bluuebunny/crossref_metadata_2025_split huggingface dataset:
An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab plus bevacizumab in patients with locally advanced unresectable or metastatic hepatocellular carcinoma.
Authors: Kim Kevin , Saeed Anwaar , Sohal Davendra , Edeline Julien , Heo Jeong , Bhansali Aditya , Kumar Shaheen , Ungerechts Guy 
Published: January 2024

TPS576 Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of atezolizumab (Atezo) plus bevacizumab (Bev) is approved frontline therapy for advanced HCC, but a minority of patients (pts) respond and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment (TME), mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus type 1 (HSV-1) that expresses the fusogenic gibbon ape leukemia virus glycoprotein with the R sequence deleted (GALV-GP-R–), an anti–CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the TME is intended to provide systemic antitumor activity and synergize with anti–PD-1/PD-L1 agents, such as Atezo. Preclinical data have demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev, supporting the clinical combination of RP3 with Bev. This study will evaluate the safety and efficacy of RP3 combined with Atezo plus Bev as first- (1L) and second-line (2L) systemic therapies for unresectable and advanced HCC (NCT05733598). Methods: The 1L and 2L cohorts will each enroll up to 30 pts. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following 1 prior line of systemic therapy, which must have included a PD-1/PD-L1–directed agent. Key inclusion criteria include advanced unresectable HCC with ≥1 measurable tumor of ≥1 cm in longest diameter, Child-Pugh class A, and an Eastern Cooperative Oncology Group performance status of 0 to 1. Key exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding and macroscopic invasion of the tumor into any major blood vessel(s) and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in the 1L cohort will receive Atezo 1200 mg and Bev 15 mg/kg every 3 weeks (Q3W) together with RP3 intratumorally Q3W for a total of up to 8 doses. Pts in the 2L cohort will receive RP3 every 2 weeks for 4 doses with Bev Q3W starting on cycle (C)1 day (D)1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. The primary endpoint is the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints are safety, ORR using HCC modified RECIST, duration of response, complete response rate, and progression-free survival. Clinical trial information: NCT05733598 .
Hindbrain boundaries as niches of neural progenitor and stem cells regulated by the extracellular matrix proteoglycan chondroitin sulphate
Authors: Hutchings Carmel , Nuriel Yarden , Lazar Daniel , Kohl Ayelet , Muir Elizabeth , Genin Olga , Cinnamon Yuval , Benyamini Hadar , Nevo Yuval , Sela-Donenfeld Dalit 
Published: January 2024

ABSTRACT
The interplay between neural progenitors and stem cells (NPSCs), and their extracellular matrix (ECM) is a crucial regulatory mechanism that determines their behavior. Nonetheless, how the ECM dictates the state of NPSCs remains elusive. The hindbrain is valuable to examine this relationship, as cells in the ventricular surface of hindbrain boundaries (HBs), which arise between any two neighboring rhombomeres, express the NPSC marker Sox2, while being surrounded with the membrane-bound ECM molecule chondroitin sulphate proteoglycan (CSPG), in chick and mouse embryos. CSPG expression was used to isolate HB Sox2+ cells for RNA-sequencing, revealing their distinguished molecular properties as typical NPSCs, which express known and newly identified genes relating to stem cells, cancer, the matrisome and cell cycle. In contrast, the CSPG− non-HB cells, displayed clear neural-differentiation transcriptome. To address whether CSPG is significant for hindbrain development, its expression was manipulated in vivo and in vitro. CSPG manipulations shifted the stem versus differentiation state of HB cells, evident by their behavior and altered gene expression. These results provide further understanding of the uniqueness of hindbrain boundaries as repetitive pools of NPSCs in-between the rapidly growing rhombomeres, which rely on their microenvironment to maintain their undifferentiated state during development.
Congenital CMV Infection: A Complex Case of Neurological Complications and Therapeutic Approaches in Infancy
Authors: Koziej Sylwia , Kowalczyk Emilia , Niemczuk Martyna , Jasiuk Adrianna , Wiekiera Mateusz 
Published: January 2024

