bluuebunny/crossref_metadata_2025 huggingface dataset:
The effectiveness of the application of modern diagnostic criteria of cervical pathology
Authors: Kazakova Anna V. , Lineva Olga I. , Kiyashko Irina S. , Dufinets Irina E. , Chechko Svetlana M. , Mishina Anna I.
Published: July 2022

BACKGROUND: Cervical cancer is one of the four most common cancers today and is the second most common cancer among women in developing countries. According to World Health Organization estimates, in 2018, the number of new cases in these countries was 570,000 (84% of all new cases globally). About 311,000 women died of cervical cancer in 2018, with more than 85% of these deaths occurring in low- and middle-income countries. The detection of the disease in its later stages has not significantly reduced since 2018 (32.6% of all cases).
AIM: The aim of this study was to compare the information contents of conventional and liquid cytology methods in women with verified human papillomavirus of high oncogenic risk.
MATERIALS AND METHODS: We retrospectively analyzed 50 outpatient records of women aged 23 to 65 years who underwent colposcopy (cervical biopsy) based on the results of cervical screening. To establish the diagnosis, all patients underwent examination of smears from the cervix and cervical canal using conventional (n = 25) and liquid (n = 25) cytology methods. A molecular genetic study was carried out to detect high-oncogenic human papillomavirus types (16, 18, 31, 33, 35, 45, 51, 56, 58) in scraping of the cervix by real-time polymerase chain reaction. Women in the both study groups also underwent colposcopy with histological examination of the cervical biopsy specimen. The analysis of the obtained data was carried out using methods of parametric and nonparametric statistics. Inclusion criteria included cytological examination, verified human papillomavirus of high oncogenic risk, and colposcopy. Exclusion criteria included pregnancy and acute infectious diseases.
RESULTS: According to the results of histological examination, the percentage of coincidence of cytological and histological diagnosis in the group of women who underwent conventional cytological examination was 48%. The total number of discrepancies in this group was 13 (52.0 9.99%). The number of women infected with human papillomavirus in the both study groups was almost the same (18 in the conventional cytology group and 19 in the liquid cytology group). The most common types of human papillomavirus among the examined patients were the 16th type (9 women) and the 18th type (6 women).
CONCLUSIONS: To date, cytological research methods have not lost their relevance, the liquid cytology method being a reliable screening test with high specificity, which reduces the number of unsatisfactory preparations for analysis and false negative results. The most informative for women with type 2 or type 3 of transformation zone is the use of the liquid cytology method.
Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes
Authors: Kaneko Shizuka ,   Division of Diabetes/Endocrinology/Lifestyle-Related Disease, Takatsuki Red Cross Hospital, Takatsuki, Japan
Published: July 2022

Gastrointestinal hormones are currently used to treat type 2 diabetes mellitus (T2D). Incretin preparations with gastric inhibitory polypeptide (GIP) activity or glucagon-like peptide-1 (GLP-1) provide new means for controlling blood glucose levels, body weight, and lipid metabolism. GIP, an incretin, has not been used due to lack of promising action against diabetes. However, recent studies have shown that GIP has an important effect on glucagon and insulin secretion under normoglycaemic conditions. Co-existence of GIP with GLP-1 and glucagon signalling leads to a stronger effect than that of GLP-1 stimulation alone. The development of a GIP/GLP-1R unimolecular dual agonist with affinity for both GIP and GLP-1 receptors is under investigation, and the drug is expected to be clinically available in the near future. Tirzepatide, a GIP/GLP-1R unimolecular dual agonist, regulates metabolism via both peripheral organs and the central nervous system. The SURPASS phase III clinical trials conducted for tirzepatide comprise 10 clinical trials, including five global trials and the global SURPASS-CVOT trial, with >13,000 patients with T2D (ClinicalTrials.gov Identifier: NCT04255433). The clinical application of tirzepatide as a therapy for T2D may provide new insights into diabetic conditions and help clarify the role of GIP in its pathogenesis.
Utilizing the New Glucometrics: A Practical Guide to Ambulatory Glucose Profile Interpretation
Authors: Doupis John ,   Department of Internal Medicine and Diabetes, Salamis Naval and Veterans Hospital, Salamis, Attiki, Greece,   Iatriko Paleou Falirou Medical Center, Diabetes Clinic, Athens, Greece, Horton Edward S ,   Harvard Medical School, Boston, MA, USA
Published: July 2022

