bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and pilot testing of an electronic guide incorporating patient values and prognostic information in preparation for older people’s decision-making near the end of life.
Authors: Cardona Magnolia , Lewis Ebony T , Bannach-Brown Alex , Ip Genevieve , Tan Janice , Koreshe Eyza , Head Joshua , Lee Jin Jie , Rangel Shirley , Bublitz Lorraine , Forbes Connor , Maréchal-Ross Isabella , Bathla Nikita , Kusnadi Ruth , Brown Peter G , Alkhouri Hatem , Ticehurst Maree , Lovell Nigel
Published: March 2022

Background
To develop an electronic resource, called Communicating Health Alternatives Tool (CHAT) that was compatible with hospital medical records software to facilitate preliminary patient-centered decision-making across health settings for frail older adults with progressive chronic disease.
Methods
Mixed methods including literature review; user-directed specifications; web-based interface development with authentication, authorisation, and secure cloud services; clinician and consumer co-design, iterative user testing; and developer integration of feedback.
Results
An internet-based conversation guide to facilitate clinician-led advance care planning was co-developed covering screening for short-term risk of death, patient values and preferences, and treatment choices for chronic kidney disease and dementia. Printed summary of such discussion could be used to begin the process in hospital or community health services. Clinicians, patients, and caregivers were generally accepting of its contents and format and supported its use in routine clinical practice.
Conclusion
CHAT is anticipated to enhance clinicians’ confidence in initiating these sensitive but important discussions with their older patients near end of life. CHAT is available to health services for implementation in effectiveness trials of patient-centered care to determine whether the interaction and documentation leads to formal decision-making, goal-concordant care, and subsequent reduction of unwanted treatments at the end of life.
NAPSB as a Predictive Marker for Prognosis and Therapy Associated with an Immuno-Hot Tumor Microenvironment in Hepatocellular Carcinoma
Authors: Zhao Qiu , Ning Yu-Mei , Lin Kun , Liu Xiao-Ping , Ding Yang , Jiang Xiang , Zhang Zhang , Xuan Yu-Ting , Liu Lan , Wang Fan , Wang Hai-Zhou , Fang Jun
Published: March 2022

Background: Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4+ T cell infiltration in pancreatic ductal adenocarcinoma. But the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined.Methods: The expression of NAPSB in pan-cancer and HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in HCC using Zhongnan cohort. Kaplan-Meier analyses, univariate and multivariate Cox regression were conducted to determine the predictive value of NAPSB on HCC prognosis. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed.Results: NAPSB was downregulated in HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), T cell inflamed score, and cancer immunity cycles and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis (PANoptosis).Conclusions: NAPSB was correlated with an immuno-hot and inflamed TME and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.
Association Between the SIRT1 and SIRT3 Levels and Gene Polymorphisms with Infertility in War Zones of Kermanshah Province, Iran .
Authors: nasiri abolfazl , Hosseini Sayed Mostafa , Rashidi Mohsen , Vaisi-Raygani asad , Mozafari Hadi
Published: March 2022

The authors have requested that this preprint be removed from Research Square.
Machine Learning the Metastable Phase Diagram of Materials
Authors: Sriniva Srilok , Batra Rohit , Luo Duan , Loeffler Troy , Manna Sukriti , Chan Henry , Yang Liuxiang , Yang Wenge , Wen Jianguo , Darancet Pierre , Sankaranarayanan Subramanian
Published: March 2022

A central feature of materials synthesis is the concept of phase diagrams, which provide information on the phases of the material at any given thermodynamic condition (i.e., state variables such as pressure, temperature and composition). Conventional phase diagram generation involves experimentation to provide an initial estimate of the set of thermodynamically accessible phases and their boundaries, followed by use of phenomenological models to interpolate between the available experimental data points and extrapolate to experimentally inaccessible regions. Such an approach, combined with high throughput first-principles calculations and data-mining techniques, has led to exhaustive thermodynamic databases (e.g. compatible with the CALPHAD method), albeit focused on the reduced set of phases observed at distinct thermodynamic equilibria. In contrast, materials during their synthesis, operation, or processing, may not reach their thermodynamic equilibrium state but, instead, remain trapped in a local (metastable) free energy minimum, which may exhibit desirable properties. A phase diagram that maps these metastable phases and their thermodynamic behavior is highly desirable but currently lacking, due to the vast configurational landscape. Here, we introduce an automated workflow that integrates first-principles physics and atomistic simulations with machine learning (ML), and high-performance computing to allow rapid exploration of the metastable phases of a given elemental composition and construct "metastable" phase diagrams for materials far-from-equilibrium. Using carbon, a prototypical system with a large number of metastable phases without parent in equilibrium, we demonstrate automated metastable phase diagram construction to map hundreds of metastable states ranging from near equilibrium to those far-from-equilibrium (400 meV/atom). Moreover, we incorporate the free energy calculations into a neural-network-based learning of the equations of state that allows for efficient construction of metastable phase diagrams. We use the metastable phase diagram and identify domains of relative stability and synthesizability of metastable materials. High temperature high pressure experiments using a diamond anvil cell on graphite sample coupled with high-resolution transmission electron microscopy (HRTEM) confirm our metastable phase predictions. In particular, we identify the previously ambiguous structure of n-diamond as a cubic-analog of diaphite-like lonsdaelite phase. The workflow presented here is general and broadly applicable to other chemical systems.
Standardization of the assessment process within telerehabilitation in chronic diseases: A scoping meta-review
Authors: Chapel Blandine , Alexandre François , Heraud Nelly , Ologeanu-Taddei Roxana , Cases Anne-Sophie , Bughin François , Hayot Maurice
Published: March 2022

