bluuebunny/crossref_metadata_2025 huggingface dataset:
Maximizing Immunotherapy in Sarcoma Using Histology, Biomarkers and Novel Approaches
Authors: Stein Jacob N ,   University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA, D'Angelo Sandra P ,   Memorial Sloan Kettering Cancer Center, New York, NY, USA
Published: July 2022

Sarcomas are rare tumours with variable treatment responsiveness. Immunotherapy represents a promising approach but has yet to be fully realized. Clinical trials have shown modest response rates to checkpoint blockade (overall response rate: 5–18%) but with wide variability across histologic subtypes (up to 70% in small series). Biomarkers may help further predict response, but traditional markers are rarely expressed and less useful within sarcoma. An overarching immune classification combining several biomarkers offers better predictive validity. Exciting novel approaches include leveraging cancer testis antigens for adoptive T-cell therapies, identifying synergistic combination regimens and targeting epigenetic mechanisms to improve immune responsiveness.
Cholangiocarcinoma: The Present and Future of Targeted Therapies
Authors: Kalyan Aparna ,   Department of Hematology and Oncology, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA, Shroff Rachna T ,   Department of Hematology and Oncology, University of Arizona Cancer Center, Tuscon, AZ, USA
Published: July 2022

Cholangiocarcinomas (CCAs) are a heterogenous group of cancers arising from the biliary epithelium. CCAs tend to metastasize with early lymph node involvement lending to poor surgical outcomes and need for systemic therapy. Given the paucity of successful therapies in these cancers, it is important to understand the molecular drivers and to develop therapeutic strategies using targeted therapies either alone or in combination. The molecular landscape offers several new potentially targetable drivers.
Anifrolumab: An Inhibitor of Type I Interferon for the Treatment of Patients with Systemic Lupus Erythematosus
Authors: Gulko Hannah E ,   Division of Rheumatology, Northwell Health, Great Neck, NY, USA, Furie Richard ,   Division of Rheumatology, Northwell Health, Great Neck, NY, USA
Published: July 2022

Anifrolumab is the only US Food and Drug Administration-approved therapy for patients with systemic lupus erythematosus (SLE) that directly targets type I interferons (IFNs). The phase I study in scleroderma and phase II study in SLE served as a foundation for the phase III programme that included the TULIP-1 and TULIP-2 SLE trials. We review the biology of IFNs and the scientific rationale for developing an inhibitor of the type I IFN pathway. The focus then turns to the specific trials that led to regulatory approvals.
Belimumab: A BAFF-specific Inhibitor for the Treatment of Systemic Lupus Erythematosus and Lupus Nephritis
Authors: Tanaka Yoshiya ,   The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
Published: July 2022

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects multiple organs. In particular, the presence of renal involvement, known as lupus nephritis, is a major determinant of prognosis. Conventional treatments for SLE include hydroxychloroquine, glucocorticoid and immunosuppressive agents. However, the use of such non-specific drugs increases the risk of side effects, such as infections. Soluble B-cell-activating factor (BAFF), belonging to the tumour necrosis factor family, is produced by dendritic cells and induces class switching of B cells and differentiation into antibody-producing cells. International phase III studies demonstrated the efficacy and safety of belimumab (a monoclonal antibody against soluble BAFF) not only in patients with SLE, but also in those with active lupus nephritis. There were no significant differences between the belimumab and placebo groups in the incidence of adverse events, including serious events and events necessitating drug cessation. Thus, belimumab could become an alternative induction treatment for lupus nephritis. This article describes the pathogenesis of SLE and lupus nephritis, and reviews the results of recent phase III trials of belimumab and its promising role for the treatment of patients.
Janus Kinase Inhibitor Selectivity in Rheumatoid Arthritis: Where Do We Stand?
Authors: Avouac Jérôme ,   Université de Paris, Service de Rhumatologie, Hôpital Cochin, AP-HP.CUP, Paris, France
Published: July 2022

The selectivity of Janus kinase inhibitors (JAKis) is still a matter of debate, as no JAKi is specific for only one Janus kinase (JAK) isoform. Currently approved JAKis in rheumatoid arthritis (RA) all inhibit JAK1, which is an effective therapeutic target in RA. Although selective JAK1 inhibition seems not to decrease drug efficacy, JAKi selectivity may modify the safety profile of this class. Indeed, the balance of benefit and risk of inhibiting JAK2, JAK3 and tyrosine kinase 2 is not certain and should be carefully evaluated in the future.
Comprehensive Review Exploring Novel Treatments for Psoriatic Arthritis and Axial Spondyloarthritis from 2016 to 2021
Authors: Rakhra Amandeep ,   Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA, Mathew Stephanie ,   Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
Published: July 2022

