bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short- and long-term outcomes from the upfront high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation in diffuse large B-cell lymphoma
Authors: Koviazin A. K. , Filatova L. V. , Zyuzgin I. S. , Artemyeva A. S. , Motalkina M. S. , Chudinovskikh Yu. A. , Dobrovolskaya E. V. , Volchenkov S. A. , Polyatskin I. L. , Shalaev S. A. , Ishmatova I. V. , Zverkova A. A. , Burda D. S. , Elkhova S. S. , Semiglazova T. Yu. 
Published: June 2022

Introduction. Diffuse large B-cell lymphoma (DLBCL) is the most common (30-35%) type of B-cell lymphomas. Only about 60% of all newly diagnosed advanced-stage DLBCL can be completely treated by x6 CHOP-R only. High dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto-HSCT) can serve an option to improve prognosis in these patients (pts).Aim. To improve prognosis in DLBCL IV stage, IPI ≥2 pts by upfront auto-HSCT.Materials and methods. Included 105 pts: DLBCL NOS, age 18-65, stage IV, IPI ≥2, CR/PR after x6 CHOP/EPOCH + R from 2010 to 2019 at NMRC of Oncology named after N.N. Petrov of MoH of Russia were retrospectively analyzed. HSCT group includes pts with upfront HDCT followed by auto-HSCT (n = 35). The control group includes pts with non-invasive follow-up after induction only (n = 70). Primary endpoints were overall (OS) and progression-free survival (PFS). Secondary endpoints were response rate, relapse rate and treatment toxicity.Results and discussion. The 3-yr OS (p = 0.01) and 3-yr PFS (p = 0.018) were significantly higher in HSCT group. The complete response rate was significantly increased after upfront auto-HSCT (p < 0.001). Early relapse served as an independent negative prognostic factor in OS (p < 0.001) and experienced statistically less in HDCT group (p = 0.027). Early (ER) and late relapse (LR) rate were higher in pts with DEL (ER - p < 0.001, LR - p < 0.001 in control group and ER - p < 0.001, LR -p = 0.013 in all pts). The overall relapse rate was higher if pts had >1 extranodal site with lung involvement (p < 0.004 in the control group and p = 0.021 in all pts). Prognostic models suggested DEL and presence of >1 extranodal site with lung involvement as an independent negative prognostic factors for increasing the relapse probability in two years after treatment.Conclusion. Upfront HSCT can serve as a clinical option to consolidate the first remission in IV stage DLBCL pts with DEL and/or >1 extranodal sites with lung involvement.
Key differences between anti-PD-1/PD-L1 inhibitors
Authors: Zhukova N. V. , Orlova R. V. , Kaledina E. A. , Naymushina P. A. , Malkova A. M. , Beliak N. P. 
Published: June 2022

Indications to immunotherapy in cancer treatment continue to expand, thus there are more and more questions about clinical aspects of using different checkpoint inhibitors. Despite similar mechanism of action between widely used antibodies to PD-1 (nivolumab, pembrolizumab, prolgolimab) and PD-L1 (durvalumab, avelumab, atezolizumab), inhibitors are different due to features of monoclonal antibodies structure they are based on. For instance, toxicity leading to discontinuation of treatment occurs more frequently with anti-PD-L1 drugs than PD-1 inhibitors. On the contrary, the average incidence of any grade IRAEs was higher in patients treated with anti-PD-1 drugs. The revealed differences in the toxicity of the analyzed groups of drugs could be associated with the type of action of the drug. The feature of the PD-L1 inhibitors is more frequent occurrence of antibody-dependent cellular cytotoxicity reactions. However, PD-1 inhibitors showed a statistically significant survival benefit, according to a meta-analysis comparing anti-PD-1 and anti-PD-L1 groups. Besides data on differences in the efficacy and toxicity profiles of these agents, in this article we also analyze different issues in the structure of drug molecules, in particular, the role of LALA mutation in anti-PD-1 inhibitors. Understanding the key distinctive points of check-point inhibitors (CPI) in the future may allow to solve the problem of rechallenge and reintroduction after management of severe IRAEs.
Immunotherapy of advanced hepatocellular carcinoma: case report and literature review
Authors: Menshikov K. V. , Sultanbaev A. V. , Musin Sh. I. , Menshikova I. A. , Abdeev R. R. , Sultanbaeva N. I. , Nigmatullin V. G. , Popova E. V. 
Published: June 2022