Background Telerehabilitation (TR) interventions are receiving increasing attention. They have been evaluated in various scientific areas through systematic reviews. However, there is a lack of data on how to standardize assessment and report on their domains to guide researchers across studies and bring together the best evidence to assess TR for chronic diseases.Aims and Objectives The aim of this study was to identify domains of assessment in TR and to qualitatively and quantitatively analyze how and when they are examined to gain an overview of assessment in chronic disease.Methods A scoping meta-review was carried out on 9 databases and gray literature from 2009 to 2019. The keyword search strategy was based on "telerehabilitation", “evaluation", “chronic disease" and their synonyms. All articles were subjected to qualitative analysis using the Health Technology Assessment (HTA) Core Model prior to further analysis and narrative synthesis.Results Among the 7412 identified articles, 80 studies met the inclusion criteria. Regarding the domains of assessment, the most frequently occurring were “social aspect” (n = 63, 79%) (e.g., effects on behavioral changes) and “clinical efficacy” (n = 53, 66%), and the least frequently occurring was “safety aspects” (n= 2, 3%). We also identified the phases of TR in which the assessment was conducted and found that it most commonly occurred in the pilot study and randomized trial phases and least commonly occurred in the design, pretest, and post-implementation phases.Conclusions Through the HTA model, this scoping meta-review highlighted 10 assessment domains which have not been studied with the same degree of interest in the recent literature. We showed that each of these assessment domains could appear at different phases of TR development and proposed a new cross-disciplinary and comprehensive method for assessing TR interventions.. Future studies will benefit from approaches that leverage the best evidence regarding the assessment of TR, and it will be interesting to extend this assessment framework to other chronic diseases.
NERS_HEAD: An New Hybrid Evolutionary Algorithm for Solving Graph Coloring Problem
Authors: Guo Ping , Guo Bin
Published: March 2022

The graph coloring problem is an NP-hard problem. Currently, the most effective method to solve the problem is the hybrid algorithm. This paper proposes a hybrid evolutionary algorithm NERS_HEAD with a new elite replacement strategy. In NERS_HEAD, a method to detect the local optimal state is proposed so that the evolutionary process can jump out of the local optimal by introducing diversity on time. A new elite structure and replacement strategy are designed to increase the diversity of the evolutionary population so that the evolution process can not only converge quickly but also jump out of the local optimum in time. Experiments based on 34 instances of the DIMACS benchmark show that compared with the current excellent graph coloring algorithm, NERS_HEAD can reduce the evolutionary generation by an average of 28.3% and the calculation time by 22.11%. Especially in the instance dsjc500.1, Nere_HEAD can reduce 56% of evolution generations and 40% of computing time; On the r1000.1c instance, it can reduce the evolution generations by 82.30% and the calculation time by 73.45%.
Personalizing the control law of an upper-limb exoskeleton using EMG signal
Authors: Treussart Benjamin , Caron Remi , Geffard Franck , Marin Frederic , Vignais Nicolas
Published: March 2022

Implementing an intuitive control law for an upper-limb exoskeleton dedicated to force augmentation is a challenging issue in the field of human-robot collaboration. The goal of this study is to adapt an EMG-based control system to a user based on individual characteristics. To this aim, a method has been designed to tune the parameters of control using objective criteria, improving user's feedback. The user's response time is used as an objective value to adapt the gain of the controller. The proposed approach was tested on 10 participants during a lifting task. Two different conditions have been used to control the exoskeleton: with a generic gain and with a personalized gain. EMG signals was captured on five muscles to evaluate the efficiency of the conditions and the user's adaptation. Results showed a statistically significant reduction of mean muscle activity of the deltoid between the beginning and the end of each situation (28.6 ± 13.5% to 17.2 ± 7.3% of Relative Maximal Contraction for the generic gain and from 24.9 ± 8.5% to 18.0 ± 6.8% of Relative Maximal Contraction for the personalized gain). When focusing on the first assisted movements, the personalized gain induced a mean activity of the deltoid significantly lower (29.0 ± 8.0% of Relative Maximal Contraction and 37.4 ± 9.5% of Relative Maximal Contraction, respectively). Subjective evaluation showed that the system with a personalised gain was perceived as more intuitive, and required less concentration when compared to the system with a generic gain.
Infant colic: from theory to practice
Authors: Kanner E. V. , Maksimov M. L. , Kanner I. D. , Lapkin N. M. , Gorelov A. V.
Published: March 2022

