bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical and Thermal Response of the Bacterivorous Ciliate Colpidium kleini, a Species Potentially at Risk of Extinction by Rising Water Temperatures
Authors: Weisse Thomas , Pröschold Thomas , Kammerlander Barbara , Sonntag Bettina , Schicker Laura 
Published: July 2024

AbstractWe investigated the food-dependent growth and thermal response of the freshwater ciliate Colpidium kleini using numerical response (NR) experiments. This bacterivorous ciliate occurs in lotic water and the pelagial of lakes and ponds. The C. kleini strain used in this work was isolated from a small alpine lake and identified by combining detailed morphological inspections with molecular phylogeny. Specific growth rates (rmax) were measured from 5 to 21 °C. The ciliate did not survive at 22 °C. The threshold bacterial food levels (0.3 − 2.2 × 106 bacterial cells mL−1) matched the bacterial abundance in the alpine lake from which C. kleini was isolated. The food threshold was notably lower than previously reported for C. kleini and two other Colpidium species. The threshold was similar to levels reported for oligotrich and choreotrich ciliates if expressed in terms of bacterial biomass (0.05 − 0.43 mg C L−1). From the NR results, we calculated physiological mortality rates at zero food concentration. The mean mortality (0.55 ± 0.17 d−1) of C. kleini was close to the mean estimate obtained for other planktonic ciliates that do not encyst. We used the data obtained by the NR experiments to fit a thermal performance curve (TPC). The TPC yielded a temperature optimum at 17.3 °C for C. kleini, a maximum upper thermal tolerance limit of 21.9 °C, and a thermal safety margin of 4.6 °C. We demonstrated that combining NR with TPC analysis is a powerful tool to predict better a species’ fitness in response to temperature and food.
Engineered polyethylene terephthalate hydrolases: perspectives and limits
Authors: Kawai Fusako , Iizuka Ryo , Kawabata Takeshi 
Published: July 2024

Abstract
Polyethylene terephthalate (PET) is a major component of plastic waste. Enzymatic PET hydrolysis is the most ecofriendly recycling technology. The biorecycling of PET waste requires the complete depolymerization of PET to terephthalate and ethylene glycol. The history of enzymatic PET depolymerization has revealed two critical issues for the industrial depolymerization of PET: industrially available PET hydrolases and pretreatment of PET waste to make it susceptible to full enzymatic hydrolysis. As none of the wild-type enzymes can satisfy the requirements for industrialization, various mutational improvements have been performed, through classical technology to state-of-the-art computational/machine-learning technology. Recent engineering studies on PET hydrolases have brought a new insight that flexibility of the substrate-binding groove may improve the efficiency of PET hydrolysis while maintaining sufficient thermostability, although the previous studies focused only on enzymatic thermostability above the glass transition temperature of PET. Industrial biorecycling of PET waste is scheduled to be implemented, using micronized amorphous PET. Next stage must be the development of PET hydrolases that can efficiently degrade crystalline parts of PET and expansion of target PET materials, not only bottles but also textiles, packages, and microplastics. This review discusses the current status of PET hydrolases, their potential applications, and their profespectal goals.

Key points
• PET hydrolases must be thermophilic, but their operation must be below 70 °C
• Classical and state-of-the-art engineering approaches are useful for PET hydrolases
• Enzyme activity on crystalline PET is most expected for future PET biorecycling

Graphical Abstract
Halophilic archaea as tools for bioremediation technologies
Authors: Martínez-Espinosa Rosa María 
Published: July 2024

Abstract
Haloarchaea are extremophilic microorganisms belonging to the Archaea domain that require high salt concentrations to be alive, thus inhabiting ecosystems like salty ponds, salty marshes, or extremely salty lagoons. They are more abundantly and widely distributed worldwide than initially expected. Most of them are grouped into two families: Halobacteriaceae and Haloferacaceae. The extreme conditions under which haloarchaea survive contribute to their metabolic and molecular adaptations, thus making them good candidates for the design of bioremediation strategies to treat brines, salty water, and saline soils contaminated with toxic compounds such as nitrate, nitrite, oxychlorates such as perchlorate and chlorate, heavy metals, hydrocarbons, and aromatic compounds. New advances in understanding haloarchaea physiology, metabolism, biochemistry, and molecular biology suggest that biochemical pathways related to nitrogen and carbon, metals, hydrocarbons, or aromatic compounds can be used for bioremediation proposals. This review analyses the novelty of the most recent results showing the capability of some haloarchaeal species to assimilate, modify, or degrade toxic compounds for most living beings. Several examples of the role of these microorganisms in the treatment of polluted brine or salty soils are also discussed in connection with circular economy-based processes.

