bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, synthesis, and docking of novel thiazolidine‐2,4‐dione multitarget scaffold as new approach for cancer treatment
Authors: Hanafy Noura S. , Aziz Nada A. A. M. , El‐Hddad Sanadelaslam S. A. , Abdelgawad Mohamed A. , Ghoneim Mohammed M. , Dawood Amal F. , Mohamady Samy , El‐Adl Khaled , Ahmed Sahar 
Published: May 2023

AbstractNovel thiazolidine‐2,4‐diones have been developed and estimated as conjoint inhibitors of EGFRT790M and VEGFR‐2 against HCT‐116, MCF‐7, A549, and HepG2 cells. Compounds 6a, 6b, and 6c were known to be the dominant advantageous congeners against HCT116 (IC50 = 15.22, 8.65, and 8.80 µM), A549 (IC50 = 7.10, 6.55, and 8.11 µM), MCF‐7 (IC50 = 14.56, 6.65, and 7.09 µM) and HepG2 (IC50 = 11.90, 5.35, and 5.60 µM) mass cell lines, correspondingly. Although compounds 6a, 6b, and 6c disclosed poorer effects than sorafenib (IC50 = 4.00, 4.04, 5.58, and 5.05 µM) against the tested cell sets, congeners 6b and 6c demonstrated higher actions than erlotinib (IC50 = 7.73, 5.49, 8.20, and 13.91 µM) against HCT116, MCF‐7 and HepG2 cells, yet lesser performance on A549 cells. The hugely effective derivatives 4e–i and 6a–c were inspected versus VERO normal cell strains. Compounds 6b, 6c, 6a, and 4i were found to be the most effective derivatives, which suppressed VEGFR‐2 by IC50 = 0.85, 0.90, 1.50, and 1.80 µM, respectively. Moreover, compounds 6b, 6a, 6c, and 6i could interfere with the EGFRT790M performing strongest effects with IC50 = 0.30, 0.35, 0.50, and 1.00 µM, respectively. What is more, 6a, 6b, and 6c represented satisfactory in silico computed ADMET profile.
Cyclic Trinickel(II) Clusters in a Metal‐Azolate Framework for Efficient Overall Water Splitting
Authors: Liu Yan‐Chen , Huang Jia‐Run , Zhao Zhen‐Hua , Liao Pei‐Qin , Chen Xiao‐Ming 
Published: May 2023

AbstractHerein, a stable metal‐azolate framework with cyclic trinickel(II) clusters, namely [Ni3(μ3‐O)(BTPP)(OH)(H2O)2] (Ni‐BTPP, H3BTPP=1,3,5‐tris((1H‐pyrazol‐4‐yl)phenylene)benzene), achieved a current density of 50 mA cm−2 at a cell voltage of 1.8 V in 1.0 M KOH solution, while the current density of 20%Pt/C@NF||IrO2@NF is just 35.8 mA cm−2 at 2.0 V under the same condition. Moreover, no obvious degradation was observed over 12 hours of continuous operation at a large current density of 50 mA cm−2. Theoretical calculations revealed that the μ3‐O atom in the cyclic trinickel(II) cluster serves as hydrogen‐bonding acceptor to facilitate the dissociation of a H2O molecule adsorbed on the adjacent Ni(II) ion, giving a lower energy barrier of H2O dissociation compared with Pt/C; meanwhile, the μ3‐O atom can also participate in the water oxidation reaction to couple with the adjacent *OH adsorbed on Ni(II) ion, providing a low‐energy coupling pathway, thus Ni‐BTPP achieves a high performance for overall water splitting.
Predictors of urinary outcomes following robotic‐assisted laparoscopic prostatectomy
Authors: Hutchison Dylan , Zillioux Jacqueline , Ali Marwan , Farhi Jacques , DeNovio Anthony , Barquin David , Rapp David E. 
Published: May 2023