Infant colic is one of the most common, yet least studied, functional disorders of the gastrointestinal tract. Until now, there is no certainty both in the understanding of the nature of this condition and in the approaches to its correction. At the same time, infant crying is of concern to parents, forcing them to seek professional help and incur considerable medical expenses and to resort, sometimes unreasonably, to dietary and medical corrections. This article provides information on the etiology, pathogenesis and management of infantile colic from an evidence-based perspective, based on a review of the current literature. Various preconditions for the occurrence and development of infantile colic are analysed in detail, none of which can affect all occurrences. Evidence for the proven efficacy of includingLactobacillus reuteriin the treatment of intestinal colic in infants is presented. Effects on the gastrointestinal tract microbiome can be of undeniable benefit.Lactobacillus reuteriis one of the most studied and scientifically documented probiotics. 203 completed clinical trials involving 17,200 participants, including 67 trials involving 8,200 participants between 0 and 3 years of age. Numerous placebo-controlled studies have shown that takingLactobacillus reuteriDSM 17938 can significantly reduce crying time in infants with colic, and in these studies, rates of 50% or more reduction in crying time were 2.3 times higher compared to controls.
Features of external therapy of allergic skin diseases in children
Authors: Kholodova I. N.
Published: March 2022

The development of inflammatory process in the skin has proven to be primarily associated with the immune system defects, in particular T-lymphocytes: the Th2 response predominates during the acute phase of the disease, when Th2 cells are stimulated with the subsequent hyperproduction of IgE; during the chronic phase, the Th2- shifts to Th1-immune response. At the same time, a significant amount of pro-inflammatory cytokines IL-4, IL-5, IL-13, IL-31 and IFN-γ move into this process. In addition, it is known that skin reactions can be induced not only by food allergens, but also by other allergens (house dust mites, Staphylococcus aureus enterotoxins, mold fungi). The prevalence of atopic dermatitis among the children’s population is up to 20%, while half of the children have skin lesions characterized by a severe long-term course, which violates their quality of life. The main goal of external therapy of dermatoses is to achieve control over subjective symptoms (especially skin itching), as well as regression of inflammatory manifestations with subsequent persistent remission of the allergic process. Local therapy of manifestations of atopic dermatitis is based on the adequate use of various external forms, as well as means in accordance with the inflammatory manifestations and localization of the inflammatory process. The article describes clinical cases of treatment of atopic dermatitis with various variants of its course using methylprednisolone aceponate cream with ceramides, emollient agents. It has been shown that the combined use of topical corticosteroids and emollients contributes to a rapid reduction of inflammation, dry skin and itching. The absence of toxic and side effects on this type of therapy in children with high treatment efficiency is emphasized.
Therapeutic efficacy and tolerability of syrup based on natural active ingredients in the treatment of cough in children with an acute respiratory infection
Authors: Zakharova I. N. , Sugyan N. G.
Published: March 2022

Introduction. Acute respiratory infections occupy the leading place in the structure of total infectious morbidity and account for more than 90% of all cases of infection. One of the most frequent clinical symptoms of acute respiratory infections is cough.Aim. To evaluate the therapeutic efficacy and tolerability of syrup based on active natural components in the treatment of cough in 2 to 7 years old children.Materials and methods. Patients 2 to 7 years old diagnosed with mild to moderate acute respiratory infections who had been coughing for no more than 3 days were included in the study.Results and discussion. We observed 123 children: 67 boys (54.5%) and 56 girls (45.5%). A statistically significant reduction in the severity of cough occurred on the 3rd day of treatment in both groups. On the 7th day of treatment, the degree of cough severity in both groups decreased on an average of 5 times. By the 7th day of taking the syrup, 97% of the children showed positive therapeutic effect: 55% of the patients’ cough symptoms resolved completely, 43% of the children had cough symptoms that became clinically insignificant. All these children recovered and were allowed to attend educational institutions. Reduction in the severity of cough when taking a syrup based on natural active components was accompanied by normalization of night sleep on average on the 4th day from the start of treatment.Conclusion. Receiving a syrup based on natural active ingredients in the early administration (within 3 days of coughing) for acute respiratory infections of mild and moderate severity allows 97% of children to cure a cough within 7 days.
Significance of fructosamine in the diagnosis of carbohydrate metabolism disorders in children with cystic fibrosis
Authors: Liabina N. V. , Simonova O. I. , Shirokova I. V. , Semikina E. L. , Mavrikidi E. F. , Kondrakhina I. I. , Gorinova Yu. V. , Kerimova V. A.
Published: March 2022

Introduction. Cystic fibrosis associated (related) diabetes mellitus (CFDM) is one of the most common severe complications of cystic fibrosis. Today, the issue of the goodness of a single measurement of fasting blood glucose, glycated hemoglobin and fructosamine to assess the degree of carbohydrate metabolism disorders in children with cystic fibrosis is a subject of debate. The gold standard for diagnosing carbohydrate metabolism disorders (impaired fasting glycemia, various pre-diabetic conditions, diabetes mellitus) is the oral glucose tolerance test. Data about the diagnostic value of fructosamine for predicting CFDM aren’t dispositive. No credible studies of fructosamine in children with cystic fibrosis have been found in the Russian medical literature.Aim. To determine the diagnostic informative value of the blood fructosamine and other single-measured glycemic marker levels in the early diagnosis of carbohydrate metabolism disorders at the pre-diabetes stage in children with cystic fibrosis.Materials and methods. The results of laboratory tests and instrumental examinations of 87 children with cystic fibrosis aged 5–18 years were reviewed. A cross-sectional study of fructosamine, fasting blood sugar and glycated hemoglobin level (some patients underwent an oral glucose tolerance test), and liver fibroelastometry were also performed.Results and discussion. An increase in the fructosamine level was observed, which indicates a possible CFDM in children (p = 0.049): CFDM is highly likely, if the level of fructosamine is ≥255.5 µmol/l (reference ranges for children are 272–285 µmol/l; sensitivity = 57.1%, specificity = 85.2%). It has been found that children with cystic fibrosis and liver cirrhosis have increased fructosamine levels: cut-off = 253.0 µmol/l (Sn – 70.0%, Sp – 85.2%).Conclusion. The fructosamine level, a single determination of fasting blood glucose and glycated hemoglobin are not informative markers for the diagnosis of pre-diabetic conditions in cystic fibrosis in children. It is important to bear in mind that concomitant liver cirrhosis can affect the fructosamine levels. CFDM can be diagnosed at the lower fructosamine level, despite the generally accepted ranges.
The importance of the nasopharyngeal mucosa protection for prevention of acute respiratory viral infections and influenza in children
Authors: Karpishchenko S. A. , Rodneva Yu. A.
Published: March 2022

