bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of human bone marrow mesenchymal stem cell-derived microvesicles on the apoptosis of the multiple myeloma cell line U266
Authors: Vafaeizadeh Mona , Abroun Saeid , Soufi Zomorrod Mina 
Published: June 2024

Abstract
Background
Microvesicles are membraned particles produced by different types of cells recently investigated for anticancer purposes. The current study aimed to investigate the effects of human bone marrow mesenchymal stem cell-derived microvesicles (BMSC-MVs) on the multiple myeloma cell line U266. BMSC-MVs were isolated from BMSCs via ultracentrifugation and characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). U266 cells were treated with 15, 30, 60, and 120 µg/mL BMSC-MVs for three and seven days and the effects of treatment in terms of viability, cytotoxicity, and DNA damage were investigated via the MTT assay, lactate dehydrogenase (LDH) assay, and 8‑hydroxy-2’-deoxyguanosine (8‑OHdG) measurement, respectively. Moreover, the apoptosis rate of the U266 cells treated with 60 µg/mL BMSC-MVs was also assessed seven days following treatment via flow cytometry. Ultimately, the expression level of BCL2, BAX, and CCND1 by the U266 cells was examined seven days following treatment with 60 µg/mL BMSC-MVs using qRT-PCR.

Results
BMSC-MVs had an average size of ~ 410 nm. According to the MTT and LDH assays, BMSC-MV treatment reduced the U266 cell viability and mediated cytotoxic effects against them, respectively. Moreover, elevated 8‑OHdG levels following BMSC-MV treatment demonstrated a dose-dependent increase of DNA damage in the treated cells. BMSC-MV-treated U266 cells also exhibited an increased apoptosis rate after seven days of treatment. The expression level of BCL2 and CCND1 decreased in the treated cells whereas the BAX expression demonstrated an incremental pattern.

Conclusions
Our findings accentuate the therapeutic benefit of BMSC-MVs against the multiple myeloma cell line U266 and demonstrate how microvesicles could be of therapeutic advantage. Future in vivo studies could further corroborate these findings.
Unraveling the significance of AGPAT4 for the pathogenesis of endometriosis via a multi-omics approach
Authors: Chen Jun , Shen Licong , Wu Tingting , Yang Yongwen 
Published: June 2024

AbstractEndometriosis is characterized by the ectopic proliferation of endometrial cells, posing considerable diagnostic and therapeutic challenges. Our study investigates AGPAT4’s involvement in endometriosis pathogenesis, aiming to unveil new therapeutic targets. Our investigation by analyzing eQTL data from GWAS for preliminary screening. Subsequently, within the GEO dataset, we utilized four machine learning algorithms to precisely identify risk-associated genes. Gene validity was confirmed through five Mendelian Randomization methods. AGPAT4 expression was measured by Single-Cell Analysis, ELISA and immunohistochemistry. We investigated AGPAT4’s effect on endometrial stromal cells using RNA interference, assessing cell proliferation, invasion, and migration with CCK8, wound-healing, and transwell assays. Protein expression was analyzed by western blot, and AGPAT4 interactions were explored using AutoDock. Our investigation identified 11 genes associated with endometriosis risk, with AGPAT4 and COMT emerging as pivotal biomarkers through machine learning analysis. AGPAT4 exhibited significant upregulation in both ectopic tissues and serum samples from patients with endometriosis. Reduced expression of AGPAT4 was observed to detrimentally impact the proliferation, invasion, and migration capabilities of endometrial stromal cells, concomitant with diminished expression of key signaling molecules such as Wnt3a, β-Catenin, MMP-9, and SNAI2. Molecular docking analyses further underscored a substantive interaction between AGPAT4 and Wnt3a.Our study highlights AGPAT4’s key role in endometriosis, influencing endometrial stromal cell behavior, and identifies AGPAT4 pathways as promising therapeutic targets for this condition.
Characterization of bacteriophages infecting multidrug-resistant uropathogenic Escherichia coli strains
Authors: Markusková Barbora , Elnwrani Sulafa , Andrezál Michal , Sedláčková Tatiana , Szemes Tomáš , Slobodníková Lívia , Kajsik Michal , Drahovská Hana 
Published: June 2024

AbstractUropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infections, and strains that are resistant to antibiotics are a major problem in treating these infections. Phage therapy is a promising alternative approach that can be used to treat infections caused by polyresistant bacterial strains. In the present study, 16 bacteriophages isolated from sewage and surface water were investigated. Phage host specificity was tested on a collection of 77 UPEC strains. The phages infected 2–44 strains, and 80% of the strains were infected by at least one phage. The susceptible E. coli strains belonged predominantly to the B2 phylogenetic group, including strains of two clones, CC131 and CC73, that have a worldwide distribution. All of the phages belonged to class Caudoviricetes and were identified as members of the families Straboviridae, Autographiviridae, and Drexlerviridae and the genera Kagunavirus, Justusliebigvirus, and Murrayvirus. A phage cocktail composed of six phages – four members of the family Straboviridae and two members of the family Autographiviridae – was prepared, and its antibacterial activity was tested in liquid medium. Complete suppression of bacterial growth was observed after 5–22 hours of cultivation, followed by partial regrowth. At 24 hours postinfection, the cocktail suppressed bacterial growth to 43–92% of control values. Similar results were obtained when testing the activity of the phage cocktail in LB and in artificial urine medium. The results indicate that our phage cocktail has potential to inhibit bacterial growth during infection, and they will therefore be preserved in the national phage bank, serving as valuable resources for therapeutic applications.
The incidence and intensity of postoperative pain and Flare-up following the use of three different intracanal medicaments in teeth with posttreatment apical periodontitis: a randomized clinical trial
Authors: Angın Adile Esen , Özkan Hicran Dönmez , Saral İlkim Pınar , Aydın Berdan 
Published: June 2024

Abstract
Objectives
This randomized clinical trial aimed to compare the effect of intracanal medicaments on the incidence of postoperative pain and flare-up with posttreatment apical periodontitis (PTAP) of retreatment cases.

Materials and methods
One hundred twenty patients diagnosed with PTAP with single-rooted teeth with single-canal without spontaneous pain or swellings were included and randomly divided into three groups according to the intracanal medicament used. Intracanal medicaments were placed into the root canals following the removal of previous root canal fillings and re-instrumentation. Calcium hydroxide (Ca (OH)2), chlorhexidine gel (CHX), calcium hydroxide and chlorhexidine gel combinations were used as intracanal medicaments. Postoperative pain scores were recorded at 6 and 12 h and 1, 2, 3, 4, 5, 6, and 7 days using a visual analog scale (VAS). Sensitivity on percussion, spontaneous pain, swelling, antibiotic and analgesic requirements of the patients were evaluated during clinical examinations performed postoperatively after 2 and 7 days.

Results
There were no statistically significant differences between groups in terms of VAS scores following the intracanal medicament application (p > 0.05). However, compared to the patients of 20–34 and 50–65 age groups, greater VAS scores were observed in patients of 35–49 age groups at 12 h, and 3, 4, 7 days (p < 0.05). Flare-up was observed in only one patient in the CHX gel group, and no flare-up was observed in other groups.

Conclusions
Similar postoperative pain incidence in all experimental groups indicates that all three medicaments are clinically acceptable in inter-appointment management of retreatment cases in terms of post-endodontic pain and flare-up.

Clinical relevance
In this randomized clinical trial, three different intracanal medicaments were utilized in nonsurgical endodontic retreatment and their effect on postoperative pain and flare-up incidence was examined. Thus, this study will be a significant contribution in the decision-making during clinical practice; since there are a limited number of prospective clinical trials in the literature about the severity of pain following retreatment procedures including intracanal medicament use.
The DECOVALEX international collaboration on modeling of coupled subsurface processes and its contribution to confidence building in radioactive waste disposal
Authors: Birkholzer Jens T. , Bond Alexander E. , Tsang Chin-Fu 
Published: June 2024

