bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single intravenous administration of oncolytic adenovirus TILT-123 results in systemic tumor transduction and immune response in patients with advanced solid tumors
Authors: Jirovec Elise , Quixabeira Dafne C. A. , Clubb James H. A. , Pakola Santeri A. , Kudling Tatiana , Arias Victor , Haybout Lyna , Jalkanen Katriina , Alanko Tuomo , Monberg Tine , Khammari Amir , Dreno Brigitte , Svane Inge Marie , Block Matthew S. , Adamo Daniel A. , Mäenpää Johanna , Kistler Claudia , Sorsa Suvi , Hemminki Otto , Kanerva Anna , Santos João M. , Cervera-Carrascon Victor , Hemminki Akseli 
Published: November 2024

Abstract
Background
A limitation of approved oncolytic viruses is their requirement for intratumoral (i.t.) injection. TILT-123 (igrelimogene litadenorepvec, Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) is a chimeric oncolytic adenovirus suitable for intravenous (i.v.) delivery due to its capsid modification and dual selectivity devices. It is armed with tumor necrosis alpha and interleukin-2 for promoting T-cell activation and lymphocyte trafficking to tumors, thereby enhancing the antitumor immune response. Here, we present the findings after a single i.v. administration of TILT-123 in three phase I dose escalation clinical trials.

Methods
Patients with advanced solid tumors initially received a single i.v. dose of TILT-123 ranging from 3 × 109 to 4 × 1012 viral particles (VP). Blood was collected at baseline, 1, 16, and 192 h (7 days) post-treatment for bioavailability and serum analysis. Tumor biopsies were collected prior to treatment and 7 days post-treatment for analysis of viral presence and immunological effects. Patients did not receive any other cancer therapies during this period.

Results
Across all three trials (TUNIMO, TUNINTIL, and PROTA), 52 total patients were treated with i.v. TILT-123. Overall, TILT-123 was found to be well-tolerated, with no dose-limiting toxicities observed. Post-treatment tumor biopsies showed expression of viral genes, presence of TILT-123 adenovirus proteins or DNA, and changes in immune cell infiltration from baseline. Increased virus dose did not lead to increased virus detection in tumors. Median overall survival was longer in patients with confirmed presence of TILT-123 in post-treatment biopsies (280 versus 190 days, p = 0.0405).

Conclusion
TILT-123 demonstrated safety and significant intratumoral immunomodulation following a single i.v. administration, warranting further investigation.

Trial registrations
TUNIMO—NCT04695327. Registered 4 January 2021, https://clinicaltrials.gov/study/NCT04695327. TUNINTIL—NCT04217473. Registered 19 December 2019, https://clinicaltrials.gov/study/NCT04217473. PROTA—NCT05271318. Registered 4 February 2022, https://clinicaltrials.gov/study/NCT05271318.
The role and perception of the caregiver in a specialized pediatric palliative care center in medicine preparation and administration: a survey study
Authors: Baratiri Fernando , Zanella Chiara , Roverato Barbara , Mengato Daniele , Camuffo Laura , Pivato Lisa , Avagnina Irene , Maghini Irene , Divisic Antuan , Rusalen Francesca , Agosto Caterina , Venturini Francesca , Benini Franca , Zanin Anna 
Published: November 2024

Abstract
Background
In pediatric palliative care, the main caregiver is primarily responsible for managing pharmaceutical therapies. Few data are available regarding the influence of this burden on quality of life in terms of time, concerns as well as a considerable risk of administration errors and adverse effects. This study aims to investigate how caregivers prepared and administrated medication, including errors and associated expectations, to identify improvement interventions.

Methods
Between October 2022 and March 2023, a descriptive single-center survey study was carried out in the tertiary care pediatric palliative center of the Padova University Hospital. Participants were the caregivers of the patients followed by our center up to 23 years old, receiving at least one drug daily and who cannot self-administer their therapy. The questionnaire consisted of 18 multiple-choice and semi-closed questions, grouped into 4 main topics: therapy preparation, therapy administration, administration errors and therapy assessment.

