bluuebunny/crossref_metadata_2025_split huggingface dataset:
BCMA-BBZ-OX40 CAR-T Therapy Using an Instant Manufacturing Platform in Multiple Myeloma
Authors: Wang Ting , Yang Yazi , Ma Lie , Feng Ru , Li Jiangtao , Zhang Chunli , Bai Jiefei , Ding Yanping , Liu Guanghua , Wu Fei , Lu Xinan , Feng Shi , Li Zhenling , He Ting , Li Jian , Liu Hui 
Published: September 2024

BackgroundChimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability.MethodsA 4-1BB-costimulated B-cell maturation antigen (BCMA) CAR-T integrating an independently-expressed OX40 (BCMA-BBZ-OX40) was designed and generated by a traditional manufacturing process (TraditionCART) or instant manufacturing platform (named InstanCART). The tumor-killing efficiency, differentiation, exhaustion, and expansion level were investigated in vitro and in tumor-bearing mice. An investigator-initiated clinical trial was performed in patients with R/R MM to evaluate the outcomes of both TraditionCART and InstanCART. The primary objective was safety within 1 month after CAR-T cell infusion. The secondary objective was the best overall response rate.ResultsPreclinical studies revealed that integrated OX40 conferred BCMA CAR-T cells with superior cytotoxicity and reduced exhaustion levels. InstanCART process further enhanced the proliferation and T-cell stemness of BCMA-BBZ-OX40 CAR-T cells. BCMA-BBZ-OX40 CAR-T cells were successfully administered in 22 patients with R/R MM, including 15 patients with TraditionCART and 7 patients with InstanCART. Up to 50% (11/22) patients had a high-risk cytogenetic profile and 36% (8/22) had extramedullary disease. CAR-T therapy caused grade 1–2 cytokine release syndrome in 19/22 (80%) patients, grade 1 neurotoxicity in 2/22 (9%) patients and led to ≥grade 3 adverse events including neutropenia (20/22, 91%), thrombocytopenia (15/22, 68%), anemia (12/22, 55%), creatinine increased (1/22, 5%), hepatic enzymes increased (5/22, 23%), and sepsis (1/22, 5%). The best overall response rate was 100%, and 64% (14/22) of the patients had a complete response or better. The median manufacturing time was shorter for InstanCART therapy (3 days) than for TraditionCART therapy (10 days). Expansion and duration were dramatically higher for InstanCART cells than for TraditionCART cells.ConclusionsBCMA-BBZ-OX40 CAR-T cells were well tolerated and exhibited potent responses in patients with R/R MM. InstanCART shortened the manufacturing period compared to TraditionCART, and improved the cellular kinetics. Our results demonstrated the potency and feasibility of OX40-modified BCMA CAR-T cells using InstanCART technology for R/R MM therapy.Trial registration numberThis trial was registered at www.clinicaltrials.gov as #NCT04537442.
MTA-cooperative PRMT5 inhibitors enhance T cell-mediated antitumor activity in MTAP-loss tumors
Authors: Chen Si , Hou Jiakai , Jaffery Roshni , Guerrero Ashley , Fu Rongjie , Shi Leilei , Zheng Ningbo , Bohat Ritu , Egan Nicholas A , Yu Chengtai , Sharif Sana , Lu Yue , He Wei , Wang Shuyue , Gjuka Donjeta , Stone Everett M , Shah Pooja Anil , Rodon Ahnert Jordi , Chen Taiping , Liu Xinli , Bedford Mark T , Xu Han , Peng Weiyi 
Published: September 2024

BackgroundHyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer.MethodsIsogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were evaluated in these isogenic tumor lines and T cellsin vitroandin vivo. Transcriptomic and proteomic changes in tumors and T cells were characterized in response to PRMT5i treatment. Furthermore, the efficacy of MRTX1719 in combination with immune checkpoint blockade was assessed in two syngeneic murine models with MTAP-loss tumor.ResultsGSK3326595 significantly suppresses PRMT5 activity in tumors and T cells regardless of the MTAP status. However, MRTX1719, a methylthioadenosine-cooperative PRMT5 inhibitor, exhibits tumor-specific PRMT5 inhibition in MTAP-loss tumors with limited immunosuppressive effects. Mechanistically, transcriptomic and proteomic profiling analysis reveals that MRTX1719 successfully reduces the activation of the PI3K pathway, a well-documented immune-resistant pathway. It highlights the potential of MRTX1719 to overcome immune resistance in MTAP-loss tumors. In addition, MRTX1719 sensitizes MTAP-loss tumor cells to the killing of tumor-reactive T cells. Combining MRTX1719 and anti-PD-1 leads to superior antitumor activity in mice bearing MTAP-loss tumors.ConclusionCollectively, our results provide a strong rationale and mechanistic insights for the clinical development of MRTX1719-based IO combinations in MTAP-loss tumors.
Identifying Accessibility and Equity Defects of Elderly Care Services in Developing Countries: Insights From Xiamen City
Authors: Wei Linjiang , Fang Ya , Zhang Liangwen 
Published: September 2024

Background: The global aging population has raised concerns about the fair distribution of elderly care resources. China, as the largest developing country, has made efforts to address population aging challenges. However, equitable distribution of elderly care resources remains a concern. This study analyzed the spatial layout and accessibility of elderly care service facilities (ECSFs) in Xiamen City to improve resource allocation and enhance the elderly care system in China. The findings provide valuable insights for other developing countries and regions seeking to improve their own elderly care resource allocation.Methods: Xiamen City was chosen as the research area due to its unique geographical location and advanced information technology infrastructure. The study examined the spatial distribution, accessibility, and equity of ECSFs. Using Python, point of interest (POI) data were collected and evaluated using the kernel density method and two‐step floating catchment area method. Spatial autocorrelation analysis identified areas of aggregation and dispersion in ECSF accessibility.Results: Xiamen currently has 660 ECSFs, including nursing homes, adult day care centers, home care agencies, and rural elderly care homes. The analysis revealed spatial disparities, with ECSFs clustering primarily in the central area of Xiamen Island. Significant differences in accessibility were found among the four types of ECSFs. Spatial autocorrelation analysis identified cold and hot spot areas, indicating variations in accessibility across regions.Conclusion: Xiamen City has made progress in allocating elderly care resources and constructing service facilities. However, equity in resource allocation remains a concern. Areas with limited accessibility were identified, leading to unequal access to elderly care resources and timely physical care. To address these challenges, decision‐making departments should consider increasing facilities, improving transportation, enhancing macro planning, and improving facility service quality and accessibility. These measures will optimize ECSF accessibility and promote equitable distribution of elderly care resources.
Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis
Authors: Kaur Japneet , Adhikari Manish , Sabol Hayley M. , Anloague Aric , Khan Sharmin , Kurihara Noriyoshi , Diaz-delCastillo Marta , Andreasen Christina Møller , Barnes Charles Lowry , Stambough Jeffrey B. , Palmieri Michela , Reyes-Castro Olivia , Zarrer Jennifer , Taipaleenmäki Hanna , Ambrogini Elena , Almeida Maria , O’Brien Charles A. , Nookaew Intawat , Delgado-Calle Jesus 
Published: September 2024