AbstractIntroductionIncontinence and urgency are common after prostatectomy. The University of Virginia prostatectomy functional outcomes program (PFOP) was developed to comprehensively assess and optimise continence outcomes following robotic‐assisted laparoscopic prostatectomy (RALP). Patients are prospectively evaluated by a Female Pelvic Medicine and Reconstructive Surgery specialist. This study assessed for predictors of 3‐ and 6‐month stress urinary incontinence (SUI) and urgency symptom outcomes following RALP.MethodsWe performed a post hoc review of patients from our PFOP receiving a minimum of 6‐month follow‐up. Urinary symptoms are prospectively assessed using the validated International Consultation on Incontinence Questionnaire‐Male Lower Urinary Tract Symptoms (ICIQ‐MLUTS) questionnaire and daily pad use (pads per day [PPD]). Primary study outcomes included ICIQ‐MLUTS SUI and urgency domain scores and PPD. Multivariable linear regression was performed to identify variables associated with outcomes at 3 and 6 months postoperatively. Variables included patient, oncologic and surgical factors. Each variable was run in a separate model with pelvic floor muscle therapy and surgeon to reduce confounding and prevent overfitting.ResultsForty men were included. In assessment of ICIQ‐MLUTS SUI domain score, at 3 months, body mass index (BMI) was associated with worse scores, and at 6 months, BMI, hypertension and estimated blood loss (EBL) were associated with worse scores, whereas bilateral nerve‐sparing technique was associated with better scores. For ICIQ‐MLUTS Urgency domain score, at 3 months, preoperative use of benign prostatic hyperplasia (BPH) medication was associated with better scores. No covariates predicted 6‐month ICIQ‐MLUTS Urgency domain scores. For PPD use, at both 3 and 6 months, BMI was a positive predictor, while preoperative use of BPH medication was a negative predictor.ConclusionIncreased BMI, EBL and hypertension are associated with worsened SUI outcomes following RALP, whereas bilateral nerve‐sparing technique and preoperative BPH medication are associated with improved SUI outcomes. These data may inform patient counselling and help identify patients who may benefit from closer surveillance and earlier anti‐incontinence intervention.
Bildbasierte Frischbetonprüfung – Teil 2: Granulometrische Eigenschaften der Gesteinskörnung
Authors: Schack Tobias , Coenen Max , Haist Michael 
Published: May 2023

AbstractBereits heute ist absehbar, dass notwendige Veränderungen in der Betontechnologie zur Erreichung der Klimaschutzziele einen signifikanten Wandel in den typischerweise eingesetzten Betonzusammensetzungen zur Folge haben werden. Die eingesetzten Ausgangsstoffe werden immer vielfältiger und komplexer. Durch den Einsatz rezyklierter Ausgangsstoffe werden auch Schwankungen in den Ausgangsstoffeigenschaften signifikant zunehmen. Eine zielsichere und zeiteffiziente Ermittlung der granulometrischen Eigenschaften der verwendeten Gesteinskörnung ist somit insbesondere für sogenannte Ökobetone zur Sicherstellung gleichbleibender Qualitätsmerkmale von entscheidender Bedeutung. Es gilt zukünftig, mögliche Qualitätsabweichungen des Frischbetons resultierend aus Schwankungen der Ausgangsstoffe zeiteffizient zu ermitteln, um so schnellstmöglich entsprechende Anpassungen im Produktionszyklus vornehmen zu können. In diesem Beitrag wird daher eine bildbasierte Methodik zur digitalen Bewertung granulometrischer Eigenschaften der Gesteinskörnung im Rahmen der Ausbreitmaßprüfung vorgestellt. Damit wird das Eigenschaftsspektrum der bereits in Teil 1 dieses Beitrags vorgestellten bildbasierten Methodik, welcher die bildbasierte Ermittlung der Konsistenz und des Leimgehalts beschreibt, hin zu einer vollumfänglichen digitalen Frischbetonprüfung entsprechend erweitert.
ISG15: A link between innate immune signaling, DNA replication, and genome stability
Authors: Wardlaw Christopher P. , Petrini John H. J. 
Published: May 2023