Results
A total of 100 caregivers responded to the survey. Mothers represented the main caregiver (91%). The prevalence of polypharmacy was 67% across the patients. 52% of caregivers handled prescriptions at least three times per day and for 32% it took to prepare them more than 5 min each time. Only 59% reported to have been trained for preparing and administrating drugs. 14% reported having made at least a drug administration error due to the tiredness or the complexity of therapeutic regimens in the preceding three months. Nearly one caregiver out of three felt their child was using too many drugs. 73% positively welcomed the possibility of having clinical pharmacist-led counseling.

Conclusions
Many caregivers of pediatric palliative care patients frequently have trouble planning, preparing and delivering pharmacological therapy to their children. Attempting to simplify medication regimens, choosing formulations that are simpler to administer and measure, investing in improved caregiver training, talking about therapies with carers, and involving clinical pharmacists to clarify their doubts could be all potential strategies to improve this condition and reduce their burden.
Claudin2 is involved in the interaction between Megalocytivirus-induced virus-mock basement membrane (VMBM) and lymphatic endothelial cells
Authors: He Jian-hui , Han Deyu , Meng Xianyu , Li Lingling , Hu Bangping , Yan Muting , Wang Zi-Ang , Weng Shaoping , He Jianguo , Xu Xiaopeng 
Published: November 2024

AbstractThe genus Megalocytivirus, belonging to the family Iridoviridae, is one of the most detrimental virus groups to fish aquaculture. Megalocytivirus creates a virus-mock basement membrane (VMBM) on the surface of infected cells. This membrane provides attachment sites for lymphatic endothelial cells (LECs), disrupting fish's endothelial cell-extracellular matrix system. This disruption triggers injury to the vascular system and can result in death. Exploring the VMBM-cell interaction mechanism is crucial for uncovering the pathogenesis of Megalocytivirus and identifying therapeutic targets. Claudins, a class of tetra transmembrane proteins, play a key role in creating tight junctions between endothelial or epithelial cells. In this study, we demonstrated that the expression of Claudin2, a member of the Claudin family in fish, was significantly up-regulated by Megalocytivirus infection. Claudin2 was found in LECs attached to the surface of infected cells. It interacted with the VMBM viral components VP23R, VP08R, and VP33L at multiple binding sites through its two extracellular loops. However, it did not interact with the host basement membrane’s nidogen. Therefore, Claudin2 is involved in the interaction of LEC with VMBM and plays a role in the disturbed distribution of extracellular matrix and endothelial cells in Megalocytivirus-infected fish tissues. This study aims to uncover the molecular mechanisms by which Megalocytivirus infection leads to pathological changes in the vascular system.
Embryotrophic effect of exogenous protein contained adipose-derived stem cell extracellular vesicles
Authors: Bang Seonggyu , Qamar Ahmad Yar , Yun Sung Ho , Gu Na-Yeon , Kim Heyyoung , Han Ayeong , Kang Heejae , Park Hye Sun , Kim Seung II , Saadeldin Islam M. , Lee Sanghoon , Cho Jongki 
Published: November 2024

Abstract
Background
Extracellular vesicles (EVs) regulate cell metabolism and various biological processes by delivering specific proteins and nucleic acids to surrounding cells. We aimed to investigate the effects of the cargo contained in EVs derived from adipose-derived stem cells (ASCs) on the porcine embryonic development.

Methods
ASCs were isolated from porcine adipose tissue and characterized using ASC-specific markers via flow cytometry. EVs were subsequently extracted from the conditioned media of the established ASCs. These EVs were added to the in vitro culture environment of porcine embryos to observe qualitative improvements in embryonic development. Furthermore, the proteins within the EVs were analyzed to investigate the underlying mechanisms.

Results
We observed a higher blastocyst development rate and increased mitochondrial activity in early stage embryos in the ASC-EVs-supplemented group than in the controls (24.8% ± 0.8% vs. 28.6% ± 1.1%, respectively). The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay of blastocysts also revealed significantly reduced apoptotic cells in the ASC-EVs-supplemented group. Furthermore, through proteomics, we detected the proteins in ASC-EVs and blastocysts from each treatment group. This analysis revealed a higher fraction of proteins in the ASC-EVs-supplemented group than in the controls (1,547 vs. 1,495, respectively). Gene analysis confirmed that ASC-EVs showed a high expression of tyrosine-protein kinase (SRC), whereas ASC-EVs supplemented blastocysts showed a higher expression of Cyclin-dependent kinase 1 (CDK1). SRC is postulated to activate protein kinase B (AKT), which inhibits the forkhead box O signaling pathway and activates CDK1. Subsequently, CDK1 activation influences the cell cycle, thereby affecting in vitro embryonic development.