ARVI is the most common children infection: children aged 0–5 years suffer, on average, 6–8 episodes of ARVI per year; and in the 1–2 years of visiting kindergarten the incidence rate is higher for 10–15% than in unorganized children, and at school the latter get sick more often. The incidence of ARVI is the highest in the period from September to April and it amounts about 87–91 thousand per 100 thousand in the population. The respiratory infectious disease protection of the organism is carried out in several stages and at various levels. It primarily depends on a mechanical barrier that prevents entering the virus agent into the organism – the mucous membrane of the nasal cavity, paranasal sinuses and nasopharynx. It can be achieved due to the peculiarities of its structure – respiratory epithelium, mucociliary transport, mucus properties and lymphoid organs associated with mucous membranes. If the pathogen nevertheless penetrates this barrier, then innate immunity starts protection activity, and after that the acquired immunity activates. Antiviral protection has differences due to the structure of the virus, it’s extremely small size, and the impossibility of reproduction outside the cells. The formed immune response persists even after elimination of the pathogen in the form of immune memory, which allows a faster and stronger reaction when the pathogen reappears. Children with primary immunodeficiency, genetic, oncological, hematological diseases, bronchial asthma, chronic ENT pathology are a special risk group in terms of the frequency and severity of ARVI and influenza. In this connection, the prevention of the incidence of ARVI and influenza is extremely important.
Case report of hypotonic dehydration with outcome in cerebral edema in a child
Authors: Tarasova Z. G. , Kirilochev O. K. , Sagitova G. R.
Published: March 2022

Dehydration is one of the most common disorders of water and electrolyte metabolism in young children. The reasons leading to the lack of water in the child’s body are very diverse. In clinical practice, a correct assessment of the pathophysiological mechanisms in various types of dehydration is necessary, which will allow timely identification of changes in various organ systems and conduct rational rehydration therapy. Water losses in children occur in a certain sequence. First of all, the intravascular subsector of the extracellular sector is subjected to water losses (clinical manifestations of dehydration in the child in this case are absent). If the pathological process continues, the intercellular subsector of the extracellular sector loses water, and then the patient first presents clinical symptoms: loss of body weight, dryness and brightness of the mucous membranes, reduction of subcutaneous fiber turgor, shrinkage of the mole in children of the first year of life, reduction of diuresis. Last of all, the intracellular sector loses its volume. Depending on the osmolarity of the extracellular fluid, isotonic, hypertonic and hypotonic dehydration are isolated. The most difficult in children is hypotonic dehydration, which is accompanied by a low osmolarity of the extracellular sector with predominant losses of sodium from the body. A retrospective analysis of a clinical case illustrates water-electrolyte disturbances in hypotonic dehydration. The child developed extracellular hypotonic dehydration because of sodium and water loss through the gastrointestinal tract. Hypotonic dehydration is characterized by an extreme degree of dissonance of the water-electrolyte balance, that is, the patient has severe extracellular dehydration and intracellular hyperhydration (edema, cell swelling). In this clinical case, violations of the waterelectrolyte balance led to the development of cerebral edema against the background of the existing cerebral deficiency, and death.
Breast milk microbiota (concept, sources, role of bacteria for a child and mother)
Authors: Zakharova I. N. , Кuchina A. E.
Published: March 2022

Scientific discoveries of recent years demonstrate a crucial role of the human microbiome in human health. The establishment of a healthy, functional gut microbiota of the newborn requires physiological conditions, one of which is breastfeeding. The role of breast milk as a “direct supplier” of live microbes for the establishment of the newborn gut microbiota became known only at the beginning of the new millennium, previously it was believed that the breast milk was sterile. Today, the breast milk microbiota can be defined as multi-species assemblage, in which microbes interact with each, representing a complex organized ecosystem, among which the genera Streptococcus and Staphylococcus are dominant. Lactobacillus, Pseudomonas, Bifidobacterium, Corynebacterium, Enterococcus, Acinetobacter, Rothia, Cutibacterium, Veillonella and Bacteroides are also often referred to the common bacterial genera. The article presents two theories of the origin of bacteria in the breast milk (endogenous and exogenous bacterial translocation pathways) and explains why both of them are true. The role of bacteria in the breast milk of healthy women, in the global sense, is viewed in the context of the establishment of the infant gut microbiota. The article lists the main producers of antibacterial peptides (bacteriocins) in the breast milk and considers the effective immunological protection using the example of the population of bifidobacteria and bacteroids prevailing in the breastfed infant gut. However, the breast milk microbiota is also important for women’s health. We tried to explain why infectious lactational mastitis is now considered to be the result of dysbiosis in the mammary ecosystem, which leads to the development of an inflammatory process, and why Streptococcus thermophilus (TCI633) shows promise in the fight against human ageing.
Is an adolescent with chronic kidney disease ready for the transition to an adult health service: translation and adaptation of questionnaires
Authors: Kulakova E. N. , Koltakova M. P. , Nastausheva T. L. , Stebletsova A. O. , Zvyagina T. G. , Ledovskih A. O.
Published: March 2022

