bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB104: Preclinical evaluation of the role of Galectin-1 in tumor immune evasion associated mechanisms using a highly selective Galectin-1 small molecule inhibitor
Authors: Holyer Ian , Slack Rob , Petersen Kristoffer , Zetterberg Fredrik , Mackinnon Alison 
Published: April 2023

Abstract
Galectin-1 (Gal-1) is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment (TME) of some aggressive cancers and whose high expression correlates strongly with poor survival. Following a data mining exercise of external publication data and additional clinical biomarker datasets, we found strong evidence concluding the potential role of Gal-1 in the establishment of a fibrotic tumor stroma and mechanisms associated with tumor invasion, metastasis and angiogenesis. However, there was limited data regarding the role of Gal-1 in immune escape by tumors to make any strong conclusions/pathway reconstruction around this specific TME mechanism of action (MOA). To further strengthen the potential role of Gal-1 in tumor immune evasion we completed a series of preclinical in vivo and in vitro activities, using a highly selective Gal-1 small molecule inhibitor developed at Galecto Biotech. To examine the role of Gal-1 inhibition in vivo, we investigated the effects on tumor volume of the highly selective Gal-1 inhibitor, in a syngeneic mouse model of lung adenocarcinoma. RNA profiling of vehicle and compound treated tumors was also implemented following completion of the in-life phase. Oral administration of the Gal-1 inhibitor reduced mouse lung adenocarcinoma growth and increased the immune gene expression within the tumors, showing a strong association to that of exacerbated NK cell activity. No additional cytotoxic T cell gene changes were uncovered in the Gal-1 inhibitor treated tumors. We further evaluated the overall T cell compartment, relevant to the clinical TME setting, by stimulating human peripheral blood mononuclear cells (hPBMC’s) incubated with and without the Gal-1 inhibitor to observe the potential blockade of any known immune checkpoint inhibitor (ICI) resistance mechanisms. Interestingly, we found a variety of immune suppressive proteins to be inhibited, including IL-17, when hPBMC’s were incubated with the Gal-1 inhibitor. In summary, the data presented suggests highly selective Gal-1 inhibition could provide an effective, monotherapy (or be used in combination with ICI's) to boost immune infiltration and/or activation in the TME of lung adenocarcinoma and potentially other aggressive cancers.
Citation Format: Ian Holyer, Rob Slack, Kristoffer Petersen, Fredrik Zetterberg, Alison Mackinnon. Preclinical evaluation of the role of Galectin-1 in tumor immune evasion associated mechanisms using a highly selective Galectin-1 small molecule inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB104.
Abstract LB218: Developing a bispecific anti-ROR1 antibody drug conjugate for hematological and solid tumor treatment
Authors: Zhao Xiaobei , Zhu Jie , Wu Zhenhua , Li Jing , zhou yaqiong , Nie Lei , Chen Gang 
Published: April 2023

