bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opportunities and Prospects for Preclinical Drug Safety Assessment Using Alternative Methods: Experience from the Toxicology in the 21st Century (Tox21) Programme in the USA
Authors: Perfilova V. N. 
Published: September 2023

SCIENTIFIC RELEVANCE. The Tox21 (Toxicology in the 21st Century) programme was developed by the US Tox21 Consortium with the aim to replace animal-based toxicity assessments of chemicals with a wide range of in vitro and in silico testing approaches and has since been successfully applied in practice.AIM. The study aimed to review information on alternative in vitro models developed as part of the Tox21 programme for testing the toxicity of chemical compounds.DISCUSSION. According to the information provided by the National Toxicology Program, Environmental Protection Agency, National Center for Advancing Translational Sciences, and other Tox21 Consortium members on their official websites and in the literature, the Tox21 Consortium has developed a quantitative high-throughput screening technology for testing the safety of chemicals and created the Tox21 10K library of chemical compounds using this screening technology. The library has been successfully used to create models that predict the toxicity of chemicals prior to preclinical studies. Researchers have proposed new approaches to studying the safety of chemical compounds in human cell lines to replace in vivo studies. Innovative organ-on-chip, multi-organ-on-chip, and organoid models are free from the drawbacks and limitations of cell-line models and offer more accurate representations of complex cell–matrix and organ–organ interactions. Developed under the Tox21 programme to search for new chemical toxicity biomarkers and gene signatures, novel transcriptomics (toxicogenomics) technologies can be used to classify toxicants according to their health risks and to identify potential side effects long before discovering any pathological changes in the body. The Interagency Coordinating Committee on the Validation of Alternative Methods conducts technical evaluation of alternative testing methods and promotes their implementation into regulatory practice.CONCLUSIONS. Thus, new tools and technologies provide an opportunity for switching from in vivo toxicity testing of candidate medicinal products to in silico and in vitro methods.
An All-Inclusive Digital Framework for Collaborative Community Transformation for Sustainable Development
Authors: Olowolayemo Akeem , Daud Nuha Hafizah , Tanni Maymuan Gulfam , Omar Ba Khadher Mohammed Abdullah 
Published: September 2023

Technology as a part of world development can be utilized for public welfare and services. In this current era, people's lives and activities depend mostly on technology. Consequently, technology can foster massive contribution to problem-solving in communities and can easily enable several services hitherto considered difficult. One area of interest is the utilization of technology to enable faster solutions to common problems in a community. Monitoring the challenges and developments in a community through a community reporting and collaborative transformation system is still not that popular despite the obvious benefits. The idea of crafting a digital collaborative transformation system becomes crucial to solving the common problems in a community and how to achieve a smooth collaborative relationship between the citizens and their respective political representatives. Consequently, this study aims to offer a comprehensive framework for the development of a digital collaborative community transformation, consisting of community members’ responses and communication channels linked with the person-in-charge, budgeting suggestions, volunteering, as well as nomination and voting systems. The approach adopted in this study is to use an exploratory strategy to discuss all the critical processes from the standpoint of the users, as well as the technology for designing, creating, and integrating the system to gather users’ inputs.
Transvenous embolization via the facial vein for intraorbital dural arteriovenous fistula: illustrative case
Authors: Ienaga Jumpei , Tsukada Tetsuya , Watanabe Toru , Sakai Yosuke , Uda Kenji , Shintai Kazunori , Araki Yoshio , Nagatani Tetsuya , Seki Yukio 
Published: September 2023

BACKGROUND
Intraorbital arteriovenous fistula (IOAVF) is a rare type of intracranial fistula that presents with ocular signs similar to those of cavernous sinus dural arteriovenous fistula. The treatment of IOAVF is based on the vascular architecture of each case due to its infrequent occurrence. The authors report the case of an IOAVF that was successfully treated with embolization via the facial vein, with good outcomes.

OBSERVATIONS
A 78-year-old woman presented with left eyelid swelling, pulsatile ocular protrusion, and left ocular conjunctival hyperemia. Ophthalmological evaluation revealed elevated intraocular pressure; time-of-flight magnetic resonance angiography revealed a dilated left superior ophthalmic vein. Digital subtraction angiography showed an arteriovenous shunt in the left superior orbital fissure, which was treated using transvenous coil embolization. The patient experienced immediate improvement in left ocular protrusion and conjunctival hyperemia. Ophthalmological evaluation 1 month after treatment showed normal intraocular pressure in the left eye. No neurological symptoms were observed, and there was no recurrence of the arteriovenous shunt 3 months postoperatively.