Traditional continuous glucose monitoring and flash glucose monitoring systems are proven to lower glycated haemoglobin levels, decrease the time and impact of hypoglycaemia or hyperglycaemia and, consequently, improve the quality of life for children and adults with type 1 diabetes mellitus (T1DM) and adults with type 2 diabetes mellitus (T2DM). These glucose-sensing devices can generate large amounts of glucose data that can be used to define a detailed glycaemic profile for each user, which can be compared with targets for glucose control set by an International Consensus Panel of diabetes experts. Targets have been agreed upon for adults, children and adolescents with T1DM and adults with T2DM; separate targets have been agreed upon for older adults with diabetes, who are at higher risk of hypoglycaemia, and women with pregestational T1DM during pregnancy. Along with the objective measures and targets identified by the International Consensus Panel, the dense glucose data delivered by traditional continuous glucose monitoring and flash glucose monitoring systems is used to generate an ambulatory glucose profile, which summarizes the data in a visually impactful format that can be used to identify patterns and trends in daily glucose control, including those that raise clinical concerns. In this article, we provide a practical guide on how to interpret these new glucometrics using a straightforward algorithm, and clear visual examples that demystify the process of reviewing the glycaemic health of people with T1DM or T2DM such that forward-looking goals for diabetes management can be agreed.
Review of Automated Insulin Delivery Systems for Type 1 Diabetes and Associated Time in Range Outcomes
Authors: Nallicheri Armaan ,   Close Concerns, San Francisco, CA, USA, Mahoney Katherine M ,   Close Concerns, San Francisco, CA, USA, Gutow Hanna A ,   Close Concerns, San Francisco, CA, USA, Bellini Natalie ,   R&B Medical Group, Williamsville, NY, USA, Isaacs Diana ,   Cleveland Clinic, Cleveland, OH, USA
Published: July 2022

Automated insulin delivery (AID) systems play an important role in the management of type 1 diabetes mellitus (T1DM). These systems include three components: a continuous glucose monitor (CGM), an insulin pump and an algorithm that adjusts the pump based on the CGM sensor glucose readings. They are not fully automated and still require the user to administer bolus insulin doses for food. Some AID systems have automatic correction boluses, while others only have automatic basal or background insulin adjustments. As CGM has become more accurate and the technology has evolved, AID systems have demonstrated improved glycaemic outcomes. The clinical evaluation of AID systems in randomized controlled trials and real-world studies have shown their utility in helping glycaemic management. In this review, we compare AID systems that are commercially available in the US and summarize the literature, with a special focus on time in range in T1DM. The review also discusses new AID systems on the horizon and explores considerations for personalized care.
Glucagon-like Peptide-1 Receptor Analogues for the Treatment of Obesity
Authors: Williams David M ,   Department of Diabetes and Endocrinology, Singleton Hospital, Swansea Bay University Health Board, Swansea, UK, Staff Matthew ,   Department of Diabetes and Endocrinology, Singleton Hospital, Swansea Bay University Health Board, Swansea, UK, Bain Stephen C ,   Department of Diabetes and Endocrinology, Singleton Hospital, Swansea Bay University Health Board, Swansea, UK,   Diabetes Research Group, Swansea University Medical School, Swansea University, Swansea, UK, Min Thinzar ,   Department of Diabetes and Endocrinology, Singleton Hospital, Swansea Bay University Health Board, Swansea, UK,   Diabetes Research Group, Swansea University Medical School, Swansea University, Swansea, UK,   Department of Diabetes and Endocrinology, Neath Port Talbot Hospital, Swansea Bay University Health Board, Swansea, UK
Published: July 2022

There is an increasing prevalence of obesity worldwide, associated with significant morbidity and mortality, which frequently reduces quality of life and life expectancy. Consequently, there is a substantial and growing personal and economic burden necessitating the development of more effective therapies for obesity. Glucagon-like peptide-1 receptor analogues (GLP-1RAs) are licensed for the treatment of type 2 diabetes (T2D), and there is substantial evidence that these drugs not only improve cardiovascular outcomes but also promote weight loss. More recent evidence supports the use of the GLP-1RAs liraglutide and semaglutide in people with obesity without T2D. This article discusses the results of the major cardiovascular outcome trials for GLP-1RAs in people with T2D, the SCALE Obesity and Prediabetes study (Effect of liraglutide on body weight in non-diabetic obese subjects or overweight subjects with co-morbidities: SCALE™ - Obesity and Pre-diabetes; ClinicalTrials.gov identifier: NCT01272219; investigating liraglutide) and the STEP studies (Semaglutide treatment effect in people with obesity; assorted studies; investigating subcutaneous semaglutide). We also highlight the importance of a cost-effective approach to obesity pharmacotherapy. Clinicians should consider the use of GLP-1RAs in people with obesity, especially those with T2D or other obesity-related diseases, such as hypertension and dyslipidaemia. Ongoing trials, as well as clinical and cost-effectiveness appraisals, are anticipated over the next 12 months, and their findings may change the current landscape of obesity pharmacotherapy.
Pembrolizumab and Chemotherapy in Cervical Cancer: A New Standard of Care?
Authors: Lebreton Coriolan ,   Medical Oncology Department, Institut Bergonié, Bordeaux, France,   Medical Oncology Department, Centre Léon Bérard, Lyon, France, Saux Olivia Le ,   Medical Oncology Department, Centre Léon Bérard, Lyon, France,   Cancer Research Center of Lyon, UMR INSERM 1052 – CNRS 5286, Centre Léon Bérard, Lyon, France, Mery Benoîte ,   Medical Oncology Department, Centre Léon Bérard, Lyon, France, Bini Marta ,   Medical Oncology Department, Centre Léon Bérard, Lyon, France,   Medical Oncology Department, IRCCS Fondazione Istituto Nazionale dei Tumori di Milano, Milan, Italy, Roméo Clémence ,   Medical Oncology Department, Centre Léon Bérard, Lyon, France, Ray-Coquard Isabelle ,   Medical Oncology Department, Centre Léon Bérard, Lyon, France,   Health Services and Performance Research Lab (EA 7425 HESPER), University Claude Bernard Lyon 1, Lyon, France
Published: July 2022

