bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PO5-25-09: rs2242652 POLYMORPHISM OF THE hTERT GENE IN WOMEN WITH BREAST CANCER
Authors: Alvares Miriam , Mascarenhas Elisa , Matos Joao 
Published: May 2024

Abstract
Introduction: Breast cancer is the most common neoplasm in women around the world. There are several risk factors for this cancer: sex, age, body mass index (BMI), hormone therapy, family history, genetic mutations, among several others.
The vast majority of breast tumors are characterized as carcinomas and may originate from ducts or lobules. Immunohistochemistry is related to the expressions of the estrogen receptor (ER) and progesterone receptor (PR), as well as the expression of the human epidermal growth factor receptor 2 (HER2), cell proliferation or the absence of any expression from receptors on the tumor membrane.
The telomeres protect the chromosomes natural endings from suffering DNA loss. Telomerase is a ribonuclear protein complex (RNA and protein) that neutralizes telomeres' shortening.
Recurrent point mutations in the TERT telomerase promoter have been identified in several cancers, and the rs2242652 polymorphism is a single nucleotide change, and has been described as associated with breast cancer risk. Objective: The objective of this study is to analyze the TERT rs2242652 polymorphism in breast cancer women and to test the correlation of such data with the prognosis and various clinical variables. Methods: The study was conducted as an observational clinical study of women with breast cancer. A blood sample was collected from the patient and PCR was performed to extract the DNA and to analyze the telomerase polymorphisms in this population. To ensure a more descriptive analysis, the data was used in the construction of tables and graphs, that were then studied in a qualitative manner. The associations were analyzed through direct correlation tests and were followed by comparisons of categorization groups. Results and discussion: Fifty-four women presented polymorphism of the telomerase hTERT gene rs2242652. They were divided into two groups according to the A or G allele that confer the GA/AA and GG gene variants.
It was found that the GA/AA group had a trend towards more aggressive tumors, presenting 33% triple negative and 22% of tumors with HER2 overexpression, different from the GG group: 19% triple negative and 10% HER2 overexpression. More aggressive T4 tumors, were more expressive in the GA/AA gene variant group representing 20% of the patients, whereas in the GG group they represented only 8%. Conclusion: The data found in this study on the telomerase TERT gene polymorphism rs2242652 with breast cancer refers to a tendency found in tumors that have a more severe prognosis, to associate with the gene variant linked to the A allele of this gene, however a larger sample number is required for statistical confirmation.
Citation Format: Miriam Alvares, Elisa Mascarenhas, Joao Matos. rs2242652 POLYMORPHISM OF THE hTERT GENE IN WOMEN WITH BREAST CANCER [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-25-09.
Abstract PO5-27-09: Pharmacological eIF4E inhibition suppresses anti-tumor activity in ER+ breast cancer
Authors: Friedersdorf Matthew , Blake Devon , Thompson Sarah , Marran Krista , Sorrentino Jessica 
Published: May 2024

Abstract
Elevated levels of eukaryotic initiation factor 4E (eIF4E) are found in a broad range of cancers, including breast, and have been associated with aggressive, drug resistant tumors. Furthermore, elevated eIF4E activity is sufficient to cause transformation in various cancers, while inhibition suppresses tumor growth. eIF4E, the main regulator and rate limiting factor of protein synthesis, is the downstream integrator of several important oncogenic signaling pathways (PI3K/AKT/mTOR, Ras/Raf/MEK, and Myc). Activation of eIF4E results in increased protein levels of key proliferation and metabolism proteins such as Cyclin D1 (CCND1) and Ornithine Decarboxylase 1 (ODC1), as well as an overall increase in cellular synthesis machinery, causing cellular growth and proliferation. Here, we describe the development and characterization of novel, potent, and selective eIF4E inhibitors. Compounds from this chemical series have nanomolar activity in multiple biochemical and biophysical m7G cap-competition assays as well as potent inhibition of translation in cellular and biochemical assays. In cells, these compounds rapidly and reversibly decrease protein levels of several oncogenes, including CCND1, leading to a G1 cell cycle arrest. We demonstrate that eIF4E inhibitors cause growth inhibition in a variety of breast cancer cell lines, including ER+ breast cancer. These inhibitors also inhibit growth of breast cancer lines with acquired resistance to Palbociclib with the same potency as the parental cell lines. Additionally, eIF4E inhibition shows an increased sensitivity in resistant cell lines when combined with standard of care (SOC), including Palbociclib. Select analogs from the series demonstrate favorable ADMET/PK properties with good oral bioavailability and low safety risk. Lastly, these compounds have demonstrated near complete tumor growth inhibition in non-breast cancer in vivo models. Ongoing experiments will address in vivo efficacy in ER+ breast cancer in both monotherapy and in combination with SOC.
Citation Format: Matthew Friedersdorf, Devon Blake, Sarah Thompson, Krista Marran, Jessica Sorrentino. Pharmacological eIF4E inhibition suppresses anti-tumor activity in ER+ breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-09.
Abstract PO5-28-01: Dynamics of Adipocyte Progenitors in the Mammary Gland during Obesity
Authors: Kwende Sharon , Nuthalapati Prashant , Ning Dun , Singh Jacqulene Sunder , Joshi Purna 
Published: May 2024

