bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of bacteriophages for the alleviation of potential bacterial contamination risks in developmental engineering
Authors: Xiang Yu , Bao Xujin , Sun Tao 
Published: June 2024

AbstractThis research aimed to address the potential bacterial contamination risks in developmental engineering (DE) using bacteriophages. To compare and contrast the exemplar Escherichia coli T4 and M13 bacteriophages, human dermal fibroblasts cultivated on culture plates, natural cellulosic scaffolds, and poly(methyl methacrylate) (PMMA) particles were utilized as two‐dimensional (2D) cell, three‐dimensional (3D) tissue, and modular tissue culture models, respectively. When directly introduced into these distinct culture systems, both phages survived, exhibited no significant effects on the cultured cells or tissues, yet displayed their potentials to alleviate the infections caused by corresponding bacterial host cells. Apart from direct addition into the culture medium, both phages were also coated on PMMA, polystyrene, poly(lactic acid) particles with different diameters (5, 10, 30, and 100 µm) and cellulosic scaffolds. The coated phages endured the coating processes and demonstrated their viabilities in plaque assays. Further testing indicated that the phages coated on the PMMA particles tolerated multiple deliberate rinses and centrifugations, but not thermal treatment at 60–80°C. In summary, T4 and M13 bacteriophages not only manifested their antibacterial functions in diverse 2D cell, 3D tissue, and modular tissue culture systems, but also demonstrated their potentials of coating modular scaffolds to alleviate the bacterial contamination risks in DE.
Synergetic light and cytokinin treatments mitigate the recombinant protein yield depression induced by high‐density cultivation of hydroponically‐grown Nicotiana benthamiana
Authors: Bilotta Stefano , Éthier Gilbert , Laliberté Ann‐Catherine , Goulet Marie‐Claire , Martel Michèle , Michaud Dominique , Pepin Steeve 
Published: June 2024

AbstractPlant molecular farming is currently operating a transition from soil‐based cultures toward hydroponic systems. In this study, we designed a whole‐plant NFT (nutrient film technique) platform for the transient expression of influenza virus‐like particles harboring hemagglutinin H1 proteins in Nicotiana benthamiana. In particular, we examined the effects of plant density during the post‐infiltration expression phase on plant growth and H1 yield in relation to the daily light integral (DLI) received by the crop and the exogenous application of 6‐BAP cytokinin (CK). We expected from previous work that high DLI and CK treatments would stimulate the development of highly productive leaves on axillary (secondary) stems and thereby improve the H1 yield at the whole‐plant scale. Increasing plant density from 35.7 to 61 plants m–2 during the post‐infiltration phase significantly decreased the proportion of axillary leaf biomass by 30% and H1 yield per plant by 39%, resulting in no additional yield gain on a whole‐crop area basis. Adding CK to the recirculated nutrient solution decreased the harvested leaf biomass by 31% and did not enhance the relative proportion of S leaves of the plants as previously reported with foliar CK application. There was a 36% increase in H1 yield when doubling the DLI from 14 to 28 mol m–2 s–1, and up to 71% yield gain when combining such an increase in DLI with the hydroponic CK treatment. Contrary to our expectations, leaves located on the main stem, particularly those from the upper half of the plant (i.e., eighth leaf and above), contributed about 80% of total H1 yield. Our study highlights the significantly different phenotype (~30% less secondary leaf biomass) and divergent responses to light and CK treatments of NFT‐grown N. benthamiana plants compared to previous studies conducted on potted plants.
Engineering strategies to mitigate toxicities associated with CAR‐T cell therapy
Authors: Wolter Tyler , Wang Yixin , Hu Quanyin 
Published: June 2024

AbstractChimeric antigen receptor (CAR) T cell therapy is a form of adoptive cell therapy that has revolutionized the field of cancer immunotherapy. Owing to the unprecedented efficacy seen in the treatment of blood cancers, the FDA has now approved multiple CAR T cell products for the treatment of various hematologic malignancies. Despite the clinical success seen in hematologic malignancies, CAR T cell therapies have demonstrated only modest efficacy in the treatment of solid tumors. Thus, great efforts are underway to increase the treatment efficacy in solid tumors and further enhance the treatment of hematologic malignancies. However, irrespective of advancements in efficacy, there are still unmet needs for patients receiving CAR T cell therapies. CAR T cell therapies carry significant risks of potentially fatal toxicities, and few of these toxicities were predicted in the animal models used to advance these therapies to the clinic. Therefore, significant advancements are needed to help reduce the incidence and severity of these toxicities to ultimately enhance patient safety and quality of life. This review will provide a brief overview of some of the major toxicities associated with CAR T cell therapies and will discuss the various engineering strategies used to mitigate such toxicities in preclinical models and clinical studies.
Effects of medicalization on case outcomes in transgender employment discrimination court decisions
Authors: Bender‐Baird Kyla , Stevenson Margaret C. 
Published: June 2024

