bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of the Composition of Combined Medicinal Pencils for the Treatment of Dental Diseases
Authors: Alekseeva I. V. , Ryumina T. E. , Novikova V. V. , Golovanenko A. L. , Kotsur Yu. M. , Shigarova L. V.
Published: September 2022

Introduction. Prevention and treatment of periodontal diseases remains one of the urgent problems of modern medicine. According to WHO, the prevalence of dental diseases among adults is 90–95 %, among adolescents – 80–83 %. The health of the body as a whole largely depends on the state of the oral cavity. It is important for the effective treatment of diseases to have a properly selected dosage form, which provides both convenience of use and purposeful use of the action of the pharmacologically active drug contained in it. Medicinal pencils as a dosage form are very limited on the pharmaceutical market, so their development is relevant. As a local anesthetic component, anilocaine is included in the composition of pencils at a concentration of 5 %, antimicrobial action is provided by the introduction of metronidazole in a concentration of 1 % in order to prevent the occurrence of infection.

Aim. Substantiation of the composition and technology of the medicinal pencil for the treatment and prevention of infectious and inflammatory diseases of the oral cavity.

Materials and methods. For the study, we used medicinal pencils with an active pharmaceutical substance – anilocaine (FS 42-2846-97, LLC "Perm Chemical Company", Perm, shelf life of 5 years), metronidazole (FS 42-0257-07, JSC "Medisorb", Perm, shelf life of 3 years); basic components – PEO-400 (FS 42-1242-96, LLC "Neftegazkhimkomplekt", Moscow, shelf life of 3 years), PEO-1500 (FS 42-1885-96, LLC "Neftegazkhimkomplekt", Moscow, shelf life of 3 years), PEO-4000 (FS 42-3337-96, LLC "Neftegazkhimkomplekt", Moscow, shelf life 3 years), second ingredient – purified water (FS.2.2.0020.18), the UVOI-"MF" 1812S6 obtained at the reverse osmosis plant (JSC "NPK Median-Filter", Russia). In the course of the research, technological, structural-mechanical and biopharmaceutical methods were used.

Results and discussion. Based on technological, structural-mechanical and biopharmaceutical studies, the composition of medicinal pencils with anesthetic, anti-inflammatory and antimicrobial effects for the treatment and prevention of infectious and inflammatory diseases of the oral cavity is proposed and justified for the first time. Biopharmaceutical availability of medicinal pencils is determined by the conductometric method.

Conclusion. The conducted complex of studies will expand the range of domestic medicines for the treatment and prevention of infectious and inflammatory diseases of the oral cavity.
Rationing of Residual Organophosphate Pesticides in Herbal Substances (Review)
Authors: Fateenkova O. V. , Savvateev A. M. , Beloborodov V. L. , Gravel I. V.
Published: September 2022

Introduction. Usage of organophosphate pesticides (OPPs) in agriculture, including farming of medical herbs, is a necessary measure for producing regular harvest. In order to maintain an adequate degree of herbal medicines security a variety of countries developed normative documents that regulate the limits of proportion of pesticides (including OPPs) in herbal substances. These documents contain the recommended methods of residual pesticides analysis as well.

Text. The article describes the recently conducted information-analytical research of limits of permissible proportion of OPPs in herbal substances and food production and of methods of extraction and analysis of OPPs mentioned in the State Pharmacopoeia of the Russian Federation XIV, international pharmacopeias, WHO information sources and the normative documents on food production. The authors specify physical-chemical characteristic of OPPs and the main mechanism of impact of this class of pesticides onto a human body. The research demonstrates that HPLC-MS and GC-MS are the most perspective analytical methods of detection of OPPs in herbal substances.

Conclusion. In the information-analytical review the authors specify a physical-chemical characteristics of OPPs, describe the mechanism of the toxic impact of this type of pesticides, provide the generalized summary of limits of permissible proportion of OPPs in herbal substances and in food production. The study shows that the rationing of OPPs proportion is harmonized in a majority of issues of modern pharmacopeias. The paper presents modern methods of detection of OPPs in herbal substances and food production. Finally, the authors demonstrate an advantage of the modern approach to rationing of OPPs in herbal substances (specification of presence and proportion of a single pesticide in combination with its toxic metabolites). The key issue is a necessity of developing a sensible and selective methodic of analysis of OPPs in accordance with physical-chemical properties of these types of pesticides in different kinds of herbal substances and phytopreparations.
Current aspects of Quality Control and Standardization of Eleutherococcus senticosus Medicines
Authors: Kurkin V. A. , Ryazanova T. K.
Published: September 2022

Introduction. Nowadays, herbal medicines are becoming more and more popular. In this regard, herbal medicinal preparations based on rhizomes and roots of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., syn. Acanthopanax senticosus (Rupr. & Maxim.) Harms, are of particular interest. Its have an adaptogenic, immunomodulatory effects mainly due to the presence of phenyl propane compounds: eleutherosides B, D, E, E1. The current pharmacopeial monographs FS.2.5.0053.15 "Eleutherococcus senticosus rhizomes and roots" and FS.3.4.0009.18 "Eleutherococcus senticosus rhizomes and roots liquid extract" in The State Pharmacopoeia of the Russian Federation XIV Edition, in our opinion, does not allow to fully objectively and uniformly assess the quality of raw materials and preparations.

Aim. The aim is substantiation of new approaches to quality control of raw materials and preparations of Eleutherococcus senticosus, consisting in changing the conditions of sample preparation and analysis of active biological compounds in comparison with pharmacopoeial methods.