Abstract
Being overweight or obese is associated with a higher risk of breast cancer (BC) and worse disease-free and overall survival compared to normal-weight BC patients. The underlying biological basis for this association is attributed to alterations in the endocrine and inflammatory milieu of adipose tissue. However, existing chemotherapy and endocrine therapy are not effective in obese BC patients. There is a critical need to pin down adipose tissue cell types that may govern increased BC risk and adverse outcome in obesity. Adipocyte progenitors are immature mesenchymal cells in adipose tissue that have adipocyte differentiation potential and reported to be dysfunctional in obesity. In previous research, we first reported mammary adipocyte progenitors (MAPs) expressing Platelet-Derived Growth Factor Receptor alpha (PDGFRα) in the stromal microenvironment that transition into epithelial lineages during expansion of the murine mammary epithelium. The contribution of MAPs to shaping a pro-tumorigenic mammary tissue milieu in obesity is not known. Here, using diet-induced obesity MAP reporter and lineage tracing mouse models combined with single-cell RNA sequencing, we reveal elevated PDGFRα+ MAPs in the local mammary stroma in obesity. MAPs in the obese mammary gland manifest alterations in proliferation, cell state and molecular mechanisms, generating an inflammatory, cancer-prone tissue microenvironment. Our findings uncover the MAP lineage as a key contributor to forging an aberrant mammary gland in obesity, providing insight into the potential utility of targeting this cell population for eradicating BC risk related to augmented adiposity.
Citation Format: Sharon Kwende, Prashant Nuthalapati, Dun Ning, Jacqulene Sunder Singh, Purna Joshi. Dynamics of Adipocyte Progenitors in the Mammary Gland during Obesity [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-28-01.
Abstract PS01-06: The relationship between margin status of &lt;2mm and local recurrence in DCIS patients
Authors: Safi Sarah Al , Yoo Tae-Kyung , Lee Sae Byul , Kim Jisun , Chung Il-Yong , Kim Hee Jeong , Ko Beom Seok , Lee Jong Won , Son Byung Ho , Lee Hee Jin , Gong Gyungyub 
Published: May 2024