Cervical cancer (CC) still has a high incidence despite screening programmes and access to human papillomavirus (HPV) vaccination, with a poor prognosis in the advanced setting. Most cases of cervical carcinoma are related to HPV infection. The pathogen-induced nature of the disease, the involvement of genes regulating the immune response and the high grade of immune infiltration provide the rationale to evaluate anti-programmed death-(ligand)1 (PD-[L]1) immune checkpoint inhibitors in CC. This article reviews the promising outcomes of the KEYNOTE-826 phase III trial, which evaluates the addition of pembrolizumab to chemotherapy in patients with PD-L1-positive disease and recurrent, persistent or metastatic cancer of the cervix, leading to an improvement of progression-free survival and overall survival. We also aim to address some outstanding questions and discuss the next steps in immunotherapy for CC.
Updates in the Management of Multiple Myeloma from the American Society of Hematology Meeting 2021
Authors: Vasudevan Sreeraj ,   Amala Institute of Medical Science, Kerala, India, Gundarlapalli Sravani ,   Myeloma Center, Division of Hematology/Oncology, Winthrop P Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, AR, USA, Thalambedu Nishanth ,   Myeloma Center, Division of Hematology/Oncology, Winthrop P Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, AR, USA, Mohan Meera ,   Medical College of Wisconsin, Froedtert Clinical Cancer Center, Division of Hematology/Oncology, WI, USA
Published: July 2022

Multiple myeloma (MM) remains largely an incurable disease with only a small percentage of patients achieving long-term remission. Here, we highlight some of the major studies on MM presented at the American Society of Hematology meeting in December 2021. Early results of the first ever population-based screening studies for precursor states of MM, iStopMM and PROMISE, were reported. These studies will inform on the risks and benefits of screening in MM and could lead to a paradigm shift towards screening and early therapy. In newly diagnosed MM, there were promising data on quadruple therapy with addition of a monoclonal antibody against the CD38 antigen to the existing backbone of lenalidomide, bortezomib and dexamethasone. T-cell–directed therapy including bispecific antibody and chimeric antigen receptor therapy demonstrated high clinical response, especially in triple-class refractory myeloma. We acknowledge that this review focuses on some exciting studies in both precursor and active MM and is not comprehensive by any means.
Advances in Targeted Therapy for Patients with Neuroendocrine Tumours
Authors: Katiyar Vatsala ,   University of Louisville, Department of Medicine, Division of Medical Oncology and Hematology, Louisville, KY, USA, Das Satya ,   Vanderbilt University Medical Center, Department of Medicine, Division of Medical Oncology, Nashville, TN, USA
Published: July 2022

Neuroendocrine neoplasms are heterogenous tumours with diverse biological behaviour. Well-differentiated neuroendocrine tumours comprise the vast majority of these malignancies. Though a subset of patients may possess indolent disease, which can be observed, most patients require systemic therapy at some point. The treatment armamentarium for patients with metastatic or advanced well-differentiated neuroendocrine tumours has expanded significantly over recent years, with multiple regulatory approvals for systemic therapies. Though peptide receptor radionuclide therapy has been a major addition to this armamentarium, several targeted therapies have also been successfully developed. Herein, we discuss the approved targeted therapies sunitinib and everolimus and highlight the clinical experience with targeted therapies in development. We focus largely on novel receptor tyrosine kinases targeting vascular endothelial growth factor, inhibitors of cell-cycle drivers, metabolic-pathway inhibitors and chemotherapy, and immune-modulating agents targeting the somatostatin receptor.
Sexual Function of Men Undergoing Active Prostate Cancer Treatment Versus Active Surveillance: Results of the Europa Uomo Patient Reported Outcome Study
Authors: Venderbos Lionne DF ,   Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, the Netherlands, Deschamps André ,   Europa Uomo, Antwerp, Belgium, Dowling John ,   Europa Uomo, Antwerp, Belgium, Carl Ernst-Günther ,   Europa Uomo, Antwerp, Belgium, Poppel Hein van ,   Department of Urology, KU Leuven, Leuven, Belgium, Remmers Sebastiaan ,   Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, the Netherlands, Roobol Monique J ,   Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center Rotterdam, the Netherlands
Published: July 2022