Conclusion
ASC-EVs promote mitochondrial activity, which is crucial for the early development of blastocysts and vital in the downregulation of apoptosis. Additionally, ASC-EVs supply SRC to porcine blastocysts, thereby elongating the cell cycle.
Mitochondrial DNA in plasma and long-term physical recovery of critically ill patients: an observational study
Authors: Galvis-Pedraza Maryory , Beumeler Lise F. E. , van der Slikke Elisabeth C. , Boerma E. Christiaan , van Zutphen Tim 
Published: November 2024

Abstract
Background
Post-intensive care syndrome (PICS) poses a notable public health concern, with survivors of critical illness experiencing long-term physical, psychological, and cognitive challenges. Mitochondrial dysfunction has gained attention for its potential involvement in PICS. However, the long-term impact of mitochondrial status on patient recovery remains uncertain. A single-centre retrospective analysis was conducted in Leeuwarden, the Netherlands, between May and November 2019, within a mixed ICU survivor cohort. Patients were assessed for mitochondrial markers (mtDNA damage represented by the presence of mtDNA fragmentation and mitochondrial DNA levels evaluated by the ratio of mtDNA and nuclear DNA), clinical factors, and long-term outcomes measured by the physical functioning (PF) domain of health-related quality of life.

Results
A total of 43 patients were included in this study divided into recovery and non-recovery groups based on age-adjusted PF scores at 12 months post-ICU. Nineteen patients scored below these thresholds. No significant differences in mitochondrial markers between groups were identified. Furthermore, no significant correlations were found between mtDNA levels and mtDNA damage at baseline and 12 months with PF scores. However, mtDNA levels decreased over time in the recovery (p-value <  < 0.01) and non-recovery groups (p-value < 0.01).

Conclusion
No significant correlation was found between mitochondrial markers and physical functioning scores. This study underscores the multifactorial nature of PICS and the need for a comprehensive understanding of its metabolic and cellular components. While mitochondrial markers may play a role in PICS, they operate within a framework influenced by various factors. This exploratory study serves as a foundation for future investigations aimed at developing targeted interventions to enhance the quality of life for ICU survivors grappling with PICS.
Stressors and difficulties in early intervention programs in Jordan from the employee’s perspective
Authors: Gharaibeh Mahmoud , Al-Bakkar Al-Muatasem M. , Abdel-Rahman Samer Z. , Almulla Abdullah Ahmed 
Published: November 2024

AbstractEarly childhood is crucial in building and shaping the personalities of children with disabilities, where employees dealing with such children face a lot of challenges. This study aimed to identify problems and challenges faced during early intervention programs in Jordan from employees’ perspectives. We conducted a questionnaire-based study on 350 from a population of 4000 employees working in early intervention programs from Jordan’s North, Central, and South territories. Participants responded to the problem and challenges scale, containing 32 items distributed over five dimensions. The findings of this study showed that employees at special education centers in Jordan who work in early intervention programs said they typically faced moderate issues and difficulties. The most significant issues and difficulties that Jordan’s early intervention programs faced were the absence of interactive cooperation among employees and the flexibility of the programs. Factor analysis of the studied items showed that, apart from the social dimension, the items of all other dimensions of the research instrument were influenced by a diverse set of underlying factors. There were no statistically significant differences in the challenges and problems facing early intervention programs in Jordan due to the employees’ gender, academic qualification, and experience. Finally, this study offered suggestions and recommendations for enhancing early intervention services and programs, putting additional rehabilitation into place, and implementing ongoing training for professionals in this sector.
Development and validation of the prediction score for augmented renal clearance in critically Ill Japanese adults
Authors: Mikami Ryusei , Imai Shungo , Hayakawa Mineji , Kashiwagi Hitoshi , Sato Yuki , Nashimoto Shunsuke , Sugawara Mitsuru , Takekuma Yoh 
Published: November 2024

Abstract
Background
Augmented renal clearance (ARC) decreases the therapeutic concentration of drugs excreted by the kidneys in critically ill patients. Several ARC prediction models have been developed and validated; however, their usefulness in Japan has not been comprehensively investigated. Thus, we developed a unique ARC prediction model for a Japanese mixed intensive care unit (ICU) population and compared it with existing models.