Abstract
Background:
There has been controversial evidence regarding adequate margin in breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS). However, the consensus is a surgical margin distance of 2 mm. Moreover, recent recommendations advised on ‘’clinical judgement’’ approach to re-excision in cases of margin distance &lt; 2mm. The ongoing controversy in DCIS margin compared to invasive cancer margin is due to the differences in post operative management. This is important as margin status is one of the modifiable risk factor for local regional recurrence in DCIS. In our study we evaluated margin distance in patient diagnosed with DCIS who underwent BCS on local recurrence
Methods:
Patients who underwent breast conserving surgery between February 2000 and December 2018 at Asan Medical Center were retrospectively reviewed. Patients with involved resection margins were excluded. Kaplan-Meier survival analysis and Cox proportional hazard models were applied to determine the relationship between negative margin width and local recurrence.
Results:
A total of 1,858 patients were included in the study. Almost half of the patients had a tumor size of 1cm or smaller (n=876, 47.1%). Only 98 (5.3%) patients did not undergo radiation therapy. A negative margin width of &lt; 1mm, &lt; 2mm, &lt; 5mm were all not associated with local recurrence (log-rank test p-value 0.1, 0.1, 0.078, respectively). For patients who underwent radiation therapy, a negative margin of any width was not related to local recurrence. Whereas, for patients who did not undergo radiation therapy, those with margins ≤2mm were significantly more likely to develop local recurrence than those with margins &lt; 2mm (10-yr local recurrence rate, 16.4% vs 5.5%, respectively; hazard ratio, 5.709; 95% CI, 1.106-29.46, p=0.038).
Conclusion:
A negative margin is not related to local recurrence in DCIS patients who undergo breast conserving surgery with radiation therapy. Routine additional surgery for wider negative margin may only be needed for patients who do not undergo radiation therapy.
Citation Format: Sarah Al Safi, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Hee Jeong Kim, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Hee Jin Lee, Gyungyub Gong. The relationship between margin status of &lt;2mm and local recurrence in DCIS patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-06.
Abstract PS03-01: Single cell analysis of paired lymph nodes and primary tumors in breast cancer patients
Authors: Fjørtoft Marit , Rye Inga , Huse Kanutte , Myklebust June , Russnes Hege , Riis Margit , Lingjærde Ole Christian , Garred Øystein , Lande Karin Teien , Bergheim Inger Riise , Schlichting Ellen 
Published: May 2024

Abstract
A sentinel lymph node (SN) is the primary node draining the tumor and is assumed to be affected early in the metastatic process. The sentinel node holds a key position in the immune response against tumor in breast, and represents a unique connection between the tumor and the host immune response. We hypothesize that the immune profile in the primary tumor and the paired lymph node (LN) is different during tumor progression.
3.7 million single cells from paired primary tumor and lymph nodes from 33 breast cancer patients (Oslo2 cohort) was analyzed by single cell mass cytometry (CyTOF) with a 47 antibody immune panel and characterized by a semi-automatic gating approach (FlowSOM).
Tumor cells were found in 11 LN. When analyzing the leucocytes from LN we identified a significant difference in immune cell type skewing towards higher abundance of memory CD4 and CD8 T cells expressing an exhausted phenotype in LN with metastasis. In addition, a higher abundance of activated Tregs and significantly lower abundance of resting Tregs was found in the metastatic LNs compared to the sentinel lymph nodes. The change in immune composition and exhaustion was correlated to the metastatic tumor burden. The skewing towards an exhausted immune profile was also found in larger primary tumors compared to smaller primary tumors.
We further analyzed tumor cells from 8 patients with paired primary tumor and LN. No differences were identified in the primary tumor when stratified by LN status, but LNs with smaller metastasis expressed lower levels of epithelial markers essential in the Epithelial-to-Mesenchymal Transition such as E-cadherin, Pan Cytokeratin and EpCAM – this in contrast to the LN with manifested metastasis in the axilla which expressed higher levels of epithelial markers and lower levels of mesenchymal markers such as Vimentin and CD44.
We identified a skewing in the immune profile from a naive phenotype towards a memory and exhausted phenotype in CD8 and CD4 T cell population in LN with manifested metastasis, as well as in larger primary tumors. We also identified that tumor cells in smaller metastatic tumors resembled a “mesenchymal like” phenotype compared to in the larger manifested tumors. These results suggest that the immune suppression is correlated with the tumor burden.
Citation Format: Marit Fjørtoft, Inga Rye, Kanutte Huse, June Myklebust, Hege Russnes, Margit Riis, Ole Christian Lingjærde, Øystein Garred, Karin Teien Lande, Inger Riise Bergheim, Ellen Schlichting. Single cell analysis of paired lymph nodes and primary tumors in breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS03-01.
On the Hunt for the Missed Genetic Causes of Multiple Primary Tumors
Authors: Chan-Pak-Choon Fiona , Foulkes William D. 
Published: May 2024