Background: Europa Uomo initiated the Europa Uomo Patient Reported Outcome Study (EUPROMS) to inform future patients with prostate cancer about the impact of prostate cancer treatment on sexual function. Methods: A one-time online survey was conducted among patients with prostate cancer who underwent treatment for the disease. The survey included the Expanded Prostate Cancer Index Composite short form 26 (EPIC-26) and questions on the use of medications or devices to aid/improve erections in men. Descriptive statistics were used to analyse the EPIC-26 sexual domain and the use of medications or devices. Results: Men on active surveillance reported the highest median sexual function scores (57.0, interquartile range [IQR]: 26.3–83.3) compared with men who underwent radical prostatectomy (20.8, IQR: 8.3–44.5) or radiotherapy (17.3, IQR: 9.7–40.3). Of the men on active surveillance, 44.7% reported “very poor to none/poor ability” to have an erection compared with 71.7–88.2% of the men undergoing active treatment for prostate cancer. Of the men treated actively, 66.6–88.3% rated their ability to function sexually as “very poor/poor” compared with 43.1% for men on active surveillance; more than half of the men who underwent radical prostatectomy viewed their lack of sexual function as a moderate or big problem for which they had tried medications or devices. Conclusions: The EUPROMS study showed that the impact of prostate cancer treatment on sexual function can be significant and non-negligible. These data can be used in daily clinical practice to guide the preference-sensitive decisionmaking process faced by patients newly diagnosed with prostate cancer.
The Role of Interleukin-23 Inhibition in the Treatment of Psoriatic Arthritis
Authors: Findeisen Kate E ,   Royal Melbourne Hospital, Melbourne, Victoria, Australia, Östör Andrew JK ,   Cabrini Medical Centre, Melbourne, Victoria, Australia,   Monash University, Melbourne, Victoria, Australia
Published: July 2022

Psoriatic arthritis is a chronic inflammatory autoimmune disease with varied manifestations, including functional limitation and reduced quality of life. Improved understanding of the immunopathogenesis of psoriatic arthritis, particularly the role of the interleukin-23 and interleukin-17 axis, has led to the development of therapeutic targets to alter the natural history of the condition. In this article, we review the role of monoclonal antibodies targeting the p19 subunit of interleukin-23 in the treatment of psoriatic arthritis.
Avacopan: An Oral Complement 5a Inhibitor for ANCA-associated Vasculitis
Authors: Mandell Matthew J ,   Division of Immunology, Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA, Gheriani Gatr-Alnada ,   Division of Immunology, Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA, Lenert Aleksander ,   Division of Immunology, Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA, Lenert Petar S ,   Division of Immunology, Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Published: July 2022

The oral complement 5a receptor antagonist, avacopan, was recently studied in phase II and III clinical trials in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This article summarizes the study findings and considers the implications for future care of patients with AAV. Avacopan was proven to be safe and noninferior to glucocorticoids for AAV in a study where patients with severe newly diagnosed or relapsing AAV were initially treated with either rituximab or cyclophosphamide. Greater improvement in the glomerular filtration rate, reduced numbers of relapses and better health-related quality of life were observed in the avacopan group compared with the prednisone group. Patients in the avacopan group also had fewer glucocorticoid-associated adverse events and, despite complement inhibition, there were no cases of Neisseria meningitidis infection reported in either group. Future studies should address the long-term safety of avacopan and whether it can completely replace glucocorticoids in AAV-induction protocols and for the management of minor disease relapses.
Novel Molecule Lotilaner Could Potentially Offer Relief to Long-suffering Demodex Blepharitis Patients
Authors: Meyer John ,   Eye Care Institute, Louisville, KY, USA
Published: July 2022

Demodex blepharitis is a highly prevalent lid margin disease that affects approximately 25 million people in the USA, yet is often missed or misdiagnosed. Many patients experience signs and symptoms including the presence of collarettes, lid erythema, and itchy and dry eyes, and psychosocial impacts such as feeling self-conscious about their eyes, or difficulties with night-time driving or wearing make-up. There are currently no therapeutics approved by the US Food and Drug Administration to treat Demodex blepharitis, but a novel molecule, lotilaner, has demonstrated statistically significant improvements for patients.
Dietary Intervention in Glaucoma
Authors: Ahmad Syed Shoeb ,   Ibn Sina Academy, Aligarh, India, Bilal Syed Mohammed ,   Kohefiza, Bhopal, India, Tariq Anam ,   Ophthalmological Clinic Oko, Volgogard, Russia, Rashid Aliya ,   Ophthalmological Clinic Oko, Volgogard, Russia
Published: July 2022

Glaucoma is a multifactorial disorder caused by risk factors dependent on, as well as those independent of, intraocular pressure. Currently, the treatment of this condition is primarily lowering of intraocular pressure. However, despite achieving the apparent target pressure, some patients continue to deteriorate. As a result, other modalities such as complementary and alternative medicine are being increasingly used to manage patients with glaucoma. These approaches include modifications or supplementations in diet and lifestyle changes, such as exercise and cessation of smoking. The objective of this review is to assess how different diets can be useful or detrimental to the visual health of patients with glaucoma. It also aims to shed light on the effect of dietary intervention on the epidemiology of glaucoma.
Descemet Membrane Detachment Following Ab-interno Canaloplasty with 360-degree Gonioscopy-assisted Transluminal Trabeculotomy: A Case Report
Authors: McSoley Matthew J ,   Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA, Chang Ta C ,   Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA, Wellik Sarah R ,   Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA
Published: July 2022

We describe two cases of Descemet membrane detachment (DMD) as a complication of gonioscopy-assisted transluminal trabeculotomy (GATT). The two patients had a history of retinal vein occlusions, subsequent intravitreal anti-vascular endothelial growth factor injections and uncontrolled intraocular pressures. They underwent ab-interno canaloplasty with 360-degree GATT without any intraoperative complications. In each case, DMD was noted on post-operative day 1. Both detachments were observed for several weeks before reattachment occurred. These cases illustrate that DMD is a potential sight-threatening complication of GATT, although the exact mechanisms involved remain uncertain. We hypothesize that the DMD may occur during the viscodilation of the Schlemm canal or due to the cleavage plane being anterior to the trabecular meshwork.
The Future of Biosimilars and Biobetters in Ophthalmology
Authors: Sharma Ashish ,   Lotus Eye Hospital and Institute, Coimbatore, Tamil Nadu, India, Kuppermann Baruch D ,   Gavin Herbert Eye Institute, University of California, Irvine, CA, USA, Loewenstein Anat ,   Division of Ophthalmology, Tel Aviv Medical Center, Tel Aviv University, Israel
Published: July 2022