Abstract
Developing a bispecific anti-ROR1 Antibody Drug Conjugate for hematological and solid tumor treatment
Receptor tyrosine kinase ROR1 is a type I transmembrane protein belongs to the ROR family members. ROR1 is a receptor for Wnt family signaling molecules Wnt5a and is a key regulator of normal cellular process, including cell proliferation, survival, and migration. It is also involved in the development and progression of many types of cancer. Although being an oncofetal protein with limited expression in most of the normal tissues, ROR1 is expressed abnormally in various hematological and solid cancers, making it a highly attractive target for antibody-drug conjugate (ADC) therapy. The current clinical results of ROR1 ADC have been promising in treating patients with relapsed and/or refractory (R/R) hematologic malignancies.
Utilizing our unique and innovated linker platform, we screened many anti-ROR1 ADCs, with defined DAR=4. Those unique ADCs consist of a humanized monoclonal antibody (mAb against single epitope) or a bispecific antibody (BsAb against two epitopes), stably conjugated to an antimitotic agent. The bispecific mAbs that target to two different epitopes of ROR1, are superior to those antibodies that target to single epitope in the binding to ROR1-expressing tumor cells, the induction of tumor cell death and anti-tumor immunity. Our novel linker structure prevents payloads from coming off of the antibody during the circulation, significantly reduced the off-target toxicity. In vitro and In vivo studies demonstrated the antitumor activity of anti-ROR1 ADCs outperformed the lead anti-ROR1 ADC currently in phase II/IIl trial, providing a promising treatment for hematological and solid cancers with a better safety profile and a larger therapeutic window. The lead candidate molecule, BR111A will start the preclinical studies soon.
Citation Format: Xiaobei Zhao, Jie Zhu, Zhenhua Wu, Jing Li, yaqiong zhou, Lei Nie, Gang Chen. Developing a bispecific anti-ROR1 antibody drug conjugate for hematological and solid tumor treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB218.
Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa
Authors: Bauer Marcus , Vetter Martina , Stückrath Kathrin , Yohannes Meron , Desalegn Zelalem , Yalew Tewodros , Bekuretsion Yonas , Kenea Tariku W. , Joffe Maureen , van den Berg Eunice J. , Nikulu Julien I. , Bakarou Kamate , Manraj Shyam S. , Ogunbiyi Olufemi J. , Ekanem Ima-Obong , Igbinoba Festus , Diomande Mohenou , Adebamowo Clement , Dzamalala Charles P. , Anele Angelica A. , Zietsman Annelle , Galukande Moses , Foerster Milena , dos-Santos-Silva Isabel , Liu Biying , Santos Pablo , Jemal Ahmedin , Abebe Tamrat , Wickenhauser Claudia , Seliger Barbara , McCormack Valerie , Kantelhardt Eva J. 
Published: April 2023

Abstract

The low overall survival rates of patients with breast cancer in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis, and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients’ prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded breast cancer samples, including samples of the “African Breast Cancer-Disparities in Outcomes (ABC-DO) Study,” were analyzed. The immune cell phenotypes, their spatial distribution in the TME, and immune escape mechanisms of breast cancer samples from SSA and Germany (n = 117) were investigated using histomorphology, conventional and multiplex IHC, and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TIL) in the 1,237 SSA breast cancer samples, while the distribution of TILs in different breast cancer IHC subtypes showed regional diversity, particularly when compared with German samples. Higher TIL densities were associated with better survival in the SSA cohort (n = 400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in breast cancer samples from Western SSA. Features of nonimmunogenic breast cancer phenotypes were associated with reduced patient survival (n = 131). We therefore conclude that regional diversity in the distribution of breast cancer subtypes, TME composition, and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies.
See related Spotlight by Bergin et al., p. 705
Jacques Copeau e o instinto dramático da criança
Authors: Scalari Rodrigo 
Published: April 2023

Este artigo apresenta parte dos resultados de minha tese de doutorado sobre a criança como modelo na pedagogia teatral. Evidencia-se a noção de instinto dramático da criança, conceito-chave no projeto pedagógico de Jacques Copeau, e a presença de noções correlatas a esta nos trabalhos de importantes psicólogos da virada do século XIX para o século XX, como a noção de instinto teatral postulada por Nicolas Evreinov e as pesquisas com crianças efetuadas por Jacques Copeau e Suzanne Bing. O objetivo é destacar o papel fundamental do conceito proposto pela emblemática École du Vieux Colombier na formação do ator.
The Duty to Accept Apologies
Authors: Fabre Cécile 
Published: April 2023

Abstract
The literature on reparative justice focuses for the most part on the grounds and limits of wrongdoers’ duties to their victims. An interesting but relatively neglected question is that of what – if anything – victims owe to wrongdoers. In this paper, I argue that victims are under a duty to accept wrongdoers’ apologies. I claim that to accept an apology is to form the belief that the wrongdoer’s apologetic utterance or gesture has the requisite verdictive, commissive and expressive dimensions; to communicate as much to him; and to recognise that his apology changes one’s normative status in relation to him, and to comport oneself accordingly. I then offer a Kantian argument for the duty to accept and qualify that argument in the light of some hard cases. I end the paper by addressing the objection that victims do not owe it to wrongdoers to engage in any form of reparative encounter.
Mechanical and Thermal Forcings of Asian Large-Scale Orography on Spring Cloud Amount and Atmospheric Radiation Budget over East Asia
Authors: Li Jiandong , Geen Ruth , Mao Jiangyu , Song Yajuan , Vallis Geoffrey K. , Wu Guoxiong 
Published: April 2023