Key points
• Haloarchaea are extremophilic microorganisms showing genuine metabolism
• Haloarchaea can metabolise compounds that are highly toxic to most living beings
• These metabolic capabilities are useful for designing soil and water bioremediation strategies
Long-term responders to nivolumab in previously treated advanced renal cell carcinoma: a sub-analysis of meet-URO15 study
Authors: Messina Carlo , Catalano Martina , Roviello Giandomenico , Gandini Annalice , Maruzzo Marco , De Giorgi Ugo , Pedrazzoli Paolo , Sbrana Andrea , Zucal Paolo Andrea , Masini Cristina , Naglieri Emanuele , Procopio Giuseppe , Milella Michele , Catalano Fabio , Fratino Lucia , Pipitone Stefania , Ricotta Riccardo , Panni Stefano , Mollica Veronica , Soraru Mariella , Prati Veronica , Atzori Francesco , Di Napoli Marilena , Messina Marco , Morelli Franco , Prati Giuseppe , Nole Franco , Malgeri Andrea , Tudini Marianna , Vignani Francesca , Cavo Alessia , Signori Alessio , Banna Giuseppe Luigi , Rescigno Pasquale , Buti Sebastiano , Rebuzzi Sara Elena , Fornarini Giuseppe 
Published: July 2024

Abstract
Background
Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment.

Materials and methods
A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses.

Results
A total of 571 patients with a median age of 61 years (range 17–85) were included in the analysis. With a median follow-up of 22.1 (1.0–89.0) months, 23.1% of patients were 2-year progression-free on treatment with nivolumab, hence they were categorized as long-term responders. Baseline characteristics, including age, gender, and histology, were similar between long- and short-term responders. Karnofsky Performance Status ≥ 80% was significantly associated with long-term response (p = 0.02), while bone metastases (p = 0.03), International mRCC Database Consortium intermediate-poor risk (p < 0.01) and Neutrophil-to-Lymphocyte Ratio ≥ 3.2 (p = 0.02) were associate with short-term responses. Long-term responders exhibited a median progression-free survival of 55.0 months versus 4.0 months of the short-term responders. The median OS was not reached in long-term responders while it was 17.0 months for short*term responders.

Conclusion
This retrospective analysis sheds light on factors associated with long-term response to nivolumab in mRCC. Understanding these clinical features will be essential for selecting patients who may mostly benefit from immunotherapy.
In vitro CAR-T cell killing: validation of the potency assay
Authors: Piccinini Claudia , Carloni Silvia , Arienti Chiara , Pancisi Elena , Fanini Francesca , Pignatta Sara , Soldati Valentina , Stefanelli Monica , Granato Anna Maria , Martinelli Giovanni , Ridolfi Laura , Petrini Massimiliano 
Published: July 2024