Materials and methods. Samples of the medicinal preparation "Eleutherococcus extract liquid" of a domestic manufacturer (5 lots) and experimental preparation "Eleutherococcus syrup". When performing high performance liquid chromatography (HPLC) analysis, a reference sample of syringin was used that met the requirements of pharmacopeial monograph VFS 42-2088-92. Methods of UV-spectroscopy and HPLC were used to determine the quantity of biologically active substances.

Results and discussion. As a result of the research, other methodological and methodological approaches have been developed to determine the content of the total of phenylpropanoids in terms of eleutheroside B (syringin) by direct UV-spectrophotometry using a standard sample of syringin or the value of its specific absorbance. New conditions for HPLC analysis of eleutheroside B (syringin) in preparations of Eleutherococcus senticosus have been selected.

Conclusion. As a result of the phytochemical study, a spectrophotometric method was developed for the determination of the total of phenylpropanoids in terms of syringin and an HPLC method for the determination of eleutheroside B (syringin) using an external standard after preliminary purification of the total extracts by filtration through a layer of aluminum oxide.
Screening of Lipophilic Fractions of Botanical Forms of Celery by GC/MS Method
Authors: Surbeeva E. S. , Sipkina N. Y. , Komova S. I. , Efremova U. A. , Terninko I. I.
Published: September 2022

Introduction. The search for new tools for the treatment and prevention of obesity – a socially significant disease characterized by high prevalence and the presence of a number of complications – is an urgent area of research. Literature data indicate the presence of pharmacological activity in different groups of BAC of plant origin – flavonoids, phenolic acids, phytosterols, etc. in relation to obesity and its associated diseases. In view of the significant accumulation of target groups of compounds, as well as the availability of a large and renewable raw material base, celery was chosen for research as a potential raw source of BAC contributing to the regulation of metabolic disorders.

Aim. To investigate the component composition of lipophilic fractions of botanical forms of celery by GC/MS and to predict the pharmacological activity of identified compounds within the target group of pathologies using the web resource PASS Оnline.

Materials and methods. Lipophilic fractions were prepared by chloroform extraction of dry crushed raw material of celery root, stalks and leaves in a Soxhlet apparatus. Obtained extracts were analyzed on gas chromatography-mass spectrometer "Clarus 600T" (PerkinElmer, USA) on the basis of the Collaborative Centre "Analytical Center" equipment. Interpretation of the mass spectra of the peaks on the chromatograms was carried out using the NIST-14 library, for further prediction of biological activity of the identified compounds we used web-resource PASS online.

Results and discussion. The composition of lipophilic fractions of celery botanical forms is represented by terpenes, benzofurans, coumarins, fatty acids and their derivatives, phytosterols. A total of 50 compounds were found in extracts from celery root, of which 68 % were identified, stalks – 36 and 61 %; leaves – 22 and 64 %, respectively. Prediction of the pharmacological activity of individual compounds of celery showed the possibility of their use for the regulation of lipid and carbohydrate metabolism, cardiovascular disorders and liver diseases, which confirms the prospects of this study.

Conclusion. The results have shown that celery roots and stalks are a source of terpenes, coumarins and benzofuran derivatives, in addition, the above-ground part of the plant shows high accumulation of phytosterols, which may have metabolic regulation activity and be used in the complex therapy and prevention of obesity.
Development and Validation of HPLC-UV Method for the Determination of Favipiravir in Human Plasma
Authors: Komarov T. N. , Karnakova P. K. , Archakova O. A. , Shchelgacheva D. S. , Bagaeva N. S. , Shohin I. E. , Zaslavskaya K. Ya. , Bely P. A.
Published: September 2022

Introduction. Coronavirus disease (COVID-19) is an acute infectious disease caused by SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2). Favipiravir is a synthetic prodrug with antiviral activity used for the treatment of COVID-19. There are oral and parenteral dosage forms of favipiravir. Compared with oral administration, parenteral administration has some advantages. Developing a method for the determination of favipiravir in human blood plasma is necessary for performing the analytical part of clinical studies of favipiravir for parenteral administration as an infusion, studying pharmacokinetics, and choosing the optimal dosage of the drug.

Aim. The aim of this study is to develop and validate a method for quantitative determination of favipiravir in human plasma by high-performance liquid chromatography with ultraviolet detection (HPLC-UV) for pharmacokinetic studies.

Materials and methods. Determination of favipiravir in human plasma by HPLC-UV. The UV detection was set at 323 ± 2 nm. The samples were processed by methanol protein precipitation. Internal standard: raltegravir. Mobile phase: 0.1 % formic acid in water with 0.08 % aqueous ammonia (eluent A), 0.1 % formic acid in acetonitrile with 0.08 % aqueous ammonia (eluent B). Column: Phenomenex Kinetex®, C18, 150 × 4.6 mm, 5 μm. Analytical range: 0.25–200.00 μg/mL.

Results and discussion. This method was validated by selectivity, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability.

Conclusion. We developed and validated the method of quantitative determination of favipiravir in human plasma by HPLC-UV. The analytical range was 0.25–200.00 μg/mL in human plasma. The method could be applied in pharmacokinetics studies of favipiravir.
Natural Deep Eutectic Solvents as Alternative Flavonoid Extractants from the Sedative Plant Composition
Authors: Dzhavakhyan M. A. , Prozhogina Yu. E. , Pavelieva O. K. , Kalenikova E. I.
Published: September 2022

Introduction. Natural deep eutectic solvents (DESs) are promising extractants for many biologically active substances from plant raw materials. They are biodegradable, safe, stable, their production is affordable and easily feasible, and the extraction efficiency is comparable to known organic solvents. In this regard, interest in deep eutectic solvents has been steadily growing in recent years, and they are being used in various fields of chemistry, pharmaceuticals and the food industry.