Methods
This retrospective study enrolled a mixed ICU population in Japan from January 2019 and June 2022. The primary outcome was the development and validation of a model to predict ARC onset based on baseline information at ICU admission. Patients admitted until May 2021 were included in the training set, and external validation was performed on patients admitted thereafter. A multivariate logistic regression model was used to develop an integer-based predictive scoring system for ARC. The new model (the JPNARC score) was externally validated along with the ARC and Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) scores.

Results
A total of 2,592 critically ill patients were enrolled initially, with 651 patients finally included after excluding 1,941 patients. The training and validation datasets comprised 456 and 195 patients, respectively. Multivariate analysis was performed to develop the JPNARC score, which incorporated age, sex, serum creatinine, and diagnosis upon ICU admission (trauma or central nervous system disease). The JPNARC score had a larger area under the receiver operating characteristic curve than the ARC and ARCTIC scores in the validation dataset (0.832, 0.633, and 0.740, respectively).

Conclusions
An integer-based scoring system was developed to predict ARC onset in a critically ill Japanese population and showed high predictive performance. New models designed to predict the often-unrecognized ARC phenomenon may aid in the decision-making process for upward drug dosage modifications, especially in resource- and labor-limited settings.
A novel conformable embolic for selective transarterial embolization of acute hemorrhages: a technical note
Authors: Yu Qian , Ahmed Osman , Chen Jiaqi , Islam Yousuf , Funaki Brian , Patel Mikin 
Published: November 2024

Abstract
Background
Obsidio conformable embolic (OCE, Boston Scientific, MA) is a novel, radiopaque and conformable embolic. The purpose of this report is to describe its use for treatment of acute intra-abdominal hemorrhages.

Methods and results
Three patients presented with acute hemorrhage and were treated with OCE, including post-paracentesis hemorrhage, penetrating trauma to the liver, and blunt trauma in the spleen. All cases were performed under moderate sedation, with hemostasis achieved by end of procedure using less than 1 vial of OCE (0.2-0.4 ml). No severe adverse events occurred. None required repeated treatment.

Short conclusion
OCE is a safe and effective embolic agent for treatment of intra-abdominal or visceral hemorrhage. Future studies with larger sample sizes and longer follow-up are warranted.
Nanoparticle ultrasonication: a promising approach for reducing bacterial biofilm in total joint infection—an in vivo rat model investigation
Authors: Ashkenazi Itay , Longwell Mark , Byers Barbara , Kreft Rachael , Ramot Roi , Haider Muhammad A. , Ramot Yair , Schwarzkopf Ran 
Published: November 2024

Abstract
Background
While the benefits of sonication for improving periprosthetic joint infection (PJI) are well-documented, its potential therapeutic effect against bacterial biofilm remains unstudied. This study aimed to investigate the safety and efficacy of a novel nanoparticle ultrasonication process on methicillin-resistant Staphylococcus aureus (MRSA) bacterial biofilm formation in a PJI rat model.

Methods
This novel ultrasonication process was designed to remove attached bacterial biofilm from implant and peri-articular tissues, without damaging native tissues or compromising implant integrity. Twenty-five adult Sprague–Dawley rats underwent a surgical procedure and were colonized with intra-articular MRSA, followed by the insertion of a titanium screw. Three weeks after the index surgery, the animals received a second procedure during which the screws were explanted, and soft tissue was sampled. The intraoperative use of the nanoparticle sonication treatment was employed to assess the device’s safety, while ex vivo treatment on the retrieved tissue and implants was used to evaluate its efficacy.

