bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B046: Lack of ER/PR expression and unresponsiveness to oral contraceptives in fallopian tube stem/progenitor cell states: reevaluating the mechanism of cancer prevention
Authors: Ritting Megan , Aalam Syed Mohammed Musheer , Bettencourt Manny , Jalagam Kinnera , Kaufmann Scott , Weroha John , Sherman Mark , Bakkum-Gamez Jamie , Kannan Nagarajan 
Published: March 2024

Abstract
Objective: Prolonged use of oral contraceptives (OC) has been associated with a reduced risk of ovarian cancer, yet the underlying mechanism remains elusive. Long-lived self-renewing fallopian tube epithelial stem cells (SCs) capable of cilio-secretory differentiation are considered a potential cell-of-origin for ovarian cancers. Using innovative stem cell methodologies, our objective is to gain insights into the mechanism by which OC exert their protective action. Methods: This research is supported by Mayo Clinic’s clinically annotated regenerative fallopian tube biobank. RNA was isolated from the SC-enriched cell fraction and differentiated cilio-secretory organoids. Absolute mRNA copies of OC targets estrogen receptor-alpha (ESR1; ER) and progesterone receptor (PGR; PR) were determined using optimum RT-ddPCR assay. OC effects on SC-enriched growth in 2D was measured using live-cell imaging. Our primary tubal cells and organoids as well as public single-cell transcriptomics datasets were analyzed for ESR1/PGR expression across tubal cell states. Results: The panel of OCs tested exhibited no growth response in patient-derived cultures enriched with stem cells, and there was an absence of ESR1/PGR expression. Clonal organoid differentiation exhibited high ESR1 levels and lack of PGR, while growth factor cocktail-dependent PGR induction was achieved. Single-cell transcriptomics identified molecular signatures associated with ER/PR-positive OC sensor cells. Conclusions: Based on our findings, we propose a model wherein ER/PR-negative SC differentiate into ER/PR-positive OC-sensors and control SC development through paracrine signals. Our in-vitro conditions to differentiate SC into OC-sensors provide an opportunity to study complex paracrine signaling and explore targets for prevention of ovarian cancers.
Citation Format: Megan Ritting, Syed Mohammed Musheer Aalam, Manny Bettencourt, Kinnera Jalagam, Scott Kaufmann, John Weroha, Mark Sherman, Jamie Bakkum-Gamez, Nagarajan Kannan. Lack of ER/PR expression and unresponsiveness to oral contraceptives in fallopian tube stem/progenitor cell states: reevaluating the mechanism of cancer prevention [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B046.
Abstract B096: Targeting RNA splicing factor RBM39 improves therapy responses in ovarian high-grade serous carcinoma
Authors: Xu Yuewei , Spear Sarah , Ma Yurui , Lorentzen Marc , Gruet Michael , McKinney Flora , Xu Yitao , Wickremesinghe Chiharu , McNeish Iain , Keun Hector , Nijhuis Anke 
Published: March 2024

Abstract
Ovarian high-grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer with limited therapeutic options and poor prognosis. In recent years, PARP inhibitors have demonstrated significant clinical benefits, especially in patients with BRCA1/2 mutations. However, acquired drug resistance and relapse is a major challenge. Indisulam (E7070) has been identified as a molecular glue that brings together splicing factor RBM39 and DCAF15 E3 ubiquitin ligase resulting in polyubiquitination, degradation and subsequent RNA splicing defects. We demonstrate that RBM39 degradation results in large scale mis-splicing events that are enriched for DNA damage repair genes, including BRCA1, RAD51 and ATM. These events lead to a reduction of these targets at protein level, aberrant cell cycle progression and replication fork stalling. The treatment with indisulam leads to increased sensitivity to platinum and PARP inhibitors in-vitro as well as improved responses to olaparib in mice bearing PARP inhibitor-resistant tumors. In summary, our work demonstrates that combining RBM39 degrading molecular glues with PARP inhibitors is a promising therapeutic approach to improve PARP inhibitor response in ovarian HGSC.
Citation Format: Yuewei Xu, Sarah Spear, Yurui Ma, Marc Lorentzen, Michael Gruet, Flora McKinney, Yitao Xu, Chiharu Wickremesinghe, Iain McNeish, Hector Keun, Anke Nijhuis. Targeting RNA splicing factor RBM39 improves therapy responses in ovarian high-grade serous carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B096.
Abstract IA017: A liquid biopsy fingerprint of disease via nanoengineering
Authors: Heller Daniel A. , Kim Mijin , Ramanathan Lakshmi , Roche Kara Long 
Published: March 2024