Abstract
Asian large-scale orography profoundly influences circulation in the North Hemisphere. Considerable spring top-of-the-atmosphere (TOA) radiative cooling over Southeast China (SEC) is very likely related to upstream orography forcing. Here we investigate the mechanical and thermal forcings of Asian large-scale orography, particularly the Tibetan Plateau (TP), on downstream East Asian cloud amount and atmospheric radiation budget during March–April using the Global Monsoons Model Intercomparison Project simulations. The thermal forcing drives significant surface heating and a low-level cyclone over the TP, pumping low-level air to the middle troposphere. Ascent and water vapor convergence triggered by the thermal forcing favor air condensation, low–middle clouds, and resultant strong spring cloud radiative cooling over SEC. Moreover, the thermal forcing moves the position of cloud radiative cooling westward toward the TP. The TP’s blocking role weakens low-level westerlies over SEC, but its deflecting role increases downstream high-level westerlies, dynamically favoring cloud formation over SEC and the eastward ocean. In addition, the TP can force ascent and increase cloud amounts over the western and central TP. The thermal forcing contributes to 57.1% of total cloud amount and 47.6% of TOA cloud radiative cooling induced by the combined orography forcing over SEC while the mechanical one accounts for 79.4% and 95.8% of the counterparts over the ocean to the east of SEC. Our results indicate that Asian large-scale orography shapes the contemporary geographical distribution of spring East Asian cloud amount and atmospheric radiation budget to a large extent.

Significance Statement
Clouds tied to large-scale topography and circulation exhibit some remarkable geographical distributions. The global strongest cloud radiative cooling, with an intensity of up to −90 W m−2, occurs over Southeast China (SEC) during March–April. The primary purpose of this study is to understand the influences of Asian large-scale orography, particularly the Tibetan Plateau (TP), on this unique climatic phenomenon using the latest climate model simulations. Our results show that Asian large-scale orography forcing significantly increases ascent, low–middle cloud formation, and resultant strong spring cloud radiative cooling over SEC and downstream ocean. The sensible-heat-driven air pump induced by the TP’s thermal forcing maintains strong cloud radiative cooling over SEC. This study provides valuable insights that link Asian large-scale orography forcing to downstream cloud–radiation characteristics.
Weakening of the Indian Ocean Dipole in the Mid-Holocene due to the Mean Oceanic Climatology Change
Authors: Liu Shanshan , Yuan Chaoxia , Luo Jing-jia , Ma Xiaofan , Zhou Xuecheng , Yamagata Toshio 
Published: April 2023

Abstract
The Indian Ocean dipole (IOD) is one of the leading modes of interannual climate variability in the tropical Indian Ocean (IO). The paleoclimate provides real climate scenarios to examine IOD behaviors and the linkage to basic states. Based on 18 models from phases 5 and 6 of the Coupled Model Intercomparison Project (CMIP5/6), the IOD change from the preindustrial period to the mid-Holocene is investigated. The multimodel mean reveals that the IOD variability weakens by 14%, as measured by the standard deviation of the dipole mode index, which is defined using the zonal sea surface temperature (SST) difference. Such attenuation is dominated by the spatially consistent suppression in the western-pole SST variability, while the eastern pole contributes little due to the opposite-signed changes in its northwestern and southeastern portions. The primary reason for the aforementioned changes comes from the altered climatic background, which displays a positive IOD-like pattern during IOD growing seasons, with intensified westward currents along the equator and northwestward currents in the southeastern equatorial IO. Such changes in the mean-state currents modulate the strength of the IOD-related anomalous advection and subsequently cause alterations in the IOD variability. Further analyses show that the IOD attenuation in the mid-Holocene is unlikely to be caused by the concurrently subdued El Niño–Southern Oscillation in the tropical Pacific, partially because of the diminished connections between the two oscillations themselves. The above simulated changes in both the IO mean climatology and IOD variability agree well with the available paleo records in literature.