AbstractSome attorneys and legal scholars argue that medicalizing transgender plaintiffs (i.e., introducing plaintiff diagnoses and/or medical procedures) in discrimination cases will enhance favorable plaintiff outcomes. Research and theory linking biological essentialism (i.e., believing social groups reflect biologically‐rooted, stable categories) to prejudice, however, suggests that medicalizing transgender plaintiffs might not help them win cases and might instead backfire and harm their case outcomes. To test these competing hypotheses, we coded all published cases involving alleged transgender discrimination (N = 124) from 1974 to 2021. Importantly, we addressed limitations of existing research that narrowly defined transgender plaintiff medicalization exclusively via diagnosis by documenting various other forms of medicalization beyond diagnosis. Contrary to legal scholars' claims and attorney intuitions, medicalization did not predict favorable outcomes for transgender plaintiffs. In fact, various forms of medicalization beyond diagnosis predicted negative plaintiff case outcomes. We discuss the implications of this research for informing scientific theory and legal practice.
Characterization of cancer survivors clustered by subjective and objective cognitive function scores
Authors: Goto Taichi , Saligan Leorey N. , Juneau Paul , Gonsalves Stephen G. , Rio Carielle Joy , Graves Letitia Y. , Von Ah Diane 
Published: June 2024

AbstractBackgroundCancer‐related cognitive impairment (CRCI) is a prevalent condition that significantly impacts the quality of life of individuals who receive cancer treatment. Clinical management of CRCI presents challenges due to the absence of a standardized assessment. This study identified clinically relevant phenotypic clusters of CRCI based on subjective and objective cognitive function scores.MethodsIn this cross‐sectional study, participants were clustered using the VARCLUS™ based on subjective cognitive impairment assessed through the PROMIS® version 1.0 short‐form subscales of cognitive abilities and cognitive concerns and the CANTAB Cambridge Cognition® scores, which included measures of visuospatial working memory capacity, visual episodic memory, new learning, working memory, executive function, and sustained attention. Each cluster's characteristics were described using demographics, physical and psychosocial factors (physical function, affect, optimism, and social support), and psychoneurological symptoms (anxiety, depression, fatigue, neuropathic pain, and sleep disturbance).ResultsWe obtained five clusters from a total of 414 participants, where 99% were female, and 93% were self‐reported white. Clusters 4 and 5 showed the highest PROMIS® cognitive abilities and the lowest measures of cognitive concern, while Clusters 1 and 2 showed the lowest cognitive abilities and the highest cognitive concerns. Clusters 4 and 5 had higher education, income, employment, and higher scores in physical function, positive affect, optimism, and social support. Additionally, individuals in these clusters were less prone to experience severe cancer‐related psychoneurological symptoms.ConclusionOur clustering approach, combining subjective and objective cognitive function information, shows promise in identifying phenotypes that hold clinical relevance for categorizing patient presentation of CRCI and facilitating individualized management strategies.
Real world, multicentre patterns of treatment and survival in metastatic renal cell carcinoma with the UK Renal Oncology Collaborative (UK ROC): Is it time to look favourably on first‐line immunotherapy containing combinations in all IMDC groups?
Authors: McGrane John , Frazer Ricky , Challapalli Amarnath , Ratnayake Gihan , Boh Zhaung , Clayton Alison , Chau Caroline , Sharma Anand , Elgendy Manal , Charnley Natalie , Mohamed Wael , Kingdon Sarah , Protheroe Andrew , Lydon Anna , Halstead Anna , Ford Vicky , Muazzam Iqtedar , Lee Dawn , Melendez‐Torres G. J. , Bahl Amit 
Published: June 2024