Abstract
Breast cancer bone metastases increase fracture risk and are a major cause of morbidity and mortality among women. Upon colonization by tumor cells, the bone microenvironment undergoes profound reprogramming to support cancer progression, which disrupts the balance between osteoclasts and osteoblasts and leads to bone lesions. A deeper understanding of the processes mediating this reprogramming could help develop interventions for treating patients with bone metastases. Here, we demonstrated that osteocytes (Ot) in established breast cancer bone metastasis develop premature senescence and a distinctive senescence-associated secretory phenotype (SASP) that favors bone destruction. Single-cell RNA sequencing identified Ots from mice with breast cancer bone metastasis enriched in senescence, SASP markers, and pro-osteoclastogenic genes. Multiplex in situ hybridization and artificial intelligence–assisted analysis depicted Ots with senescence-associated satellite distension, telomere dysfunction, and p16Ink4a expression in mice and patients with breast cancer bone metastasis. Breast cancer cells promoted Ot senescence and enhanced their osteoclastogenic potential in in vitro and ex vivo organ cultures. Clearance of senescent cells with senolytics suppressed bone resorption and preserved bone mass in mice with breast cancer bone metastasis. These results demonstrate that Ots undergo pathological reprogramming by breast cancer cells and identify Ot senescence as an initiating event triggering lytic bone disease in breast cancer metastases.
Significance: Breast cancer cells remodel the bone microenvironment by promoting premature cellular senescence and SASP in osteocytes, which can be targeted with senolytics to alleviate bone loss induced by metastatic breast cancer.
See related commentary by Frieling and Lynch, p. 3917
Mimetic Possibilities: Collaboration through Movement in Multimedia Opera
Authors: Mikolajczyk Kurt , Har Austin Oting , Wachsmann Laura , Bown Oliver , Ferguson Samuel 
Published: September 2024

Abstract
In the opera The Ghost, artists with backgrounds in music composition, Greek tragedy, creative coding, and opera performance collaborated to create an artwork that engages with philosophy and technology. A light sculpture with a novel Internet of Things (IoT) architecture was adapted for the opera’s stage, where both the sculpture and its controlling interface were programmed to visually represent musical processes within the composer’s approach. During filming, the light sculpture contributed to the dramatic context through movement and gestural interaction between the sculpture and the soprano. Drawing upon human-computer interaction (HCI) research and its inquiry into movement for engaging with new technology expressively, movement and gesture transpiring from mimetic techniques in the opera were central in this interdisciplinary collaboration.
Towards Equitable Artscience Collaborations: Synthesizing Performance Art and Social Psychology for Social Change
Authors: Amir Einat , Hasson Yossi 
Published: September 2024

Abstract
The article proposes a novel model for ArtScience collaborations that is based on more equal collaborations. With better power balance, artists and scientists can together create projects that truly synthesize their fields. Additionally, it is suggested that these collaborations can significantly contribute to social change through socially engaged research. The article focuses on the transformative potential of the collaboration process itself. The presented case study is the authors' collaboration in creating hybrids of participatory performance art and social psychology experiments. It contributes new methodological approaches to the expanding field of ArtScience collaborations.
“Carlos Trilnick: an electronic image-processing pioneer from Argentina”
Authors: Cantú Mariela 
Published: September 2024

Abstract
The author analyzes three 1980s video works by Argentinian pioneer artist Carlos Trilnick (1957-2020), whose insubordinate interventions with image-processing tools served the purpose of a reflection upon time, challenging traditional narratives of sequentiality, segmentation, and cause-effect linearity. These video works display a virtuous interconnection of art and technology, built upon a solid political perspective on audiovisual representation, art history, and territorial disputes. Acknowledging the work of this artist contributes to the expansion of global dialogues about the use of image-processing tools, incorporating Latin America into traditional narratives dominated by Europe-US exchanges.
Philip Mallory Jones’s Electronic Consciousness in Afrodiasporic Video
Authors: Kim Liz 
Published: September 2024

Abstract
Philip Mallory Jones’s videomation was an early video image processing technique from the 1970s that superimposed multiple forms of image-making to convey the aesthetics of Afrodiasporic rhythms. While videomation’s application in Jones’s collaboration with Gunilla Mallory Jones in Beyond the Mountains, More Mountains (1975) was a disillusionment that tested the limits of Afrodiasporic connections between the US and Haiti, he later refined this technique through splicing and weaving of visual polyrhythms in his collaboration with the Burkinabe media pioneer Moustapha Thiombiano, Wassa (1989), as an expression of double consciousness.
Hot Software: Towards a Thermopolitics of Art and Technology
Authors: Kirsch Corinna 
Published: September 2024