LESSONS
The authors report a rare case of IOAVF treated with embolization via the facial vein with a good outcome. A thorough understanding of the vascular architecture using three-dimensional images is useful for determining endovascular access and procedures.
Upper cervical intramedullary schwannoma of the spinal cord presenting with myelopathy: illustrative case
Authors: Duvuru Shyam , Sanker Vivek , Syed Naureen , Mishra Shubham , Ghosh Sayantika , Dave Tirth 
Published: September 2023

BACKGROUND
Intramedullary schwannomas account for 1.1% of all spinal schwannomas. Preoperative diagnosis is best accomplished by thoroughly evaluating clinical and radiological characteristics, accompanied by a high index of suspicion. The authors report a case of C2–3 intramedullary schwannoma in a young male who presented with neck pain and vertigo. The current literature is also reviewed.

OBSERVATIONS
The authors reviewed the data of a young male with a 2-month history of neck pain and vertigo. Magnetic resonance imaging of the brain and cervical spine showed an intramedullary mass at C2–3 with a syrinx extending into the cervicomedullary junction. Laminectomy, myelotomy, and microsurgical excision of the mass under intraoperative neurological monitoring (IONM) were done. Postoperative pathology reported the specimen as a schwannoma.

LESSONS
Gross-total resection of a schwannoma using IONM is the treatment of choice because of the lesion’s benign nature, a better prognosis, and defined cleavage plane. Schwannomas should be included in the differential diagnosis of intramedullary spinal tumors. Because of its progressive nature, early surgery is recommended in symptomatic patients.
Ischemic stroke in a young adult with a known epileptogenic arteriovenous malformation: illustrative case
Authors: Kuribara Seiji , Maeda Takuma , Yanagawa Taro , Tsukagoshi Eisuke , Kohyama Shinya , Kurita Hiroki 
Published: September 2023

BACKGROUND
Brain arteriovenous malformations (AVMs) usually manifest as hemorrhages or seizures. They rarely present with ischemic symptoms, especially in young patients. We present a case of an epileptogenic AVM that led to cerebral infarction due to paradoxical embolic occlusion of the middle cerebral artery (MCA) involving the main feeder of the lesion.

OBSERVATIONS
A 35-year-old male had been suffering from AVM-associated epilepsy for 10 years and was scheduled for surgery. He suddenly developed right-sided hemiconvulsions followed by hemiparalysis and impaired consciousness. Computed tomography revealed no intracerebral hemorrhage, and symptoms were initially thought to indicate epilepsy and Todd’s palsy. Because of his prolonged symptoms, he underwent magnetic resonance imaging, which revealed a large cerebral infarction due to occlusion of the MCA involving the main feeder of the AVM. The patient underwent AVM resection, and the partially thrombosed nidus was completely removed. Histopathological investigation revealed a fresh thrombus in totally occluded nonarteriosclerotic feeders. He had no atrial fibrillation; however, subsequent transesophageal echocardiography revealed a patent foramen ovale, suggesting a paradoxical embolism.

LESSONS
This case serves as a reminder that AVMs can present with considerable variability. Acute cerebral infarction should be considered a possible mechanism of seizures, even in patients with epileptogenic AVM.
Effect of kinesio taping and exercise on functional impairment in patients with different degrees of knee osteoarthritis
Authors: Mahmoud Waleed S. 
Published: September 2023