Over the past decade, numerous novel therapies have been approved for use in the seronegative spondyloarthritides, including psoriatic arthritis and axial spondyloarthritis. With large variability seen in the spondyloarthritides with respect to presentation and perhaps pathogenesis, potential therapies continue to be discovered and trialled in the hope of better controlling disease activity. This review details therapies that have emerged for the treatment of psoriatic arthritis and axial spondyloarthritis from 2016 to 2021. We discuss those that have been approved for use in the USA and those that remain under investigation.
Corneal Cross-linking in Thin Corneas: From Origins to State of the Art
Authors: Hafezi Farhad ,   Laboratory for Ocular Cell Biology, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Switzerland,   ELZA Institute, Dietikon, Switzerland,   USC Roski Eye Institute, University of Southern California, Los Angeles, CA, USA,   Faculty of Medicine, University of Geneva, Geneva, Switzerland,   School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China, Hillen Mark ,   ELZA Institute, Dietikon, Switzerland, Kollros Léonard ,   ELZA Institute, Dietikon, Switzerland, Hafezi Nikki L ,   ELZA Institute, Dietikon, Switzerland, Torres-Netto Emilio A ,   Laboratory for Ocular Cell Biology, Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Switzerland,   ELZA Institute, Dietikon, Switzerland
Published: July 2022

Corneal cross-linking (CXL) can halt ectasia progression and involves saturating the stroma with riboflavin, followed by ultraviolet-A (UV-A) light irradiation. This generates reactive oxygen species that covalently cross-link together stromal molecules, strengthening the cornea. The ‘Dresden protocol’ left a 70 µm uncross-linked region at the base of the stroma to protect the corneal endothelium from UV damage; however, this limited CXL to corneas ≥400 µm. Approaches made to overcome this limitation involved artificial corneal thickening to ≥400 μm through swelling the stroma with hypo-osmolaric riboflavin, applying riboflavin-soaked contact lenses during UV irradiation or leaving ‘epithelial islands’ over the thinnest corneal regions. The drawbacks to these three approaches are unpredictable swelling, suboptimal stiffening and unpredictable cross-linking effects, respectively. Newer approaches adapt the irradiation protocol to the cornea to deliver CXL that maintains the 70 μm uncross-linked stroma safety margin. The sub400 protocol employs an algorithm that models the interactions between UV-A energy, riboflavin, oxygen diffusion and stromal thickness. It requires only corneal pachymetry measurements at the thinnest point and the selection of the appropriate UV irradiation time from a look-up table to cross-link corneas as thin as 200 µm safely and effectively.
Ophthalmic Telemedicine in the Pandemic–Endemic World: Present and Future Perspectives
Authors: Biran Amit ,   Ophthalmology Division, Tel Aviv Medical Center, Tel Aviv, Israel, Loewenstein Anat ,   Ophthalmology Division, Tel Aviv Medical Center, Tel Aviv, Israel, Mezad-Koursh Daphna ,   Ophthalmology Division, Tel Aviv Medical Center, Tel Aviv, Israel, Iglicki Matias ,   University of Buenos Aires, Buenos Aires, Argentina, Zur Dinah ,   Ophthalmology Division, Tel Aviv Medical Center, Tel Aviv, Israel
Published: July 2022

COVID-19 restrictions have increased the need and use of telemedicine in ophthalmology but this approach requires remote data collection and reliable technologies to ensure accurate and safe examination and diagnosis. This article reviews the existing telemedicine technologies for age-related macular degeneration (AMD), diabetic retinopathy (DR) and paediatric ophthalmology, and discusses their applicability in the COVID-19 era. We conducted a literature search of PubMed using telemedicine keywords for all relevant pathologies (AMD, DR and paediatric ophthalmology) to identify English-language articles published between 2001 and 2021. We assessed whether existing telemedicine technologies would meet the needs of patients under COVID-19 restrictions. Our findings showed that there are reliable existing home-monitoring technologies. However, self-operated home optical coherence tomography is still an investigational technology for AMD monitoring and is not yet available for routine use. Computerized algorithms aimed at identifying DR pathology and or deterioration in relevant parameters under investigation have shown excellent results. In paediatric ophthalmology, parents can conduct basic testing of their child's ophthalmic parameters; improvements in parental testing will require the development of quick and reliable automatic instruments. In conclusion, current technologies lend themselves to remote use for ophthalmic examination by non-professional individuals, which is particularly relevant for ophthalmic care provision in the pandemic setting. Further investigative effort is needed in order to improve home monitoring and computerized data processing.
Towards the Development of Longer and More Efficacious Therapies for Wet and Dry Age-related Macular Degeneration
Authors: Arrigo Alessandro ,   IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, Bandello Francesco ,   IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
Published: July 2022

Age-related macular degeneration (AMD) is a leading cause of vision loss in developed countries. The advanced stages of AMD are characterized by the onset and progression of macular neovascularization or geographic atrophy. Several treatments are currently available for managing the neovascular form of AMD, based on intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs. Although these agents are efficient in inducing fluid regression and preserving visual function, their limited duration of action and treatment burden are stimulating the development of new molecules with more prolonged pharmacological activity. The future of exudative AMD therapies will include new generations of anti-VEGF drugs, surgical anti-VEGF port delivery systems and novel molecules acting on other AMD pathogenic pathways. In contrast, dry AMD and geographic atrophy have no approved treatments; nutraceutical approaches still represent the only way to reduce the probability of AMD progression and the onset of complications. Several ongoing clinical trials are testing different molecules that have been developed to slow the progression of geographic atrophy, including complement system inhibitors, integrin inhibitors, gene therapies and cell-based therapies. In this review, we provide an overview of the current state of the art and future perspectives for the management of dry and wet AMD.
Update on Avacincaptad Pegol for Geographic Atrophy
Authors: Ewing Tyler M ,   Sierra Eye Associates, Reno, NV, USA, Khan Hannah ,   Sierra Eye Associates, Reno, NV, USA,   The University of Nevada, Reno School of Medicine, Reno, NV, USA, Wadsworth Adam LC ,   Sierra Eye Associates, Reno, NV, USA, Vannavong Jordyn ,   Sierra Eye Associates, Reno, NV, USA, Khanani Arshad M ,   Sierra Eye Associates, Reno, NV, USA,   The University of Nevada, Reno School of Medicine, Reno, NV, USA
Published: July 2022