Results
Clinical and histological assessments did not indicate any macro- or micro-damage to the host tissue. Sonication of the retrieved tissues demonstrated an average bacterial removal of 2 × 103 CFU/mL and 1 × 104 CFU/gram of tissue. Compared to the standard-of-care group (n = 10), implants treated with sonication (n = 15) had significantly lower remaining bacteria, as indicated by crystal violet absorbance measurements (P = 0.012).

Conclusions
This study suggests that nanoparticle sonication technology can successfully remove attached bacterial biofilms from explanted orthopedic hardware and the joint capsule, without negatively affecting native tissue. The study provides initial results supporting the potential of nanoparticle sonication as an adjuvant treatment option during a DAIR (debridement, antibiotics, and implant retention) procedure for PJI, paving the way for future clinical trials.
Conformational and processing properties of a high-active ingredient involving soy protein isolates bound with anthocyanins and its application in cake baking
Authors: Wu Han , Li Bin , Corradini Maria , Zhong Liang , Zhou Jianzhong , Liu Xiaoli 
Published: November 2024

AbstractSoybean protein is of plant origin and is commonly appropriate for improving the processing characteristics of foods. This study aimed to explore a novel functional ingredient that contained soybean protein isolate (SPI) and blueberry anthocyanins (BANs). The spatial conformation and secondary structure of SPI-BANs complexes were analyzed using circular dichroism and fluorescence spectroscopy, the processing properties were investigated as well as the retention of antioxidant activity during thermal treatments. Results showed that the contents of free sulfhydryl and free amino groups in complexes increased to 3.50 and 1.19 folds than those of SPI, respectively, while the surface hydrophobicity decreased by 74.23%. Compared with SPI, the BANs-modified SPI had a smaller particle size of 29.12 nm and a lower zeta-potential of -8.73 mV and on the other hand, the complexes possessed higher solubility (83.08%) and foaming and emulsifying properties (115.08% and 54.03 m2/g). After fortification with SPI-BANs, the baking loss rate and adhesiveness of chiffon cake were reduced by 10.82% and improved to 0.24 N.mm, respectively. The high antioxidant activities of SPI-BANs under heat led to the cake’s bioactivities largely enhanced by 1.99 ~ 12.71 folds, being 345.19 µg Trolox/g for the DPPH radical scavenging activity. This study developed the functional food ingredients as antioxidants and a substitute for animal-based proteins in bakery products, which was safe and sustainable by using the dietary components from plant resources.
Graphical Abstract
Induced polarization of clay-rich materials — Part 4: Water content and temperature effects in bentonites
Authors: El Alam J. , Revil A. , Dick P. 
Published: November 2024

Deep geological disposals (DGDs) are widely seen to be the best solution to contain high-level radioactive wastes safely. Compacted bentonite and bentonite-sand mixtures are considered the most appropriate buffers or sealing materials for access drifts, ramps, and shafts due to their favorable physicochemical and hydromechanical properties. Bentonite-sand mixtures are expected to swell and seal all voids when in contact with water, forming an impermeable barrier to radioactive elements. The parameters that will most affect the hydraulic performance of these seals are their water content, dry density, water salinity, and temperature. Monitoring and assessing these parameters are, therefore, crucial to confirm that the seals’ safety functions are fulfilled during the life of a DGD. Induced polarization (IP) is a nonintrusive geophysical method able to perform this task. However, the underlying physics of bentonite-sand mixtures has not been checked. The complex conductivity spectra of 42 compacted bentonite-sand mixtures are measured in the frequency range of 1 Hz–45 kHz in order to develop workable relationships between in-phase and quadrature conductivities versus water content and saturation, pore water conductivity, bentonite-sand ratio (10% to 100%), temperature (10°C–60°C), and dry density (0.97 to 1.64 [Formula: see text]). We observe that conductivity is mostly dominated by surface conductivity associated with the Stern layer coating the surface of smectite, the main component of bentonite. At a given salinity and temperature, the in-phase and quadrature conductivities obey power law relationships with water content and saturation. The in-phase and quadrature conductivities depend on temperature according to a classical linear relationship with the same temperature coefficient. A Stern layer-based model is used to explain the dependence of the complex conductivity with water content, dry density, water salinity, and temperature. It could be used to interpret IP field data to monitor the efficiency of the seal of DGD facilities.