BACKGROUND: Kinesio Taping (KT) is used for musculoskeletal problems. KT optimizes and reduces mechanical stresses on soft tissues. However, the benefits of KT and traditional exercises for different severities of knee osteoarthritis (OA) remains controversial. OBJECTIVES: This study aimed to investigate the effects of tension KT and traditional physical therapy on different severities of knee OA. METHODS: Fifty-six male patients with knee OA, aged 60–75-y years, were allocated to groups A and B based on grades 1 and 2 and grades 3 and 4 on the Kellgren-Lawrence scale, respectively. Tension KT and traditional physical therapy were administrated to both groups for 6-wks. The extensor peak moment of quadriceps and knee flexion range of motion (ROM) were recorded using an isokinetic dynamometer and universal goniometer, respectively. Visual analog scale (VAS) was used to score pain level. Statistical analysis was performed using the ANCOVA test. RESULTS: ANCOVA revealed an increase in peak extensor moment of quadriceps (Pre: 51.6 [Formula: see text] 2.8 Nm; Post: 63.3 [Formula: see text] 4.3 Nm), knee flexion ROM (Pre: 112.8∘ 7.2; Post: 122.9∘ 4.8), and pain improvement (Pre: 5.1 [Formula: see text] 1.07; Post: 2.8 [Formula: see text] 1.6) in group A ([Formula: see text] 0.001). Group B showed insignificant improvements in all outcome measures ([Formula: see text] 0.05). CONCLUSION: KT with traditional physical therapy improved knee pain, quadriceps strength, and knee ROM in older males with knee OA grades 1 and 2. KT and traditional physical therapy were insufficient to produce considerable effects on grades 3 and 4 of knee OA.
Indicators of endothelial dysfunction and the rate of thrombotic complications in patients with type 2 diabetes mellitus at different periods after COVID-19
Authors: Alieva A.V. 
Published: September 2023

Introduction. Damage to the vascular endothelium and hypercoagulation are two of the main causes of post-­COVID-19 complications. The aim of our study was to evaluate endothelial dysfunction and thrombotic complications at different periods after COVID-19 in patients with type 2 diabetes mellitus. Patients and methods. We conducted a cross-­sectional study of 135 patients with type 2 diabetes mellitus who applied for inpatient treatment at the RSSPMCE clinic (Tashkent, Uzbekistan) in the period from 3 to 24 months after the acute period of COVID-19. The following laboratory parameters were assessed: fibrinogen, INR, APTT, D-dimer, von Willebrand factor, and cell adhesion molecules (VCAM-1, ICAM-1). Results. Despite normal or near-normal INR, APTT and fibrinogen levels, many patients had elevated levels of D-dimer (41.4 % of cases), von Willebrand factor (27.6 % of cases) and vascular cell molecules up to 24 months after infection. The concentrations of ICAM-1 and VCAM-1 did not have statistically significant correlations with the degree of compensation of diabetes mellitus (HbA1c level). At various times after COVID-19, cases of ischemic forms of diabetic foot syndrome and thrombosis affecting the cavernous sinus and upper extremities were recorded. Conclusion. Taking into account the results obtained, patients with type 2 diabetes mellitus after SARS-CoV-2 infection require careful monitoring, and, in addition to assessing standard coagulation parameters, determining the level of cell adhesion molecules may have diagnostic value.
11-dehydrothromboxane B2 as a marker of acetylsalicylic acid resistance in patients with stable coronary artery disease
Authors: Lukianets K.Yu. , Pchelin I.Yu. 
Published: September 2023

Introduction. Acetylsalicylic acid (ASA, aspirin) resistance is the inability to reduce thromboxane A2 synthesis in platelets and inhibit platelets activation and aggregation while taking ASA. Assessment of urinary 11-dehydrothromboxane B2 (11-dhTxB2) levels is one of the methods to identify aspirin resistance. Our research aimed to investigate whether urinary 11-dhTxB2 levels and other clinical and laboratory parameters are associated with a history of major adverse cardiovascular events (MACE) including myocardial infarction and ischaemic stroke in aspirin-treated patients with stable coronary artery disease. Patients and methods. In a cross-­sectional study we investigated 82 patients with stable coronary artery disease who took ASA at doses of 75–150 mg/day. We used the evaluation of the urinary 11-dhTxB2 levels standardized by creatinine as a method to identify aspirin resistance. Statistical analysis was performed using Mann-­Whitney U-test, ROC-analysis and multivariable logistic regression. Results. The medians of urinary 11-dehydrothromboxane B2 level in patients with and without MACE were 587.8 (Q1-Q3 512.8–800.3) pg/mg creatinine and 438.3 (Q1–Q3 337.6–577.9) pg/mg creatinine, respectively (p=0.001). The threshold level of urinary 11-dhTxB2, which predicted a high risk of aspirin resistance, was 521.1 pg/mg creatinine, and in 36 (43.9 %) patients the concentration of the 11-dhTxB2 exceeded this level. The regression model characterising the dependence of the presence of a history of MACE was constructed. It included platelet count, urinary levels of 11-dhTxB2 and the presence of type 2 diabetes. Sensitivity and specificity of the model were 55 % and 88.9 %, respectively. Conclusions. The results of the study demonstrate that the antiplatelet effect of aspirin is weaker in stable coronary artery disease patients with a history of MACE than in those without a history of MACE.
The Genesis of Dyspnea in Patients After COVID-19
Authors: Pozdnyakova T.D. , Sukhanov D.S. , Isakov V.A. , Korshunova A.L. 
Published: September 2023