Introduction. The issue of the readiness of adolescents with chronic kidney disease (CKD) for the transition to the adult service in the Russian healthcare system remains unexplored. One of the reasons of this problem is the lack of Russian tools for evaluating patient transition readiness.The goal of this study is to develop Russian-language questionnaires to evaluate the readiness of adolescents for the transition to an adult health service based on the English-language originals.Materials and methods. A literature search was carried out to identify English questionnaires, as well as recommendations for their translation and adaptation. Development of the Russian versions of the questionnaires included the following major stages: preparation, two forward translations, their reconciliation, adaptation and creation of an intermediate version, back-translation into English, cognitive interviewing of the adolescents, proofreading and approval of the final version by the authors of the original English questionnaires. Cognitive interviewing was performed with 10 adolescents with CKD aged 15–17 years.Results. Four English questionnaires were identified. They were studied and comparatively analysed. Translated versions of these questionnaires into foreign languages were revealed. Two most promising questionnaires for translation into Russian were identified: UNC TRxANSITION Index and STARx. Russian versions of these questionnaires were developed based on the international recommendations. Cognitive interviewing provided additional adaptation and linguistic validation of the translated versions based on the adolescents’ opinions. UNC TRxANSITION Index is a provider-administered questionnaire and includes 32 questions. STARx is a self-report questionnaire and includes 18 questions.Conclusions. Russian versions of questionnaires for evaluating adolescents’ transition readiness are available for use by health professionals and social workers. A further study of their psychometric properties and confirmation of the validity of their results in the context of the Russian healthcare system is required.
Clinical and microbiological rationale for the use of a herbal preparation in children with rhinopharyngitis
Authors: Chelpachenko O. E. , Danilova E. I. , Chainikova I. N. , Bekpergenova A. V. , Bondarenko T. A. , Sumenko V. V.
Published: March 2022

Introduction. The work includes the results of clinical and microbiological studies that determine the feasibility of using the herbal preparation EPS® 7630 for the treatment of rhinopharyngitis (RF) in children. The introduction provides a brief review of the literature data on the role of the microbial factor and the important contribution of dysbiotic disorders of the URT microflora in the development of the Russian Federation. The porpose of persistent properties of opportunistic microorganisms (UPM) is outlined: the ability to biofilm formation – BPO and inactivation of lysozyme – ALA as dysbiotic markers of RF, which create conditions for relapses and chronicity of the disease, reduce the effectiveness of antimicrobial therapy. Goal.

The aim of the work was the clinical and microbiological substantiation of the effectiveness of using EPS® 7630 in the treatment of RF in children.

Materials and methods. The study involved 79 children aged 3 to 15 years. 1st group – 43 children who received treatment, including, along with traditional treatment, the drug Umckalor EPS® 7630, 2nd group (comparison) – 36 children who did not receive the tested drug. Microbiological examination was carried out by taking swabs from the pharynx and nose before and after treatment; BPO and ALA were determined according to the methods of Bukharin O.V. et al. (1999).

Results. Conducted clinical studies have established a reduction in the timing of relief of the main symptoms of RF (cough, rhinitis, sore throat, fever) in children treated with EPS® 7630 compared to the comparison group. Microbiological studies of microorganisms isolated from the nasopharynx of children with RF revealed the ability of EPS® 7630 to suppress bacterial persistence factors (BPO and ALA) by 60% or more from the initial level.

Conclusions. The data obtained reveal one of the mechanisms of the antimicrobial action of EPS® 7630, which consists in suppressing the persistent potential of UPM and regulating the effect of the drug on the microbiocenosis of the URT. The clinical and microbiological efficacy of using EPS® 7630 in the treatment of RF in children has been proven.
Treatment of fever in acute upper respiratory tract infections in children
Authors: Zakharova I. N. , Berezhnaya I. V. , Sugyan N. G. , Tvorogova T. M. , Kolushkin D. S. , Pupykina V. V. , Rodionov I. E.
Published: March 2022