AbstractInterferon stimulated gene 15 (ISG15) encodes a ubiquitin‐like protein that is highly induced upon activation of interferon signaling and cytoplasmic DNA sensing pathways. As part of the innate immune system ISG15 acts to inhibit viral replication and particle release via the covalent conjugation to both viral and host proteins. Unlike ubiquitin, unconjugated ISG15 also functions as an intracellular and extra‐cellular signaling molecule to modulate the immune response. Several recent studies have shown ISG15 to also function in a diverse array of cellular processes and pathways outside of the innate immune response. This review explores the role of ISG15 in maintaining genome stability, particularly during DNA replication, and how this relates to cancer biology. It puts forth the hypothesis that ISG15, along with DNA sensors, function within a DNA replication fork surveillance pathway to help maintain genome stability.
Development of a perfusion process for continuous lentivirus production using stable suspension producer cell lines
Authors: Klimpel Maximilian , Terrao Monica , Ching Nilakshi , Climenti Vanessa , Noll Thomas , Pirzas Vicky , Laux Holger 
Published: May 2023

AbstractThe large‐scale production of clinical‐grade lentiviral vectors (LVs) for gene therapy applications is a remaining challenge. The use of adherent cell lines and methods like transient transfection are cost‐intensive and hamper process scalability as well as reproducibility. This study describes the use of two suspension‐adapted stable packaging cell lines, called GPRGs and GPRTGs, for the development of a scalable and serum‐free LV production process. Both stable packaging cell lines are based on an inducible Tet‐off system, thus requiring doxycycline removal for initiation of the virus production. Therefore, we compared different methods for doxycycline removal and inoculated three independent 5 L bioreactors using a scalable induction method by dilution, an acoustic cell washer and manual centrifugation. The bioreactors were inoculated with a stable producer cell line encoding for a LV carrying a clinically relevant gene. LV production was performed in perfusion mode using a cell retention device based on acoustic wave separation. Comparable cell‐specific productivities were obtained with all three methods and cumulative functional yields up to 6.36 × 1011 transducing units per bioreactor were generated in a 234‐h long process, demonstrating the usability of stable Tet‐off cell lines for an easily scalable suspension process. Remarkably, cell viabilities >90% were maintained at high cell densities without compromising productivity throughout the whole process, allowing to further extend the process time. Given its low effects of toxicity during virus production, the presented cell lines are excellent candidates to develop a fully continuous LV production process to overcome the existing bottlenecks in LV manufacturing.
Cationic polymer precipitation for enhanced impurity removal in downstream processing
Authors: Li Zhao , Chen Justin , Martinez‐Fonts Kirby , Rauscher Michael , Rivera Shannon , Welsh John , Kandula Sunitha 
Published: May 2023

AbstractPrecipitation can be used for the removal of impurities early in the downstream purification process of biologics, with the soluble product remaining in the filtrate through microfiltration. The objective of this study was to examine the use of polyallylamine (PAA) precipitation to increase the purity of product via higher host cell protein removal to enhance polysorbate excipient stability to enable a longer shelf life. Experiments were performed using three monoclonal antibodies (mAbs) with different properties of isoelectric point and IgG subclass. High throughput workflows were established to quickly screen precipitation conditions as a function of pH, conductivity and PAA concentrations. Process analytical tools (PATs) were used to evaluate the size distribution of particles and inform the optimal precipitation condition. Minimal pressure increase was observed during depth filtration of the precipitates. The precipitation was scaled up to 20L size and the extensive characterization of precipitated samples after protein A chromatography showed >75% reduction of host cell protein (HCP) concentrations (by ELISA), >90% reduction of number of HCP species (by mass spectrometry), and >99.8% reduction of DNA. The stability of polysorbate containing formulation buffers for all three mAbs in the protein A purified intermediates was improved at least 25% after PAA precipitation. Mass spectrometry was used to obtain additional understanding of the interaction between PAA and HCPs with different properties. Minimal impact on product quality and <5% yield loss after precipitation were observed while the residual PAA was <9 ppm. These results expand the toolbox in downstream purification to solve HCP clearance issues for programs with purification challenges, while also providing important insights into the integration of precipitation–depth filtration and the current platform process for the purification of biologics.
Characterization of three‐dimensional bone‐like tissue growth and organization under influence of directional fluid flow
Authors: de Wildt Bregje W. M. , Zhao Feihu , Lauwers Iris , van Rietbergen Bert , Ito Keita , Hofmann Sandra 
Published: May 2023

