bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aerosolizable Lipid-Nanovesicles Encapsulating Voriconazole Effectively Permeate Pulmonary Barriers and Target Lung Cells
Authors: Kaur Ranjot , Dennison Sarah R , Rudramurthy Shivaprakash M , Katare O P , Sharma Teenu , Singh Bhupinder , Singh Kamalinder K 
Published: March 2022

The entire world has recently been witnessing an unprecedented upsurge in microbial lung infections. The major challenge encountered in treating the same is to ensure the optimum drug availability at the infected site. Aerosolization of antimicrobials, in this regard, has shown immense potential owing to their localized and targeted effect. Efforts, therefore, have been undertaken to systematically develop lung-phosphatidylcholine-based lipid nanovesicles of voriconazole for potential management of the superinfections like aspergillosis. LNVs, prepared by thin-film hydration method, exhibited a globule size of 145.4 ± 19.5 nm, polydispersity index of 0.154 ± 0.104 and entrapment efficiency of 71.4 ± 2.2% with improved in vitro antifungal activity. Aerodynamic studies revealed a microdroplet size of ≤5 μm, thereby unraveling its promise to target the physical barrier of lungs effectively. The surface-active potential of LNVs, demonstrated through Langmuir-Blodgett troughs, indicated their ability to overcome the biochemical pulmonary surfactant monolayer barrier, while the safety and uptake studies on airway-epithelial cells signified their immense potential to permeate the cellular barrier of lungs. The pharmacokinetic studies showed marked improvement in the retention profile of voriconazole in lungs following LNVs nebulization compared to pristine voriconazole. Overall, LNVs proved to be safe and effective delivery systems, delineating their distinct potential to efficiently target the respiratory fungal infections.
Riboflavin for COVID-19 Adjuvant Treatment in Patients With Mental Health Disorders: Observational Study
Authors: Akasov R. A. , Khaydukov E. V. , Andreyuk D. S. , Sholina N. V. , Sheremeta A. N. , Romanov D. V. , Kostyuk G. P. , Panchenko V. Ya. , Kovalchuk M. V. 
Published: March 2022

Background: COVID-19 treatment remains a challenge for medicine because of the extremely short time for clinical studies of drug candidates, so the drug repurposing strategy, which implies the use of well-known and safe substances, is a promising approach.Objective: We present the results of an observational clinical study that focused on the influence of riboflavin (vitamin B2) supplementation on the immune markers of COVID-19 severity in patients with mental health disorders.Results: We have found that 10 mg of flavin mononucleotide (a soluble form of riboflavin) intramuscularly twice a day within 7 days correlated with the normalization of clinically relevant immune markers (neutrophils and lymphocytes counts, as well as their ratio) in COVID-19 patients. Additionally, we demonstrated that total leucocytes, neutrophils, and lymphocytes counts, as well as the neutrophils to leucocytes ratio (NLR), correlated with the severity of the disease. We also found that patients with organic disorders (F0 in ICD-10) demonstrated higher inflammation then patients with schizophrenia (F2 in ICD-10).Conclusion: We suggest that riboflavin supplementation could be promising for decreasing inflammation in COVID-19, and further evaluation is required.This observational clinical trial has been registered by the Sverzhevsky Research Institute of Clinical Otorhinolaryngology (Moscow, Russia), Protocol No. 4 dated 05/27/2020.
The Influence of CYP3A4 Genetic Polymorphism and Proton Pump Inhibitors on Osimertinib Metabolism
Authors: Gao Nanyong , Zhang Xiaodan , Hu Xiaoqin , Kong Qihui , Cai Jianping , Hu Guoxin , Qian Jianchang 
Published: March 2022