Hepatocellular carcinoma is a common type of liver malignancy and one of the leading causes of cancer death worldwide. In the Russian Federation, according to statistical reports, there is also an increase in the incidence. For over 10 years, the tyrosine kinase inhibitor sorafenib has been the only approved treatment for advanced hepatocellular carcinoma. Lenvatinib was registered as the second drug for the treatment of advanced hepatocellular carcinoma in the first line. In the era of checkpoint inhibitors, the possibility of such therapy in the first and subsequent lines of advanced hepatocellular carcinoma remains relevant. The combination of atezolizumab with bevacizumab in a phase III study (IMbrave150) improved treatment outcomes such as overall survival and progression-free survival. The results of the phase III randomized trial IMbrave 150 showed undoubtedly better efficacy of the atezolizumab + bevacizumab combination compared to sorafenib in terms of a median progression-free survival of 6.8 vs 4.3 months. The above clinical observation demonstrates the result of treatment of a patient with advanced hepatocellular carcinoma with a combination of atezolizumab and bevacizumab. After verification of the diagnosis, since January 2021, therapy with a combination of atezolizumab 1200 mg, bevacizumab 15 mg/kg was started with an interval of 21 days.At present, 20 courses of therapy have been carried out in this regimen, and the stabilization of the disease is maintained. Against the background of the ongoing therapy, no adverse events were noted, including immune-mediated ones that required the abolition or reduction of doses of drugs. In the above clinical observation, a patient with severe comorbidity achieved stabilization of the disease in the first three months of therapy. Combination therapy showed a favorable tolerability profile.
Identification of Neural Progenitor Cell-associated Chemoradiotherapy Resistance
Gene Set (ARL4C, MSN, TNFAIP6) for Prognosis of Glioma
Authors: Yang Yongchang , Xu Xing , Xie Yang , Liu Yancheng , Ning Chunlan , Ai Yiding , Lv Chao , Wei Haotian , Ge Xianglian , Yi Tailong , Piao Yongjun , Wang Xiaoguang , Jin Xun 
Published: June 2022

Background:
Glioma is the most common malignant intracranial tumor with high lethality. Despite surgery combined with chemoradiotherapy, the prognosis for patients with glioma remains poor. This is primarily due to acquired chemoradiotherapy resistance. Therefore, to improve the prognosis of glioma, further study into the mechanism of chemoradiotherapy resistance is needed.

Objective:
This study aimed to (1) evaluate the prognosis of patients with glioma by using a prognostic risk score model constructed by chemoradiotherapy resistance genes, (2) provide new targets and directions for precise treatment of glioma, and (3) discuss the tumor heterogeneity of tumor cells.

Methods:
According to therapy class and overall survival (OS), we identified 53 genes associated with glioma chemoradiotherapy resistance in The Cancer Genome Atlas Glioblastoma (TCGA GBM) database. Considering the improtant role of chemoradiotherapy resistance-related genes in the prognosis of glioma, we preliminarily screened and identified vital prognostic factors among these genes by using Cox regression model of absolute contraction and selection operators in the TCGA GBM lower-grade glioma (TCGA GBMLGG) dataset. Next, the heterogeneity of the chemoradiotherapy resistance-associated genes in different glioma cells was revealed by single-cell sequencing in the GSE117891 cohort.

Results:
A prognostic risk score model consisting of three genes (ARL4C, MSN, TNFAIP6) was constructed. The expression of this model was high in glioma neural progenitor cells (NPCs) and low in glioma oligodendrocytes. The OS rates were significantly lower in the high- vs low-risk group.

Conclusion:
Our 3 gene risk score complements current glioma diagnosis and provides a novel insight into chemoradiotherapy resistance mechanisms for the prognosis of patients with glioma.
A Network Pharmacology Approach for Uncovering the Mechanism of
'Kouchuangling' in Radiation-induced Oral Mucositis Treatment
Authors: Li Bo , Sheng Pei , Xie Jing , Wu Yuqing , Xia Xiaotong , Wu Mianhua 
Published: June 2022

Background:
Radiation-induced oral mucositis (RIOM) is an intractable inflammatory
disease whose pathogenesis needs to be clarified. “Kouchuangling” (KCL), a traditional Chinese
medicine formula, is composed of Lonicerae Japonicae Flos, Radix Paeoniae Rubra, and Radix
Sanguisorbae. Although all of them are Chinese folk medicines which have long been utilized for
ameliorating inflammation, the mechanism of KCL to RIOM remains unclear.