Aim. The purpose of this work was to study the possibility of extracting flavonoids from plant raw materials using deep eutectic solvents, as well as to compare the efficiency of their extraction with traditional solvents.

Materials and methods. The extraction of flavonoids was carried out from the collection of a plant composition consisting of the herb of motherwort cordial (common motherwort) (Leonurus cardiaca L.), the herb of St. John's wort (Hypericum perforatum L.), the herb of lemon balm (Melissa officinalis L.) and the herb of creeping thyme (thyme) (Thymus serpyllum L.) in a ratio of 4 : 2.5 : 2.5 : 1, crushed to a particle size of 2–3 mm. 21 eutectic solvents based on betaine hydrochloride and choline bitartrate as hydrogen bond acceptors were used as extractants.

Results and discussion. The extracting ability of 21 experimental compositions of DESs was studied. The influence of the water content in the composition of DES, as well as the effect of temperature on the extraction process, has been studied. Quantitative determination of flavonoids in terms of rutin was carried out by differential spectrophotometry at a wavelength of 410 ± 2 nm. The maximum yield of flavonoids was achieved using a 40 % aqueous solution of DES based on betaine hydrochloride and propylene glycol in a molar ratio of 1 : 3 at 60 °C.

Conclusion. The recovery ability of the obtained DES is comparable in efficiency and even slightly exceeds that of the classic extractant for the investigated composition – 70 % ethyl alcohol. Further development and optimization of the process of using DESs is a promising direction for the development of chemistry and pharmaceutical technology.
Emicizumab in hemophilia A with inhibitors: clinical and economic impact of its use in a Cuban patient
Authors: Castillo-Gonzàles Dunia , Álvarez Sardiñas Irianys , Macías Abraham Consuelo , Muñoz Bedoya Alex G.
Published: September 2022

Introduction: The management of a patient with severe hemophilia A with inhibitors is a challenge for any healthcare professional. The present analysis shows the clinical and economic impact of the therapeutic approach in the most critical patient of the Cuban Hemophilia Cohort.
Objective: To evaluate the economic and clinical impact of the implementation of Emicizumab therapy in the first Cuban patient.
Case presentation: Adult patient who started to use recombinant activated factor VII episodically during adolescence when he was diagnosed with the presence of high-responding antibodies against factor VIII. During the years that he used this medication, he had recorded between 95 and 105 bleeds annually. In 2018, he presented with severe hemoperitoneum and was admitted to the intensive care unit with high doses of recombinant factor VII activated, multiple transfusions of packed red blood cells, and other care typical of a critically ill patient; his evolution was satisfactory. He started emicizumab prophylaxis 7 months after this event and is currently on Week 133 of treatment. He has not presented with further bleeding, nor has he reported adverse reactions to this treatment. The biannual cost savings for on-demand treatment and prophylaxis have been US $792,509.24.
Conclusions: Emicizumab prophylaxis improved the patient’s quality of life and that of his family. From the perspective of the Cuban health system, the use of emicizumab in this clinical case was satisfactory and its experience will be analyzed in new patients.
Avaliação da estabilidade de geleia de maracujá adicionada da farinha da casca do maracujá e inulina por meio de indicadores físicos, físico-químicos e microbiológicos
Authors: Garrido Ingrid Paloma Conrado , Morais Sinthya Kelly Queiroz , Coutinho Emily Bezerra , Oliveira Elizabeth Alves de , Gouveia Deyzi Santos , Vieira Patricia Pinheiro Fernandes , Mota Mércia Melo de Almeida , Martins Jorge Jacó Alves
Published: September 2022

Dentre as frutas produzidas no Brasil, o maracujá pode ser utilizado para preparação dos mais diversos produtos. A geleia, por exemplo, tem se tornado uma alternativa para a utilização de frutas por proporcionar o aumento da vida de prateleira e agregar valor ao produto, por meio da fruta completa ou de seus resíduos, quando possuírem valor tecnológico. A casca do maracujá é rica em pectina, fibras e carboidratos. A inulina é uma fibra solúvel, comumente extraída da chicória ou da alcachofra, que oferece vários benefícios nutricionais e tecnológicos. Com a crescente busca por alimentos com propriedades funcionais e a expressiva quantidade de resíduos gerados pelas indústrias, objetivou-se elaborar uma geleia de maracujá adicionada da farinha da sua casca e inulina e avaliar sua estabilidade. Os parâmetros físicos e físico-químicos analisados foram acidez titulável, pH, atividade de água, sólidos solúveis, teor de água, açúcares redutores e não-redutores e, quanto às análises microbiológicas, realizou-se a contagem de coliformes totais e termotolerantes, e de bolores e leveduras. Observou-se que todas as formulações se enquadraram nos padrões estabelecidos pela legislação para geleias de frutas, com exceção do pH, que somente a formulação F4 mostrou-se adequada. Concluindo-se que a geleia com 1% de farinha da casca de maracujá e 4% de inulina é a mais viável para uma produção em escala industrial.
Türkiye’deki Kamu Kurum ve Kuruluşlarında Belge Yönetimi Politikası Gerekliliği Üzerine Bir Çalışma
Authors: CENGİZ MATER Emine , ÖZDEMİR ŞAHİN Lale
Published: September 2022