Biosimilars have been spreading widely in the field of ophthalmology since the patent expiry of innovator molecules. The patent of the ranibizumab innovator has already expired, and the aflibercept patent will expire in the next few years. India was the first country to launch the biosimilar of ranibizumab (Razumab, Intas Pharmaceuticals Ltd, Ahmedabad, Gujarat, India) in 2015, whose usage has increased over time. After the US Food and Drug Administration approval of ranibizumab's biosimilar, ranibizumab-nuna (Byooviz™, Biogen, Cambridge, MA, USA), it will be interesting to witness the future of these molecules along with that of biobetters, which are yet to be well defined.
Combined Pars Plana Vitrectomy, Phacoemulsification and Intraocular Lens Implantation: A review on the Advantages and Limitations of Phacovitrectomy
Authors: Le Nhon T ,   Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA, Marshall Brigid ,   Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA, Houser Kourtney ,   Department of Ophthalmology, Duke Eye Center, Duke University School of Medicine, Durham, NC, USA, Khandelwal Sumitra S ,   Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, TX, USA
Published: July 2022

When vitreoretinal and anterior segment surgeons collaborate to perform concomitant cataract-vitreoretinal surgery (also known as phacovitrectomy) in the appropriate clinical setting, combined surgery can expedite visual recovery, improve the view and surgical access to the retina in cases with significant cataract, avoid multiple rounds of anaesthesia and reduce the financial burden on the patient. While combined surgery overcomes several limitations of sequential surgery, it is important to understand that phacovitrectomy may be associated with increased postoperative inflammation and less predictable refractive outcomes. We typically recommend combined phacovitrectomy in patients with significant cataract and vitreoretinal pathology, especially if the cataract impairs the view to the retina or if the patient is too ill to undergo several rounds of anaesthesia. In patients with high refractive expectations who have an early cataract or mild retinal pathology, combined surgery is not likely to be a viable or reasonable management option.
Circulating tumor DNA as a marker of minimal residual disease in non‑small cell lung cancer
Authors: Kazakov A.  М. , Laktionov K.  K. , Gordiev M.  G. , Akhmedov B. B. , Kuzmina V.  A.
Published: July 2022

Circulating tumor DNA (ctDNA) refers to small fragments of nucleic acid (approximately 166 base pairs) that are not associated with cells or cell fragments and circulate in the bloodstream. Circulating tumor DNA has been proven to be a marker of minimal residual disease (MRD), a tumor process that cannot be detected using routine investigations. Circulating tumor DNA can be used as a marker of MRD because tumor cells secrete their DNA into the blood during necrosis, apoptosis, and functioning (with extracellular vesicles, etc.); therefore, it is possible to detect it and identify MRD. Circulating tumor DNA accounts for 0,01 % to several percent of all circulating extracellular DNA depending on the size of the tumor, its vascularization and biological properties. Currently, much attention is paid to the detection of minimal residual disease after radical surgery for non‑small cell lung cancer (NSCLC), since a number of large studies have shown postoperative plasma ctDNA to be a negative prognostic sign. For example, Chaudhuri et al. showed that 36‑month relapse‑free survival (RFS) in patients with and without postoperative plasma ctDNA was nearly 0 % and 90–99 %, respectively. The status of MRD determined by postoperative plasma ctDNA levels may be potentially used for adjuvant treatment selection in the postoperative period. In the DYNAMIC study, MRD‑positive patients (with postoperative plasma ctDNA) who received adjuvant therapy had an RFS of 22,4 months while those who did not receive adjuvant treatment had an RFS of 9,3 months.

Thus, the status of MRD based on the plasma ctDNA level after radical surgery may allow a personalized treatment approach for patients undergoing radical surgery for non‑small cell lung cancer (NSCLC).
Metastatic risk of prognostic fine-needle aspiration biopsy in u veal melanoma patients
Authors: Levashov I. A. , Yarovoi A. A. , Yarovaya V. A. , Bulgakova E. S.
Published: July 2022

Despite the widespread u se of fine-needle aspiration biopsy (FNAB) of uveal melanoma (UM) for prognostic purposes, there are still doubts about the safety of this procedure. No analysis of such data can be found in domestic literature, and foreign authors have published only a few papers on this issue.

The purpose of this study is to analyze the risk of metastasis in patients with UM during FNAB.

Two groups of patients were formed: the main group, where FNAB was performed during brachytherapy (BT) (BT + FNAB) (n = 70), and the control group, where only BT was performed (n = 144).