Introduction. The WHO recommends using acetaminophen (paracetamol) and ibuprofen in fever treatment in children and does not recommend their use in sequence to avoid overdose. However, in recent years, preparations containing both medicinal components have appeared, which allows fever to be relieved safely and the daily dosage of the medicines to be reduced.Objective. To obtain additional data on the efficacy and safety of antipyretic drug combination in comparison with mono drugs in children with the febrile syndrome in acute upper respiratory tract infectionsMaterials and methods. Single-center non-interventional (observational) comparative study was conducted in children from 3 to 12 years of age with acute respiratory infections accompanied by fever. Children were divided into 3 groups: the treatment group (83 children) received a combined antipyretic drug in the form of dispensable tablets (100 mg ibuprofen and 125 mg paracetamol); control group 1 (42 children) received paracetamol in the form of suspension; control group 2 (43 children) received ibuprofen in the form of suspension. The clinical efficacy and safety of antipyretic therapy and also the satisfaction of the patients’ parents, were evaluated in the dynamics.Results. The results showed similar efficacy and safety of all three medications, but the daily dose of medications with the combined dispersible tablets was lower, more so for paracetamol and somewhat less so for ibuprofen. In the combined dispersible tablets group, the proportion of patients with a temperature < 37.2 °C was statistically significantly higher 1 hour after administration than in the paracetamol and ibuprofen drug groups. Ibuprofen only compared with the study drug in terms of efficacy after 2 hours, while paracetamol was already effective after 3 hours.Conclusions. The study showed that the combined drug in the form of dispersible tablets (100 mg of ibuprofen and 125 mg of paracetamol) showed statistically significant efficacy parameters, is safe and well-tolerated by patients.
Spatiotemporal characteristics analysis of water saving potential and economic effectiveness of rainwater harvesting system in China
Authors: Shiguang Chen , Yu Zhang , Xinkuang Lin , Xiaochun Lu
Published: March 2022

The financial viability of a rainwater harvesting (RWH) system is highly determined by regional conditions such as rainfall pattern and water prices. Successful implementation of rainwater harvesting systems depends largely on the identiﬁcation of suitable sites. This paper presents the water saving potential and economic effectiveness of rainwater harvesting systems across eight major cities in China, using a daily water balance model. Results show six to 81 days (or 1.6% to 22.2%) of dependability can be achieved by using a rainwater harvesting system over these cities. The annual water saving efficiency ranges from 10% to 37% and the benefit–cost ratio varies between 0.45 and 1.20 across the studied cities. South China achieves the maximum annual water saving and the highest benefit–cost ratio, while southeast China has the most regular profile of precipitation use. Northwest China was found to be the region with the worst performance, both in yearly water saving and in regularity of rainwater use on a yearly scale. It was also found that the RWH system is not financially feasible in the northeast, southwest and central plains due to the benefit–cost ratios being smaller than 1.0.
The hydraulic investigation of inflatable weirs
Authors: Sarvarinezhad S. Behnam , Bina Mahmoud , Afaridegan Ehsan , Parsaie Abbas , Avazpour Fatemeh
Published: March 2022

In this research, the models of Inflatable weirs with internal pressures of 0.5 and 1.4 at three heights of 0.15, 0.2 and 0.25 m were constructed. The deflectors were used in two geometric sections, including rectangular and triangular shapes, and they were installed at angles of 30, 45, and 60 degrees downstream of the weir body. The results showed that the value of the Cd changes between 0.28 and 0.35 while the range of the ratio of the upstream flow head on the crest to the radius of the downstream side of the inflatable weir varies between 0.2 and 1.5. The flow by crossing over the inflatable weir and colliding with the surface of the downstream stilling basin loses its energy by about 10–85%. The relative horizontal distance of the projectile-jet from the crest varies between 1.6 and 2.8. The effect of the deflector on the Cd is negligible due to being located in the supercritical part of the weir. Examination of the obtained results declared that the deflector has a considerable effect on energy dissipation.
NO SABER Y NO RECONOCER: DOS METÁFORAS PARA PENSAR LA CRISIS DESDE LA RESURRECCIÓN DE JESÚS
Authors:   Pontificia Universidad Católica de Chile, Espinosa Arce Juan Pablo
Published: March 2022

El presente artículo busca ofrecer una lectura espiritual a la crisis a partir de los conceptos de imaginario y metáfora. En la bibliografía se indica que dichas categorías favorecen una desmesura interpretativa de las imágenes tradicionales, poéticas, filosóficas, teológicas y bíblicas. Por medio de ellas se inaugura una nueva forma de interpretación de la realidad. A partir de ello, y de un modo más específico, se buscará pensar cómo la Resurrección de Jesús expresada en dos metáforas, “no saber” y no “reconocer”, nos permite repensar y dar un nuevo significado a la crisis sanitaria, eclesial y sociopolítica actual.
Role of Artificial Intelligence in Cancer Diagnosis and Drug Development
Authors: Paliwal Deepika , Srivastava Shubham
Published: March 2022

Cancer is a vast form of the disease that can begin in almost any organ or tissue of the
body when abnormal cells grow uncontrollably and attack nearby organs. The traditional approaches
to cancer diagnosis and drug development have certain limitations, and the outcomes
achieved through the traditional approaches applied to cancer diagnosis and drug development are
not quite promising. Artificial intelligence is not new to the medical research sector. AI-based algorithms
hold great potential for identifying mutations and abnormal cell division at the initial
stage of cancer. Advanced researchers are also focusing on bringing AI to clinics in a safe and ethical
manner. Early cancer detection saves lives and is critical in the fight against the disease. As a
result, as part of earlier detection, computational approaches such as artificial intelligence have
played a significant role in cancer diagnosis and drug development.
An Immune-Related Gene Signature Predicting Prognosis and Immunotherapy
Response in Hepatocellular Carcinoma
Authors: Ren Zhenggang , Yin Xin , Zhang Feng , Cai Jialiang , Hu Keshu , Liu Wenfeng , Lu Shenxin , Tang Bei , Li Miao , Wu Weizhong
Published: March 2022

Background:

Hepatocellular carcinoma (HCC) is inflammation-associated cancer
with high incidence and poor prognosis. In the last decade, immunotherapy has become an important
strategy for managing HCC.