AbstractIntroductionClinical trials show improved progression‐free survival (PFS) and overall survival (OS) in first‐line metastatic renal cell carcinoma (mRCC) patients with immunotherapy containing systemic anti‐cancer therapies (SACT). However, in the favourable international metastatic renal cell cancer database consortium (IMDC) group there is no trial evidence for OS benefit despite clear PFS improvement when comparing anti‐VEGF tyrosine kinase inhibitor (TKI) monotherapy and (immunotherapy and TKI) IO/TKI combinations.ObjectiveTo assess the impact of first‐line SACT choice on the clinical outcomes of PFS and OS in mRCC. To evaluate this impact of initial SACT for allcomers and the favourable IMDC group.MethodsA multicentre retrospective review of patients who started SACT for mRCC (01/01/2018–30/06/2021) at 17 UK NHS trusts. Patient demographics and IMDC group were analysed. Survival data were compared using Kaplan–Meier curves, and the statistical significance of differences in outcome between the groups was assessed with the log‐rank test. Univariable and multivariable Cox proportional hazard modelling estimate the hazard ratios (HRs) for survival outcomes associated with IMDC and treatment subtype.ResultsOne thousand three hundred and nineteen patients were identified with a median age of 64. 294 (22.3%), 695 (52.7%) and 321 (24.3%) were IMDC group favourable, intermediate and poor, respectively. 311 (23.6%), 197 (14.9%) and 778 (59%) patients received checkpoint inhibitor and anti‐CTLA4 monoclonal antibody (IO/IO), IO/TKI and TKI first‐line SACT across all IMDC groups. Significant PFS improvement favouring IO/TKI versus TKI was demonstrated in allcomers HR = 0.61. In the favourable risk group, Log rank testing demonstrated a significant benefit for IO/TKI over TKI for PFS (HR = 0.60, 95% CI [0.39, 0.91]) and OS (HR = 0.42, 95% CI [0.18, 0.99]).ConclusionIn this real‐world evidence cohort, we have shown OS and PFS benefit with IO/TKI versus TKI in the favourable IMDC risk group. This has not been previously reported from trial outcomes and would support use of front‐line IO/TKI in mRCC favourable risk patients.
Barriers, facilitators, and other factors associated with health behaviors in childhood, adolescent, and young adult cancer survivors: A systematic review
Authors: de Beijer Ismay A. E. , Bouwman Eline , Mulder Renée L. , Steensma Philippa , Brown Morven C. , Araújo‐Soares Vera , Balcerek Magdalena , Bardi Edit , Falck Winther Jeanette , Frederiksen Line Elmerdahl , van Gorp Marloes , Oberti Sara , van Kalsbeek Rebecca J. , Kepak Tomas , Kepakova Katerina , Gsell Hannah , Kienesberger Anita , van Litsenburg Raphaële , Mader Luzius , Michel Gisela , Muraca Monica , van den Oever Selina R. , van der Pal Helena J. H. , Roser Katharina , Skinner Roderick , Stolman Iridi , Uyttebroeck Anne , Kremer Leontien C. M. , Loonen Jacqueline , van Dalen Elvira C. , Pluijm Saskia M. F. ,   the PanCareFollowUp Consortium
Published: June 2024

AbstractBackgroundHealthy behaviors are paramount in preventing long‐term adverse health outcomes in childhood, adolescent, and young adult (CAYA) cancer survivors. We systematically reviewed and synthesized existing literature on barriers, facilitators, and other factors associated with health behaviors in this population.MethodsMEDLINE and PsycInfo were searched for qualitative and quantitative studies including survivors aged 16–50 years at study, a cancer diagnosis ≤25 years and ≥2 years post diagnosis. Health behaviors included physical activity, smoking, diet, alcohol consumption, sun exposure, and a combination of these behaviors (defined as health behaviors in general).ResultsBarriers, facilitators, and other factors reported in ≥2 two studies were considered relevant. Out of 4529 studies, 27 were included (n = 31,905 participants). Physical activity was the most frequently examined behavior (n = 12 studies), followed by smoking (n = 7), diet (n = 7), alcohol (n = 4), sun exposure (n = 4), and health behavior in general (n = 4). Relevant barriers to physical activity were fatigue, lack of motivation, time constraints, and current smoking. Relevant facilitators were perceived health benefits and motivation. Influence of the social environment and poor mental health were associated with more smoking, while increased energy was associated with less smoking. No relevant barriers and facilitators were identified for diet, alcohol consumption, and sun exposure. Barriers to healthy behavior in general were unmet information needs and time constraints whereas lifestyle advice, information, and discussions with a healthcare professional facilitated healthy behavior in general. Concerning other factors, women were more likely to be physically inactive, but less likely to drink alcohol and more likely to comply with sun protection recommendations than men. Higher education was associated with more physical activity, and lower education with more smoking.ConclusionThis knowledge can be used as a starting point to develop health behavior interventions, inform lifestyle coaches, and increase awareness among healthcare providers regarding which survivors are most at risk of unhealthy behaviors.
Targeted agents in patients with progressive glioblastoma—A systematic meta‐analysis of randomized clinical trials
Authors: Ippen Franziska Maria , Scherm Angelika , Kessler Tobias , Hau Peter , Agkatsev Sarina , Baurecht Hansjörg , Wick Wolfgang , Knüttel Helge , Leitzmann Michael F. , Seliger‐Behme Corinna 
Published: June 2024