Abstract
Serum biomarkers are often insufficiently sensitive or specific to facilitate cancer screening or diagnostic testing. In many cancers, including high-grade serous carcinoma (HGSC), biomarkers fail to detect early-stage cancer detection or to substantially impact mortality rates. We developed a perception-based sensing method that captures a biomarker-agnostic ‘disease fingerprint’ of HGSC using serum. Instead of measuring individual biomarkers, the method collects large data sets of molecular binding interactions to a diverse array of moderately-selective sensors, which were used to train machine learning algorithms. In an initial study using serum from 264 patients, we built a prediction model of nanosensor responses that reliably identified HGSC substantially better than CA125. We believe that the improvement of such a method, using larger nanosensor arrays, more sophisticated AI algorithms, and larger patient cohorts, could improve the detection of HGSC and facilitate biomarker discovery efforts.
Citation Format: Daniel A. Heller, Mijin Kim, Lakshmi Ramanathan, Kara Long Roche. A liquid biopsy fingerprint of disease via nanoengineering [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr IA017.
Insights into the Molecular Mechanisms of Genetic Predisposition to Hematopoietic Malignancies: The Importance of Gene–Environment Interactions
Authors: Cobaleda Cesar , Godley Lucy A. , Nichols Kim E. , Wlodarski Marcin W. , Sanchez-Garcia Isidro 
Published: March 2024

Summary:
The recognition of host genetic factors underlying susceptibility to hematopoietic malignancies has increased greatly over the last decade. Historically, germline predisposition was thought to primarily affect the young. However, emerging data indicate that hematopoietic malignancies that develop in people of all ages across the human lifespan can derive from germline predisposing conditions and are not exclusively observed in younger individuals. The age at which hematopoietic malignancies manifest appears to correlate with distinct underlying biological pathways. Progression from having a deleterious germline variant to being diagnosed with overt malignancy involves complex, multistep gene–environment interactions with key external triggers, such as infection and inflammatory stimuli, driving clonal progression. Understanding the mechanisms by which predisposed clones transform under specific pressures may reveal strategies to better treat and even prevent hematopoietic malignancies from occurring.
Recent unbiased genome-wide sequencing studies of children and adults with hematopoietic malignancies have revealed novel genes in which disease-causing variants are of germline origin. This paradigm shift is spearheaded by findings in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) as well as acute lymphoblastic leukemia, but it also encompasses other cancer types. Although not without challenges, the field of genetic cancer predisposition is advancing quickly, and a better understanding of the genetic basis of hematopoietic malignancies risk affects therapeutic decisions as well as genetic counseling and testing of at-risk family members.
Biodiversity Medicine: New Horizon and New Opportunity for Cancer
Authors: Hong Jing Han , Lim Abner Herbert , Kaewnarin Khwanta , Chan Jason Yongsheng , Ng Cedric Chuan Young , Teh Bin Tean 
Published: March 2024