Geographic atrophy (GA) secondary to age-related macular degeneration is the leading cause of permanent vision loss in patients over the age of 50 in developed countries. GA is characterized by the atrophy of retinal pigment epithelium and photoreceptors and can lead to central or peripheral vision loss, depending on the location of the atrophy. Currently, there are no US Food and Drug Administration-approved treatments for GA. Avacincaptad pegol (Zimura®; IVERIC Bio Inc, New York, NY, USA) is a C5-specific inhibitor that is being investigated as a potential treatment for GA. C5 is a key protein within the complement system, which maintains retina integrity and health under normal conditions. It is hypothesized that unregulated activation of the complement system (indicated by elevated levels of active proteins such as the membrane attack complex) can exacerbate the progression of GA. This article reviews the latest data regarding avacincaptad pegol as an investigational therapeutic for GA.
The Impact of Continuous Positive Airway Pressure Use on Dry Eye Disease
Authors: Matossian Cynthia ,   Matossian Eye Associates, Hopewell and Hamilton, NJ, USA; Doylestown, PA, USA
Published: July 2022

Continuous positive airway pressure (CPAP) use is highly beneficial. However, many patients using CPAP or nasal mask therapy (NMT) develop secondary ocular disorders. Adding to earlier research, a recent retrospective descriptive analysis of 330,926 patients with no diagnosis of dry eye disease prior to their first CPAP or NMT device claim provides further information on the prevalence and incidence of dry eye disease among patients using CPAP or other NMT devices to treat sleep apnoea. Researchers found clear evidence that, compared with the incidence of dry eye disease in the general adult population in the USA, the incidence of dry eye disease was higher in patients who used CPAP or a NMT device, particularly in the second year of use. Furthermore, the incidence of dry eye disease increased based on the length of time the CPAP device was used. This research reveals the need for multispecialty collaboration based on evidence that patients may be at risk for eye irritation secondary to airflow from mask leakage or retrograde nasolacrimal air escape.
Blepharoptosis in the Setting of an Ocular Prosthesis: A Literature Review and Description of the Novel Use of a Template Prosthesis
Authors: Kwan Changyow C ,   Division of Oculofacial Plastic and Orbital Surgery, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California-Irvine, Irvine, California, USA, Dermarkarian Christopher R ,   Division of Oculofacial Plastic and Orbital Surgery, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California-Irvine, Irvine, California, USA, Cypen Sanja G ,   Division of Oculofacial Plastic and Orbital Surgery, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California-Irvine, Irvine, California, USA, Kennedy John ,   Eye Design Ocular Prosthetics, Tustin, California, USA, Tao Jeremiah P ,   Division of Oculofacial Plastic and Orbital Surgery, Gavin Herbert Eye Institute, Department of Ophthalmology, University of California-Irvine, Irvine, California, USA
Published: July 2022

Blepharoptosis in acquired anophthalmia is common, yet the best treatment methods remain uncertain. We review the literature for descriptions of pathophysiology or management of blepharoptosis in acquired anophthalmic sockets and describe a technique and results of using a template prosthesis to facilitate intraoperative adjustment during external levator resection ptosis repair. The PubMed database was searched in October 2021 to identify all studies in English describing the pathophysiology or treatment of anophthalmic blepharoptosis. Seventy-one articles were identified; 13 met inclusion criteria and were reviewed. We also reviewed the charts of 12 adult patients with acquired anophthalmia undergoing external levator resection using a limbal templated, non-detailed, customshaped prosthesis. We assessed results (margin to reflex distance 1 [MRD1] and symmetry), as well as the number of eye prosthesis modifications. According to the literature, levator pathophysiology and orbital volume loss are important variables in anophthalmic ptosis. Prosthesis augmentation may be useful to treat ptosis in many instances, but may be limited by decreased motility and a poorer overall prosthesis fit. A variety of blepharoptosis repair surgical techniques have been described with reported success rates of 88–100%. The use of a template prosthesis to facilitate intraoperative lid positioning in ptosis repair was effective in 12 patients. All patients had MRD1 within 1 mm of target and with good facial symmetry. There were no complications or need for revision ptosis repair or redundancy in prosthesis fabrication at 3 years (mean; minimum 6-month) follow-up.
Breast cancer as part of Cowden syndrome
Authors: Byakhova M.  M. , Semenova A.  B. , Galkin V.  N. , Homushku C.  V. , Zod»binova A.  E. , Makarova M.  V. , Baranova E.  E. , Sagaydak O.  V. , Chernevskiy D.  K. , Belenikin M.  S. , Krinitsina A.  A. , Vorontsova M.  V. , Bodunova N.  A. , Danishevich A.  M. , Khatkov I.  E. , Degterev D.  A. , Yanova T.  I.
Published: July 2022

Cowden syndrome is a rare disease characterized by multiple hamartomas and increased breast, thyroid, kidney and uterine neoplasm risk. The lifetime breast cancer risk for patients with Cowden syndrome is 85 %, with an average age of diagnosis between 38 and 46 years. The diagnostic criteria for Cowden syndrome have been established by the International Cowden Consortium (ICC) and the National Comprehensive Cancer Network (NCCN), and are regularly revised, but the diagnosis of Cowden syndrome remains difficult due to the variety of phenotypic and clinical features of the disease. At the same time, the genetic variants associated with Cowden syndrome analysis is not a standard for patients with breast cancer.