AbstractFor advanced therapy medicinal products, the development and validation of potency assays are required, in accordance with international guidelines, to characterise the product and obtain reliable and consistent data. Our purpose was to validate the killing assay for the evaluation of autologous anti-CD19 chimeric antigen receptor (CAR) T potency. We used CD4 + and CD8 + lymphocytes or anti-CD19 CAR-T cells as effector cells and REH (CD19 +) or MOLM-13 (CD19 −) cell lines as target cells. After co-culturing target and effector cells (1:1 ratio) for 24 h, samples were labelled with 7-AAD, anti-CD3 and anti-CD19 antibodies and the frequency of CD19 + dead cells was evaluated by flow cytometry. In order to verify the CAR-T specificity for the CD19 + target, the co-culture between CAR-T and REH or MOLM-13 at different effector-to-target ratios was scheduled. Moreover, not transduced CD4 + and CD8 + lymphocytes were tested in comparison with CAR-T from the same donor to demonstrate the assay specificity. Linearity and accuracy were evaluated, and established acceptance criteria were compiled for both parameters (r2 ≥ 0.97 for linearity and average relative error ≤ 10% for accuracy). Furthermore, the method was considered robust when performed between 23 and 25 h of co-culture, and the intra-assay, inter-assay and inter-day precision was obtained. Finally, in order to verify the inter-analyst precision, the test was executed by three different operators and the intra-class correlation coefficient was > 0.4 in both cases. In conclusion, we consider this CAR-T potency assay as validated and usable in all steps of product development and quality control.
Monocyte infiltration is an independent positive prognostic biomarker in vulvar squamous cell carcinoma
Authors: Abdulrahman Ziena , Kortekaas Kim E. , Welters Marij J. P. , van Poelgeest Mariette I. E. , van der Burg Sjoerd H. 
Published: July 2024

Abstract
Background
Vulvar squamous cell carcinoma (VSCC) arises after an HPV infection or the mutation of p53 or other driver genes and is treated by mutilating surgery and/or (chemo) radiation, with limited success and high morbidity. In-depth information on the immunological make up of VSCC is pivotal to assess whether immunotherapy may form an alternative treatment.

Methods
A total of 104 patient samples, comprising healthy vulva (n = 27) and VSCC (n = 77), were analyzed. Multispectral immunofluorescence (15 markers) was used to study both the myeloid and lymphoid immune cell composition, and this was linked to differences in transcriptomics (NanoString nCounter, 1258 genes) and in survival (Kaplan–Meier analyses).

Results
Healthy vulva and VSCC are both well infiltrated but with different subpopulations of lymphoid and myeloid cells. In contrast to the lymphoid cell infiltrate, the density and composition of the myeloid cell infiltrate strongly differed per VSCC molecular subtype. A relative strong infiltration with epithelial monocytes (HLADR−CD11c−CD14+CD68−CD163−CD33−) was prognostic for improved survival, independent of T cell infiltration, disease stage or molecular subtype. A strong infiltration with T cells and/or monocytes was associated with drastic superior survival: 5-year survival > 90% when either one is high, versus 40% when both are low (p < 0.001).

Conclusion
A hot myeloid and/or lymphoid infiltrate predicts excellent survival in VSCC. Based on the response of similarly high-infiltrated other tumor types, we have started to explore the potential of neoadjuvant checkpoint blockade in VSCC.
Systemic delivery of oncolytic herpes virus using CAR-T cells enhances targeting of antitumor immuno-virotherapy
Authors: Zhang Zongliang , Yang Nian , Xu Long , Lu Huaqing , Chen Yongdong , Wang Zeng , Lu Qizhong , Zhong Kunhong , Zhu Zhixiong , Wang Guoqing , Li Hexian , Zheng Meijun , Zhou Liangxue , Tong Aiping 
Published: July 2024

AbstractRecent studies have indicated that combining oncolytic viruses with CAR-T cells in therapy has shown superior anti-tumor effects, representing a promising approach. Nonetheless, the localized delivery method of intratumoral injection poses challenges for treating metastatic tumors or distal tumors that are difficult to reach. To address this obstacle, we employed HSV-1-infected CAR-T cells, which systemically delivery HSV into solid tumors. The biological function of CAR-T cells remained intact after loading them with HSV for a period of three days. In both immunocompromised and immunocompetent GBM orthotopic mouse models, B7-H3 CAR-T cells effectively delivered HSV to tumor lesions, resulting in enhanced T-cell infiltration and significantly prolonged survival in mice. We also employed a bilateral subcutaneous tumor model and observed that the group receiving intratumoral virus injection exhibited a significant reduction in tumor volume on the injected side, while the group receiving intravenous infusion of CAR-T cells carrying HSV displayed suppressed tumor growth on both sides. Hence, CAR-THSV cells offer notable advantages in the systemic delivery of HSV to distant tumors. In conclusion, our findings emphasize the potential of CAR-T cells as carriers for HSV, presenting significant advantages for oncolytic virotherapy targeting distant tumors.
γδ T cells in human colon adenocarcinomas comprise mainly Vδ1, Vδ2, and Vδ3 cells with distinct phenotype and function
Authors: Rodin William , Szeponik Louis , Rangelova Tsvetanka , Tamiru Kebede Firaol , Österlund Tobias , Sundström Patrik , Hogg Stephen , Wettergren Yvonne , Cosma Antonio , Ståhlberg Anders , Bexe Lindskog Elinor , Quiding Järbrink Marianne 
Published: July 2024