Abstract
Software (1970) was one of the first exhibitions to bring together art and computers. In subsequent decades, this ambitious exhibition has been regarded largely through a lens of failure: it was beset with nonworking machines and conflict between exhibition organizers and artists, with blame placed on humans and their unsuccessful technological mastery. This essay presents a more expansive review by tracing the agency of the environment--and environmental issues such as air pollution--on the technical and social breakdowns of the exhibition. Recent scholarship into other-than-human materialities helps lay the foundation for the exhibition as a site of conflict between the immateriality of information and the active conditions of thermal media.
Early Image Processing and Computer Animation in Colorado: Pat Lehman’s Video Vitae in Context
Authors: Pytlinski Deanne 
Published: September 2024

Abstract
In 1975, Pat Lehman screened her experimental video, Video Vitae at the New York Women’s Video Festival. Lehman worked in Colorado, where she also started the first video program in the state’s college system. This paper examines Video Vitae as an example of image-processed video and early computer animation in the context of second-wave feminism. The author charts Lehman’s influences and access to the Scanimate computer used to produce Video Vitae, arguing that the significance of Lehman’s feminist narrative and the technology were deeply intertwined. Such explicit feminist narratives were extremely rare among artists engaged in early image-processing and animation.
Responsivity and Responsibility in Responsive Environments: Art and Interactivity on a Rupturing Planet
Authors: Wodak Joshua 
Published: September 2024

Abstract
The late-twentieth-century art form Responsive Environments comprised interrelations between artist, artwork, and audience, wherein responsivity and responsibility to an other, be it the social and/or physical environment of the artwork, could be tangibly evoked. Currently, such self-other understanding has become existentially critical, as the ecological and climate crisis collide with a new dearth of understanding concerning human-ecology and human-human responsivities and responsibilities. This article considers how Responsive Environments offered a unique means for exploring responsivity and responsibility between artist, artwork, and audience, and considers what the debates it once evoked might contribute to self-other relations in an age of human-induced planetary rupture, as expressed in climate crisis and mass extinction.
Latent Space Bayesian Optimization With Latent Data Augmentation for Enhanced Exploration
Authors: Boyar Onur , Takeuchi Ichiro 
Published: September 2024

Abstract
Latent space Bayesian optimization (LSBO) combines generative models, typically variational autoencoders (VAE), with Bayesian optimization (BO), to generate de novo objects of interest. However, LSBO faces challenges due to the mismatch between the objectives of BO and VAE, resulting in poor exploration capabilities. In this article, we propose novel contributions to enhance LSBO efficiency and overcome this challenge. We first introduce the concept of latent consistency/inconsistency as a crucial problem in LSBO, arising from the VAE-BO mismatch. To address this, we propose the latent consistent aware-acquisition function (LCA-AF) that leverages consistent points in LSBO. Additionally, we present LCA-VAE, a novel VAE method that creates a latent space with increased consistent points through data augmentation in latent space and penalization of latent inconsistencies. Combining LCA-VAE and LCA-AF, we develop LCA-LSBO. Our approach achieves high sample efficiency and effective exploration, emphasizing the significance of addressing latent consistency through the novel incorporation of data augmentation in latent space within LCA-VAE in LSBO. We showcase the performance of our proposal via de novo image generation and de novo chemical design tasks.
A Systematic Review of Surgical Characteristics and Adverse Events of an Active, Transcutaneous Bone Conduction Device
Authors: Jukic Alma , Munhall Christopher C. , Stevens Shawn M. 
Published: September 2024