Objective: To demonstrate the non‑BRCA hereditary breast cancer detection using whole genome sequencing on the Cowden syndrome clinical case example.

Materials and methods: The article describes a clinical case of a 37‑year‑old female patient with breast cancer, normal intelligence and phenotype, structural abnormalities of the thyroid gland (multinodular goiter). Whole genome sequencing was used to identify clinically significant genetic variants associated with hereditary tumor syndromes.

Clinical case: The article presents a brief literature review on the clinical presentation of Cowden syndrome and indications for its molecular diagnosis. Also, the presented clinical case describes patient R., 37 years old female with breast cancer, who underwent treatment in the City Clinical Oncological Hospital № 1 of the Moscow City Health Department in 2021. The patient was fully examined and enrolled in the whole genome sequencing project under the Order № 69 of Moscow Healthcare Department dated February 1, 2021 «Oncogenetic research organization in Moscow». The results revealed a pathogenic variant in the PTEN gene, previously associated with Cowden syndrome.

Conclusion: The use of whole genome sequencing allows to identify hereditary tumor syndromes, the clinical manifestation of which may be breast cancer.
Current approach in the treatment for resectable esophageal squamous‑cell carcinoma
Authors: Akhmedov P.  I. , Kononets P.  V. , Abou-Haidar O.  B. , Sogov I.  Z. , Gladilina I.  A. , Malilkhova O.  A. , Tryakin A.  A.
Published: July 2022

Esophageal cancer is one of the most aggressive malignancies of the gastrointestinal tract, characterized by high malignancy potential and poor prognosis. Surgical treatment is the standard for localized esophageal cancer, but the results of only surgery for locally advanced tumors remain unsatisfactory. The use of neoadjuvant chemotherapy, as well as neoadjuvant chemoradiation therapy, leads to a downstaging of the tumor, improves its resectability and increases an overall and disease‑free survival rates. The method of choice for unresectable esophageal cancer, as in case of refusal or intolerance to surgical treatment, is definitive chemoradiotherapy. Until recently, adjuvant therapy after R0 resection was not carried out, however, there is evidence that the postoperative use of nivolumab, an immune checkpoint inhibitor, significantly improves progression‑free survival in patients with evidence of residual tumor.

This article presents a current review of the treatment for resectable squamous‑cell carcinoma of the esophagus.
Independent Tendency of ACE2 and GRP78 Expression in SARS-CoV2 Infection
Authors: Adiningrat Arya , Khairunnisa Sekar Hasna
Published: July 2022

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) is a virus that attacks the respiratory tract and causes the COVID-19 pandemic. This virus utilizes the host receptor as a cellular entry. Angiotensin-converting enzyme 2 (ACE2) has been assumed to be the essential host receptor for SARS-CoV2 infection. Furthermore, another costimulatory molecule, such as glucose-related protein 78 (GRP78), has also been reported. However, there are several inconsistent clinical data that could be observed regarding these molecules' involvement during SARS-CoV2 infection. This study aims to observe the possible involvement of ACE2 and GRP78 during the infection phase through gene expression profile analysis. Clinical specimens used in this study were taken in positive and negative clinical samples after the standard swab sampling procedure from both oropharyngeal and nasopharyngeal swabs. Subsequently, nucleic acid samples were proceeded by conventional Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) to analyze the expression of ACE2 and GRP78. Agarose gel electrophoresis was then performed before the densitometric analysis. Statistical analysis using Mann-Whitney Test and Independent Sample t-Test was applied to justify the gene profile difference between ACE2 and GRP78. Our study suggested the enhancement tendency while they were not statistically significant in both ACE2 and GRP78 expression from the positive SARS-CoV2 samples.
Desafios para a Reformulação da Concepção Pedagógica de um Curso de Especialização Lato Sensu Durante a Pandemia da COVID-19: um Relato de Experiência
Authors: Prado Livia Deris , Oliveira Camila Areias de , Souza Mariana Conceição de
Published: July 2022

A Escola de Governo Fiocruz é responsável por prover diversos cursos lato sensu para a formação de profissionais na área da saúde. Neste artigo, será relatada a experiência do curso Tecnologias Industriais Farmacêuticas que repensou toda a concepção pedagógica durante a pandemia da COVID-19. Em uma análise histórica verifica-se a necessidade de atualização do currículo em conjunto com a modernização das formas de mediar o processo ensino-aprendizagem, especialmente no que tange o uso de tecnologias para tal. As primeiras mudanças coincidiram com o início da pandemia da COVID-19 e a necessidade imediata de virtualizar as atividades. Dentro de uma perspectiva que envolveu a capacitação de coordenadores e docentes, algumas grandes mudanças foram propostas, entre elas: criação de instância coletiva deliberativa com representante docente e discente, fortalecimento do acolhimento dos estudantes como estratégia de engajamento, revisão curricular, implementação do portfólio digital como instrumento reflexivo e avaliativo e flexibilização das modalidades de trabalhos de conclusão de curso. Atribui-se o sucesso da implementação das mudanças e a superação de desafios ao comprometimento conjunto dos profissionais da gestão acadêmica, coordenação, docentes e estudantes em fazer do curso uma construção coletiva baseada em preceitos clássicos e modernos da educação.