The aim of this study was to 1) investigate the effects of 27 CYP3A4 variants on the metabolism of osimertinib and 2) study the interactions between osimertinib and others as well as the underlying mechanism. A recombinant human CYP3A4 enzymatic incubation system was developed and employed to determine the kinetic profile of CYP3A4 variants. Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was applied to detect the concentration of the main metabolite, AZ5104. The results demonstrated that the relative clearance rates of CYP3A4.19, 10, 18, 5, 16, 14, 11, 2, 13, 12, 7, 8, and 17 in catalyzing osimertinib were significantly reduced to a minimum of 25.68% compared to CYP3A4.1, while those of CYP3A4.29, 32, 33, 28, 15, 34, and 3 were obviously enhanced, ranging from 114.14% to 284.52%. The activities of the remaining variants were almost equal to those of CYP3A4.1. In addition, 114 drugs were screened to determine the potential interaction with osimertinib based on the rat liver microsome (RLM) reaction system. Sixteen of them inhibited the production of AZ5104 to 20% or less, especially proton pump inhibitors, among which the IC50 of rabeprazole was 6.49 ± 1.17 μM in RLM and 20.39 ± 2.32 μM in human liver microsome (HLM), with both following competitive and non-competitive mixed mechanism. In an in vivo study, Sprague–Dawley (SD) rats were randomly divided into groups, with six animals per group, receiving osimertinib with or without rabeprazole, omeprazole, and lansoprazole. We found that the AUC(0–t), AUC(0–∞), and Cmax of osimertinib decreased significantly after co-administration with rabeprazole orally, but they increased remarkably when osimertinib was administered through intraperitoneal injection. Taken together, our data demonstrate that the genetic polymorphism and proton pump inhibitors remarkably influence the disposition of osimertinib, thereby providing basic data for the precise application of osimertinib.
Oral Lisinopril Raises Tissue Levels of ACE2, the SARS-CoV-2 Receptor, in Healthy Male and Female Mice
Authors: Brooks Steven D. , Smith Rachel L. , Moreira Aline S. , Ackerman Hans C. 
Published: March 2022

Angiotensin-converting enzyme 2 (ACE2) is the established cellular receptor for SARS-CoV-2. However, it is unclear whether ACE1 inhibitors (e.g., lisinopril) or angiotensin receptor blockers (e.g., losartan) alter tissue ACE2 expression. This study sought to determine whether lisinopril or losartan, as monotherapies or in combination, changes tissue levels of ACE2 in healthy male and female mice. Mice received lisinopril (10 mg/kg/day), losartan (10 mg/kg/day), or both for 21 days via drinking water. A control group received water without drug. The ACE2 protein index (ACE2 protein/total protein) was determined on the small intestine, lung, kidney, and brain. Oral lisinopril increased the ACE2 protein index across all tissues (p &lt; 0.0001 vs. control). In contrast, the combination of lisinopril plus losartan did not increase ACE2 levels in any tissue (p = 0.89 vs. control) and even decreased tissue expression of the Ace2 gene (p &lt; 0.001 vs. control). Tissue ACE2 remained elevated in the mice 21 days after cessation of lisinopril (p = 0.02). Plasma ACE2 did not correlate with the ACE2 protein index in any tissue. A sex difference was observed: kidney ACE2 levels were higher in male than in female mice (p &lt; 0.0001). Oral lisinopril increases ACE2, the cellular receptor for SARS-CoV-2, in tissues that are relevant to the transmission and pathogenesis of COVID-19. Remarkably, the addition of losartan prevented lisinopril-induced increases in ACE2 across tissues. These results suggest that ACE inhibitors and angiotensin receptor blockers interact to determine tissue levels of ACE2.
Utility of Lymphocyte Transformation Test for Assisting Updated Roussel Uclaf Causality Assessment Method in Drug-Induced Liver Injury: A Case-Control Study
Authors: Rodríguez Amelia , García-García Irene , Martínez de Soto Lucía , Gómez López De Las Huertas Arturo , Borobia Alberto M. , González-Torbay Andrea , Akatbach-Bousaid Ibtissam , González-Muñoz Miguel , Ramírez Elena 
Published: March 2022