Kamu kurum ve kuruluşları yasal olarak belgelerini arşive transfer edecekleri noktaya kadar olan süreçte yönetmek zorundadırlar. Etkili belge yönetimi, karar verme süreçlerinin ve kurumsal faaliyetlerin denetlenmesini ve gözden geçirilmesini sağlamakla birlikte kurumdaki bilgi yönetişim uygulamalarının da sağlam olmasını sağlar. Kamu sektörünün kararlarında şeffaf ve hesap verebilir olması gerektiğinden oldukça önemlidir ve karar alma süreçlerinde kullanılan bilgi varlıklarının yönetimi de aynı şekilde şeffaf ve hesap verebilir olmalıdır. Belge yönetimi, tüm çalışanların uygulamaları için kapsamlı bir belge yönetimi politikası ile desteklenmelidir. Bununla birlikte, Türkiye'de belge yönetimi politikalarının oluşturulması pek yaygın değildir. Bu çalışma, kurumsal belge yönetimi politikalarının gerekliliğini incelemekte ve uygulamanın sadece yasal uygunluğu sağlamak için değil, aynı zamanda kamu sektöründeki belge yönetimi profilini yükseltmek için de zorunlu olması gerektiğini savunmaktadır. Bu çalışmada betimleme, doküman incelemesi ve anket tekniği gibi araştırma yöntemleri kullanmıştır. Çalışmanın hipotezi, “Türkiye’deki kamu kurum ve kuruluşları belge yönetimi politikasına sahip olma bakımından yeterli/beklenilen düzeyde değildir” olarak belirlenmiştir. Çalışma kapsamında 120 kamu kurumunda anket çalışması gerçekleştirilmiştir. Çalışma sonucunda kamu kurumlarının çok büyük bir çoğunluğunun belge yönetimi politikalarının olmadığı ve yine çoğunluğunun belge yönetimi politikasına ihtiyaç duyduğu ortaya çıkmıştır.
Tarihsel Süreçte Bibliyoterapi ve Kütüphanelerin Bu Süreçteki Yeri
Authors: DEMİR Güler
Published: September 2022

Bu çalışmanın amacı, okumanın oldukça önemli bir yönüne işaret eden ve kökleri yüzyıllar öncesine dayanan bibliyoterapinin işlevlerine ilişkin farkındalığı geliştirmektir. Bu amaca koşut olarak, bibliyoterapinin kavramsal irdelemesi ile beraber tarihsel gelişimi ve bu süreçte kütüphaneler ile kütüphanecilerin rolü hakkında bilgiler verilmesi hedeflenmiştir. Çalışma kapsamında, öncelikle, bibliyoterapi kavramına ilişkin açıklamalar ile çeşitli bibliyoterapi türleri ve yaklaşımları tartışılmaktadır. Daha sonra, bibliyoterapinin hangi süreçleri/aşamaları içerdiği ve yararları ele alınarak bu çerçevede kütüphaneler ve kütüphanecilerin rolüne değinilmektedir. Çalışmada, tarihsel yönü ile “Birinci ve İkinci Dünya savaşı dönemlerinde sağaltım işlevi gören kütüphaneler” başlığına özel olarak yer verilmiştir çünkü savaş dönemleri bu konuda farkındalık ve çalışmaların en yoğun olduğu dönemlerdir. Kütüphanelerde bibliyoterapi kullanımına ilişkin dünyadan bir takım örnekler sunulmakta, Türkiye’de ise bu çerçevede yapılan sınırlı çalışmalara yer verilmektedir. Çalışma, elde edilen bilgilere dayanarak, gelecekteki uygulamalara ilişkin önerilerin de sunulduğu sonuç bölümü ile tamamlanmaktadır. Çalışmada, literatüre dayalı betimleme yöntemi uygulanmıştır. Çalışmadan elde edilen bulgular, köklü tarihsel geçmişine ve önemine karşın bibliyoterapinin hak ettiği yeri yeterince bulmadığını ve kütüphane bilimi ile uygulama alanında da konumunun muğlak kaldığını göstermektedir. Bibliyoterapinin arınma/katarsis etkisi ile pek çok sorun ve travmanın üstünden gelinmesi; kişilerde oluşturacağı özgüven ve daha güçlü kişilik yapısıyla olası sorunlara karşı mücadele edebilmeyi sağlaması gibi nedenlerle çok büyük öneme sahip olduğu ve bu bağlamda daha fazla çalışma ve uygulamalara gereksinim olduğu sonucuna varılmıştır. Özellikle kütüphane bilimine ilişkin yerli literatürde bu konunun sınırlı olarak ele alınmış olması nedeni ile bibliyoterapi kavramını tarihsel ve bütüncül bir perspektiften irdeleyen bu çalışmanın özgün yapıda olduğu düşünülmektedir.
Body growth assessment in children with IgE-mediated cow's milk protein allergy fed with a new amino acid-based formula
Authors: Nocerino Rita , Coppola Serena , Carucci Laura , Paparo Lorella , De Giovanni Di Santa Severina Anna Fiorenza , Berni Canani Roberto
Published: September 2022

Background

Amino acid-based formula (AAF) is a relevant dietary option for non-breastfed children. The present study was designed to evaluate the body growth pattern in cow's milk protein allergy (CMPA) children treated for 6 months with a new AAF.