AbstractBackgroundGlioblastoma (GB) is the most common malignant primary brain tumor in adults and is associated with a poor prognosis. Current treatment guidelines outline the standard of care for patients with newly diagnosed GB; however, there is currently no well‐established consensus for the treatment of progressive GB. With this systematic meta‐analysis of recently published randomized controlled trials (RCTs), we aim to establish evidence on targeted agents in the treatment of patients with progressive GB.Material and MethodsWe conducted searches across the Cochrane Library, Pubmed, MEDLINE (Ovid), ClinicalTrials.gov, WHO‘s International Clinical Trials Registry Platform and Google Scholar, encompassing the time span from 1954 to 2022, aiming to identify RCTs evaluating targeted therapies in patients with progressive GB. In order to perform a random‐effects meta‐analysis, we extracted hazard ratios (HRs) of overall survival (OS) and progression‐free survival (PFS).ResultsWe included 16 RCTs (n = 3025 patients) in the systematic meta‐analysis. Formally, regorafenib (RR 0.50; 95% CI 0.33–0.75), Depatux‐M + TMZ (RR 0.66; 95% CI 0.47–0.93) and rindopepimut + bevacizumab (RR 0.53; 95% CI 0.32–0.88) were associated with an improved OS compared to the control arm. The combination of bevacizumab + CCNU (RR = 0.49; 95% CI 0.35–0.69) and regorafenib (RR 0.65; 95% CI 0.44–0.95) were formally associated with improved PFS.ConclusionsThe aim of this systematic meta‐analysis was to establish evidence for the use of targeted therapies in progressive GB. While some studies demonstrated benefits for OS and/or PFS, those results have to be interpreted with caution as most studies had major methodological weaknesses, including potential differences in sample size, trial design, or the initial distribution of prognostic factors.
Fully automated viability and toxicity screening—A reliable all‐in‐one attempt
Authors: Liedtke Victoria , Weiss Romano , Skifov Anastasia , Rödiger Stefan , Schenk Lysann 
Published: June 2024

AbstractBackgroundThe CRISPR/Cas9 technology is nowadays a common tool for genome editing to achieve new insights into, for example, diagnostics and therapeutics in cancer and genetic disorders. Cell proliferation and anticancer drug response studies are widely used to evaluate the impact of editing. However, these assays are often time‐consuming, expensive, and reproducibility is an issue. To overcome this, we developed a fast and cheap assay that combines a fully automated multispectral fluorescence microscopy platform with a nuclei staining and open‐source software analysis.MethodsHere, we generated different LEDGF/p75 model cell lines to validate the effect on proliferation and chemosensitivity. Therefore, a fast protocol for an optimized all‐in‐one attempt for cytotoxicity screenings and proliferation analysis of adherent cells in a 96‐well plate format was established using differential staining with two fluorescent dyes (Hoechst 33342 and propidium iodide) for live/dead cell discrimination. Subsequently, an automated cell nuclei count and analysis were performed using bioimage informatics.ResultsWith the new established assay technology, up to 50,000 cells/well can be detected and analyzed in a 96‐well plate, resulting in a fast and accurate verification of viability and proliferation with consistency of 98% compared to manual counting. Our screening revealed that LEDGF depletion using CRISPR/Cas9 showed a diminished proliferation and chemosensitivity independent of cell line origin. Moreover, LEDGF depletion caused a significant increase in 𝛾H2AX foci, indicating a substantial increase in DNA double strand breaks. LEDGF/p75 overexpression enhanced proliferation and chemoresistance underlining the role of LEDGF in DNA damage response.ConclusionIndependent of cancer cell type, LEDGF/p75 is a central player in DNA damage repair and is implicated in chemoresistance. Moreover, our automated fluorescence biosensor technology allowed fast and reliable data acquisition without any fixation or additional washing steps. Additionally, data analysis was implemented using the modular open‐source software that can be adapted as needed.
Bioinformatics‐based identification of hepatocellular carcinoma‐associated hub genes and assessment of the restorative effect of tannic acid in rat liver exposed to monosodium glutamate
Authors: Tosun Hilal , Karadas Habibe , Ceylan Hamid 
Published: June 2024