Significance Statement
Understanding variations in the Indian Ocean dipole (IOD) and its relationship to the altered background mean state can advance our knowledge of tropical climate dynamics. The paleoclimate provides the opportunity to address this issue under real climate scenarios in the past. Based on multiple models from CMIP5/6, we investigate IOD changes during the mid-Holocene compared to the preindustrial period. The result shows a weakening of the IOD, and the main mechanism lies in the altered anomalous advection modulated by changes in the mean-state currents. The simulated changes in both the mean state and IOD variability are consistent with available paleo data. The present study extends the research scale of IOD dynamics beyond instrumental periods and provides scientific bases for deciphering geological records.
Psychiatric nurses’ perception of dignity in patients who attempted suicide
Authors: Mohammadi Fateme , Sadeghian Efat , Masoumi Zahra , Oshvandi Khodayar , Bijani Mostafa 
Published: April 2023

Background Maintaining the dignity of patients who attempted suicide is one of the caregivers’ main ethical duties. Yet, in many cases, these patients are not treated with dignity. The concept of dignity is abstract, and there is no research on the dignity of suicidal patients. So, the present study is done to investigate psychiatric nurses’ perception of dignity in patients who attempted suicide. Objective The present study explores the concept of dignity in patients who attempted suicide from the perspective of psychiatric nurses. Research design The present study is a qualitative, descriptive work of research Participants and research context A total of 20 psychiatric nurses from 2 hospitals affiliated with a university of medical sciences in the southeast of Iran were selected via purposeful sampling. Ethical considerations The Research Ethics Committee of the Hamadan University of Medical Sciences approved the study’s protocol, and ethical principles were followed in general. Findings From the findings of the study, three main themes, namely “ respect for personal; identity,” “management of psychological tension,” and “compassion-focused therapy,” with 12 sub-themes were extracted. Discussion and conclusion In the perspective of caregivers, patients who attempted suicide need to be cared for in supportive environments with compassionate and respectful behaviors to control their psychological tensions. These conditions would maintain such patients’ dignity and result in appropriate behavioral outcomes. Policy-makers and administrators can use the present study’s findings to create an appropriate clinical environment in which the dignity of patients who attempted suicide is properly maintained.
Deoxyschizandrin Inhibits PTEN to Regulate Inflammation in Doxorubicin-induced Hepatotoxicity
Authors: Wang Jinhai , Zhou Naijing 
Published: April 2023

Aim Doxorubicin (DOX) has long been criticized for its cardiotoxicity, yet one cannot overlook its hepatotoxicity. Deoxyschizandrin (Deo) is a type of monomer used in traditional Chinese medicine that has a powerful anti-inflammatory action and is frequently used to treat a variety of inflammatory diseases. However, its therapeutic effect on DOX-induced hepatotoxic inflammatory reactions is still unknown. Materials and Methods In this study, DOX was used to induce hepatotoxicity in rats, and the effects of Deo on hepatotoxicity and hepatic inflammation were investigated. Results The results show that Deo protects liver function by inhibiting PETN, which regulates DOX-induced liver inflammation. Conclusion The anti-inflammatory effect of Deo in DOX-induced hepatotoxicity is attributed to the inhibition of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and the increase in AKT phosphorylation.
Duration of Home Oxygen Therapy in Preterm Infants Utilizing a Remote Patient Monitoring Program to Wean: Trajectory Patterns
Authors: White Heather , Lee Austin , Rhein Lawrence 
Published: April 2023