Palavras-chave: Atividades formativas. Educação continuada. Emergência sanitária. Indústria farmacêutica.
A Política de Cooperação como Estratégia para a Inclusão de Pessoas com Deficiência Visual na Educação a Distância
Authors: Tavares Daniela Cardoso , Oliveira Sandra de , Santos Filipe , Bassani Patricia
Published: July 2022

Esta pesquisa aborda a importância da adoção de estratégias inclusivas na educação a distância (EAD), com o objetivo de oferecer uma aprendizagem de qualidade para todos. O presente estudo, de abordagem qualitativa e exploratória, apresenta os resultados de entrevistas com 21 voluntários com deficiência visual, em relação as razões para escolher a EAD e suas percepções sobre a acessibilidade nessa modalidade educativa. Também analisamos a contribuição da cooperação entre todos os envolvidos no processo de ensino-aprendizagem e desenvolvimento de um curso a distância (como por exemplo alunos, professores, profissionais de informática, entre outros) para a promoção de uma comunicação acessível. A partir dos dados obtidos, concluímos que a política de cooperação é uma potente estratégia de inclusão de pessoas com deficiência visual na EAD, ao promover a diminuição de barreiras comunicacionais e aumentar a troca de conhecimento entre todos.

Palavras-chave: Deficiência visual. Educação a distância. Inclusão. Política de cooperação. Tecnologia assistiva.
The effect of Ganoderic Acid A on miR-17-5p and miR-181b expression level and apoptosis induction in human leukemia Nalm-6 cells
Authors: Mortazavie Faezeh , Taheri Simin , Tandel Parisa , Zare Farahnaz , Tamaddon Gholmhossein
Published: July 2022

Background: In various cancers, Ganoderic Acid A (GAA), an active triterpenoid derived from Ganoderma lucidum, has been proved to show potent anti-tumor effects. However, the possible impacts of GAA on the human leukemia cell line (Nalm-6) are not fully elucidated. Therefore, this research aimed to study the antineoplastic effect of GAA on Nalm-6 cells.
Materials and Methods: In this laboratory trial study, Nalm6 cells were cultured in vitro and treated with different doses of GAA (25, 50, 100, 200, and 400 μg/mL) for 24, 48, and 72 hours. The optimal treatment concentration of GAA was determined by the MTT assay. Flow cytometry was used to determine the death of Nalm-6 cells caused by GAA treatment by utilizing FITC-conjugated propidium iodide (PI) and annexin V staining. After incubation, the expression levels of miR-17-5p and miR-181b were monitored using real-time polymerase chain reaction (PCR).
Results: Based on the half-maximal inhibitory concentration (IC50) measurements of the MTT assay, the optimal treatment concentration of GAA was 140 μg/mL (in a dose and time-dependent manner, p<0.0001). The GAA treatment was selectively toxic to the leukemia Nalm-6 cells and could remarkably induce cell apoptosis (p<0.0001). Besides, GAA downregulated the expression of miR-17-5p and miR-181b in the Nalm-6 cells compared with the untreated cells (P=0.0067 and P=0.0014, respectively).
Conclusions: Based on the present findings, GAA merits further investigation as a promising natural reagent for treating hematologic malignancies.
Volume, Conductivity and Scatter parameters of Neutrophils in Neonatal Sepsis – Is it a Cost-Effective Tool?
Authors: Ganesan Nidhya , Mohan Anupama , Srinivasan Ramesh , Rao T.M. Subba
Published: July 2022

Background: Early diagnosis of neonatal sepsis is quite challenging. I/T ratio (immature to mature neutrophil ratio) is a highly sensitive marker of sepsis but is time-consuming and subjective. Off late, volume conductivity and scatter (VCS) of neutrophils are among the newer parameters available for screening a septic neonate. This study aimed to determine the correlation between the I/T ratio and VCS parameters in neonatal sepsis and estimate a cut-off value of VCS parameters to diagnose neonatal sepsis using receiver operating curve analysis.
Materials and Methods: This prospective observational study was conducted by the Department of Pathology and Neonatology from April 2019 to March 2020 in a tertiary care center. A total of 110 newborns were included in this study and were divided into two groups (probable sepsis and sepsis). Data were collected from the hospital database, and analysis was done using SPSS software. Correlation between the I/T ratio and VCS parameters was done using Spearman’s correlation. Results were expressed as mean ± standard deviation (SD). A P-value of <0.05 was considered statistically significant. 
Results: Correlation between the I /T ratio and VCS parameters showed negative correlation values of -0.22, -0.23, and +0.39 (P-values of 0.0198, 0.0153, and <0.0001) for mean neutrophil conductivity (MNC), mean neutrophil scatter (MNS) and mean neutrophil volume (MNV) respectively. MNV with a cut-off of > 156.4 had sensitivity and a negative predictive value of 100 % in the diagnosis of sepsis and was found to be higher in the sepsis group when compared to the probable sepsis group.
Conclusion: Based on the significant difference in VCS parameters of neutrophils in the sepsis group, this aids as an additional marker for the early diagnosis of neonatal sepsis.
Evaluation of serum Fibroblast growth factor-23 in patients with beta-thalassemia major compared to healthy population
Authors: Saki Forough , Ranjbar Omrani Gholamhossein
Published: July 2022