AbstractBackgroundHepatocellular carcinoma (HCC) is the most common type of primary liver cancer, occurring mostly in individuals with chronic liver disease, but biomarkers for therapeutic diagnosis and prognosis are lacking. This study aimed to investigate the possible effect of the common food additive monosodium glutamate (MSG) and tannic acid (TA), a phenolic compound, on the key molecular actors responsible for HCC development.MethodsEight HCC‐related public microarray datasets (GSE84005, GSE14520, GSE25097, GSE57958, GSE22058, GSE84402, GSE54238, and GSE36376) were extracted from the gene expression omnibus (GEO) database and analyzed to identify differentially expressed genes (DEGs). To make sense of the identified biological data and to identify hub genes, protein–protein interaction (PPI) network and enrichment analysis were performed. The mRNA expression profiles of the identified hub genes, expression changes in different stages of HCC, and their prognostic significances in HCC were determined using GEPIA, UALCAN, and Kaplan–Meier Plotter databases, respectively. Finally, mRNA expression changes of identified hub genes in the liver tissues of rats treated with MSG and TA were measured by the quantitative real‐time PCR (qPCR) method.ResultsTwo up‐regulated (AURKA and CCNB2) and two down‐regulated (F9 and CYP2E1) genes were identified between the HCC tumor and adjacent non‐tumor liver tissue samples. qPCR results showed that the mRNA expression of up‐regulated DEGs involved in HCC development increased significantly in rat liver tissues exposed to MSG, while this increase was remarkably suppressed by TA treatment. It was observed that the mRNA expressions of down‐regulated DEGs involved in HCC development decreased markedly in the presence of MSG, while this decrease was alleviated with TA.ConclusionOur results provide new insights into pivotal molecular candidates that should be focused on in future in vivo and in vitro HCC research. Moreover, MSG may play a crucial role in HCC development and progression and TA may be used as a favorable restorative agent in HCC.
Phase II clinical trial of nab‐paclitaxel plus cisplatin plus gemcitabine (NABPLAGEM) in patients with untreated advanced pancreatic cancer
Authors: Jameson Gayle S. , Hosein Peter J. , Pierce Erin , Kamgar Mandana , Gordon Michael S. , Snyder Courtney , Roe Denise J. , Wertheim Betsy C. , Davey Marina , Barrett Michael T. , Von Hoff Daniel D. , Borazanci Erkut 
Published: June 2024

AbstractBackgroundA previous phase IB/II study of nab‐paclitaxel + cisplatin + gemcitabine (NABPLAGEM) in 25 patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC) demonstrated favorable results. This phase II study was conducted to further evaluate the safety, efficacy, and impact on quality of life (QOL) of NABPLAGEM in a multi‐center setting.MethodsParticipants were ≥18 years; had measurable PDAC; Karnofsky performance status of ≥70%; life expectancy ≥12 weeks; <grade 2 pre‐existing peripheral neuropathy, and adequate hematologic, hepatic, and renal function. Study treatment included nab‐paclitaxel (125 mg/m2), cisplatin (25 mg/m2), and gemcitabine (1000 mg/m2), on Days 1 and 8 of a 21‐day cycle. The primary endpoint was 12‐month overall survival (OS).ResultsA total of 42 patients were enrolled with a median age of 66.8 years, a majority were male (66.7%) and white (76.2%). Treatment‐related adverse events ≥grade 3 were: thrombocytopenia (64.3%), anemia (47.6%), and neutropenia (26.1%). OS at 12 months was 38.1%, with 12% of patients alive as of last contact (20–40+ months). In 37 evaluable participants responses included: partial response (40.5%), stable disease (43.2%), and progressive disease (16.2%), with overall response rate of 40.5% and DCR of 88.6%. Statistically significant improvement in QOL was reported during the first three cycles.ConclusionThe primary objective of achieving a 12‐month survival comparable to the previous phase Ib/II NABPLAGEM PCRT 12‐001 was not achieved in this trial. NABPLAGEM has efficacy in advanced PDAC, demonstrating early disease control noted by improvement in patient symptoms, decrease in tumor volume and tumor markers within the first 9 weeks. The activity and tolerability make this a suitable regimen for further testing in the neoadjuvant setting.