Summary:
Accessibility to standard of care remains a challenge to patients in low- and middle-income countries (LMIC), hampering efforts to alleviate the burden of cancer and to improve overall health outcomes. In response to this pressing global health care issue, we propose here a new strategy to create affordable, easily accessible, and effective therapeutic solutions to address this inequity in cancer treatment: the use of science-based biodiversity medicine as an alternative to modern drug therapy, in which we will leverage and combine high-throughput omics technologies with artificial intelligence, to study local biodiversity, their potential anticancer properties, and short- and long-term clinical response and outcomes.
Higher Frequency of Premature Atrial Contractions Correlates With Atrial Fibrillation Detection after Cryptogenic Stroke
Authors: Shimada Yuki , Todo Kenichi , Doijiri Ryosuke , Yamazaki Hidekazu , Sonoda Kazutaka , Koge Junpei , Iwata Tomonori , Ueno Yuji , Yamagami Hiroshi , Kimura Naoto , Morimoto Masafumi , Kondo Daisuke , Koga Masatoshi , Nagata Eiichiro , Miyamoto Nobukazu , Kimura Yoko , Gon Yasufumi , Okazaki Shuhei , Sasaki Tsutomu , Mochizuki Hideki , Sugiyama Shintaro , Ohara Mariko , Ikegami Takeshi , Wadayama Tomoya , Murakami Yasutaka , Sakurai Rei , Moriyama Takuya , Oi Kiyotaka , Ikenouchi Hajime , Yamaguchi Eriko , Egashira Shuhei , Takizawa Shunya , Honma Kazunari , Nakayama Taira , Kadokura Ayana , Hanano Hideyuki , Yamamoto Shiro 
Published: March 2024

BACKGROUND:
Covert atrial fibrillation (AF) is a major cause of cryptogenic stroke. This study investigated whether a dose-dependent relationship exists between the frequency of premature atrial contractions (PACs) and AF detection in patients with cryptogenic stroke using an insertable cardiac monitor (ICM).

METHODS:

We enrolled consecutive patients with cryptogenic stroke who underwent ICM implantation between October 2016 and September 2020 at 8 stroke centers in Japan. Patients were divided into 3 groups according to the PAC count on 24-hour Holter ECG: ≤200 (group L), >200 to ≤500 (group M), and >500 (group H). We defined a high AF burden as above the median of the cumulative duration of AF episodes during the entire monitoring period. We evaluated the association of the frequency of PACs with AF detection using log-rank trend test and Cox proportional hazard model and with high AF burden using logistic regression model, adjusting for age, sex, CHADS
2
score.

RESULTS:

Of 417 patients, we analyzed 381 patients with Holter ECG and ICM data. The median age was 70 (interquartile range, 59.5–76.5), 246 patients (65%) were males, and the median duration of ICM recording was 605 days (interquartile range, 397–827 days). The rate of new AF detected by ICM was higher in groups with more frequent PAC (15.5%/y in group L [n=277] versus 44.0%/y in group M [n=42] versus 71.4%/y in group H [n=62]; log-rank trend
P
<0.01). Compared with group L, the adjusted hazard ratios for AF detection in groups M and H were 2.11 (95% CI, 1.24–3.58) and 3.23 (95% CI, 2.07–5.04), respectively, and the adjusted odds ratio for high AF burden in groups M and H were 2.57 (95% CI, 1.14–5.74) and 4.25 (2.14–8.47), respectively.

CONCLUSIONS:
The frequency of PACs was dose-dependently associated with AF detection in patients with cryptogenic stroke.
Impact of Monocular Retinal Lesions on Blob Size in Adult Human V1
Authors: Marcondes Marco , Farias Mariana F. , Pary Luis F. , Fiorani Mario , Lima Bruss , Amorim Ana Karla J. , Gattass Ricardo 
Published: March 2024

Abstract
We studied the attributes of cytochrome c oxidase (CytOx)-rich blobs and ocular dominance columns (OD) in human V1 associated with monocular retinal lesions. Interblob distance, blob cross-sectional area, OD width, and OD arrangement pattern were analyzed in CytOx-reacted tangential sections of flat-mounted V1 preparations. Monocular deprivation induces differential expression of CytOx in the corresponding ODs in V1. We were thereby able to identify the V1 regions associated with the lesioned area in the retina, assign which OD was associated with each eye, and assign the corresponding blob in Layer III as deprived or nondeprived of visual input. We found that nondeprived blobs are more conspicuously stained than blobs outside the lesioned area. Notably, we found a selective expansion of blobs associated with the nonlesioned eye, whereas blobs associated with the deprived eye showed no significant change in size. Blob size in the latter condition was similar to the one observed in normal participants. These effects were present throughout the representation of the lesion in V1, suggesting that the underlying plasticity mechanisms do not depend on eccentricity. Retinal lesion caused no change in interblob distance, which was comparable to the normal brain (i.e., participants with no retinal lesion). This indicates that blob center is a stable hallmark of cortical organization. Finally, the width of ODs associated with the nonlesioned eye tended to be larger compared with ODs of the lesioned eye. However, this effect did not reach statistical significance. The stability of ODs thereby contrasts with blob plasticity, suggesting that the retinal lesion-triggered imbalance in the thalamocortical projection to Layer IVc has a limited impact on OD CytOx reactivity. On the other hand, we argue that ocular imbalance supports intracortical lateral competition that increases CytOx reactivity in the periblob region associated with the nonlesioned eye, accounting for the blob expansion we observe.
Investigating the Effect of Contextual Cueing with Face Stimuli on Electrophysiological Measures in Younger and Older Adults
Authors: Nagy Boglárka , Kojouharova Petia , Protzner Andrea B. , Gaál Zsófia Anna 
Published: March 2024