Methods

This was an open-label, single arm study evaluating body growth pattern in immunoglobulin E (IgE)-mediated CMPA infants receiving a new AAF for 6 months. The outcomes were anthropometry (weight, length, head circumference), adherence to the study formula and occurrence of adverse events (AEs).

Results

Fifteen children [all Caucasian and born at term; 53.3% born with spontaneous delivery; 80% male; 80% with familial allergy risk; mean age (±SD) 3 ± 2.5 months at IgE-mediated CMPA diagnosis; mean age (±SD) 16.7 ± 5.9 months at enrolment, mean total serum IgE (±SD) 298.2 ± 200.4 kU/L] were included and completed the 6-month study. Data from fifteen age- and sex-matched healthy controls were also adopted as comparison. At baseline, all CMPA patients were weaned and were receiving the new AAF. All 15 patients completed the 6-month study period. For the entire CMPA pediatric patients’ cohort, from baseline to the end of the study period, the body growth pattern resulted within the normal range of World Health Organization (WHO) growth references and resulted similar to healthy controls anthropometric values. The formula was well tolerated. The adherence was optimal and no AEs related to AAF use were reported.

Conclusions

The new AAF ensured normal growth in subjects affected by IgE-mediated CMPA. This formula constitutes another suitable safe option for the management of pediatric patients affected by CMPA.
Application of three-dimensional-printed porous tantalum cones in total knee arthroplasty revision to reconstruct bone defects
Authors: Ao Yunong , Guo Lin , Chen Hao , He Rui , Yang Pengfei , Fu Dejie , Gu Lingchuan , Peng Yang , Xiong Ran , Yang Liu , Wang Fuyou
Published: September 2022

Purpose: Three-dimensional (3D) printing technology has emerged as a new treatment method due to its precision and personalization. This study aims to explore the application of a 3D-printed personalized porous tantalum cone for reconstructing the bone defect in total knee arthroplasty (TKA) revision.

Methods: Between November 2017 and October 2020, six patients underwent bone reconstruction using 3D-printed porous tantalum cones in TKA revision. The knee function was assessed using the Hospital for Special Surgery (HSS) score pre- and postoperatively. The pain was measured by the visual analog scale (VAS) pre- and postoperatively. The quality of life was measured using the 36-Item Short Form Health Survey (SF-36) to pre- and postoperatively evaluate the relief of pain. Operation time, intraoperative blood loss, postoperative drainage volume, and complications were also recorded. At the last follow-up, all patients received X-ray and computed tomography (CT) to confirm the effect of bone reconstruction.

Results: After an average follow-up duration of 26.3 months, no patients developed any operation-related complications. The average intraoperative blood loss and postoperative drainage volumes were 250.1 ± 76.4 ml and 506.7 ± 300.8 ml, respectively. At the last follow-up, the HSS score was significantly higher than that before operation, indicating that the knee function was significantly improved (p < 0.001). During the follow-up, the mean VAS score decreased and the mean SF-36 score increased, both of which were significantly improved compared with preoperative conditions (p < 0.001). Radiological examination at the final follow-up showed that cones implanted into the joint were stable and bone defects were effectively reconstructed.

Conclusion: This study demonstrated that 3D-printed porous tantalum cones could effectively reconstruct bone defects and offer anatomical support in TKA revision. Further studies are still needed to confirm the long-term effect of 3D-printed tantalum cones for reconstructing bone defects.
Non-destructive characterization of bone mineral content by machine learning-assisted electrochemical impedance spectroscopy
Authors: Banerjee Aihik , Tai Youyi , Myung Nosang V. , Nam Jin
Published: September 2022

Continuous quantitative monitoring of the change in mineral content during the bone healing process is crucial for efficient clinical treatment. Current radiography-based modalities, however, pose various technological, medical, and economical challenges such as low sensitivity, radiation exposure risk, and high cost/instrument accessibility. In this regard, an analytical approach utilizing electrochemical impedance spectroscopy (EIS) assisted by machine learning algorithms is developed to quantitatively characterize the physico-electrochemical properties of the bone, in response to the changes in the bone mineral contents. The system is designed and validated following the process of impedance data measurement, equivalent circuit model designing, machine learning algorithm optimization, and data training and testing. Overall, the systematic machine learning-based classification utilizing the combination of EIS measurements and electrical circuit modeling offers a means to accurately monitor the status of the bone healing process.
Identifying transdiagnostic biological subtypes across schizophrenia, bipolar disorder, and major depressive disorder based on lipidomics profiles
Authors: Tao Shiwan , Zhang Yamin , Wang Qiang , Qiao Chunxia , Deng Wei , Liang Sugai , Wei Jinxue , Wei Wei , Yu Hua , Li Xiaojing , Li Mingli , Guo Wanjun , Ma Xiaohong , Zhao Liansheng , Li Tao
Published: September 2022