Abstract
The long-lived radiotoxicity of the high-level radioactive waste generated by nuclear power plants requires safe isolation from the biosphere for many hundreds of thousands of years. An international consensus has emerged that such isolation can best be provided by disposal in mined geologic repositories, a strategy that today is pursued by most countries dealing with radioactive waste. However, the need to predict the performance of such repositories over very long time periods generates large uncertainties that have to be accounted for in safety assessments. The findings from such safety assessments need to be conveyed to all stakeholders in a clear way, such that public confidence in geologic disposal solutions can be achieved. It is suggested here that close international collaboration on the technical aspects of geologic waste disposal has helped, and will continue to help, building trust and increasing confidence. This paper discusses a particular international collaboration initiative referred to as DECOVALEX, which brings together multiple teams and disciplines to collectively tackle complex experimental and modeling challenges related to geologic disposal. By describing how DECOVALEX works and by providing joint research examples, a case is made that such international collaboration contributes to knowledge transfer and confidence building in radioactive waste disposal science.
Recent developments and future directions of first-line systemic therapy combined with immunotherapy for advanced or metastatic urothelial carcinoma: a historical perspective on treatment evolution
Authors: Kawashima Atsunari , Ishizuya Yu , Yamamoto Yoshiyuki , Kato Taigo , Hatano Koji , Nonomura Norio 
Published: June 2024

AbstractUrothelial carcinoma presents significant treatment challenges, especially in advanced stages. Traditionally managed with platinum-based chemotherapy, the advent of immunotherapies, particularly immune checkpoint inhibitors, has revolutionized urothelial carcinoma treatment. This review explores the evolution of urothelial carcinoma management, focusing on the transition from immune checkpoint inhibitors monotherapy to innovative combination therapies. Pembrolizumab, following the KEYNOTE-045 trial, emerged as a pivotal ICI in pretreated metastatic urothelial carcinoma, outperforming traditional chemotherapy. However, limitations surfaced in untreated metastatic urothelial carcinoma patients, particularly in those with low PD-L1 expression, as evidenced by trials like IMvigor130 and KEYNOTE-361. These challenges led to the exploration of combination therapies, including immune checkpoint inhibitors with platinum-based chemotherapy, tyrosine kinase inhibitors, and antibody–drug conjugates. Notably, the CheckMate 901 trial demonstrated improved outcomes with a nivolumab–chemotherapy combination. A significant breakthrough was achieved with the combination of enfortumab vedotin, an antibody–drug conjugates, and pembrolizumab, setting a new standard in first-line treatment for locally advanced or metastatic urothelial carcinoma. Future directions involve further exploration of antibody–drug conjugates and immune checkpoint inhibitors, as seen in the TROPHY-U-01 and TROPiCS-4 trials. The review concludes that the locally advanced or metastatic urothelial carcinoma treatment landscape is rapidly evolving, with combination therapies offering promising avenues for improved patient outcomes, signaling a new era in urothelial carcinoma management.
Prognosis of microscopic polyangiitis is well predictable in the first 2 weeks of treatment
Authors: Owaki Akiko , Tanaka Akihito , Furuhashi Kazuhiro , Watanabe Yu , Koshi-Ito Eri , Imaizumi Takahiro , Maruyama Shoichi 
Published: June 2024

Abstract
Background
Kidney and life outcomes remain unsatisfactory in patients with microscopic polyangiitis (MPA). Appropriate treatment intensity must be provided to the appropriate patients. To identify severe cases early, we investigated the factors related to kidney and life outcomes.

Methods
We included patients diagnosed with MPA based on myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positivity and kidney histopathology results after kidney biopsies between January 1, 2021, and May 11, 2023, at 10 affiliated centers, including our hospital. Death, maintenance dialysis, and estimated glomerular filtration rate (eGFR) < 15 after 6 months of treatment were defined as poor prognosis groups, and factors associated with these conditions were investigated.

Results
We included 84 (36 men and 48 women) patients in this study. Median age was 73.8 (interquartile range: 71–81) years. After 6 months of treatment, the proportion of patients in the poor prognosis group was 16.7 %, with a mortality of 7.1 % and a poor kidney prognosis rate of 9.5 %. Area under the receiver operating characteristic curve showed that eGFR at 2 weeks had a comparable prognostic performance equal as eGFR at 4 weeks (area under the curve: 0.875 and 0.896, respectively). After adjustment by various factors, eGFR at 2 weeks was related with prognosis significantly (p = 0.031).

Conclusion
Kidney function 2 weeks after the start of treatment for MPA can predict prognosis.