Introduction and purpose
Congenital Cytomegalovirus (CMV) infection stands as the prevalent infection among newborns and it may be associated with later complications such as progressive sensorineural hearing loss or neurological diseases. Infection occurs during pregnancy or during childbirth. Congenital CMV infections manifest in various ways, ranging from asymptomatic cases to severe complications such as microcephaly, hepatosplenomegaly, and chorioretinitis. Routine antibody screenings for pregnant women are not common, underlining the significance of early infection detection to minimize the risks of transmission to the fetus and potential complications in the child.
The aim of this case report is to present the course of congenital CMV infection and its complication. This case report explores the challenges of managing an infant with congenital CMV infection complicated by hydrocephalus and viral co-infections. The infant underwent various treatments, including antiviral therapy, highlighting the need for multidisciplinary approaches.
Conclusion
With no available vaccine, prevention of congenital CMV infection relies on educating reproductive-age women and expectant mothers about infection risks. Early detection, frequent medical check-ups, and preventive education are crucial due to the absence of vaccines. Ongoing exploration of antiviral treatments and prompt interventions is imperative to improve outcomes for infants and families affected by the virus.
Karakter Serial Animasi Astronomi Berbasis Edutainment Untuk Siswa Sekolah Dasar
Authors: Ramadhani Nugrahardi , Annam Khoirul 
Published: January 2024

Astronomy is one of the derivative subjects of science. The progress of astronomy and other sciences is closely related to the progress of a nation's science and technology. However, there are limitations such as the lack of learning facilities that support astronomy learning in schools. In addition, because the subject has many theories and terms, science is a subject that is difficult for students to like or master. Therefore, the animation medium was chosen to introduce astronomy material. To support animation design, it is necessary to design characters as a way of conveying astronomical information. Character design has an important role in conveying storylines and messages to the target audience. This design uses two research methods, namely qualitative and quantitative methods. For qualitative methods, competitor and comparator analysis, in-depth interviews, photo studies, and literature studies are used. As for the quantitative method, a research strategy was used in the form of distributing questionnaires to the target audience of elementary school students. The media output that will be designed is astronomy educational animation with an edutainment approach. The concept of the characters designed is social diversity in accordance with the motto of the Indonesian nation, Bhinneka Tunggal Ika.
Keyword - Animation, Education, Astronomy, Character Design, Elementary School
Effects of oxygen-prebreathing on tissue nitrogenation in normobaric and hyperbaric conditions
Authors: Ashworth Edward Tom , Ogawa Ryotaro , Vera David Robert , Lindholm Peter 
Published: January 2024

Background
Breathing pure oxygen causes nitrogen washout from tissues, a method commonly deployed to prevent decompression sickness from hypobaric exposure. Theoretically prebreathing oxygen increases the capacity for nitrogen uptake and potentially limits supersaturation during dives of short duration. We aimed to use 13N2, a radioactive nitrogen isotope, to quantify tissue nitrogen following normobaric and hyperbaric exposures.

Methods
Twenty Sprague Dawley rats were divided in 4 conditions; normobaric prebreathe, normobaric control, hyperbaric prebreathe, hyperbaric control. Prebreathed rats breathed oxygen for 1 h prior to the experiment whilst controls breathed air. Normobaric rats breathed air containing 13N2 at 100 kPa for 30 min, whereas hyperbaric rats breathed 13N2 at 700 kPa before being decompressed and sedated using air-isoflurane (without 13N2 for a few minutes). After euthanization, blood, brain, liver, femur and thigh muscle were analyzed by gamma counting.

Results
At normobaria prebreathing oxygen resulted in higher absolute nitrogen counts in blood (p = .034), as well as higher normalized counts in both the liver and muscle (p = .034). However, following hyperbaric exposure no differences were observed between conditions for any organ (p>.344). Both bone and muscle showed higher normalized counts after hyperbaria compared to normobaria.