Post-COVID syndrome is an actual problem at the present time. The shortness of breath is one of the most common complaints in this group of patients. Dyspnea is one of the most significant disabling symptoms that negatively affect the quality of life of patients. The causes and mechanisms for the development of dyspnea in the post-COVID period are varied. In particular, one of the main causes of dyspnea is fibrosis-like and fibrous changes in the. Fatigue and / or muscle weakness, in particular of the respiratory muscles, can also be the cause of dyspnea. Direct SARS-CoV-2 infection of skeletal muscles, drug-induced myopathy, prolonged immobilization of hospitalized patients may also result in muscle weakness. Increased risks of thrombosis and pulmonary embolism (PE) after COVID-19, creating conditions for the development of chronic thromboembolic pulmonary hypertension, represent another factors for the development of shortness of breath. In patients with no abnormalities in blood gases or any other parameters that assess the functioning of the cardiovascular and respiratory systems, hyperventilation syndrome can be the cause of dyspnea. Thus, studying pathogenetic and molecular mechanisms of dyspnea development is an urgent problem, due to the need for specialists to choose the right tactics and select effective drugs and non-drug therapy for managing patients with this complaint.
Selection and Use of Antioxidants-radioprotectors in the Composition of Therapeutic Radiopharmaceuticals (Review)
Authors: Pavlenko E. P. , Larenkov A. A. , Mitrofanov Iu. A. 
Published: September 2023

Introduction. The use of radiopharmaceuticals for targeted radionuclide therapy (TRT), the efficacy of which was established during clinical trials, is safe and effective for various pathological conditions, including cancer. The main feature of therapeutic radiopharmaceuticals (RPs) is the use of β–- and α-emitting radionuclides (RNs) in the finished dosage form (FD). Among the radionuclides used for radionuclide therapy, lutetium-177 is currently one of the most popular in clinical practice because of its chemical and nuclear characteristics. The list of RPs based on lutetium-177 is constantly expanding, and Lutathera® ([177Lu]Lu-DOTA-TATE) and Pluvicto™ ([177Lu]Lu-PSMA-617) have been approved for clinical use in several countries.Text. Because of the high activity of RNs in a single dose of therapeutic RPs (up to 8 GBq in a monodose for 177Lu), ionizing radiation of the used RNs leads to a decrease in RPs quality owing to radiolytic degradation of the vector molecule. This leads to a decreased specific accumulation of radioactivity in the foci of pathology, reduced therapeutic effect, and potentially increases the risk of radiotoxicity to non-target organs and tissues. The degree and intensity of radiolytic degradation of the vector molecule and, consequently, the shelf life of RPs depend on many factors, among which the activity concentration of the radionuclide in the preparation, its half-life, and the energy of the emitted particles are the most important. To suppress the effects of radiolysis, various excipients with antioxidant (radioprotective) properties were introduced into the compositions of the finished dosage forms. Among the substances studied, the most popular were gentisic acid, ascorbic acid, and ethanol. In this work, the advantages and disadvantages of various antioxidants and their combinations used in therapeutic RPs were considered in lutetium-177 preparations.Conclusion. Selection of the optimal composition of the dosage form is an urgent task, as it will ensure high-quality RPs both at the time of preparation and during the shelf life and delivery to the end user, which will greatly facilitate the use and centralized supply of therapeutic RPs. The necessity of creating a unified approach for the selection of antioxidants at the pharmaceutical development stage of radiopharmaceuticals is shown. For this purpose, an approach combining studies of radical reaction kinetics with studies of radiation-chemical yields of radiolysis products under identical or maximally similar conditions with subsequent verification of the stability of RPs dosage form seems to be very promising and has proven to be effective. In contrast, the empirical approach, which implies the selection of radioprotectors based on a direct study of their influence on the preservation of the level of radiochemical purity, is suboptimal because of the high market value of both radionuclides and non-radioactive precursors.
Equine maternal aging affects the metabolomic profile of oocytes and follicular cells during different maturation time points
Authors: Catandi G. D. , Bresnahan D. R. , Peters S. O. , Fresa K. J. , Maclellan L. J. , Broeckling C. D. , Carnevale E. M. 
Published: September 2023