Background: The role of phosphate hemostasis in development of thalassemia bone disease has not been extensively studied yet. Due to the lack of sufficient human studies about the changes of serum Fibroblast growth factor-23(FGF23) in patients with beta-thalassemia major as the first step of investigating the role of FGF23 in thalassemia bone disease, the present study aimed to investigate the serum level of FGF23 in patients with thalassemia major.
Material and Method: In this case-control study, 25 patients with beta thalassemia major and their age- and sex-matched healthy volunteers were enrolled. Serum phosphorous, calcium, parathyroid hormone (PTH), 25(OH) D, erythropoietin (EPO), serum intact FGF23 (iFGF23) and 1,25 (OH)2 D were checked and analyzed.
Result: Patients with beta-thalassemia major had lower 1,25 (OH)2D, (p = 0.025), higher phosphate (p = 0.002), and higher PTH (P <0.001) compared to the control group; however, all of them were in their normal blood range. They also had higher serum FGF23 (p = 0.007) and higher EPO (P<0.001). Serum FGF23 had an independent association with serum Iron (p=0.016), 1, 25(OH)2 Vitamin D (p<0.001), and hemoglobin (p=0.002).
Conclusion: Serum FGF23 was associated with serum Iron, 1, 25(OH)2 Vitamin D, and hemoglobin in beta-thalassemia major patients. Hence, it seems that regular transfusions and chelating agents which can decrease the serum iron and increase hemoglobin level can be associated with lower iFGF23.
The role of cytokine and its relation to depression and infection complications in pediatric cancer
Authors: Pourakrami Moslem , Sheikhpour Elnaz , Mehrabani Sanaz
Published: July 2022

Inflammation plays a critical role in the progression of cancer in children. On the other hand, children with cancer experience abnormal activation of the inflammatory system. Moreover, it is known that these patients have a predisposition to depression. According to studies, moderate to severe depression was observed in about 63% of children with cancer and acute illness. Therefore, identifying inflammation-related biomarkers and targets in this regard is essential. The inflammation changes are related to cytokine deregulation, which in turn may influence the expression of depressive symptoms. Studies have reported that the deregulation of serum inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α may influence depressive disorder in pediatric cancer patients.  In addition, determining the risk of severe bacterial infection complications in pediatric cancer is essential to reduce the cost of therapy and hospitalization. However, the role of cytokines as an infection marker in these children is still a debate. Determining these plasma cytokine levels may have diagnostic value in assessing febrile neutropenia, although their crucial role in systemic inflammation is known. Given that evidence regarding the role of pro-inflammatory cytokine levels and relation to clinical parameters, including depression and infection in pediatric cancer patients is limited, we assessed the role of cytokine and its relation to depression and infection complications in pediatric cancer.
Improving the Metrological Characteristics of a Fiber-Optic Temperature Sensor by Effective Signal Processing Methods
Authors: Ershov I.A.
Published: July 2022

Signal processing in a fiber optic temperature sensor has a major impact on the metrological performance of the instrument. Therefore, continuous improvement of the signal processing algorithm is an important aspect of remaining competitive. Using a fiber-optic temperature sensor based on the Raman effect manufactured by Keepline LLC, it is shown how the application of effective signal processing methods can significantly reduce the instrument error. A fiber 8258 m long was used as a sensitive element, the spatial resolution of the instrument was 2 m. It is found that the noise in the signal is distributed according to the normal law. Measurements were made at instrument temperatures of 25.95 and 44.73 °C. Using linear regression analysis, it was found that heating the instrument causes a slope of the thermogram, which needs to be corrected. A logarithmic function was used to correct the thermogram. Thus, it was possible to reduce the range of temperature values along the length of the fiber from 3.47 to 2.35 °C, and RMS from 0.579 to 0.392 °C. In addition, the dependence of the transient process on the heating of the instrument is given and recommendations for adjusting the calibration coefficients are provided
Bitcoin Cryptocurrency Address Grouping Methods
Authors: Belova N.S. , Ivanov I.P.
Published: July 2022