According to the obtained data, the probability of metastases during a 3‑year follow-up period did not significantly differ between the two groups (p = 0.22 by Fisher's exact test and p = 0.11 by log-rank test when assessing survival using the Kaplan – Meier method), the relative risk (RR) was 1.43 [95 % CI 0.79 to 2.24]. In addition, there was no significant difference in the main clinical outcomes of local treatment associated with worse prognosis: the degree of tumor regression (p = 0.46), extrascleral growth, the need for additional brachytherapy (p = 0.32) or secondary enucleation (p = 0.99).

The absence of a significant difference in patient survival between the BT and BT + FNAB groups opens up prospects for a more extensive use of FNAB in patients with UM for prognostic purposes.
Comparison of the effects of two different doses of Filgrastim in febrile neutropenia management in childhood malignancy: A randomized clinical trial
Authors: Mirbehbahani Nargesbeigom , Bagheri Sepide , Roshandel Gholamreza , Jahazi Azam , Rashidbaghan Azam
Published: July 2022

Background: Febrile neutropenia (FN) is most often caused due to chemotherapy. Solid or certain lymphoproliferative malignancies can increase the duration of hospitalization and other complications in cancer patients. Filgrastim is used in childhood FN management. This study aimed to compare the effect of two different doses of Filgrastim on hematological and paraclinical factors in hospitalized febrile neutropenic patients with cancer. 
Materials and methods: In this randomized clinical trial, 60 febrile neutropenic patients with cancer complying with the inclusion criteria were assigned to both groups A and B. Thirty patients in group A received Filgrastim 5μg/kg/day whereas 30 others in group B received Filgrastim 15μg/kg/day. Hematological factors, physical examination findings, antibiotic administration period, and type of malignancy were then recorded. Complete blood count with differential (CBC diff) was also tested. Lung infiltration was examined by chest X-ray (CXR), and the spleen and abdomen were monitored by ultrasound.
Results: The mean age of patients was 6 ± 3 years old. The most prevalent malignancies included acute lymphoblastic leukemia (ALL) (35.0%), neuroblastoma (18.3%), osteosarcoma (11.7%), acute myeloid leukemia (AML) (8.3%), and Rhabdomyosarcoma (8.3%). The frequency distribution of malignancies significantly differed between the two groups (P= .01). Changes in hematological factors, including white blood cells (WBC), mature neutrophil cells, and absolute neutrophil count (ANC) in group A, appeared lower than those in the other group. However, none of the studied factors, including hematological factors, physical examination findings, and antibiotic administration period, were found to differ significantly between the two groups (P> 0.05).
Conclusion: Much as a higher dose of Filgrastim seems to bear a better effect on ANC, no significant difference was identified between the two groups. Further studies should be designed with a larger population to address the issue.
Frequency Determination of c.1115_1118delTTGG and c.3788_3790delTCT FANCA Gene Mutation in North of Khyber Pakhtunkhwa (KPK) Pakistan Fanconi’s Anemia Population
Authors: Ayaz Kinza , Khan Adnan , Arabdin Maria , Masood Tariq , Taj Abid Sohail , Ayaz Maaz
Published: July 2022

Background: This study aimed to assess the frequency determination of c.1115_1118delTTGG and c.3788_3790delTCT Fanconi's anemia A gene (FANCA) gene mutation in the North of Khyber Pakhtunkhwa (KPK) Pakistan Fanconi’s Anemia Population.
Materials and Methods: A cross-sectional study was conducted at Khyber Medical University, Peshawar, Pakistan. For the Exon 13 mutation c.1115_1118delTTGG, the amplification-refractory mutation system polymerase chain reaction (ARMS PCR) was developed. Sanger sequencing confirmed the ARMS PCR results for Exon 13 and found an exon 38 mutation of the FANCA (Fanconi anemia complementation group A) gene (c.3788_3790delTCT). Sanger sequencing results analyzed on Bio edit sequence aligner software confirmed the results of PCR. The four incidental single nucleotide polymorphisms (SNPs) discovered were examined in several variation databases.
Results:  The mean age for the patients was 9.68±3.02 years, with an age range of 5–16 years. Pedigree analysis of Fanconi Anemia patients revealed an autosomal recessive pattern of inheritance. Physical characteristics such as skeletal abnormalities, specifically thumb abnormalities and Fanconi's facies, are distinctive diagnostic features of FA. Pedigrees also showed bone marrow hypoplasia in 65% of patients and red cell aplasia in 6%. PCR results from all samples revealed tahat none of them had the Exon 13 mutation. In addition, none of the samples had the Exon 38 mutation. Four SNPs were found in the Sanger sequencing. Two of them were in the intron 12 region, one in each of Exons 13 and 38.
Conclusion: Results show that mutations in Exon 13 and Exon 38 of the FANCA gene are uncommon in our Pakistani FA population. SNPs established in the Pakistani population of Khyber Pakhtunkhwa (KPK) province have not been reported before.
The spectrum of Alpha and Beta Thalassemia Mutations: A 10-year Population-based Study of the Premarital Health Screening Program in West of Iran
Authors: Pooladi Arash , Ghanei Gheshlagh Reza , Kahrizi Nahid , Roshani Daem , Jalali Chia , Moradveisi Borhan
Published: July 2022