Background Up to one-third of preterm infants diagnosed with bronchopulmonary dysplasia will require home oxygen therapy (HOT) after hospital discharge. Currently, no consensus-based guidelines exist for safely managing HOT. The Recorded Home Oximetry (RHO) trial was the first to evaluate a structured weaning guideline. At the conclusion of the trial, our home institution implemented the RHO program in June 2019, utilizing the same RHO protocol as the original trial. The purpose of this project was to evaluate the duration and weaning trajectory of infants followed and identify any risk factors associated with flow rate increases or longer trajectories. Methods This is a prospective analysis of infants born <37 weeks gestation followed by the RHO program between June 2019 and June 2021. Results The study included 26 infants with a total of 407 RHO epochs. There was nearly equal distribution of males and females with a mean birth gestational age of 27.5 (±3.4 SD) weeks. The median time of successful discontinuation of HOT was 2.1 months. Infants starting on higher initial flow rates had faster weaning trajectories compared to those who started on lower flow rates ( P value <.0001). Infants born small for gestational age were about twice as likely to have longer maintenance on one flow rate compared to appropriate for gestational age infants (RR = 2.81, 95% CL 1.64-4.81, P = .0002). Conclusion The RHO program, a structured telemedicine weaning guideline, reduces the duration of HOT in preterm infants and does not cause unnecessary swings in oxygen flow rates.
How Hard Is It Really? Assessing Game-Task Difficulty Through Real-Time Measures of Performance and Cognitive Load
Authors: Seyderhelm Andrew J.A. , Blackmore Karen L. 
Published: April 2023

Background Serious and entertainment game designers strive to create engaging, immersive, and often, challenging games. This task involves modifying game mechanics or environments to create experiences with differing levels of challenge to meet player skill. The balance between different game mechanics or environments, and the differing levels of challenge they pose, is typically understood through iterative testing. Balance and challenge becomes increasingly important in serious games and simulation training as these games commonly need to be engaging and impart learning content. Overburdening players’ cognitive capacity with either too much gameplay challenge or learning content may reduce the educational effectiveness of the game. Aim. In this research, we develop a game-based driving simulation with different gameplay tasks to explore the impact of different types of challenges and game aesthetics on real-time cognitive load and task performance, which may inform serious game design. We also test the validity of a game-embedded real-time cognitive load measuring method. Method A total of 31 participants undertook the driving simulation experiment under three different aesthetic conditions using a within-subject experimental design. Cognitive load was measured using three different methods, and performance was measured via in-game metrics. Additionally, demographic and engagement surveys were also completed. Results Player performance and cognitive load respond differently to different types of challenge, and an appropriate level of game challenge can lower cognitive load. The embedded cognitive load measure was validated as an effective method for evaluating real-time cognitive load during gameplay. Conclusion The results demonstrate the validity of a dual measure approach for future adaptive serious games and simulation training environments combining performance and cognitive load. An easy to implement, and robust, in-game measure for cognitive load has been validated in real-world conditions. From these results, a system for dynamic difficulty adjustment is proposed tailored towards serious games and simulation.
Autonomic Correlates of Letter Cancelation Task: What the Attention Load May Evoke?
Authors: Shikha Deep , Ojha Pooja , Shukla Kamla Kant , Bhagat Om Lata , Dixit Abhinav 
Published: April 2023

Objective: Attention can be assessed through Letter cancelation tasks (LCT) that employ visuospatial selection and appropriate motor responses. We examined the performance in the LCT with increasing attention load, and determined the related autonomic changes. Methods: Autonomic parameters were estimated in healthy males at baseline and during three different cognitive load conditions using the LCT. Results: Results revealed a statistically significant difference ( n = 30) in the percent accuracy (χ2(2) = 15.2, p < .001) and percent omission (χ2(2) = 13.3, p = 0.001) with the increasing challenge in the LCT. The vagally-mediated measures of heart rate variability were significantly decreased with the commencement of the task revealing a parasympathetic withdrawal. The respiratory sinus arrythmia was decreased, and the photoplethysmography amplitude was significantly reduced (χ2(3) = 14.2, p = 0.003) as the attention demand increased. Conclusion: The performance declined with the increasing attention load. LCT evokes autonomic perturbations though overall autonomic variability does not change remarkably.