Purpose:
To predict the active ingredients of KCL and identify the mechanism of KCL on RIOM.

Material and Methods:
We identified the chemical ingredients in KCL using TCM Systems
Pharmacology (TCMSP), TCM@Taiwan, PubChem, and SuperPred databases and used the oral
bioavailability (OB), drug-like properties (DL) and Degree of compounds for screening. Targets
for oral mucositis were obtained from the Online Mendelian Inheritance in Man (OMIM), Therapeutic
Target Database (TTD), PharmGKB, and DrugBank databases. Cytoscape 3.7.0 was used to
visualize the compound-target-disease network for KCL and RIOM. The biological processes of
target gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways
were analyzed using DAVID.

Results:
Based on OB≥30%, DL≥0.18 and Degree≥3, 24 active ingredients and 960 targets on
which the active components acted were identified. A total of 1387 targets for oral mucositis were
screened. GO enrichment and KEGG pathway analyses resulted in 43 biological processes (BPs), 3
cell components (CCs), 5 molecular functions (MFs), and 32 KEGG pathways, including leishmaniasis,
Toll-like receptor signaling, TNF signaling, and Influenza A pathways.

Conclusion:
This experiment preliminarily verified that the active ingredients of KCL play a role
in the treatment of RIOM through multiple targets and pathways, providing a reference for further
study of the pharmacological mechanism of Chinese herbal medicine.
Dysregulated YAP1/Hippo Pathway Contributes to Doxorubicin (ADM)
Resistance in Acute Myeloid Leukemia (AML)
Authors: Chen Xi , Song Yan , Huang Rui , Liu Juan 
Published: June 2022

Background:
Dysregulated Yes-associated protein 1 (YAP1) is closely associated with cancer progression and chemo-resistance. We aim to explore the role of YAP1/Hippo pathway in regulating doxorubicin (ADM)-resistance in acute myeloid leukemia (AML).

Methods:
In this study, we established two ADM-resistant cell lines (THP-1/ ADM and K562/ ADM). Then cell viability and apoptosis were detected by MTT assay and FCM assay, respectively. Real time PCR were performed to examine the expression of genes in the AML/ADM cells and the clinic BM samples. The levels of all related proteins were examined by Western blot.

Results:
We found that the YAP1 and its downstream target genes, including EGFR, SOX2, and OCT4, were associated with ADM-resistance, evidenced by the increased expression in ADM-resistant AML/ADM cells and clinical BM specimens. Additionally, YAP1 ablation enhanced the promoting effects of ADM treatment on cell death in AML/ADM cells. Conversely, YAP1 increased ADM-a resistance in the original ADM-sensitive AML cells. These results may provide important new insights into understanding this role of YAP1 regulates AML resistance by affecting CSCs characteristics.

Conclusion:
In summary, we evidenced that the dysregulated YAP1/Hippo pathway influenced ADM-resistance in AML. YAP1 might be novel biomarkers for treatment of drug-resistance in AML.
New Era on Combining Both Imaging and Drug Delivery to Treat Cancer
Authors: Siafaka Panoraia , Çağlar Emre Şefik , Gündoğdu Evren Atlıhan , Okur Neslihan Üstündağ 
Published: June 2022

Abstract:
It is well documented that cancer is one of the leading causes of death worldwide. During
the pandemic, cancer screening was suspended, and only symptomatic patients were referred for
screening. It is believed that deaths related to various cancer types have increased by around 10%, and
the screening suspension was assumed as the main reason. It is well documented that the early diagnosis
of cancer is important for the outcome; last decades, the introduction of nanotechnology-based
carriers, which can serve as both imaging and therapeutic modalities, has risen. Although the combination
of imaging and drug delivery for targeting cancer is a hopeful field, it is still under investigation
and has not met clinical standards. Nanotheranostics, as they are also referred to, can combine both
imaging and delivery and improve the survival rates and overall quality of life of patients. Would cancer
patients have a chance to live a normal life if nano theranostics were incorporated into the daily
clinical oncology practice? This review tries to answer this question by providing the most current
applications of nanotheranostics targeting different types of cancer and summarizing their most significant
characteristics.
Effects of MCU-mediated Ca2+ Homeostasis on Ovarian Cancer
Cell SKOV3 Proliferation, Migration and Transformation
Authors: Zhao Lantao , Jiang Man , Tian Tian , Wang Guanqun , Mei Yingying , Fu Guangming , Zhou Na 
Published: June 2022

Background:
Atlas human proteomics database showed MCU as highly
expressed in various tumor tissues, especially in ovarian cancer. Rare studies on the
role of MCU and its regulation in ovarian cancer have been reported.