Nowadays, Bitcoin cryptocurrency is an alternative means of payment for purchases in many areas of our lives. However, fraudsters trying to seize cryptocurrency funds and often attack Bitcoin users. In this regard, methods are being developed to determine reliability of the transfer and prevent the loss of funds by the user. Data on all transactions in the Bitcoin network is publicly available, but does not contain any information about the user, except for the cryptocurrency wallet address, and the user is able to create a new transfer address for each transaction. To check reliability of a potential transfer recipient, algorithms for classifying the Bitcoin users are being developed. For classification, it is necessary to join Bitcoin addresses into groups related to the same user. As a rule, address grouping methods are based on the heuristic of combining transaction inputs and the heuristic of determining the recipient address in the transaction. However, such methods provide inaccurate and incomplete results, which leads to development of new approaches having their own advantages and disadvantages, which limits their scope. Data structure of the Bitcoin cryptocurrency blockchain is considered, as well as comparison of existing approaches to address grouping is provided
Mathematical Simulation of Nonlinear Vibrations of a Channel Wall Interacting with a Vibrating die Via Viscous Liquid Layer
Authors: Mogilevich L.I. , Popov V.S. , Popova A.A. , Khristoforova A.V.
Published: July 2022

The article considers the developed mathematical model and investigates the dynamics of the interaction of a channel wall supported by a nonlinear spring with a vibrating opposite wall through a viscous fluid layer filling the channel. A flat slotted channel formed by two absolutely rigid rectangular walls, parallel to each other was investigated. One of the channel dimensions in the plan was much larger than the other, which leads to the transition to a plane problem. The bottom channel wall rested on a spring with a cubic nonlinear characteristic, and the upper wall was a die oscillating according to a given law. The gap between the walls was assumed to be much smaller than the channel longitudinal dimension, and the amplitudes of wall vibrations were much less than the channel gap. The movement of the viscous fluid in the channel was considered to be creeping. The mathematical model of the channel under consideration consisted of an equation of the dynamics of a single-mass system with a spring having a cubic nonlinearity, as well as the Navier --- Stokes and continuity equations, supple-mented by the boundary conditions for fluid nonslip on the channel walls and its free outflow at the ends. The steady-state nonlinear vibrations of the bottom channel wall at the fundamental frequency were studied, and its hydroelastic response was determined. The proposed model can be used to study nonlinear vibrations of elastically fixed elements that are in contact with liquid and are parts of modern devices and assemblies
Features of the Design and Technology of Cylindrical Sapphire Soldering with Metals Used in Gas-Discharge Lamps
Authors: Gavrish S.V. , Puchnina S.V.
Published: July 2022

The article considers the design and technology features of cylindrical soldering of sapphire (corundum) with niobium and kovar alloy (alloy 29NK), developed for use in flash lamps with a discharge in alkali metal vapors. The performance of a gas-discharge lamp is analyzed and the basic requirements for the junctions are determined. The main types of defects determining the optical transparency and mechanical strength of a corundum monocrystal grown by directional crystallization the Stepanov method are shown, and the main requirements for a profiled sapphire tube are formulated. The results of internal stresses reduction studies during heat treatment of a corundum pipe before soldering are presented. The special attention is paid to the study of physicochemical phenomena occurring in the process of soldering sapphire with niobium using glass-ceramic solder and with kovar copper. It is proved that for the soldering corundum with niobium it is necessary to introduce up to 1 % zirconium impurity into the metal structure, which allows reducing the recrystallization of the alloy and decreasing the migration rate of the formed grains. In the case of active soldering sapphire with kovar, the importance of observing the recommended temperature regimes for melting solder to prevent the formation of titanium intermetallic compounds is shown. The main design solutions of sapphire soldered joints and the results of their tests for resistance to mechanical and climatic factors are given
Using Sliding Mode Control to Set Up a Rotating Electrodynamic Space Tether System
Authors: Lu H. , Wang C. , Zabolotnov Yu.M.
Published: July 2022

The paper considers the process of imparting rotation at a given angular velocity to an electrodynamic space tether system in a near-Earth orbit. The tether system is a linear cluster of three microsatellites connected by insulated conductive cables. Initially the system is gravitationally stabilised in the approximate vertical direction. Electromagnetic forces generated in the conductive cables by the geomagnetic field impart rotation to the system. We stated the equations of motion for the system in the Earth-fixed coordinate system, taking into account distributed load produced by gravitational and electromagnetic forces. The system is moving in a fairly high, almost circular orbit, so aerodynamic forces are not taken into account. Adjusting the current will reduce the strain in the tethers. The model under consideration represents those as a set of material points connected by unilateral elastic links. We propose a feedback current controller based on sliding mode control. The system variables lie on a single surface, moving across which ensures asymptotic stability of the control process. We used a simplified system motion model to synthesise the controller parameters. We analysed the angular motion of microsatellites with respect to the tether direction while rotation is imparted to the system. Numerical examples confirm the efficiency of our approach to setting up a rotating space tether system
Numerical Investigation of Work Cycle Characteristics in the Combustion Chamber of a Lox/Methane Liquid-Propellant Rocket Engine Featuring Reductant Power Gas Combustion
Authors: Sidlerov D.A. , Fedorov S.A.
Published: July 2022