Emerging evidence has demonstrated overlapping biological abnormalities underlying schizophrenia (SCZ), bipolar disorder (BP), and major depressive disorder (MDD); these overlapping abnormalities help explain the high heterogeneity and the similarity of patients within and among diagnostic categories. This study aimed to identify transdiagnostic subtypes of these psychiatric disorders based on lipidomics abnormalities. We performed discriminant analysis to identify lipids that classified patients (N = 349, 112 with SCZ, 132 with BP, and 105 with MDD) and healthy controls (N = 198). Ten lipids that mainly regulate energy metabolism, inflammation, oxidative stress, and fatty acylation of proteins were identified. We found two subtypes (named Cluster 1 and Cluster 2 subtypes) across patients with SCZ, BP, and MDD by consensus clustering analysis based on the above 10 lipids. The distribution of clinical diagnosis, functional impairment measured by Global Assessment of Functioning (GAF) scales, and brain white matter abnormalities measured by fractional anisotropy (FA) and radial diffusivity (RD) differed in the two subtypes. Patients within the Cluster 2 subtype were mainly SCZ and BP patients and featured significantly elevated RD along the genu of corpus callosum (GCC) region and lower GAF scores than patients within the Cluster 1 subtype. The SCZ and BP patients within the Cluster 2 subtype shared similar biological patterns; that is, these patients had comparable brain white matter abnormalities and functional impairment, which is consistent with previous studies. Our findings indicate that peripheral lipid abnormalities might help identify homogeneous transdiagnostic subtypes across psychiatric disorders.
Eomes function is conserved between zebrafish and mouse and controls left-right organiser progenitor gene expression via interlocking feedforward loops
Authors: Talbot Conor D. , Walsh Mark D. , Cutty Stephen J. , Elsayed Randa , Vlachaki Eirini , Bruce Ashley E. E. , Wardle Fiona C. , Nelson Andrew C.
Published: September 2022

The T-box family transcription factor Eomesodermin (Eomes) is present in all vertebrates, with many key roles in the developing mammalian embryo and immune system. Homozygous Eomes mutant mouse embryos exhibit early lethality due to defects in both the embryonic mesendoderm and the extraembryonic trophoblast cell lineage. In contrast, zebrafish lacking the predominant Eomes homologue A (Eomesa) do not suffer complete lethality and can be maintained. This suggests fundamental differences in either the molecular function of Eomes orthologues or the molecular configuration of processes in which they participate. To explore these hypotheses we initially analysed the expression of distinct Eomes isoforms in various mouse cell types. Next we compared the functional capabilities of these murine isoforms to zebrafish Eomesa. These experiments provided no evidence for functional divergence. Next we examined the functions of zebrafish Eomesa and other T-box family members expressed in early development, as well as its paralogue Eomesb. Though Eomes is a member of the Tbr1 subfamily we found evidence for functional redundancy with the Tbx6 subfamily member Tbx16, known to be absent from eutherians. However, Tbx16 does not appear to synergise with Eomesa cofactors Mixl1 and Gata5. Finally, we analysed the ability of Eomesa and other T-box factors to induce zebrafish left-right organiser progenitors (known as dorsal forerunner cells) known to be positively regulated by vgll4l, a gene we had previously shown to be repressed by Eomesa. Here we demonstrate that Eomesa indirectly upregulates vgll4l expression via interlocking feedforward loops, suggesting a role in establishment of left-right asymmetry. Conversely, other T-box factors could not similarly induce left-right organiser progenitors. Overall these findings demonstrate conservation of Eomes molecular function and participation in similar processes, but differential requirements across evolution due to additional co-expressed T-box factors in teleosts, albeit with markedly different molecular capabilities. Our analyses also provide insights into the role of Eomesa in left-right organiser formation in zebrafish.
Nestin-GFP transgene labels immunoprivileged bone marrow mesenchymal stem cells in the model of ectopic foci formation
Authors: Karpenko Dmitriy , Kapranov Nikolay , Bigildeev Aleksei
Published: September 2022

Immune privileges are demonstrated for different types of quiescent stem cells of adult mammalian organisms. Mesenchymal stem cells (MSCs) are believed to have immune privileges; however, an accurate experimental confirmation hasn’t been presented. Here, we provide direct experimental evidence that MSCs of C57Black/6J murine bone marrow (BM) are immune privileged in vivo and retain their functionality after prolonged exposure to the uncompromised immune system. The BM of Nes-Gfp transgenic mice was implanted as a tissue fragment under the kidney capsule in isogenic C57Black/6J immunocompetent recipients. Nestin-Gfp strain provides a fluorescent immunogenic marker for a small fraction of BM cells, including GFP+CD45– MSCs. Despite the exposure of xenogenically marked MSCs to the fully-functional immune system, primary ectopic foci of hematopoiesis formed. Six weeks after implantation, multicolor fluorescence cytometry revealed both GFP+CD45– and GFP+CD45+ cells within the foci. GFP+CD45– cells proportion was 2.0 × 10–5 ×÷9 and it didn’t differ significantly from syngenic Nes-GFP transplantation control. According to current knowledge, the immune system of the recipients should eliminate GFP+ cells, including GFP+ MSCs. These results show that MSCs evade immunity. Primary foci were retransplanted into secondary Nes-GFP recipients. The secondary foci formed, in which CD45–GFP+ cells proportion was 6.7 × 10–5 ×÷2.2, and it didn’t differ from intact Nes-GFP BM. The results demonstrate that MSCs preserve self-renewal and retain their functionality after prolonged immune exposure. The success of this study relied on the implantation of BM fragments without prior dissociation of cells and the fact that the vast majority of implanted cells were immunologically equivalent to the recipients.
Research on nano H2/O2 bubble generating mechanism and characteristics
Authors: Kuo Chia-Lung , Chen Chin-Ta , Ho Chao-Ching
Published: September 2022