AbstractΓδ T cell infiltration into tumours usually correlates with improved patient outcome, but both tumour-promoting and tumoricidal effects of γδ T cells have been documented. Human γδ T cells can be divided into functionally distinct subsets based on T cell receptor (TCR) Vδ usage. Still, the contribution of these different subsets to tumour immunity remains elusive. Here, we provide a detailed γδ T cell profiling in colon tumours, using mass and flow cytometry, mRNA quantification, and TCR sequencing. δ chain usage in both the macroscopically unaffected colon mucosa and tumours varied considerably between patients, with substantial fractions of Vδ1, Vδ2, and non-Vδ1 Vδ2 cells. Sequencing of the Vδ complementarity-determining region 3 showed that almost all non-Vδ1 Vδ2 cells used Vδ3 and that tumour-infiltrating γδ clonotypes were unique for every patient. Non-Vδ1Vδ2 cells from colon tumours expressed several activation markers but few NK cell receptors and exhaustion markers. In addition, mRNA analyses showed that non-Vδ1 Vδ2 cells expressed several genes for proteins with tumour-promoting functions, such as neutrophil-recruiting chemokines, Galectin 3, and transforming growth factor-beta induced. In summary, our results show a large variation in γδ T cell subsets between individual tumours, and that Vδ3 cells make up a substantial proportion of γδ T cells in colon tumours. We suggest that individual γδ T cell composition in colon tumours may contribute to the balance between favourable and adverse immune responses, and thereby also patient outcome.
Engineered CD147-CAR macrophages for enhanced phagocytosis of cancers
Authors: Chupradit Koollawat , Muneekaew Saitong , Wattanapanitch Methichit 
Published: July 2024

AbstractChimeric antigen receptor (CAR) T cell therapy has shown promising results in hematologic malignancies, but its effectiveness in solid cancers remains challenging. Macrophages are immune cells residing within the tumor microenvironment. They can phagocytose tumor cells. Recently, CAR macrophages (CAR-M) have been a promising candidate for treating solid cancers. One of the common cancer antigens overexpressed in various types of cancer is CD147. CAR-T and NK cells targeting CD147 antigen have shown significant efficacy against hepatocellular carcinoma. Nevertheless, CAR-M targeting the CD147 molecule has not been investigated. In this study, we generated CAR targeting the CD147 molecule using the THP-1 monocytic cell line (CD147 CAR-M). The CD147 CAR-M exhibited typical macrophage characteristics, including phagocytosis of zymosan bioparticles and polarization ability toward M1 and M2 phenotypes. Furthermore, the CD147 CAR-M demonstrated enhanced anti-tumor activity against K562 and MDA-MB-231 cells without exhibiting off-target cytotoxicity against normal cells. Our research provides valuable insights into the potential of CD147 CAR-M as a promising platform for cancer immunotherapy, with applications in both hematologic malignancies and solid cancers.
Graphical abstract
Spatial Variation in Agricultural BMPs and Relationships with Nutrient Yields Across New York State Watersheds
Authors: Schewe Rebecca , Iavorivska Lidiia , Kelleher Christa 
Published: July 2024

AbstractAgricultural nutrients nitrogen and phosphorus can subsequently be transported to waterways and are often managed through the adoption of best management practices (BMPs). However, we have a poor understanding of how the use of BMPs varies spatially and how BMP adoption might be related to nutrient yields in surface waters. To address this, we performed a survey of agricultural landowners across New York State and compared this with estimates of annual incremental nitrogen and phosphorus yields of agricultural origin from the Spatially Referenced Regressions On Watershed attributes (SPARROW) model. Using these socio-behavioral data and SPARROW predictions, we perform colocation analysis to identify areas where watersheds with high nutrient yield from agriculture are collocated with non-use of agricultural BMPs. This colocation analysis offers a novel methodology for identifying areas where monitoring of waterways and promotion of best management practices could be targeted to achieve the greatest benefits.
A sub-pharmacological test dose does not predict individual docetaxel exposure in prostate cancer patients
Authors: Heerma van Voss Marise R , Notohardjo Jessica , van Dodewaard-de Jong Joyce , Bloemendal Haiko J , ter Heine Rob 
Published: July 2024