Abstract
Extracting repeated patterns from our surroundings plays a crucial role in contextualizing information, making predictions, and guiding our behavior implicitly. Previous research showed that contextual cueing enhances visual search performance in younger adults. In this study, we investigated whether contextual cueing could also improve older adults' performance and whether age-related differences in the neural processes underlying implicit contextual learning could be detected. Twenty-four younger and 25 older participants performed a visual search task with contextual cueing. Contextual information was generated using repeated face configurations alongside random new configurations. We measured RT difference between new and repeated configurations; ERPs to uncover the neural processes underlying contextual cueing for early (N2pc), intermediate (P3b), and late (r-LRP) processes; and multiscale entropy and spectral power density analyses to examine neural dynamics. Both younger and older adults showed similar contextual cueing benefits in their visual search efficiency at the behavioral level. In addition, they showed similar patterns regarding contextual information processing: Repeated face configurations evoked decreased finer timescale entropy (1–20 msec) and higher frequency band power (13–30 Hz) compared with new configurations. However, we detected age-related differences in ERPs: Younger, but not older adults, had larger N2pc and P3b components for repeated compared with new configurations. These results suggest that contextual cueing remains intact with aging. Although attention- and target-evaluation-related ERPs differed between the age groups, the neural dynamics of contextual learning were preserved with aging, as both age groups increasingly utilized more globally grouped representations for repeated face configurations during the learning process.
L’élaboration d’une normativité en droit des gens: le recours au discours historique dans le De legationibus d’Alberico Gentili
Authors: Colpaint Emilie 
Published: March 2024

Summary
The development of normativity in international law: the use of historical discourse in Alberico Gentili’s De legationibus. – The aim of this article is to examine the sources used and the method employed by Alberico Gentili in his De legationibus, to elaborate a norm for the law of embassies. Although legal sources feature prominently in this treatise, the majority of them are derived from a variety of sources from Antiquity (historians, philosophers, rhetors, poets, etc.). Alberico Gentili mainly uses historical sources, and more specifically the exemplum, in his treatise. By mobilizing historical exempla alongside legal sources, the jurist created a rational normative system capable of responding to the diplomatic challenges of the sixteenth century brought about by constantly evolving practice.
Reframing Revolution and Solidarity: Photography and Visual Culture in ospaaal Poster Art (1967–1990)
Authors: Schmiedecke Natália Ayo , Zerwes Erika , Generoso Lídia 
Published: March 2024

Abstract
This article analyses the uses of photography in the posters produced and distributed by the Organisation of solidarity of the Peoples of Africa, Asia and Latin America (ospaaal) between 1967 and 1990. Founded during the Tricontinental Conference of 1966, ospaaal was active until 2019 and had as one of its main tasks the creation of propaganda materials helping promote causes supported by the Cuban government across the three continents. The organisation produced over 300 posters distributed globally along with its official magazine, the Tricontinental. We combine thematic and visual perspectives in examining how ospaaal posters published during the Cold War period made use of photography. Our goal is to understand how ospaaal contributed to a reframing of ‘solidarity’ and ‘revolution’ through tricontinental lenses. The article is structured to provide an overview of how the organisation utilised photography in its poster production, to demonstrate how this body of work is connected to inter-war photographic traditions and contemporary left-wing visual culture, and to reflect on ospaaal’s contributions to revolutionary iconography.
Morphological, structural, and ultrastructural key features of hyperhydricity in Beta vulgaris L. var. saccharifera
Authors: Petrus-Vancea Adriana , Petrus Cristian Mircea 
Published: March 2024