Objective:
The objective of this study was to determine role of MCU in ovarian cancer
cell SKOV3 proliferation, migration, and transformation, and explore the possible
mechanism.

Methods:
MCU siRNA on lentiviral particles were stably transfected into SKOV3 cells. CCK-8 assay was performed to analyze cell proliferation. Soft-agar colony formation assay was employed to evaluate the tumorigenesis. Western blot and immunohistochemistry analyses were performed to evaluate the expression of MCU, MICU1 and phosphorylate of Akt in ovarian cancer cell and tissue specimens. Scratch assay was combined with trans-well plates assay to detect the migration ability of cancer cells. The ROS production and Ca2+ were also determined.

Results:
MCU expression was significantly higher in ovarian cancer tissues than normal
tissues. MCU silencing decreased SKOV3 cell proliferation, migration, and
transformation. ROS production was decreased after MCU silencing, depending on
disturbed Ca2+ homeostasis. MICU1 expression has been found to be decreased and
phosphorylation of Akt increased when MCU was silenced.

Conclusions:
Down-regulation of MCU inhibited SKOV3 cell proliferation, migration, and
transformation via disturbing Ca2+ homeostasis and decreasing ROS production. MICU1
and phosphorylation of Akt are associated with MCU-mediated ovarian cancer
malignancy.
Extraction, Purification, and Development of Sublingual Film (SLIT
Films) Comprising Cockroach Allergen for Treatment of Allergy
Authors: Anita Leishangthem , D. P Venkatesh , B Sajeev Kumar , Kanni Paranjothy , Ramnarayanan Chandramouli , Karki Roopa , Komarla Nagendra Prasad , Janadri Suresh 
Published: June 2022

Aim:
Allergy associated with cockroaches are mostly from the American cockroach (Periplaneta americana) and German cockroach (Blattella germanica). The effective and safe treatment for cockroach allergy is Sublingual immunotherapy (SLIT). In this study SLIT Films containing purified allergen extract of Periplaneta americana were prepared by solvent casting and were evaluated for their efficiency in delivery.

Methodology:
Cockroach allergen extract was prepared and purified by ultrafiltration and chromatography. The molecular weight of protein content was identified and estimated by SDS- PAGE and ELISA. SLIT films were developed by the Quality by Design (QbD) approach and were evaluated for allergen-excipient compatibility, swelling index, taste, diffusion, in vitro dissolution, local toxicity, and stability analysis.

Results:
Cockroach allergen protein extracts (cut-off 25-71KDa) were identified by SDS-PAGE and quantified by indirect ELISA, further selected for sublingual film preparation. The indirect ELISA results show a higher optical density (OD) value compared to crude extract. The weight uniformity and thickness of the film were between 13-18 mg and 0.04-0.06 mm. The disintegration time was found to be less than 1 min. The cumulative percentage release was also found to be satisfactory.

Conclusion:
SLIT Film containing cockroach allergen from Periplaneta americana were successfully developed and evaluated. SLIT films of cockroach allergen could be more beneficial and convenient for emergency use in patients when compared to subcutaneous immunotherapy. SLIT films provide dose accuracy and are a promising alternative for SCIT and SLIT drops and tablets.
Acute and Subchronic Treatment of Roasted and Unroasted Argan Oil on Postprandial Glycemia and Its Effect on Glucose Uptake by Isolated Rat Hemidiaphragm
Authors: Daoudi Nour Elhouda , Bouhrim Mohamed , Bouziane Omar , Abdnim Rhizlan , Bouknana Saliha , Elrherabi Amal , Mekhfi Hassane , Aziz Mohammed , Legssyer Abdelkhaleq , Ziyyat Abderrahim , Bnouham Mohamed 
Published: June 2022