Background: The Roussel Uclaf Causality Assessment Method (RUCAM) is a validated tool for assessing causality in cases of suspected drug-induced liver injury (DILI). However, RUCAM cannot discriminate between concomitant hepatotoxic drugs with the same temporal sequence.Objective: To analyse the utility of the lymphocyte transformation test (LTT) for assisting updated RUCAM in 45 patients and 40 controls with a clinical diagnosis of DILI.Methods: Suspected DILI cases were detected through the Prospective Pharmacovigilance Program from Laboratory Signals in Hospital (PPLSH) or by consultations. The controls completed the drug therapy with no adverse reactions during the study period. A receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut-off value for the stimulation index (SI), corresponding to the largest sum for the specificity and sensitivity values of LTT for true DILI cases.Results: Out of 45 patients diagnosed with DILI, 42 cases were detected by the PPLSH, two cases by consultation and one case by both methods. Most DILI cases (64.4%) arose during hospitalization. According to the biochemical parameters, 24 cases (53.3%) had the hepatocellular phenotype, 14 (31.1%) had the cholestatic phenotype, and 7 cases (15.6%) had the mixed phenotype. Considering the severity criteria, 7 (15.5%) cases were classified as moderate DILI, and 4 (8.9%) were severe DILI; there were no fatal cases. A total of 149 drugs (median/case, 3; IQR, 2–5) were suspected to be involved in the DILI cases (RUCAM score ≥3). In 8 cases, only one drug was suspected, and polypharmacy (≥5 drugs) was identified in 29% of the cases. Of all DILI cases, 46 (30.9%) of the 149 suspected drugs produced positive LTT results, and the LTT was positive in 34 (75.5%) of the 45 patients. No exposed controls produced positive LTT results. The optimal cut-off of 1.95 for the SI was obtained with a sensitivity of 77% and specificity of 100% (area under the curve, 0.91; 95% asymptotic confidence interval 0.84–0.97; p &lt; 0.001). The sensitivity of the hepatocellular phenotype was 92%.Conclusion: Our results demonstrate that LTT is an add on strengthening causality in cases of suspected idiosyncratic DILI, especially for patients with several suspected drugs and a hepatocellular phenotype.
Compound Cavity Passively Q-Switched Single-Longitudinal-Mode Diode-Pumped Laser
Authors: Chen Bin , Bai Zhenxu , Zhao Guijuan , Zhang Yu , Yan Bingzheng , Qi Yaoyao , Ding Jie , Wang Kun , Wang Yulei , Lu Zhiwei 
Published: March 2022

A compact solid-state single-longitudinal-mode (SLM) Q-switched laser based on a compound cavity is demonstrated. SLM operation is achieved through the enhancement of mode competition (via manipulation of the effective reflectivity of the resonator mirrors and intracavity field accumulation time) and does not require the use of a feedback loop. In this work, SLM emission with a linewidth of 254.3 MHz is demonstrated, and a high SLM ratio of up to 99.6% is achieved. The laser operates at a repetition rate of 10 Hz, producing 10 ns pulses with a pulse energy of 14.81 mJ.
Evaluating the Methodological Quality of Postexercise Hypotension Aerobic Exercise Interventions
Authors: Day Christina , Wu Yin , Pescatello Linda S. 
Published: March 2022

BackgroundPostexercise hypotension (PEH) is the immediate reduction in blood pressure (BP) of 5–8 mmHg that occurs after a single bout of aerobic exercise among adults with hypertension. Across PEH studies, there are variations in the level of rigor of the study designs and methods that limit the conclusions that can be made about PEH.ObjectiveTo develop and then apply a methodological study quality evaluation checklist to aerobic exercise PEH studies to provide methodological guidance.MethodsWe developed a PEH checklist (PEH√list) based upon contemporary methodological study quality standards. The PEH√list contains 38 items divided into three categories: sample (n = 10 items), study (n = 23 items), and intervention characteristics (n = 5 items). We then systematically searched six databases to January 2019 to identify and then evaluate studies that: (1) enrolled adults ≥18 years with hypertension and without other chronic diseases or conditions; (2) included a bout of aerobic exercise and a non-exercise control session; and (3) were published in English.ResultsOf 17,149 potential studies, 64 qualified. Participants (N = 1,489) were middle-aged (38.6 ± 15.6 year), overweight (26.1 ± 2.5 kg/m2) mostly men (64.4%) with elevated BP (systolic BP 129.5 ± 15.2/diastolic BP 81.0 ± 10.1 mmHg). Overall, the qualifying studies satisfactorily reported 53.9 ± 13.3% (24.2–82.8%) of the relevant items on the PEH√list. Of note, only 20.3% of the studies disclosed BP was measured following professional guidelines, 18.8% reported BP was taken by the same assessor pre- and post-intervention, and 35.5% stated participants abstained from caffeine, alcohol, and physical activity prior to testing. Half (51.5%) indicated they statistically controlled for pre-exercise/baseline BP. Meanwhile, 100% of the studies reported the setting in which the BP measurements were taken, time from the end of the exercise to the start of the BP measurements, and if relevant, the length of the ambulatory BP monitoring period.ConclusionOverall, the PEH√list items were not well satisfied; especially items with potential confounding effects on PEH. We contend the PEH√list provides guidance to investigators on the important methodological study considerations in PEH aerobic exercise studies that should be attended to in the future.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [#CRD42020221996].
Towards an Integrated Healthcare System: Evolutionary Game Analysis on Competition and Cooperation Between Urban and Rural Medical Institutions in China
Authors: Xu Xinglong , Liu Jiajie , Ampon-Wireko Sabina , Asante Antwi Henry , Zhou Lulin 
Published: March 2022