We performed a numerical investigation of cumulative efficiency and the structure in detail concerning the working process in the combustion chamber of a lox/methane liquid-propellant rocket engine operating in steady-state, boosted and throttled modes. In order to do it, we used tools developed by JSC SSC "Center Keldysh", that is, physical and mathematical models, numerical methods and software packages for numerical simulation of two-phase turbulent flows with combustion in liquid-propellant engine combustion chambers. The paper presents numerical simulation and investigation results concerning the specifics of fuel component flows, their mixing and combustion in the combustion chamber of a lox/methane liquid-propellant rocket engine using staged combustion cycle with reductant gas in steady-state, boosted (117 % by thrust) and throttled (30 % by thrust) operation modes. We performed a comparative analysis of work cycle parameters in combustion chambers at different fuel component consumption rates and pressure levels. The paper shows that the boosted mode increases the interaction of fuel jets, which intensifies mixing and burnout processes, while the deep throttling mode decreases the mixing and fuel burnout amplitudes as compared to the steady-state mode. The numerical simulation results may be used to investigate fuel combustion processes in combustion chambers of promising liquid-propellant rocket engines at the stages of development, design and refinement
Experimental Analysis of Elemental Composition of Materials used to Manufacture Gas Generators for Vehicle Airbag Modules
Authors: Gonsales A.A.V. , Goncharov R.B. , Malishchuk T.S.
Published: July 2022

The airbag is a part of the Supplementary Restraint System; along with the safety belt, it is the most important system that protects the driver and passengers if the vehicle collides with static or moving objects. Certain interrelated studies and measures are required so as to develop scientific, technical, design and technological foundations for producing airbag modules for various vehicle types: for example, determining the range of suitable domestic materials and alloys, as well as the compositions of pyrotechnic gas-generating charges to manufacture gas generators. We experimentally evaluated mechanical properties and elemental composition of materials that gas generator parts consist of, which allowed us to establish their domestic analogues. We determined the elemental chemical composition of pyrotechnic gas-generating charges (main and auxiliary) and the primer igniter charge. We used the following methods in our work: an experimental full-scale airbag module deactivation method for subsequently decomposing gas generators to obtain the necessary sample parts to investigate; a method for determining the microhardness of material samples to subsequently evaluate their ultimate tensile strengths; finally, laser-induced breakdown spectroscopy, X-ray fluorescence spectrometry, X-ray and infrared spectroscopy, ion and liquid chromatography, Raman spectroscopy and nuclear magnetic resonance to determine the elemental composition of materials
Genetic analysis of the fungicide resistance in Fusarium oxysporum associated to Vanilla planifolia
Authors: González-Oviedo Nelly Abigail , Iglesias-Andreu Lourdes Georgina , Flores-de la Rosa Felipe Roberto , Rivera-Fernández Andrés , Luna-Rodríguez Mauricio
Published: July 2022

Vanilla planifolia is attacked by the fungus F. oxysporum f. sp. vanillae. Since there are no resistant genotypes available to producers, they opt for the use of synthetic fungicides to control the disease, however, there is no information on a possible resistance of the pathogen to these commercial fungicides. The goal of the work was to analyze the response of F. oxysporum strains, pathogenic (nine) and non-pathogenic (three) of V. planifolia, to three fungicides of the benzimidazole family and to chlorothalonil, as well as the genetic bases by studying the target proteins of these active ingredients, ?-tubulin and GPDH. It was observed that the 12 strains studied were susceptible to the fungicides benomyl and carbendazim, while 11 of them were resistant to thiophanate methyl and nine to chlorothalonil. No relationship was found between the pathogenic character or the origin of the strains and the susceptibility to fungicides. It was found that resistance to thiophanate methyl is not conferred by a point mutation of the ?-tubulin coding sequence, as previously hypothesized; apparently, it could be more related to the absence of protein motifs. No relationship was observed between variation in the gene GPDH with the resistance or susceptibility of the strains.
Genetic Diversity and Correlation Coefficient Studies in Muskmelon (Cucumis melo L.)
Authors: Indraja G. , Sadarunissa Syed , Madhumathi C. , Priya B. Tanuja , Sekhar M. Reddi
Published: July 2022

Background: Genetic diversity provides opportunity for plant breeders to develop new and improved cultivars with desirable characteristics, which include both farmer-preferred traits (yield potential and large seed, etc.) and breeder preferred traits (pest and disease resistance and photosensitivity, etc.). Yield being a complex quantitative character, direct selection for yield may not result in successful improvement. Information on character association and direct and indirect effects of component traits on yield would greatly help in formulating the selection criteria and using them effectively in crop improvement programme. Therefore present study was aimed to evaluate genetic diversity in 25 muskmelon genotypes. Methods: 25 muskmelon genotypes were evaluated at Dr. Y.S.R Horticultural University, College of Horticulture, Anantharajupeta, during 2017-2018 in randomized block design with three replications. Genetic diversity among genotypes was estimated using Mahalanobis D2 statistics. Result: Cluster analysis revealed distinctive clustering pattern and grouped the genotypes in to seven clusters. cluster II was the largest comprising of eight genotypes, while cluster III, IV, VI, VII consist of only one genotype. Cluster VII and IV were found to be considerably different from the rest of the clusters. Genotypes falling in these clusters which are genetically more diverse, can be exploited in a hybridization programmes. Genetic variability in terms of correlation analysis were studied for yield and yield attributing traits. Fruit yield had a positive correlation with fruit volume, fruit diameter, number of fruits per plant, fruit weight and flesh thickness. While it had a negative correlation with days to appearance of first pistillate flower and days to first fruit harvest.