disproportionately affected. However, since COVID-19 testing is now easily available, there is a need to evaluate whether routine testing should be performed for asymptomatic health care workers.ObjectiveThis study aimed to provide a quantitative analysis of the predicted impact that regular testing of health care workers for COVID-19 may have on the prevention of the disease among emergency department patients and staff.MethodsUsing publicly available data on COVID-19 cases and emergency department visits, as well as internal hospital staffing information, we developed a mathematical model to predict the impact of periodic COVID-19 testing of asymptomatic staff members of the emergency department in COVID-19–affected regions. We calculated various transmission constants based on the Diamond Princess cruise ship data, used a logistic model to calculate new infections, and developed a Markov model based on the average incubation period for COVID-19.ResultsOur model predicts that after 180 days, with a transmission constant of 1.219e-4 new infections/person2, weekly COVID-19 testing of health care workers would reduce new health care worker and patient infections by approximately 3%-5.9%, and biweekly testing would reduce infections in both by 1%-2.1%. At a transmission constant of 3.660e-4 new infections/person2, weekly testing would reduce infections by 11%-23% and biweekly testing would reduce infections by 5.5%-13%. At a lower transmission constant of 4.067e-5 new infections/person2, weekly and biweekly COVID-19 testing for health care workers would result in an approximately 1% and 0.5%-0.8% reduction in infections, respectively.ConclusionsPeriodic COVID-19 testing for emergency department staff in regions that are heavily affected by COVID-19 or are facing resource constraints may significantly reduce COVID-19 transmission among health care workers and previously uninfected patients.
Do adjunctive interventions in patients undergoing rapid maxillary expansion increase the treatment effectiveness?
Authors: Santana Lucas Garcia , Marques Leandro Silva 
Published: October 2020

ABSTRACT

Objectives
To evaluate the clinical effectiveness of adjunctive interventions in individuals undergoing rapid maxillary expansion (RME).

Materials and Methods
MEDLINE, Web of Science, Cochrane, Scopus, LILACS, and Google Scholar were searched without restrictions up to June 2020. Trials involving participants undergoing orthopedic or surgical RME, along with adjunctive interventions, were included. Risk-of-bias assessments were performed using the Cochrane tool for randomized trials-2. The certainty level of evidence was assessed through the Grading of Recommendations Assessment, Development and Evaluation tool.

Results
Six randomized clinical trials, with low to high risk of bias, were included. Low certainty of the evidence suggested that low-level laser facilitated opening of the midpalatal suture during the active phase of RME. Likewise, moderate certainty demonstrated that low-level laser accelerated the healing process of the suture during the retention phase. The clinical impact of this outcome, that is, stability and retention time, was not evaluated. Very low evidence indicated that osteoperforations along the midpalatal suture increased maxillary transverse skeletal gains in young adults undergoing RME. Low evidence suggested that platelet-rich plasma therapy did not minimize the vertical and thickness bone loss after RME in the short term.

Conclusions
Based on currently available information, the use of low-level laser associated with maxillary expansion seems to provide a more efficient suture opening and bone healing. Limited evidence suggests that osteoperforations improve the skeletal effects of RME in non-growing individuals. There are no adjunctive interventions capable of reducing the periodontal side effects of RME.
Trends in Glucose-Lowering Drug Use, Glycemic Control, and Severe Hypoglycemia in Adults With Diabetes in Hong Kong, 2002–2016
Authors: Yang Aimin , Wu Hongjiang , Lau Eric S.H. , Ma Ronald C.W. , Kong Alice P.S. , So Wing Yee , Luk Andrea O.Y. , Chan Juliana C.N. , Chow Elaine 
Published: October 2020

OBJECTIVE
There has been a shift toward new classes of glucose-lowering drugs (GLDs) in the past decade but no improvements in glycemic control or hospitalization rates due to severe hypoglycemia (SH) in previous surveys. We examined trends in GLDs use, glycemic control, and SH rate among patients with diabetes in Hong Kong, which introduced a territory-wide, team-based diabetes care model since 2000.

RESEARCH DESIGN AND METHODS
Using population-based data from the Hong Kong Diabetes Surveillance Database, we estimated age- and sex-standardized proportion of GLD classes, mean hemoglobin A1c (HbA1c) levels, and SH rates in 763,809 patients with diabetes aged ≥20 years between 2002 and 2016.

RESULTS
Between 2002 and 2016, use declined for sulfonylureas (62.9% to 35.3%) but increased for metformin (48.4% to 61.4%) and dipeptidyl peptidase 4 inhibitors (DPP-4is) (0.01% in 2007 to 8.3%). The proportion of patients with HbA1c of 6.0–7.0% (42–53 mmol/mol) increased from 28.6% to 43.4%, while the SH rate declined from 4.2/100 person-years to 1.3/100 person-years. The main improvement in HbA1c occurred between 2007 and 2014, decreasing from mean (SD) 7.6% (1.6) (59.5 [19.0] mmol/mol) to 7.2% (1.7) (54.8 [18.9] mmol/mol) (P &lt; 0.001). The 20–44 years age-group had the highest proportion of HbA1c ≥9% (75 mmol/mol) and rising proportions not on GLDs (from 2.0% to 7.7%).

CONCLUSIONS
In this 15-year survey, the modest but important improvement in HbA1c since 2007 coincided with diabetes service reforms, increase in metformin, decrease in sulfonylureas, and modest rise in DPP-4i use. Persistently poor glycemic control and underuse of GLDs in the youngest group calls for targeted action.
FORECASTING MODEL OF AGRICULTURE COMMODITY OF VALUE EXPORT OF COFFEE; APPLICATION OF ARIMA MODEL
Authors: Erlina RR , Azhar Rialdi 
Published: October 2020

Indonesia is currently one of the largest coffee producers in the world, and involved in exporting coffee countries. The financial series data such export value of coffee is highly volatile in both mean and variance. Thereby, the model of ARIMA with order p,d,q is one way to deal with this error. The aim of this study is to determine the best-fitted ARIMA(p,d,q) model to forecast the monthly series of export of coffee from January 2005 to April 2020. The findings suggest that ARIMA(1,3,1) is the best-selected model due to its very significant p-value (less than 0.0001), which showed that the model is applicable for forecasting. The model is then used to establish the prediction of ExCof monthly data for the next 12 months.