AbstractThe transition in the field of bone tissue engineering from bone regeneration to in vitro models has come with the challenge of recreating a dense and anisotropic bone‐like extracellular matrix (ECM). Although the mechanism by which bone ECM gains its structure is not fully understood, mechanical loading and curvature have been identified as potential contributors. Here, guided by computational simulations, we evaluated cell and bone‐like tissue growth and organization in a concave channel with and without directional fluid flow stimulation. Human mesenchymal stromal cells were seeded on donut‐shaped silk fibroin scaffolds and osteogenically stimulated for 42 days statically or in a flow perfusion bioreactor. After 14, 28, and 42 days, constructs were investigated for cell and tissue growth and organization. As a result, directional fluid flow was able to improve organic tissue growth but not organization. Cells tended to orient in the tangential direction of the channel, possibly attributed to its curvature. Based on our results, we suggest that organic ECM production but not anisotropy can be stimulated through the application of fluid flow. With this study, an initial attempt in three‐dimensions was made to improve the resemblance of in vitro produced bone‐like ECM to the physiological bone ECM.
Scientific seminars in lockdown: Lessons for a post‐pandemic time in defense of a permanent platform for science dissemination in the world
Authors: Sabatke Bruna , Rossi Izadora Volpato , Ramirez Graciela E. , Ramirez Marcel I. 
Published: May 2023

AbstractIn an academic semester, living in social isolation and under restrictions of the pandemic, we organized weekly multidisciplinary seminars from a postgraduate course program in Curitiba, Southern Brazil, integrating students from different regions of Brazil and South America. Outstanding researchers from Brazil, Germany, France, Argentina, Mexico, Portugal, England, and United States’ institutions gave seminars on chronic and infectious diseases with immunological, pharmacological, biochemical, cellular, and molecular biology point of views. The meetings were longer than traditional seminars, containing a part with scientific debate and other with a humanization or deconstruction of the researcher including trajectory, hobbies, scientific, and social thoughts. To facilitate learning and conceptualization, the seminars were available through YouTube and we applied weekly questionnaires to be answered rescuing scientific and motivational topics to give companionship and support to the students in pandemic times. Here, we are defending the creation of permanent platforms for scientific diffusion, with higher accessibility, connecting centers of different levels and giving academic excellence and opportunities for young researchers. Feedback received from participants indicates that this seminar structure can increase confidence and improve their perception of scientific processes and inspire researchers with development trajectories. We have discussed multidisciplinarity, scientific excellence, regional isolation and economic inequality, integration, humanization, and the value of science in society.
Multidimensional financial hardship among uninsured and insured young adult patients with metastatic breast cancer
Authors: Wheeler Stephanie B. , Spencer Jennifer C. , Manning Michelle L. , Samuel Cleo A. , Reeder‐Hayes Katherine E. , Greenup Rachel A. , Spees Lisa P. , Rosenstein Donald L. 
Published: May 2023