Conclusions
Oxygen prebreathing caused nitrogen elimination in normobaria that led to a larger “sink” and uptake of 13N2. The lack of difference between conditions in hyperbaria could be due to the duration and depth of the dive mitigating the effect of prebreathing. In the hyperbaric conditions the lower counts were likely due to off-gassing of nitrogen during the sedation procedure, suggest a few minutes was enough to off-gas in rodents. The higher normalized counts under hyperbaria in bone and muscle likely relate to these tissues being slower to on and off-gas nitrogen. Future experiments could include shorter dives and euthanization while breathing 13N2 to prevent off-gassing.
Civilized Global North versus rebellious Global South: a socio-semiotic analysis of media visual discourse
Authors: Bashir Rahat , Yasmin Musarat 
Published: January 2024

Abstract
The COVID-19 pandemic has transformed the ideological, social, economic, and political aspects of life on planet Earth. This study examines the visuals associated with COVID-19 published in Pakistani English newspapers. Visual data were collected through purposive sampling, analyzed using social semiotic theory, and discussed through a post-colonial lens. The visual data were grouped as Global South and North owing to socioeconomic and political categorization among countries. The results show that the Pakistani media portrayed the Global South as rebellious, miserable, and noisy against the government. However, the Global North is depicted as civilized, stress-free, and abiding by all the instructions of the authority. Analysis shows that the two realms are visually represented as remarkably divergent from each other, and media portrayal has attached stereotypes identities to the nations. Pakistani media follows a basic restricted code of conduct, which should be extended to avoid labelling and politicizing groups and nations.
Topological optimization of structures with thermomechanical loading under compliance constraints for 3D printing applications
Authors: Mojiri Soroush , Shafiei Alireza , Nourollahi Amin 
Published: January 2024

Abstract
Currently, due to the high costs of production and expensive raw materials, approaches, including, making models smaller and lighter, are especially considered in the design of structures. In order to better describe the capabilities, efficiency, and limitations of an innovative field in design methodology, called topology optimization, various practical problems under different loadings and boundary conditions were evaluated in this study. Optimization algorithms were used in ANSYS software for the optimization of a cantilever beam under static loading, double-girder beam and a dome-shaped geometry under static and thermal loading, a hot fluid transfer tee and an engine exhaust manifold under static loading and convection heat transfer. The results showed that the reduced volume in the final models were equal to 52.88%, 50.05%, 51.85%, and 35.02%, respectively. Consequently, this reduced volume causes some increase in the tension, and displacement of the final model, which the designer can adjust them according to the limitations governing the problem. Furthermore, the amount of increase in the average value of the stress in the cantilever beam, double-girder beam, and dome-shaped geometry were 88, 800, and 6 MPa, and the average amount of displacement in these samples increased by 10.2%, 200%, and 3.3%, respectively. Unforeseen challenges, and manufacturability of optimized problems were investigated by 3D printing of a dome-shaped model using the FDM method, which illustrated that the output product has a suitable level of accuracy and smoothness. Subsequently, by using supporting structures, three-dimensional holes were created with proper precision in the 3D-printed sample, which satisfied the manufacturability of relatively complex models without using traditional production methods.
Monthly Hydropower Scheduling of Cascaded Reservoirs Using Genetic Algorithm with Simulation Procedure
Authors: Baima Deji , Qian Guoyuan , Luo Jingzhen , Wang Pengcheng , Zheng Hao , Wang Jinwen 
Published: January 2024

Abstract

This study introduces an innovative approach for the monthly hydropower scheduling of cascaded reservoirs in the Jinsha River, China, utilizing a Genetic Algorithm (GA) with a simulation procedure. The proposed methodology incorporates a field-leveling (FL) procedure within the GA framework, employing push-and-pull strategies to enhance the efficiency and quality of feasible solutions, particularly when guided by spillage minimization. The study sequentially optimizes firm yield, total energy, and spillage in order of priority. Comparative analyses with a Sequential Quadratic Programming (SQP) model demonstrate the superiority of GA in achieving an 8.3% improvement in firm yield at the highest priority despite higher spillage. Additionally, the study explores the convergence behavior of the GA procedure, highlighting its efficiency. The results emphasize the significance of spillage minimization in FL for preserving firm yield and present a comprehensive analysis of the scheduling outcomes for different hydrological scenarios, providing valuable insights for optimizing hydropower generation in cascaded reservoir systems.
Development of a Prognostic Model Based on Lysosome-Related Genes for Ovarian Cancer: Insights into Tumor Microenvironment, Mutation Patterns, and Personalized Treatment Strategies
Authors: Sun Ran , Li Siyi , Ye Wanlu , Lu Yanming 
Published: January 2024