In this research, electrolysis water is used to produce hydrogen and oxygen for carrying out the vertical cutting through high-speed water in order that the bubbles will be refined for generating the nano H2/O2 bubble liquid. In the meantime, a Nanobubble Generator is developed to verify the basic characteristics of the produced nano H2/O2 bubbles. Its purpose is to identify the maximum concentration of bubbles in the nano H2/O2 bubble liquid, the bubble production efficiency and bubble electrification characteristics as well as the effect of reducing the pipe flow friction resistance together with the characteristics of nanobubbles containing varied gases. By verifying the nano H2/O2 bubbles, it is hoped that the flowing rate of the hollow electrode can be elevated.
Recent advances and future prospective of topical and transdermal delivery systems
Authors: Tapfumaneyi Pronalis , Imran Mohammad , Mohammed Yousuf , Roberts Michael S.
Published: September 2022

Recent advances in topical and transdermal drug delivery systems have enabled targeted delivery of therapeutics to the site of action by enhancing drug permeation across the stratum corneum and increased bioavailability. Despite various technological advancements, some dermatoses still have limited treatment options due to potential adverse effects and challenges in formulation development. To address some of the limitations posed by conventional dermatotherapy, nano-based technologies have been developed and have demonstrated a significant improvement in dermatotherapy. Their distinct physicochemical properties demonstrate their overall superior therapeutic efficacy in providing sustained and effective targeted drug release, as well as improved solubility of hydrophobic actives with optimized drug formulations. These nanocarriers are commonly classified as polymeric, lipid-based, metallic, and vesicular nanocarriers, including nanoemulsions, nanofibers, and microneedles. This mini-review aims to address recent advances in nano-based technologies, providing a brief insight on some of the current and prospective technologies and approaches aimed at improving transdermal delivery.
From compute to care: Lessons learned from deploying an early warning system into clinical practice
Authors: Pou-Prom Chloé , Murray Joshua , Kuzulugil Sebnem , Mamdani Muhammad , Verma Amol A.
Published: September 2022

Background

Deploying safe and effective machine learning models is essential to realize the promise of artificial intelligence for improved healthcare. Yet, there remains a large gap between the number of high-performing ML models trained on healthcare data and the actual deployment of these models. Here, we describe the deployment of CHARTwatch, an artificial intelligence-based early warning system designed to predict patient risk of clinical deterioration.

Methods

We describe the end-to-end infrastructure that was developed to deploy CHARTwatch and outline the process from data extraction to communicating patient risk scores in real-time to physicians and nurses. We then describe the various challenges that were faced in deployment, including technical issues (e.g., unstable database connections), process-related challenges (e.g., changes in how a critical lab is measured), and challenges related to deploying a clinical system in the middle of a pandemic. We report various measures to quantify the success of the deployment: model performance, adherence to workflows, and infrastructure uptime/downtime. Ultimately, success is driven by end-user adoption and impact on relevant clinical outcomes. We assess our deployment process by evaluating how closely we followed existing guidance for good machine learning practice (GMLP) and identify gaps that are not addressed in this guidance.

Results

The model demonstrated strong and consistent performance in real-time in the first 19 months after deployment (AUC 0.76) as in the silent deployment heldout test data (AUC 0.79). The infrastructure remained online for >99% of time in the first year of deployment. Our deployment adhered to all 10 aspects of GMLP guiding principles. Several steps were crucial for deployment but are not mentioned or are missing details in the GMLP principles, including the need for a silent testing period, the creation of robust downtime protocols, and the importance of end-user engagement. Evaluation for impacts on clinical outcomes and adherence to clinical protocols is underway.

Conclusion

We deployed an artificial intelligence-based early warning system to predict clinical deterioration in hospital. Careful attention to data infrastructure, identifying problems in a silent testing period, close monitoring during deployment, and strong engagement with end-users were critical for successful deployment.
Geochemical characteristics of geothermal and hot spring gases in Beijing and Zhangjiakou Bohai fault zone
Authors: Yang Mingbo , Liu Guiping , Liu Zhe , Ma Jingchen , Li Liwu , Wang Zhiguo , Hua Peixue , Xing Lantian , Sun Xiaoru , Han Kongyan , Cui Bowen , Wu Xiaodong
Published: September 2022

The Beijing and Zhangjiakou-Bohai Fault Zone is a group of NW-W orderly active fault zones with high seismic activity and abundant geothermal resources since the Cenozoic. Many violent earthquakes occurred here, where it was an important area for earthquake monitoring and research. In order to explore the temporal and spatial variation characteristics of gas geochemistry in the Zhangjiakou-Bohai Fault Zone of the capital circle, this study cited the previous two-stage survey data of 23 geothermal hot springs in the west and east of the Zhangjiakou-Bohai Fault Zone of the capital circle in 2013 and 2018. In order to fill the gap in hot spring gas geochemistry in Beijing (the middle of the Zhangjiakou-Bohai Fault Zone), 21 emergent gas samples from hot springs were collected after many field surveys from October 2020 to November 2021. The test results of 44 gas samples with chemical compositions and isotope changes of helium, neon, and carbon showed that: (1) The helium isotope ratio (3He/4He (Rc/Ra)) of hot spring gases in the Zhangjiakou-Bohai Fault Zone ranged between 0.03 and 2.86Ra (Ra = air, 3He/4He = 1.39 × 10−6), and the calculated maximum proportion of mantle-derived helium was up to 35.4%. It was revealed that although the geological fluid in the fault zone mainly came from crustal source, the mantle-derived helium was still considerable. The hot spring gases in Beijing (the middle of the Zhangjiakou-Bohai Fault Zone) were mainly composed of nitrogen, whose concentration was more than 69%, featuring a low CO2 concentration of 0–6.1% and a δ13CCO2 value ranging from −19‰ to −9.6‰ (vs.PDB) and showing the mixing characteristics of organic sediments and mantle sources. (2) The upwelling release of mantle-derived materials in Zhangjiakou-Bohai Fault Zone shared a good corresponding relationship with regional seismicity, which could promote the inoculation and occurrence of regional earthquakes. In the peak area, the transition zone from the western mountainous area of the Zhangjiakou-Bohai Fault Zone to the plain showed that more mantle-derived materials upwelled, and more deep fluid upwelled. The comparative analysis of regional seismicity showed that deep fluid played an important role in controlling regional seismicity in the area with relatively strong upwelling of deep fluid in the Zhangjiakou-Bohai Fault Zone.
Study on the propagation probability characteristics and prediction model of meteorological drought to hydrological drought in basin based on copula function
Authors: Wang Huiliang , Zhu Yujia , Qin Tianling , Zhang Xiangyang
Published: September 2022