AbstractBackgroundLittle is known about the heterogeneous nature of financial hardship in younger patients with metastatic disease and the extent to which insurance protects against it. We examine the association between insurance status and multidimensional indicators of financial hardship in a national sample of women with metastatic breast cancer.MethodsWe conducted a national, retrospective online survey in partnership with the Metastatic Breast Cancer Network. Eligible participants were ≥18 years, diagnosed with metastatic breast cancer, and able to respond in English. We estimated multivariate generalized linear models predicting two distinct dimensions of financial hardship—financial insecurity (the ability to afford care and living costs) and financial distress (the extent of emotional/psychological distress experienced due to costs)—as a function of insurance status.ResultsParticipants responded from 41 states (N = 1054; median age: 44 years). Overall, 30% were uninsured. Financial insecurity was more frequently reported by uninsured respondents. In adjusted analyses, uninsured participants were more likely than insured participants to report contact by debt collectors (adjusted risk ratio [aRR]: 2.38 [2.06, 2.76]) and being unable to meet monthly expenses (aRR: 2.11 [1.68, 2.66]). Financial distress was reported more frequently by insured participants. For example, insured participants were more likely to worry about future financial problems due to cancer and distress about lack of cost transparency. After adjustment, uninsured participants remained about half as likely as insured participants to report financial distress.ConclusionsYoung adult women with metastatic cancer reported a high burden of financial toxicity. Importantly, insurance does not protect against financial distress; however, the uninsured are the most materially vulnerable.
Sodium‐glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors on new‐onset overall cancer in Type 2 diabetes mellitus: A population‐based study
Authors: Chung Cheuk To , Lakhani Ishan , Chou Oscar Hou In , Lee Teddy Tai Loy , Dee Edward Christopher , Ng Kenrick , Wong Wing Tak , Liu Tong , Lee Sharen , Zhang Qingpeng , Cheung Bernard Man Yung , Tse Gary , Zhou Jiandong 
Published: May 2023

AbstractBackgroundCancer is currently the second leading cause of death globally. There is much uncertainty regarding the comparative risks of new‐onset overall cancer and pre‐specified cancer for Type 2 diabetes mellitus (T2DM) patients on sodium‐glucose cotransporter 2 inhibitors (SGLT2I) versus DPP4I.MethodsThis population‐based cohort study patients included patients who were diagnosed with T2DM and administered either SGLT2 or DPP4 inhibitors between 1 January 2015 and 31 December 2020 in public hospitals of Hong Kong.ResultsThis study included 60,112 T2DM patients (mean baseline age: 62.1 ± 12.4 years, male: 56.36%), of which 18,167 patients were SGLT2I users and 41,945 patients were dipeptidyl peptidase 4 inhibitor (DPP4I) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of all‐cause mortality (HR: 0.92; 95% CI: 0.84–0.99; p= 0.04), cancer‐related mortality (HR: 0.58; 95% CI: 0.42–0.80; p ≤ 0.001) and new diagnoses of any cancer (HR: 0.70; 95% CI: 0.59–0.84; p ≤ 0.001). SGLT2I use was associated with a lower risk of new‐onset breast cancer (HR: 0.51; 95% CI: 0.32–0.80; p ≤ 0.001), but not of other malignancies. Subgroup analysis on the type of SGLT2I, dapagliflozin (HR: 0.78; 95% CI: 0.64–0.95; p = 0.01) and ertugliflozin (HR: 0.65; 95% CI: 0.43–0.98; p = 0.04) use was associated with lower risks of new cancer diagnosis. Dapagliflozin use was also linked to lower risks of breast cancer (HR: 0.48; 95% CI: 0.27–0.83; p = 0.001).ConclusionSodium‐glucose cotransporter 2 inhibitor use was associated with lower risks of all‐cause mortality, cancer‐related mortality and new‐onset overall cancer compared to DPP4I use after propensity score matching and multivariable adjustment.
Genetic associations of leisure sedentary behaviors and the risk of 15 site‐specific cancers: A Mendelian randomization study
Authors: Chen Jinwei , Yang Kaibin , Qiu Youyu , Lai Weijie , Qi Sifan , Wang Gaoyuan , Chen Lin , Li Kunpeng , Zhou Dan , Liu Qing , Tang Linglong , Liu Xu , Du Xiaojing , Guo Rui , Ma Jun 
Published: May 2023