Abstract
Purpose
Docetaxel is a cytotoxic drug used for first-line treatment of various malignancies. It has a narrow therapeutic index and shows wide interpatient variability in clearance and toxicity. Tools for individual dose optimization are needed to maximize efficacy and avoid toxicity.

Methods
We performed a proof-of-concept study (EudraCT 2016-003785-77) to evaluate whether pharmacokinetics after a sub-pharmacological test dose of 1000 µg docetaxel (millidose) could be used to predict therapeutic dose exposure. Thirty prostate cancer patients eligible for treatment with docetaxel as part of routine clinical care were included. An intravenous docetaxel millidose was administered 1–7 days prior to therapeutic docetaxel. After both doses plasma docetaxel concentrations were measured by ultra- high performance liquid chromatography-tandem mass spectrometry. The docetaxel clearance was estimated with non-linear mixed effects modeling.

Results
Geometric mean docetaxel clearance was 57.9 L/h (GCV 78.6%) after admission of a millidose and 40.3 L/h (GCV 60.7%) after admission of a therapeutic dose. The millidose and therapeutic dose in a single patient were not significantly correlated (Spearman’s rho R = 0.02, P = 0.92).

Conclusion
Docetaxel pharmacokinetics at milli- and therapeutic dose level showed insufficient correlation for individual dose optimization. However, the clearance of a docetaxel millidose and full dose are within the same order of magnitude. Therefore, docetaxel millidose pharmacokinetics could potentially facilitate prediction of docetaxel pharmacokinetics at a population level in situations where therapeutic dose levels are impractical, such as pharmacokinetic drug-drug interaction studies or pediatric studies.
The persistence of bipartite ecological communities with Lotka–Volterra dynamics
Authors: Dopson Matt , Emary Clive 
Published: July 2024

AbstractThe assembly and persistence of ecological communities can be understood as the result of the interaction and migration of species. Here we study a single community subject to migration from a species pool in which inter-specific interactions are organised according to a bipartite network. Considering the dynamics of species abundances to be governed by generalised Lotka–Volterra equations, we extend work on unipartite networks to we derive exact results for the phase diagram of this model. Focusing on antagonistic interactions, we describe factors that influence the persistence of the two guilds, locate transitions to multiple-attractor and unbounded phases, as well as identifying a region of parameter space in which consumers are essentially absent in the local community.
Decision support for prioritizing critical societal services in optimal post-disaster critical lifeline recovery
Authors: Shahverdi Bahar , Miller-Hooks Elise , Isaac Shabtai 
Published: July 2024

AbstractCritical societal services, such as health care, education, law enforcement, and emergency response, are key to societal well-being and safety. Disruption to these services may arise from direct damage to the buildings from which the services are provided, or indirectly as a consequence of damage to supporting lifelines. The order in which lifeline elements are restored post-disaster affects not only the timing for restoring the lifeline services to its customers, but also the timing for restoring critical services that rely on these lifelines. In this paper, a mathematical formulation of the problem of prioritizing critical societal services in lifeline service restoration treated by multiple, specialized crews and exact algorithmic approach for its solution are proposed. Two approaches to accelerate the solution algorithm for use in realistic settings, where efficiency and scalability are essential, are presented. The developed techniques can be embedded in a decision support tool for real-time application with real-time information. To illustrate the proposed modeling and solution methodology and assess its efficiency for large, complex multi-lifeline applications, numerical experiments were run on a synthetic yet real-world network involving three key lifelines, including power, water, and transportation, as well as two hospitals that rely on them. The analysis of this case study shows that cross-lifeline collaboration in prioritization and scheduling in restoration action affects not only the return of services from the individual lifelines, but also of critical services on which, particularly in disaster settings, lives may depend.