Background: In various cancers, Ganoderic Acid A (GAA), an active triterpenoid derived from Ganoderma Background: Thalassemia refers to a category of inherited disorders resulting from defects in synthesizing one or several chains of hemoglobin (Hb). The present study aimed to determine the frequency of alpha and beta-thalassemia mutations in Kurdistan province, Iran.
Materials and Methods: In this retrospective cross-sectional study, the laboratory data of 340 patients with thalassemia (170 females and 170 males), who were candidates for genetic testing in Kurdistan province, were examined over ten years (2006-2016). The participants were Kurd couples selected from the premarital health screening program.
Results: In this demographic study, 20 beta mutations and nine alpha mutations were identified. Among the beta-thalassemia mutations, intervening sequence or intron No. 2- first nucleotide change as splice site mutation (IVS-II-1) (26.1%), codons 8/9 (14.8%), and intervening sequence or intron No. 1- first nucleotide (IVS-I-1) (12.2%) change as splice site mutation), had the highest frequency rates, respectively, constituting 53% of the beta mutations. In addition, α3.7(82.7%), -α4.2(8.3%), and --MED (Mediterranean deletion) (3.75%) were the most frequent alpha mutations, which constituted more than 90% of the alpha mutations.
Conclusion: According to the results, the most frequent mutations in the HBB gene are IVS-II-1, Codons 8/9, and IVS-I-1, and in the HBA gene are α3.7, -α4.2, and –MED in Kurdistan province. In addition, the role of race and ethnicity as significant, influential factors in thalassemia was observable in the findings. The obtained results also indicated the communication pattern between the studied region's populations. Identifying common thalassemia mutations in an area could greatly benefit the early detection of thalassemia carriers in genetic laboratories and enhance thalassemia prevention programs.
An Unfavorable Metastatic Site at Initial Diagnosis in a 2-year-old Boy with Neuroblastoma
Authors: Yousofian Saeed , Zolfaghari Mohammad , Baghbeheshti Maryam , Moazzam Shadrooz
Published: July 2022

Neuroblastoma (NB) is considered one of the malignant tumors of the nervous system which originates from primordial neural crest cell and is known as the most common extra-cranial solid tumor in childhood. This tumor which is often intra-abdominal, metastases in various sites including the skull, long bones, liver, bone marrow and lymph nodes, but lung metastasis at initial diagnosis is rare (0.2-3.7%). Here, the authors reported a two-year-old boy who referred to Imam Hussein Children's Hospital affiliated to Isfahan University of Medical Sciences, Iran in April 2017 with complaint of abdominal pain and distension along with diarrhea, vomiting and fever. In physical examination, a palpable mass was observed at the right side of the abdomen, that in further studies, NB with lung metastasis along with poorly differentiated, low MKI, positive MYCN amplification was reported. This is the first documented case report of NB with lung metastasis from Iran. In conclusion, although lung is considered as an unfavorable metastatic site for NB, in high grade and poor prognosis cases, this organ should also be examined in metastatic site examinations. Therefore, lung High-resolution computed tomography (HRCT) is introduced as the gold standard modality for this work.
Structural Mapping of Global Optimization Algorithms to Graphics Processing Unit Architecture
Authors: Seliverstov E.Yu.
Published: July 2022

Graphics processing units (GPU) deliver a high execution efficiency for modern metaheuristic algorithms with a high computation complexity. It is crucial to have an optimal task mapping of the optimization algorithm to the parallel system architecture which strongly affects the efficiency of the optimization process. The paper proposes a novel task mapping algorithm of the parallel metaheuristic algorithm to the GPU architecture, describes problem statement for the mapping of algorithm graph model to the GPU model, and gives a formal definition of graph mapping and mapping restrictions. The algorithm graph model is a hierarchical graph model consisting of island parallel model and metaheuristic optimization algorithm model. A set of feasible mappings using mapping restrictions makes it possible to formalize GPU architecture and parallel model features. The structural mapping algorithm is based on cooperative solving of the optimization problem and the discrete optimization problem of the structural model mapping. The study outlines the parallel efficiency criteria which can be evaluated both experimentally and analytically to predict a model efficiency. The experimental section introduces the parallel optimization algorithm based on the proposed structural mapping algorithm. Experimental results for parallel efficiency comparison between parallel and sequential algorithms are presented and discussed
Theoretical Assessment of Possible Reduction in Mass Leaks of Working Medium from a Reciprocating Compressor Chamber
Authors: Busarov S.S. , Kobylskiy R.E. , Sinitsin N.G.
Published: July 2022

The paper considers mass leaks of compressible medium through piston seals from the working chamber of a reciprocating compressor and possible ways of reducing those. We propose a monolithic lip piston design that should reduce mass leaks of the working medium and increase the efficiency of the piston compressor unit. We developed a computational technique that takes into account the processes inside the actual second compressor stage, including gas flows through imperfect seals in the working chamber. Combining previously published analytical equations with our promising piston seal design led to improving the following integral characteristics of the compressor stage: energy conversion efficiency, volumetric efficiency, gas compression temperature. Using the monolithic lip piston proposed should increase the reciprocating compressor unit efficiency by approximately 18 % via reducing the equivalent gap and increase volumetric efficiency by approximately 20 %, as mass leaks decrease while the mass of gas in the working chamber increases; as a result, the gas compression temperature should increase by approximately 18 %. We consider the monolithic lip piston proposed to be a promising piston seal design capable of reducing existing mass leaks, improving the indicated efficiency of the long-stroke second compressor stage along with the volumetric efficiency, and increasing the performance
Study into Solid Particles Moving in the Working Areas of Part-Flow Hydrodynamic Filters with a Rotating Perforated Baffle
Authors: Devisilov V.A. , L'vov V.A. , Fatova A.V.
Published: July 2022