Studying the probability characteristics of meteorological drought transmission to hydrological drought can help alleviate drought and optimize the allocation of water resources. This study takes the Yiluo River as the research object, and Standardized Precipitation Index (SPI) and Standardized Streamflow Index (SSI) were used to represent meteorological and hydrological drought, respectively. First, the stability of the precipitation and stream flow sequence is tested by using the heuristic segmentation algorithm. The correlation between meteorological and hydrological watershed was analyzed using cross wavelet transform and lag correlation to study the transmission time of meteorological drought to hydrological drought. Second, the characteristics of drought such as drought duration, drought intensity, and drought intensity are discussed by using the run theory. Finally, the joint distribution of the SPI and SSI sequence is constructed using Copula function. From the perspective of conditional probability, the propagation probability and propagation threshold from different levels of meteorological drought to hydrological drought are calculated. A hydrological drought prediction model based on the SPI—P(SSI|SPI) relation curve is proposed. The model is also validated based on the historical data. The results show that the model is suitable for light and middle hydrological drought prediction.
Renal oncometabolite L-2-hydroxyglutarate imposes a block in kidney tubulogenesis: Evidence for an epigenetic basis for the L-2HG-induced impairment of differentiation
Authors: Taub Mary , Mahmoudzadeh Nader H. , Tennessen Jason M. , Sudarshan Sunil
Published: September 2022

2-Hydroxyglutarate (2HG) overproducing tumors arise in a number of tissues, including the kidney. The tumorigenesis resulting from overproduced 2HG has been attributed to the ability of 2HG alter gene expression by inhibiting α-ketoglutarate (αKG)-dependent dioxygenases, including Ten-eleven-Translocation (TET) enzymes. Genes that regulate cellular differentiation are reportedly repressed, blocking differentiation of mesenchymal cells into myocytes, and adipocytes. In this report, the expression of the enzyme responsible for L2HG degradation, L-2HG dehydrogenase (L2HGDH), is knocked down, using lentiviral shRNA, as well as siRNA, in primary cultures of normal Renal Proximal Tubule (RPT) cells. The knockdown (KD) results in increased L-2HG levels, decreased demethylation of 5mC in genomic DNA, and increased methylation of H3 Histones. Consequences include reduced tubulogenesis by RPT cells in matrigel, and reduced expression of molecular markers of differentiation, including membrane transporters as well as HNF1α and HNF1β, which regulate their transcription. These results are consistent with the hypothesis that oncometabolite 2HG blocks RPT differentiation by altering the methylation status of chromatin in a manner that impedes the transcriptional events required for normal differentiation. Presumably, similar alterations are responsible for promoting the expansion of renal cancer stem-cells, increasing their propensity for malignant transformation.
Serum Metrnl levels are decreased in subjects with overweight or obesity and are independently associated with adverse lipid profile
Authors: Ding Xiaoyu , Chang Xiaona , Wang Jiaxuan , Bian Nannan , An Yu , Wang Guang , Liu Jia
Published: September 2022

Background

Meteorin-like (Metrnl), a novel adipokine, is highly expressed in adipose tissue and has a beneficial effect on energy metabolism. However, data on circulating Metrnl levels in obesity are scarce and inconsistent. This study aimed to evaluate the serum levels of Metrnl in adults with obesity and its association with glucose and lipid metabolism.

Methods

182 subjects were included in the cross-sectional study. The participants were divided into three groups according to BMI: normal (n = 95), overweight (n = 46), and obesity (n = 41). Serum Metrnl concentrations were measured by enzyme-linked immunosorbent assay.

Results

Serum Metrnl levels in overweight or obese subjects were significantly lower than in the normal group. Circulating Metrnl levels were negatively correlated with TG, TC, LDL-C, and sdLDL and positively correlated with HDL-C before and after adjusting for age, sex, BMI, diabetes, HOMA-IR, and eGFR (all P < 0.05). Furthermore, logistic regression analysis indicated that compared with the highest tertile, the lowest tertile of Metrnl levels were significantly associated with the presence of hyper-TG, hyper-TC, and Hyper-LDL after full adjustment (all P for trend < 0.05).

Conclusions

Serum Metrnl levels were reduced in individuals with overweight or obesity and were independently associated with adverse lipid profile, suggesting that modifying circulating Metrnl levels may serve as a potential therapeutic target for atherogenic dyslipidemia.