AbstractBackground and AimsLeisure sedentary behavior (LSB) is associated with the risk of cancer, but the causal relationship between them has not been clarified. The aim of this study was to assess the potential causal association between LSB and risk of 15 site‐specific cancers.MethodsThe causal association between LSB and cancer were assessed with univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR). 194 SNPs associated with LSB (from the UK Biobank 408,815 individuals) were adopted as the instrument variables. Sensitivity analyses were performed to ensure the robustness of the results.ResultsUVMR analysis revealed that television watching significantly increased the risk of endometrial cancer (OR = 1.29, 95% CI = 1.02–1.64, p = 0.04) (mainly the endometrioid histology [OR = 1.28, 95% CI = 1.02–1.60, p = 0.031])，breast cancer (OR = 1.16, 95% CI = 1.04–1.30, p = 0.007) (both ER+ breast cancer [OR = 1.17, 95% CI = 1.03–1.33, p = 0.015], and ER− breast cancer [OR = 1.55, 95% CI = 1.26–1.89, p = 2.23 × 10−5]). Although causal association was not found between television watching and ovarian cancer, it was seen in low grade and low malignant potential serous ovarian cancer (OR = 1.49, 95% CI = 1.07–2.08, p = 0.018). However, significant results were not obtained in the UVMR analysis between driving, computer use and the 15 types of cancer. Further MVMR analysis indicated that the above results are independent from most metabolic factors and dietary habits, but mediated by educational attainment.ConclusionLSB in form of television watching has independent causal association with the risk of endometrial cancer, breast cancer, and ovarian cancer.
A phase II study of alternating sunitinib and temsirolimus therapy in patients with metastatic renal cell carcinoma
Authors: Ness Dylan B. , Pooler Darcy B. , Ades Steven , Highhouse Brian J. , Labrie Bridget M. , Zhou Jie , Gui Jiang , Lewis Lionel D. , Ernstoff Marc S. 
Published: May 2023

AbstractBackgroundSunitinib is a multi‐target tyrosine kinase inhibitor (TKI) that inhibits VEGF receptor 1, 2, 3 (VEGFRs), platelet‐derived growth factor receptor (PDGFR), colony‐stimulating factor receptor (CSFR), and the stem cell factor receptor c‐KIT. Temsirolimus inhibits mammalian target of rapamycin (mTOR) through binding to intracellular protein FKBP‐12. Both agents are approved for the treatment of metastatic renal cell carcinoma (mRCC), have different anticancer mechanisms, and non‐overlapping toxicities. These attributes form the scientific rationale for sequential combination of these agents. The primary objective of the study was to investigate the efficacy of alternating sunitinib and temsirolimus therapy on progression‐free survival (PFS) in mRCC.MethodsWe undertook a phase II, multi‐center, single cohort, open‐label study in patients with mRCC. Patients were treated with alternating dosing of 4 weeks of sunitinib 50 mg PO daily, followed by 2 weeks rest, then 4 weeks of temsirolimus 25 mg IV weekly, followed by 2 weeks rest (12 weeks total per cycle). The primary endpoint was PFS. Secondary endpoints included clinical response rate and characterization of the toxicity profile of this combination therapy.ResultsNineteen patients were enrolled into the study. The median observed PFS (n = 13 evaluable for PFS) was 8.8 months (95% CI 6.8–25.2 months). Best responses achieved were five partial response, nine stable disease, and three disease progression according to RECIST 1.1 guidelines (two non‐evaluable). The most commonly observed toxicities were fatigue, platelet count decrease, creatinine increased, diarrhea, oral mucositis, edema, anemia, rash, hypophosphatemia, dysgeusia, and palmar‐plantar erythrodysesthesia syndrome.ConclusionAlternating sunitinib and temsirolimus did not improve the PFS in patients with mRCC.