AbstractImproved cancer screening and treatment programs have led to an increased survivorship of patients with cancer, but consequently also to the rise in number of individuals with multiple primary tumors (MPT). Germline testing is the first approach investigating the cause of MPT, as a positive result provides a diagnosis and proper clinical management to the affected individual and their family. Negative or inconclusive genetic results could suggest non-genetic causes, but are negative genetic results truly negative? Herein, we discuss the potential sources of missed genetic causes and highlight the trove of knowledge MPT can provide.See related article by Borja et al., p. 209
Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension
Authors: Tang Haiyang , Gupta Akash , Morrisroe Seth A. , Bao Changlei , Schwantes-An Tae-Hwi , Gupta Geetanjali , Liang Shuxin , Sun Yanan , Chu Aiai , Luo Ang , Ramamoorthi Elangovan Venkateswaran , Sangam Shreya , Shi Yinan , Naidu Samisubbu R. , Jheng Jia-Rong , Ciftci-Yilmaz Sultan , Warfel Noel A. , Hecker Louise , Mitra Sumegha , Coleman Anna W. , Lutz Katie A. , Pauciulo Michael W. , Lai Yen-Chun , Javaheri Ali , Dharmakumar Rohan , Wu Wen-Hui , Flaherty Daniel P. , Karnes Jason H. , Breuils-Bonnet Sandra , Boucherat Olivier , Bonnet Sebastien , Yuan Jason X.-J. , Jacobson Jeffrey R. , Duarte Julio D. , Nichols William C. , Garcia Joe G.N. , Desai Ankit A. 
Published: May 2024

BACKGROUND:
The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1.

METHODS:

Tissues from animal pulmonary hypertension models as well as human pulmonary artery endothelial cells from patients with PAH exhibited increased vascular UCHL1 staining and protein expression. Exposure to LDN57444, a UCHL1-specific inhibitor, reduced human pulmonary artery endothelial cell and smooth muscle cell proliferation. Across 3 preclinical PAH models, LDN57444-exposed animals,
Uchl1
knockout rats (
Uchl1
−/−
), and conditional
Uchl1
knockout mice (
Tie2Cre-Uchl1

fl/fl

) demonstrated reduced right ventricular hypertrophy, right ventricular systolic pressures, and obliterative vascular remodeling. Lungs and pulmonary artery endothelial cells isolated from
Uchl1
−/−
animals exhibited reduced total and activated Akt with increased ubiquitinated Akt levels. UCHL1-silenced human pulmonary artery endothelial cells displayed reduced lysine(K)63-linked and increased K48-linked AKT1 levels.

RESULTS:

Supporting experimental data, we found that rs9321, a variant in a GC-enriched region of the
UCHL1
gene, is associated with reduced methylation (n=5133), increased
UCHL1
gene expression in lungs (n=815), and reduced cardiac index in patients (n=796). In addition,
Gadd45α
(an established demethylating gene) knockout mice (
Gadd45α
−/−
) exhibited reduced lung vascular UCHL1 and AKT1 expression along with attenuated hypoxic pulmonary hypertension.

CONCLUSIONS:
Our findings suggest that UCHL1 deficiency results in PAH attenuation by means of reduced AKT1, highlighting a novel therapeutic pathway in PAH.
Direct Retrieval of Orthographic Representations in Chinese Handwritten Production: Evidence from a Dynamic Causal Modeling Study
Authors: He Jieying , Zhang Qingfang 
Published: May 2024

Abstract
This present study identified an optimal model representing the relationship between orthography and phonology in Chinese handwritten production using dynamic causal modeling, and further explored how this model was modulated by word frequency and syllable frequency. Each model contained five volumes of interest in the left hemisphere (angular gyrus [AG], inferior frontal gyrus [IFG], middle frontal gyrus [MFG], superior frontal gyrus [SFG], and supramarginal gyrus [SMG]), with the IFG as the driven input area. Results showed the superiority of a model in which both the MFG and the AG connected with the IFG, supporting the orthography autonomy hypothesis. Word frequency modulated the AG → SFG connection (information flow from the orthographic lexicon to the orthographic buffer), and syllable frequency affected the IFG → MFG connection (information transmission from the semantic system to the phonological lexicon). This study thus provides new insights into the connectivity architecture of neural substrates involved in writing.
Global Precipitation Experiment—A New World Climate Research Programme Lighthouse Activity
Authors: Zeng Xubin , Alves Lincoln , Boucher Marie-Amélie , Cherchi Annalisa , DeMott Charlotte , Dimri A. P. , Gettelman Andrew , Hanna Edward , Horinouchi Takeshi , Huang Jin , Lennard Chris , Leung L. Ruby , Luo Yali , Thamban Meloth , Palanisamy Hindumathi , Pryor Sara C. , Saint-Lu Marion , Sobolowski Stefan P. , Stammer Detlef , Steiner Jakob , Stevens Bjorn , Uhlenbrook Stefan , Wehner Michael , Zuidema Paquita 
Published: May 2024