Objective:

This study aimed to establish an immune-related gene signature for predicting prognosis
and immunotherapy response in HCC.

Methods:

We identified immune-related differentially expressed genes (IRDEGs) based on The
Cancer Genome Atlas (TCGA) database and the Immunology Database and Analysis Portal (ImmPort)
database. The weighted gene co-expression network analysis (WGCNA) and Cox proportional
hazard model were utilized to determine hub immune-related genes (IRGs). The TIDE tool
and R package pRRophetic were used to assess the correlation between the immune-related gene
signature and the clinical responses to immunotherapy and chemotherapy.

Results:

By using WGCNA combined with Cox proportional hazard model, PRC1, TOP2A, TPX2,
and ANLN were identified as hub IRGs. The prognostic value of the newly developed gene signature
(IRGPI) was demonstrated in both the TCGA database and the Gene Expression Omnibus
(GEO) database. The TIDE tool showed that the high- and low-IRGPI groups presented significantly
different tumor immune microenvironment and immunotherapy responses. Furthermore, the
high-IRGPI group also had significantly lower chemoresistance to cisplatin than the low-IRGPI
group.

Conclusions:

The IRGPI is a tool for predicting prognosis as well as responsiveness to immunotherapy
and chemotherapy in HCC.
Prospective Analysis of Proteins Carried in Extracellular Vesicles with
Clinical Outcome in Hepatocellular Carcinoma
Authors: Tang Donge , Chen Wenbiao , Zhang Feng , Xu Huixuan , Hou Xianliang
Published: March 2022

Background:

Extracellular vehicles (EVs) contain different proteins that relay information
between tumor cells, thus promoting tumorigenesis. Therefore, EVs can serve as an ideal marker for
tumor pathogenesis and clinical application.

Objective:

Here, we characterised EV-specific proteins in hepatocellular carcinoma (HCC) samples
and established their potential protein-protein interaction (PPI) networks.

Materials and Methods:

We used multi-dimensional bioinformatics methods to mine a network module
to use as a prognostic signature and validated the model’s prediction using additional datasets. The
relationship between the prognostic model and tumor immune cells or the tumor microenvironment
status was also examined.

Results:

1134 proteins from 316 HCC samples were mapped to the exoRBase database. HCC-specific
EVs specifically expressed a total of 437 proteins. The PPI network revealed 321 proteins and 938 interaction
pathways, which were mined to identify a three network module (3NM) with significant
prognostic prediction ability. Validation of the 3NM in two more datasets demonstrated that the model
outperformed the other signatures in prognostic prediction ability. Functional analysis revealed that
the network proteins were involved in various tumor-related pathways. Additionally, these findings
demonstrated a favorable association between the 3NM signature and macrophages, dendritic, and
mast cells. Besides, the 3NM revealed the tumor microenvironment status, including hypoxia and inflammation.

Conclusion:

These findings demonstrate that the 3NM signature reliably predicts HCC pathogenesis.
Therefore, the model may be used as an effective prognostic biomarker in managing patients with
HCC.
AAV9-coGLB1 Improves Lysosomal Storage and Rescues Central Nervous
System Inflammation in a Mutant Mouse Model of GM1 Gangliosidosis
Authors: Wu Xiaobing , Huang Yonglan , Liu Sichi , Ma Wenhao , Feng Yuyu , Zhang Yan , Jia Xuefang , Tang Chengfang , Tang Fang
Published: March 2022

Background:

GM1 gangliosidosis (GM1) is an autosomal recessive disorder characterized
by the deficiency of beta-galactosidase (β-gal), a ubiquitous lysosomal enzyme that catalyzes the hydrolysis
of GM1 ganglioside.

Objective:

The study aims to explore the application of the AAV9-coGLB1 for effective treatment in a
GM1 gangliosidosis mutant mouse model.

Methods:

We designed a novel adeno-associated virus 9 (AAV9) vector expressing β-gal (AAV9-
coGLB1) to treat GM1 gangliosidosis. The vector, injected via the caudal vein at 4 weeks of age,
drove the widespread and sustained expression of β-gal for up to 32 weeks in the Glb1G455R/G455R mutant
mice (GM1 mice).

Results:

The increased levels of β-gal reduced the pathological damage occurring in GM1 mice. Histological
analyses showed that myelin deficits and neuron-specific pathology were reduced in the cerebral
cortex region of AAV9-coGLB1-treated mice. Immunohistochemical staining showed that the
accumulation of GM1 ganglioside was also reduced after gene therapy. The reduction of the storage in
these regions was accompanied by a decrease in activated microglia. In addition, AAV9 treatment reversed
the blockade of autophagic flux in GM1 mice.