BackgroundThe game of interest is the root cause of the non-cooperative competition between urban and rural medical and health institutions. The study investigates competition and cooperation among urban and rural medical institutions using the evolutionary game analysis.MethodsWith the evolutionary game model, analysis of the stable evolutionary strategies between the urban and rural medical and health facilities is carried out. A numerical simulation is performed to demonstrate the influence of various values.ResultsThe result shows that the cooperation mechanism between urban and rural medical Institutions is relevant to the efficiency of rural medical institutions, government supervision, reward, and punishment mechanism.ConclusionsSuggestions for utilizing the government's macro regulation and control capabilities, resolving conflicts of interest between urban and rural medical and health institutions is recommended. In addition, the study again advocates mobilizing the internal power of medical institutions' cooperation to promote collaboration between urban and rural medical and health institutions.
ỨNG DỤNG GIẢI THUẬT TÌM KIẾM TỐI ƯU DỰA THEO CHUYỂN ĐỘNG ION CHO BÀI TOÁN TÌM KIẾM THAM SỐ TỐI ƯU CỦA BỘ ĐIỀU KHIỂN MỜ
Authors: Thương Dương Mai , Thu Đào Thị , Tuyển Nguyễn Thị 
Published: March 2022

Trong thực tế, chúng ta thường sử dụng bộ điều khiển PI để ổn định tốc độ động cơ điện một chiều với chất lượng điều khiển ở mức chấp nhận được. Khi cần nâng cao hơn nữa chất lượng điều khiển và đáp ứng với các tốc độ đặt khác nhau, bộ điều khiển mờ là một sự lựa chọn phù hợp. Tuy nhiên, việc thiết kế bộ điều khiển mờ thường gặp khó khăn do việc xác định các tham số của bộ điều khiển này phụ thuộc rất nhiều vào kinh nghiệm của người thiết kế. Trong bài báo này, các tác giả trình bày cách thức áp dụng giải thuật tìm kiếm tối ưu dựa trên chuyển động ion để tự động tìm kiếm tham số tối ưu của bộ điều khiển mờ cho bài toán ổn định tốc độ động cơ một chiều. Các kết quả đạt được thông qua mô phỏng và thực nghiệm cho thấy, bộ điều khiển mờ với các tham số được xác định bởi giải thuật IMO có chất lượng hoạt động rất tốt với thời gian xác lập nhanh (1.42378 s), độ quá điều chỉnh thấp (0.51%) và thích ứng nhanh khi các tốc độ đặt của động cơ thay đổi liên tục.
Infection COVID-19 and Recipients of Renal Graft:Options of Correction Immunosuppression and Treatment
Authors: Комиссаров К.С. , Чеботарева Т.К. , Калачик О.В. 
Published: March 2022