Abstract

Background: Ovarian cancer (OC) is often associated with an unfavorable prognosis. Given the crucial involvement of lysosomes in tumor advancement, lysosome-related genes (LRGs) hold promise as potential therapeutic targets.
Methods: To identify differentially expressed lysosome-related genes (DE-LRGs), we performed a matching analysis between differentially expressed genes (DEGs) in OC and the pool of LRGs. Genes with prognostic significance were analyzed using multiple regression analyses to construct a prognostic risk signature. The model's efficacy was validated through survival analysis in various cohorts. We further explored the model's correlation with clinical attributes, tumor microenvironment (TME), mutational patterns, and drug sensitivity. The quantitative real-time polymerase chain reaction (qRT-PCR) validated gene expression in OC cells.
Results: A 10-gene prognostic risk signature was established. Survival analysis confirmed its predictive accuracy across cohorts. The signature served as an independent prognostic element for OC. The high-risk and low-risk groups demonstrated notable disparities in terms of immune infiltration patterns, mutational characteristics, and sensitivity to therapeutic agents. The qRT-PCR results corroborated and validated the findings obtained from the bioinformatic analyses.
Conclusions: We devised a 10-LRG prognostic model linked to TME, offering insights for tailored OC treatments.
Is the Individual Idiolect Substantially a Genetic Inheritance?
Authors: Murphy Terence Patrick 
Published: January 2024

Abstract

Although stylometric studies tends to situate itself within the field of forensic analysis, most stylometricians appear averse to considering genetic explanations for their findings. Instead, they try to work with a range of what they construe as environmental factors in attempting to understand the clustering of individual authorial idiolects. However, researchers in behavioral genetics have demonstrated that the traits for cognitive abilities, including language ability, are among the most heritable. In this paper, I set out the major postulate and eight corollaries for the genetic hypothesis and the major postulate and five corollaries for the environmental hypothesis for explaining the clustering of individual idiolects in dendrogram analysis, using stylo in R. Using a corpus of Anglo-American modernist poetry, I then demonstrate that the individual idiolects of each of the Sitwell siblings—Edith, Osbert and Sacheverell—cluster together. In this way, I aim to help researchers decide which of the two hypotheses is the most likely explanation for the attested idiolectal similarities among the members of a number of important British and French literary families.
Modular system pond cultivation model for the survival of milkfish (Chanos chanos): case study of Pangkajene Kepulauan Regency, Indonesia
Authors: Sambu Abdul Haris , Burhanuddin Burhanuddin , Malik Abdul , Tamrin Tamrin 
Published: January 2024

Abstract

This study aims to to analyze survival rates in milkfish modular cultivation systems and their correlation with fluctuations in temperature and salt content. The modular system method was used, with three plots: plot A as the nursery plot, plot B as the first rearing plot, and plot C as the enlargement plot 2. The research was conducted over one year with three maintenance cycles, each cycle lasting four months. The organisms were placed in plot A for a period of 1–8 months. Thus, in one year, plot A gets the opportunity to rest for four months while preparing, then in grow-out plot 1 and grow-out plot 2 for two months each, so that each grow-out plot gets the opportunity to rest while preparing for the next maintenance cycle. Results revealed the temperature, salt content, pH, and dissolved oxygen were within the optimal range, with an average value of 29.40C., pH of 6.9, and dissolved oxygen of 31 ppm. However, the salt content fluctuated a lot, with values ranging between 5 and 45 ppt with an average value of 26.9 ppm. The average survival rate was 91% with a correlation of R2 = 0.906 (cycle 1), 95% with a correlation of R2 = 0.890 (cycle 2), and 97% with a correlation of R2 = 0.997 (cycle 3). To conclude, the modular cultivation system, apart from increasing survival rates, can also improve the pond soil environment. This system is highly suitable as a promising approach for sustainable fisheries development in the region.
The Effect of Intra Spinal Administration of Cerium Oxide Nanoparticles on Central pain mechanism: An Experimental Study Running Title: CeONP Administration Effect on Chronic Pain
Authors: Mostaar Ahmad , Behroozi Zahra , Nezhad Ali Motamed , Hajimirzaei Pooya , Mojarad Negin , Ramezani Fatemeh , Janzadeh Atousa 
Published: January 2024