Abstract
Hyperhydricity, as a phenomenon specific to in vitro plants, triggers a series of changes at the cell and tissue level, which modify the plants’ physiological processes. For a better understanding of this phenomenon, we found it useful to present here the fundamental research on establishing the steps of structural and ultrastructural degradation of cells and tissues, observed by light microscopy (LM) and transmission electron microscopy (TEM) analyses, in the leaves of Beta vulgaris var. saccharifera, at 30 days of secondary culture, and their correlation with viability in the third culture. Comparative with control (non-hyperhydric plants), three degradation steps of hyperhydricity were identified in plants regenerated on a culture medium with 2.5 mg·L-1 6-benzyladenine. The first step involved cell wall deformation, which lost its rigidity and became sinuous, causing the enlargement of the intercellular spaces. In the second step, these spaces formed gaps through their union, and the whole membrane system suffered: both chloroplasts and tonoplast were broken (the cytoplasm and vacuolar composition were mixed), the nuclear membrane presented undulations, just before the damage to the tonoplast, and the nucleus became pyknotic. In step 3, the cell showed the beginning of lysis, which leads to necrosis, the cell had nothing in common with a normal ultrastructure. For in vitro plants in this final step, there was no chance of surviving but in steps I and II, the viability was 55-75%. These features can be useful to producers to calculate the level of culture damage and start measures to prevent losses.
A Change Towards Preschool Inclusion: A Case Study
Authors: Lundqvist Johanna , Arvidsson Patrik 
Published: March 2024

Abstract
The aim is to examine the work at a Swedish preschool that is striving to become inclusive for a group of children with disabilities. The bioecological model and a mixed method case study design were adopted. One head teacher, ten preschool staff members, and four children with disabilities participated. Data were collected by way of observations, one focus group interview, and two retrospective interviews. Statistical and thematic data analyses were conducted. Ethical approval was obtained. A decision is made to create a new unit in the preschool. The unit is given a specialised organisational typology. The preschool integrates activities and different types of support provisions. The quality of inclusion practices and support provisions in the preschool is almost good. At a time when inclusion is valued, this study can provide a basis for interesting discussions about preschool inclusion in Sweden and other countries.
Statistical Characteristics and Synoptic Patterns of Convection Initiation over the Middle Reaches of the Yangtze River Basin as Observed Using the Fengyun-4A Satellite
Authors: Li Shanshan , Wang Xiaofang , Sun Jianhua , Ma Zheng , Zhang Yuanchun , Gao Yuan , Hu Yang , Zhang Wengang 
Published: March 2024

Abstract
Convection initiations (CIs) observed using the advanced geosynchronous radiation imager on the Chinese Fengyun-4A satellite were identified over the middle reaches of the Yangtze River basin during warm season (May–September) of 2018–21. A hybrid objective tracking algorithm combining the conventional area overlapping with the Kalman filter method was applied. Subsequently, spatial and temporal variations in the identified CIs and their synoptic circulation patterns were analyzed. The frequency of CIs was highest in August and lowest in May. Nearly 81% of CIs occurred during noon–afternoon (1100–1859 LST), with the highest frequency in the southern mountains of the study region, whereas the CIs with relatively low frequency moved to the plains from afternoon to morning (1700–1059 LST). The diurnal variation of CIs throughout the study region exhibited a unimodal structure, with a peak appearing at noon (1200–1259 LST). CIs during noon–afternoon in July and August had faster cloud-top cooling rates. The synoptic circulations without tropical cyclones during noon–afternoon hours were classified into four patterns by hierarchical clustering; two dominant patterns (i.e., SW-Flows and S-Flows) had broader areas of higher most unstable convective available potential energy (MUCAPE), whereas the 0–3-km shear (SHR3) was the weakest in the S-Flows pattern. It was clear that the high-frequency areas of CIs were most likely to occur in stronger MUCAPE and weaker SHR3 environments, and CIs were more controlled by thermally unstable environments. We further illustrated that CIs tend to concentrate in unstable and moisture flux convergence areas affected by mountains.