В настоящее время отсутствует специфическое лечение инфекции COVID-19, в связи с этим большинство нефрологических обществ считает, что реципиенты с почечным трансплантатом с легкой и средней степенью тяжести течения COVID-19 должны продолжать получать ингибиторы кальциневрина (ИК) и предписанную дозу глюкокортикоидов, но прием антипролиферативных препаратов следует прекратить. В случае тяжелого течения подтвержденного COVID-19, требующего госпитализации в отделение интенсивной терапии и искусственной вентиляции легких, следует немедленно отменить ИК и антипролиферативные препараты, а дозы глюкокортикоидов следует увеличить до 16–20 мг/сутки. В настоящее время неизвестно, следует ли применять антицитокиновые препараты, такие как ингибиторы ИЛ-6 или ингибиторы комплемента, а также отсутствуют результаты единого анализа данных о лечении инфекции COVID-19 у позитивных реципиентов почечного трансплантата с использованием противовирусных лекарственных средств.
At the present time, there is no specific treatment of infection COVID-19 in this connection most nephrological societies consider that recipients of kidney graft in mild and medium clinical severity of disease have to continue to get calcineurin inhibitors (CNIs) and prescribed dose of glucocorticoids but taking of antiproliferative drugs should stop. In case of severe COVID-19 infection needed to hospitalization into intensive care unit and pulmonary mechanical ventilation, it is necessary to cancel CNIs and antiproliferative drugs and to increase amount of glucocorticoids by 16–20 mg per day. At the present time it is unclear whether anticytokines drugs like interleukin 6 inhibitors or complement inhibitors should be used and there were no results of unified data analysis of treatment of COVID-19 positive recipients of kidney graft with antiviral medical drugs.
Iron Deficiency Anemia: Assessment of Iron Status in the Human Body by Serum Ferritin Level,Taking into Account WHO Recommendations (2020)
Authors: Попович М.Ю. 
Published: March 2022

В статье приведены сведения о ферритине, белке – депо железа в организме. Отображены его физиологическая роль и клиническое значение. Продемонстрирована динамика изменений содержания ферритина в процессе лечения пациентов с железодефицитной анемией и лиц с латентным дефицитом железа. Сделан вывод о том, что уровень ферритина в сыворотке крови является важным динамическим показателем для лабораторной диагностики железодефицитных состояний.
In the article, the information about ferritin, protein – depot of iron in the body is given. Its physiological role and clinical importance is showed. Dynamics of changes of the content of ferritin during treatment of patients with iron deficiency anemia and persons with latent deficiency of iron is demonstrated. There was made the conclusion that the level of ferritin in the blood serum is the important dynamic parameter for laboratory diagnostics of iron.
Organization of Technological Process of Specialized Medical Care for Children with Arrhythmias in Grodno Region: Rational Useof Resources, Problems, Potential Reserves
Authors: Томчик Н.В. , Ляликов С.А. , Кизелевич А.И. , Миклаш Н.В. 
Published: March 2022

Цель. Продемонстрировать организацию технологического процесса оказания специализированной медицинской помощи детям с аритмиями в Гродненской области, указать на проблемы, обнаружить потенциальные резервы повышения качества работы детской кардиологической службы.Материалы и методы. Проанализирована деятельность детской кардиологической службы за 2013–2019 гг., оценена общая и первичная заболеваемость аритмиями. Проведен анализ электрокардиографического скрининга, в ходе которого было обследовано 10 353 ребенка без признаков органической патологии сердца в возрасте 0–17 лет.Результаты и обсуждение. Продемонстрирована многоуровневая система оказания медицинской помощи детскому населению с нарушениями сердечного ритма и проводимости в Гродненской области. Установлено, что аритмии встречаются у 27,78% детей г. Гродно, в гендерной структуре преобладают мальчики. Обобщен опыт работы кардиологической службы на профилактическом, диагностическом, диспансерном и госпитальном этапах.Выводы. Установлены потенциальные резервы для дальнейшего развития в современных социально-экономических условиях.
Purpose. To demonstrate the process of organization of specialized medical care for children with arrhythmias in Grodno region, to identify the problems, to discover potential enhancement reserves of the quality of work of the pediatric cardiology service.Materials and methods. The activity of the pediatric cardiology service in 2013–2019 was analyzed, thegeneralandprimaryincidenceofarrhythmiaswasestimated.Theanalysisofelectrocardiographic screening was carried out, during which 10 353 children without the signs of organic heart disease at the age of 0–17 years were examined.Results and discussion. The organizational technology of the multilevel system of medical care for children with cardiac arrhythmias and conduction disorders in the Grodno region is demonstrated. It was revealed that arrhythmias occur in 27.78% of Grodno children; boys dominate in the gender structure. The experience of the cardiological service at the preventive, diagnostic, dispensary and hospital stages is presented.Conclusions. Potential reserves for further development in the current socio-economic conditions of domestic health care are established.