Introduction: Oocyte quality and fertility decline with advanced maternal age. During maturation within the ovarian follicle, the oocyte relies on the associated somatic cells, specifically cumulus and granulosa cells, to acquire essential components for developmental capacity.Methods: A nontargeted metabolomics approach was used to investigate the effects of mare age on different cell types within the dominant, follicular-phase follicle at three time points during maturation. Metabolomic analyses from single oocytes and associated cumulus and granulosa cells allowed correlations of metabolite abundance among cell types.Results and Discussion: Overall, many of the age-related changes in metabolite abundance point to Impaired mitochondrial metabolic function and oxidative stress in oocytes and follicular cells. Supporting findings include a higher abundance of glutamic acid and triglycerides and lower abundance of ceramides in oocytes and somatic follicular cells from old than young mares. Lower abundance of alanine in all follicular cell types from old mares, suggests limited anaerobic energy metabolism. The results also indicate impaired transfer of carbohydrate and free fatty acid substrates from cumulus cells to the oocytes of old mares, potentially related to disruption of transzonal projections between the cell types. The identification of age-associated alterations in the abundance of specific metabolites and their correlations among cells contribute to our understanding of follicular dysfunction with maternal aging.
Transcriptional analysis of human peripheral blood mononuclear cells stimulated by Mycobacterium tuberculosis antigen
Authors: Wei Jing , Guo Fangzheng , Song Yamin , Xu Kun , Lin Feiyang , Li Kangsheng , Li Baiqing , Qian Zhongqing , Wang Xiaojing , Wang Hongtao , Xu Tao 
Published: September 2023

BackgroundMycobacterium tuberculosis antigen (Mtb-Ag) is a polypeptide component with a molecular weight of 10-14 kDa that is obtained from the supernatant of the H37Ra strain after heat treatment. It stimulates the activation and proliferation of γδT cells in the blood to produce an immune response against tuberculosis. Mtb-Ag is therefore crucial for classifying and detecting the central genes and key pathways involved in TB initiation and progression.MethodsIn this study, we performed high-throughput RNA sequencing of peripheral blood mononuclear cells (PBMC) from Mtb-Ag-stimulated and control samples to identify differentially expressed genes and used them for gene ontology (GO) and a Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Meanwhile, we used PPI protein interaction network and Cytoscape analysis to identify key genes and qRT-PCR to verify differential gene expression. Single-gene enrichment analysis (GSEA) was used further to elucidate the potential biological functions of key genes. Analysis of immune cell infiltration and correlation of key genes with immune cells after Mtb-Ag-stimulated using R language.ResultsWe identified 597 differentially expressed genes in Mtb-Ag stimulated PBMCs. KEGG and GSEA enrichment analyzed the cellular pathways related to immune function, and DEGs were found to be primarily involved in the TNF signaling pathway, the IL-17 signaling pathway, the JAK-STAT signaling pathway, cytokine-cytokine receptor interactions, and the NF-κB signaling pathway. Wayne analysis using GSEA, KEGG, and the protein-protein interaction (PPI) network showed that 34 genes, including PTGS2, IL-1β, IL-6, TNF and IFN-γ et al., were co-expressed in the five pathways and all were up-regulated by Mtb-Ag stimulation. Twenty-four DEGs were identified using qRT-PCR, including fourteen up-regulated genes (SERPINB7, IL20, IFNG, CSF2, PTGS2, TNF-α, IL36G, IL6, IL10, IL1A, CXCL1, CXCL8, IL4, and CXCL3) and ten down-regulated genes (RTN1, CSF1R CD14, C5AR1, CXCL16, PLXNB2, OLIG1, EEPD1, ENG, and CCR1). These findings were consistent with the RNA-Seq results.ConclusionThe transcriptomic features associated with Mtb-Ag provide the scientific basis for exploring the intracellular immune mechanisms against Mtb. However, more studies on these DEGs in pathways associated with Mtb-Ag stimulation are needed to elucidate the underlying pathologic mechanisms of Mtb-Ag during Mtb infection.