Background:Argan oil is one of the products used for antidiabetic purposes in Morocco.Objective:This work aims to study the acute and subchronic effect treatment of the roasted (Roil) and unroasted (UnRoil) Argan oils on oral glucose tolerance test (OGTT) and body weight in normal and diabetic rats, evaluate the effect of these oils on glucose absorption by the diaphragm and determine total polyphenol, flavonoids, tannins, chlorophyll and carotenoids amounts.Methods:The anti-hyperglycemic effect of Roil and UnRoil was investigated in normal and alloxanediabetic rats by treating the animals orally with 2 mLKg-1/day of oils for 1 day (Acute treatment) and 4 weeks (Subchronic treatment). Then, OGTT was carried out at the end of each treatment, and the body weight was checked for each week. Besides, these oils (1 gL-1) were tested on glucose absorption by the diaphragm isolated from Wistar rats in vitro.Results:This work shows that Roil and UnRoil significantly decrease the postprandial glycemic level in acute and subchronic treatments in normal and diabetic rats. Besides, the intake of these oils in diabetic rats significantly attenuates the postprandial glycemia compared to the acute-treated group. In vitro glucose uptake by the hemidiaphragm study shows that Argan oils promote glucose consumption by the muscles.Conclusion:Argan oils showed a very important anti-hyperglycemic effect, which could be explained by promoting peripheral glucose uptake. UnRoil shows a better effect than Roil on glucose consumption, meaning that the roasting process influences the phytoconstituent responsible for this activity.
Preclinical Large Animal In-Vivo Experiments for Surgically Implanted
Atrioventricular Valve: Reappraisal and Systematic Review
Authors: Sazzad Faizus , Kollengode Ramanathan , Beverly Chan Li Xuan , Kiat Tan Ying , Ganesh Geetha , Kofidis Theo 
Published: June 2022

Background:
The development of atrioventricular bioprosthesis has witnessed an
increasing drive toward clinical translation over the last few decades. A significant challenge in the
clinical translation of an atrioventricular bioprosthesis from bench to bedside is the appropriate
choice of a large animal model to test the safety and effectiveness of the device.

Methods:
We conducted a systematic review of pre-clinical in vivo studies that would enable us to
synthesize a recommended framework. PRISMA (Preferred Reporting Items for Systematic Reviews
and MetaAnalyses) guidelines were followed to identify and extract relevant articles.

Results:
Sheep was the most common choice of animal, with nine out of the 12 included studies
being conducted on sheep. There were acute and chronic studies based on our search criteria. An
average of ~20 and 5 animals were used for chronic and acute studies. One out of three acute
studies and eight out of nine chronic studies were on stented heart valve bioprosthesis. All analyses
were conducted on the implantation of atrioventricular valves with trileaflet, except for one chronic
study on unileaflet valves and one chronic and acute study on bileaflet valves.

Conclusion:
Understanding the variance in past pre-clinical study designs may increase the appropriate
utilization of large animal models. This synthesized evidence provides a pre-clinical in vivo
studies framework for future research on an atrioventricular bioprosthesis.
A Study of Variance and its Utility in Machine Learning
Authors: Sharma Krishna Gopal , Singh Yashpal 
Published: June 2022

Abstract:
With the availability of inexpensive devices like storage and data sensors, collecting and
storing data is now simpler than ever. Biotechnology, pharmacy, business, online marketing websites,
Twitter, Facebook, and blogs are some of the sources of the data. Understanding the data is crucial today
as every business activity from private to public, from hospitals to mega mart benefits from this.
However, due to the explosive volume of data, it is becoming almost impossible to decipher the data
manually. We are creating 2.5 quintillion bytes per day in 2022. One quintillion byte is one billion Gigabytes.
Approximately, 90% of the total data is created in the last two years. Naturally, an automatic
technique to analyze the data is a necessity today. Therefore, data mining is performed with the help of
machine learning tools to analyze and understand the data. Data Mining and Machine Learning are
heavily dependent on statistical tools and techniques. Therefore, we sometimes use the term – “Statistical
Learning” for Machine Learning. Many machine learning techniques exist in the literature and
improvement is a continuous process as no model is perfect. This paper examines the influence of variance,
a statistical concept, on various machine learning approaches and tries to understand how this
concept can be used to improve performance.