Abstract
The future state of the global water cycle and the prediction of freshwater availability for humans around the world remain among the challenges of climate research and are relevant to several United Nations Sustainable Development Goals. The Global Precipitation Experiment (GPEX) takes on the challenge of improving the prediction of precipitation quantity, phase, timing, and intensity, characteristics that are products of a complex integrated system. It will achieve this by leveraging existing World Climate Research Programme (WCRP) activities and community capabilities in satellite, surface-based, and airborne observations, modeling, and experimental research and by conducting new and focused activities. It was launched in October 2023 as a WCRP Lighthouse Activity. Here, we present an overview of the GPEX Science Plan that articulates the primary science questions related to precipitation measurements, process understanding, model performance and improvements, and plans for capacity development. The central phase of GPEX is the WCRP Years of Precipitation for 2–3 years with coordinated global field campaigns focusing on different storm types (atmospheric rivers, mesoscale convective systems, monsoons, and tropical cyclones, among others) over different regions and seasons. Activities are planned over the three phases (before, during, and after the Years of Precipitation) spanning a decade. These include gridded data evaluation and development, advanced modeling, enhanced understanding of processes critical to precipitation, multiscale prediction of precipitation events across scales, and capacity development. These activities will be further developed as part of the GPEX Implementation Plan.
How Does Vertical Wind Shear Influence Updraft Characteristics and Hydrometeor Distributions in Supercell Thunderstorms?
Authors: Mulholland Jake P. , Nowotarski Christopher J. , Peters John M. , Morrison Hugh , Nielsen Erik R. 
Published: May 2024

Abstract
Vertical wind shear is known to affect supercell thunderstorms by displacing updraft hydrometeor mass downshear, thereby facilitating the storms’ longevity. Shear also impacts the size of supercell updrafts, with stronger shear leading to wider, less dilute, and stronger updrafts with likely greater hydrometeor production. To more clearly define the role of shear across different vertical layers on hydrometeor concentrations and displacements relative to supercell updrafts, a suite of idealized numerical model simulations of supercells was conducted. Shear magnitudes were systematically varied across the 0–1, 1–6, and 6–12 km AGL layers, while the thermodynamic environment was held fixed. Simulations show that as shear magnitude increases, especially from 1 to 6 km, updrafts become wider and less dilute with an increase in hydrometeor loading, along with an increase in the low-level precipitation area/rate and total precipitation accumulation. Even with greater updraft hydrometeor loading amid stronger shear, updrafts are more intense in stronger shear simulations due to larger thermal buoyancy owing to wider, less dilute updraft cores. Furthermore, downshear hydrometeor displacements are larger in environments with stronger 1–6-km shear. In contrast, there is relatively less sensitivity of hydrometeor concentrations and displacements to variations in either 0–1- or 6–12-km shear. Results are consistent across free tropospheric relative humidity sensitivity simulations, which show an increase in updraft size and hydrometeor mass with increasing free tropospheric relative humidity owing to a reduction in entrainment-driven dilution for wider updrafts in moister environments.

Significance Statement
Rotating thunderstorms, known as supercells, are able to persist for multiple hours. One common explanation is that large changes in wind speed and/or direction with height, or shear, transport rain/hail away from supercell updrafts, supporting their maintenance. The strong shear within supercell environments, however, may also lead to greater rail/hail amounts, thereby leading to weaker storms due to this extra mass of water/ice within updrafts. Furthermore, the impact of shear across different height layers on supercell rain/hail characteristics has not been thoroughly investigated. In this study, computer simulations of supercells were conducted to determine that shear occurring between 1 and 6 km above ground level has a large impact on rain/hail distribution in supercells and that stronger shear in this layer leads to wider/stronger supercells with greater rain/hail accumulations at the surface. Additionally, some of the extra mass of water/ice is transported farther away from updrafts due to the stronger environmental storm-relative winds.