Abstract

Background: Cerium oxide nanoparticles (CeONPs) have antioxidant and anti-inflammatory attributes. This study investigated its effect on central neuropathic pain (NP), which is resistant to treatment, along with part of the mechanism of action.
Materials and Methods: The compressive method of spinal cord injury (SCI) model was used for pain induction. For that purpose, three groups were formed by a random allocation of 24 rats. In the treatment group, CeONPs were injected above and below the lesion site immediately after inducing SCI. We evaluated pain symptoms using acetone, Radian Heat, and Von Frey tests weekly for six weeks. Finally, we counted fibroblasts using H & E staining. We evaluated the expression of Connexin43 (a pain marker), GAD65 (an anti-pain marker), and HDAC2 (an epigenetic marker of pain) proteins using the western blot method. The analysis of results was done by PRISM software.
Results: At the end of the study, we found CeONPs reduced pain symptoms to levels similar to those observed in normal animals. CeONPs also increased the expression of GAD65 and CX43 proteins but did not affect HDAC2 inhibition.
Conclusion: Our study suggests CeONPs have a pain-alleviating effect on chronic pain, which is likely achieved by preventing the reduction of GAD65 and CX43 protein expression and inhibiting the entry of fibroblasts. These findings give us a new understanding of the potential therapeutic applications of CeONPs for NP management. Further research is needed to validate these findings and explore the optimal dosage and administration of CeONPs for NP treatment.
Improving Photocleavage Efficiency of Photocleavable Protein for
Antimicrobial Peptide Histatin 1 Expression
Authors: Zhou Nana , An Tai , Zhang Yuan , Zhao Guomiao , Wei Chao , Shen Xuemei , Li Fan , Wang Xiaoyan 
Published: January 2024

Background:
Antimicrobial peptides (AMPs) are promising alternative agents for
antibiotics to overcome antibiotic resistance problems. But, it is difficult to produce large-scale antimicrobial research due to the toxicity towards expression hosts or degradation by peptidases in
the host. Therefore, heterologous recombinant expression of antimicrobial peptides has always
been a challenging issue.

Objective:
To overcome toxicity to the expression host and low expression level, a new photocleavable protein fusion expression method for antimicrobial peptides is provided.

Methods:
Through directed evolution and high throughput screening, a photocleavable protein mutant R6-2-6-4 with a higher photocleavage efficiency was obtained. The DNA coding sequence of
antimicrobial peptide Histatin 1 was fused within the sequence of R6-2-6-4 gene. The fusion gene
was successfully expressed in Escherichia coli expression system.

Results:
Antimicrobial peptide Histatin 1 could be successfully expressed and purified by fusing
within PhoCl mutant R6-2-6-4. The antimicrobial activity was rarely affected, and the MIC value
was 33 ug/mL, which was basically equivalent to 32 ug/mL of the chemically synthesized Histatin
1. After amplification in a 5 L fermenter, the expression of PhoCl mutant (R6-2-6-4)-Histatin1 improved up to 87.6 mg/L in fermenter, and Histatin1 obtained by photocleavage also could up to 11
mg/L. The prepared Histatin1 powder remained stable when stored at 4oC for up to 4 months without any degradation. In addition, the expression and photocleavage of β -Defensin105 and Lysostaphin verified the certain universality of the PhoCl mutant fusion expression system.

Conclusion:
Antimicrobial peptides Histatin 1, β -Defensin 105 and Lysostaphin were successfully expressed and purified by photocleavable protein mutant. This may provide a novel strategy to
express and purify antimicrobial peptides in the Escherichia coli expression system.