Conclusion:

These results show that AAV9-coGLB1 reduces the pathological signs of GM1 gangliosidosis
in a mouse model.
Evaluation of Extended-release of Piroxicam-loaded Pectin-zein Hydrogel
Microspheres: In vitro, Ex vivo, and In vivo Studies
Authors: Bobokalonov Jamshed , Muhidinov Zayniddin , Nasriddinov Abubakr , Jomnurodov Abduvaly , Khojaeva Farangis , Komilova Gulnora , Yusufi Salomudin , Liu LinShu
Published: March 2022

Objective:

This study evaluated drug delivery systems based on Pectin (P) and Zein (Z) hydrogel
microspheres. Piroxicam (Px) loaded P/Z hydrogel microspheres (P/Z HM) were developed, and
their extended-release pharmacokinetic properties were evaluated.

Methods:

Experiments were executed under three different conditions: in vitro, ex vivo, and in vivo.
Then, the in vitro-in vivo correlations (IVIVC) and ex vivo-in vivo correlations (EVIVC) were examined.

Results:

Analysis of drug release mechanisms were evaluated by fitting the in vitro data into the Ritger-
Peppas equation, showing the contribution of both polymers’ relaxation and drug diffusion from the
hydrogel microspheres. The fraction absorbed in vivo was determined by the deconvolution of plasma
concentration data using the Loo-Riegelman method. After oral single-dose administration of the two
formulations, their basic independent model parameters were calculated.

Conclusion:

P/Z HM had different drug release behaviors in in vitro and in vivo conditions. However, the ex vivo and in vivo characteristics were similar (R² = 0.99). This seemed reasonable to use the ex vivo method to predict the in vivo drug absorption behavior during the polymeric drug delivery system developmental studies. The P/Z HM formulation maintained the drug dose at the colon site for a long duration and could be applied for delivery of active pharmaceutical and food ingredients to the colon site.
Identification of Novel and Known LDLR Variants Triggering Severe
Familial Hypercholesterolemia in Saudi Families
Authors: Alnouri Fahad , Al-Allaf Faisal A. , Athar Mohammad , Al-Rasadi Khalid , Alammari Dalal , Alanazi Menwar , Abduljaleel Zainularifeen , Awan Zuhier , Bouazzaoui Abdellatif , Dairi Ghida , Elbjeirami Wafa M , Karra Hussam , Kinsara Abdulhalim J , Taher Mohiuddin M.
Published: March 2022

Background:

Familial hypercholesterolemia (FH) is a common illness mainly caused by
variants occurring in the low-density lipoprotein receptor (LDLR) gene. FH is a leading cause of coronary
artery disease.

Objective:

This study aims to determine genetic defect(s) in homozygous and heterozygous FH index
patients and their first-degree blood relatives and understand the genotype-phenotype correlation.

Methods:

This study employed the genetic screening of FH-related genes by next-generation sequencing
and cascade screening by capillary sequencing.

Results:

We identified the presence of a novel frameshift variant [c.335_336insCGAG,
p.(F114Rfs*17)] and three known missense variants [c.622G>A, p.(E208K)], [c.1474G>A, p.(D492N)],
[c.1429G>A, p.(D477N)] in the LDLR gene of four unrelated Saudi families with FH. In proband 1, a
nonsense variant c.1421C>G, p.(S474*) was also detected at exon 9 of the lipoprotein lipase gene. The
segregation arrangement of the identified variants corresponded with the clinical characteristics. In this
study, all the detected variants were confined in the ligand-binding domain and epidermal growth factor
(EGF)-precursor homology domain of the LDLR protein, which portrayed severe clinical phenotypes of
FH. Moreover, these LDLR variants were in a highly conserved residue of the proteins.

Conclusion:

In addition to the finding of the novel variant in the LDLR gene that extends the spectrum
of variants causing FH, the results of this study also support the need for diagnostic screening and cascade
genetic testing of this high-risk condition and to understand the genotype-phenotype correlation,
which could lead to better prevention of coronary artery disease.
A Motif in Metallopeptidase Inhibitor Decreases Effectively the Activity of
Macrophage Metalloproteinases
Authors: Najafi Mohammad , Esfandiari Golnaz , Ghasempour Ghasem , Kakavandi Naser , Soleimani Ali Akbar , Abkenar Borhan Rahimi , Bahraini Elham , Khosravi Mohsen
Published: March 2022

Objective:

The tissue remodeling process and cellular migration relate to the activities of
matrix metalloproteinases (MMPs). The aim of this study was to investigate the effects of a predicted
motif from TIMPs on the MMP-2 and MMP-9 activities secreted from the differentiated macrophages.

Methods and Materials:

The monocytes were isolated from the healthy individuals by RosetteSep
kit and were differentiated into macrophages using M-CSF. A 4-amino acid motif (TCAP) was predicted
using bioinformatics tools. Zymography technique was applied for the measurement of MMP
activities. The docking studies were also investigated between MMPs, tetrapeptide, and Batimastat.

Results:

The TCAP inhibited significantly the differentiated macrophage MMP-2 and MMP-9 activities
(p=0.0001and p=0.01, respectively). The docking results suggested that some MMP amino acids
are involved with both tetrapeptide (TCAP) and Batimastat,

Conclution:

The data showed that the small motif (TCAP) of TIMPs inhibits effectively the MMP-
2 activity.