The purpose of the research was to consider solid particles moving in part-flow hydrodynamic filters with a rotating perforated baffle and simulate liquid flows in the working zones of filters. The paper introduces the results of the study. Within the research, we determined the averaged values of the tangential, radial and axial components of the movement velocitis depending on the radius of the device, confirmed the validity of using a cylindrical filter wall, and established the presence of low-pressure and pressure modes of liquid cleaning in the filters. We revealed that in the low-pressure mode solid particles move in a typical for centrifuges way, and in the pressure mode the particles movement is characteristic of that of small-sized hydrocyclones. The study introduces a technique for obtaining averaged deterministic characteristics that make up the liquid flow velocity in height, azimuth and radius in the working zones of a hydrodynamic filter and estimates the averaged components of the liquid velocity. Compared to the tangential component, the axial velocity component is one order of magnitude smaller, and the radial component, two orders of magnitude smaller. Findings of the research show that the designs of such hydrodynamic filters implement a four-stage liquid cleaning system and emphasize that in transport equations not only deterministic components but also random components of ongoing processes should be taken into account for particles smaller than 40 μm
On the Results of Investigating the Efficiency of Ball Screws with Separators
Authors: Abdulin R.R. , Bolshakov V.V. , Podshibnev V.A. , Rozhnin N.B. , Samsonovich S.L.
Published: July 2022

Extensive use of ball screws with separators is due to manufacturing simplicity and increased reliability as compared to ball screws with recirculating rolling elements. The issues of determining the efficiency of such mechanisms have not been sufficiently studied. The paper presents analytically derived primary dimension ratios for parts of ball screws with separators, taking into account those tolerances that should be observed to ensure that the mechanism assembly is guaranteed and the preloads affecting the breakaway forces and the mechanism efficiency are prevented. We provide guidelines for designing parts of ball screws with separators. We plotted the interacting forces in the parts constituting ball screws with separators and analytically determined the efficiency of such mechanisms as a function of contact angles and lead angles. The experimental investigation results concerning electro-mechanical drive prototypes based on ball screws confirm the analytical expressions obtained. Adhering to the dimension ratios proposed for parts of ball screws with separators reveals that the analytically and experimentally determined efficiency values converge. Using the efficiency plots presented for ball screws with separators while designing electromechanical drives is appropriate to assess energy losses in mechanical transmissions
Validation of Models for Simulating the Soil Moisture Characteristics
Authors: Rank P.H. , Vishnu B.
Published: July 2022

Background: The determination of the soil moisture characteristic is a tedious, lengthy and costly laboratory methods. However, for the specific soil texture, once it is known, the soil moisture at various tension can be simulated through modelling approach which eliminates the requirements of performing the experiments every time. Therefore, the attempt was made for the determinations of the soil moisture characteristics during the year-2019 and validating the various models’ using these empirical data. Methods: The present research covers the experimentation during the year 2019 for determination of the soil moisture characteristics and fitting the obtained empirical data to mathematical frames of the various models. The moisture characteristics was obtained by measuring different moisture content values at different suction values through two experiments viz. wetting cycle (Absorption phase) and drying cycle (Desorption phase). The desorption curve was obtained by using the pressure plate apparatus and the wetting curve was measured through the capillary rise open tube method. Result: The saturation, field capacity, permanent wilting, residual moisture content, void ratio and saturated hydraulic conductivity were found as 43.5%v/v, 25.88%v/v, 12.05%v/v, 8.1%v/v. 0.77 and 0.2808 m/day respectively. Among the fitted models, the van Genuchten model was found best fit to observe data to simulate the desorption and sorption phase of the soil moisture retention characteristics. The soil moisture retention characteristics of the sorption and desorption phases indicated a hysteresis of approximately two log cycles.
Morpho-physiological Variability and Yield Determinants for Drought Tolerance in Blackgram [Vigna mungo (L.) Hepper]
Authors: Bordoloi D. , Sarma A. , Sarma D.
Published: July 2022

Background: An understanding of genotypic differences to water deficit stress can help in identifying genotypes that can tolerate drought with reasonable grain yield. The present experiment was conducted to assess the physiological and yield-related parameters of ten black gram genotypes under water deficit stress environment. Methods: We evaluated ten diverse black gram genotypes for yield and drought-related traits under water deficit stress (3.98% moisture content) and non-stress (14.35% moisture content) environments in separate pot experiments following complete randomized designs with three replications during Kharif 2015-16. Result: Analysis of variance revealed significant genetic variation among the genotypes for almost all the observed traits. The traits viz., 100-seed weights, proline content, pods per plant, relative leaf water content, chlorophyll content and seed yield per plant showed high heritability estimates coupled with a high genetic advance under both the environments. Based on grain yield efficiency index, the genotypes AKU 10-6, COBG 10-06 and NDUK 13-4 were drought efficient with high yield under stress condition.