Objective: A new, active transcutaneous bone conduction device (BCD) was FDA-approved in 2019 in the USA. This systematic review sought to evaluate early outcomes associated with Osia implantation. Methods: A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Four databases were reviewed: PubMed, Scopus, Cochrane CENTRAL, and CINAHL. Studies were included if they described audiometric, surgical characteristics/complications, or adverse events associated with the Osia BCD. Exclusion criteria: non-English language studies, animal investigations, reviews/meta-analyses, case reports, database studies. Results: Eighteen studies with 336 patients were included. Mean age at implantation was 37.9 years. About 79.5% of patients had MHL/CHL and 19.5% had SSD/SHL. Mean operative time was 71.6 minutes. Mean PTA gain from unaided conditions was 35.4 dB. Mean functional gain at high frequency (6 kHz and above) from aided conditions was 16.1 dB. Mean improvement in speech recognition thresholds was 19.1 dB from unaided conditions. Adverse events (all types) were reported in 20.1% of cases. Across all studies, the postoperative infection rate was 5%. About 2% of patients reported magnet retention issues. About 1.65% of cases were complicated by hematomas. Conclusions: Under systematic literature review, the Osia BCD has been associated with low complication rates, relatively short operative times, and good audiometric and speech outcomes, notably high frequency gain >6 kHz. More advanced audiometric outcome reporting remains limited and audiometric data and patient reported outcome measures were reported heterogeneously.
Pathways to suicide for children and youth in Guyana: A life charts analysis
Authors: Shaw Charlotte , Stuart Jaimee , Thomas Troy , Kõlves Kairi 
Published: September 2024

Background: Suicide is the third leading cause of death among youth aged 15 to 29 years old globally. Guyana has the highest rate of youth suicide in the world, yet only limited research exists. Aim: The aim of this study is to identify key features of the suicide pathway for Guyanese children and youth and to distinguish meaningful subgroups. Method: The psychological autopsy (PA) method was used to generate life charts for 15 Guyanese children and youth (10–29 years) who died by suicide. Nineteen close contacts of these individuals were interviewed about the life events of the decedent between 6 months and 5 years after their death. Semi-structured interviews lasting 30 to 150 min took place between November 2021 and January 2022. The interview data were converted into life charts and these were reviewed to uncover meaningful subgroups of suicide pathways. Results: Three groups with distinct suicide pathways were identified: hard life (46%), mental illness (20%) and interpersonal stress (20%). There were also two male youths for whom the suicidal antecedents and pathways were unclear. Interpersonal stress, alcohol, exposure to suicide and family history of suicide were common factors identified across groups. Conclusions: The findings emphasise the role of both acute and protracted interpersonal stress for child and youth suicide in Guyana. The structure and dynamics of Indo-Guyanese families are discussed. Interventions recommended include enhancing child and youth community engagement, improving mental health and suicide literacy, alcohol restriction, increasing access to support services, and reducing stigma.
Current status and usefulness of therapeutic drug monitoring implementation of theophylline in elderly patients based on a nationwide database study and modeling approach
Authors: Okada Akira , Sera Shoji , Taguchi Maho , Yamada Hiroaki , Nagai Naomi 
Published: September 2024

Objectives: Theophylline is used in the treatment of chronic obstructive pulmonary disease but readily causes symptoms of intoxication and exhibits high risks in elderly patients. However, there have only been a few recent reports on the significance of therapeutic drug monitoring (TDM) implementation, especially in elderly patients. To examine the usefulness of theophylline TDM, we evaluated the current status of prescriptions containing theophylline and its side effects and assessed the influence of aging, sex, drug formulation, and concurrent drugs use on theophylline exposure using data from various nationwide databases and a pharmacokinetic modeling approach. Methods: We utilized sampling data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Using the data of patients aged ≥80 years, we conducted an association analysis of theophylline and concurrent drugs. The transition in plasma theophylline concentration levels of elderly patients was estimated based on a previously reported physiological-based pharmacokinetic model. Results: Altogether, 3973 patients using theophylline were registered in our dataset, and about 50% were over 70 years old and used theophylline. Therapeutic drug monitoring implementation was confirmed in only 1.13% of patients. The association analysis confirmed a frequent co-occurrence with allopurinol and famotidine, which increase theophylline exposure, in elderly patients aged ≥80 years. The physiologically based pharmacokinetic model indicated that theophylline trough concentrations were 1.65-fold higher in elderly patients aged 80 years compared to those aged 30 years and 1.35-fold higher in females compared to males. Conclusion: This study effectively combined information on the nationwide health care database and modeling approach, indicating the importance of proactive TDM and dose justification for female and elderly patients.