bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A058: Mesenchymal stem cells act as a selective pressure for High Grade Serous Ovarian Cancer initiation
Authors: Garcia Geyon L. , Atiya Huda I. , Coffman Lan G. 
Published: March 2024

Abstract
High grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian cancer accounting for 80-90% of diagnoses. Despite its high incidence and mortality, the mechanisms of cancer initiation are unclear. The majority of HGSOC originates in the fallopian tube epithelium (FTE) with support of underlying mesenchymal stromal/stem cells (MSCs). MSCs are stromal progenitor cells that play important roles in wound healing and, in the context of cancer, tumor progression. We showed that MSCs within the tumor microenvironment, termed cancer associated MSCs (CA-MSCs) harbor a unique, age-associated epigenetic signature that is essential for tumor growth and metastasis. Surprisingly, we identified rare subsets of MSCs from benign tubes that exhibit similar epigenetic changes to cancer educated CA-MSCs suggesting that the pro-oncogenic MSC phenotype exists prior to cancer initiation. These “high risk” MSCs (hrMSCs) increase with age, are enriched in BRCA mutation carrier patients, promote cancer cell proliferation, and most notably, elicit tumor formation in primary, non-cancerous FTE. To elucidate the mechanism of hrMSC-induced malignant transformation of FTE, we characterized the effect that hrMSCs have on primary FTE. HrMSCs promoted increased growth of FTE relative to normal/low risk MSCs (lrMSCs) derived from the same patient. These MSCs lack the epigenetic signature/transcriptome of hrMSCs/CA-MSCs. Intriguingly, we co-cultured FTE with hrMSCs at a 1:1 ratio and discovered robust DNA damage in the form of DNA double strand breaks (53BP1 foci) in FTE at 24 hours. Furthermore, conditioned media from hrMSCs supported the recovery of FTE following damage with other DNA damaging agents. We hypothesize that the DNA damage function of hrMSCs serves as a selective pressure for mutation in FTE (1st hit). Additionally, we hypothesize that hrMSCs simultaneously provide growth signals to FTE allowing for evasion of DNA damage-induced cell death (2nd hit). Lastly, we hypothesize that both hrMSC functions are required for genesis of HGSOC.
Citation Format: Geyon L. Garcia, Huda I. Atiya, Lan G. Coffman. Mesenchymal stem cells act as a selective pressure for High Grade Serous Ovarian Cancer initiation [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 A058.
Abstract IA008: Rare ovarian cancers: the sequelae of specific interactions between cell contexts mutations and microenvironments
Authors: Huntsman David 
Published: March 2024

Abstract
There are many pathologically and clinically distinct types of ovarian cancer and uterine cancers. These are not flavors of the same disease nor can they be solely explained by different mutations or other genomic findings; rather each may be thought to represent distinct interactions between cells of origin, mutations, and the microenvironment in which these cancers occur. Although many know gaps remain this may explain many curious features of these cancers. Fors instance, how endometrioid and clear cell carcinomas have similar mutations yet are distinct biologic and clinical entities. Also, why they occur at similar rates from ovarian endometriomas, yet clear cell cancers are much rarer in the endometrium. As an example of the importance microenvironment, findings will be presented suggesting that expression of Cystathionine gamma-lyase (CTH or CSE), a key enzyme within the transsulfuration pathway, enables CCC precursor cells to survive in endometriotic cysts becoming a defining feature of this cancer, one that may explain its biologic properties, aggressive course and relative chemoresistance. Other cancers will be considered using this model including rare stromal cancers.
Citation Format: David Huntsman. Rare ovarian cancers: the sequelae of specific interactions between cell contexts mutations and microenvironments [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 IA008.
Abstract P07: Identification of the unique preleukemic bone marrow niche in acute myeloid leukemia
Authors: Goda Chinmayee , Kulkarni Rohan , Rudich Alexander , Karunasiri Malith , Bustos Yaphet , Chidester Sadie , Balcioglu Ozlen , Garfinkle Elizabeth AR , Mundy-Bosse Bethany , Mardis Elaine R , Marcucci Guido , Garzon Ramiro , Miller Katherine , Dorrance Adrienne M 
Published: March 2024

Abstract
Preleukemic stem cells (LSCs) can remain dormant within the bone marrow (BM) for decades before disease onset, suggesting acquisition of mutations within hematopoietic stem/progenitor cells (HSPCs) alone is insufficient for acute myeloid leukemia (AML). It is likely that alterations within BM microenvironment (BMM) also occur due to dysregulated crosstalk with mutant HSCs thus favoring LSC growth over normal HSCs. Uncovering novel mechanisms by which preleukemic LSCs remodel the BMM is critical in understanding therapy resistance and to develop novel therapies targeting aberrant pathways in both the LSCs and cells within the BMM. To address this, we compared cells of the BMM of wildtype (WT) mice to our Mll-PTD;Flt3-ITD mouse model of AML, which has a distinct preleukemic phase. Using single cell RNA-sequencing we identified 17 stromal cell clusters and observed substantial changes in both cell numbers and transcriptional profiles of several key stromal cell subpopulations. Specifically, we found decreases in normal HSC regulatory populations such as LepR+ MSCs and Cdh5+ ECs (2 and 2.7-fold decreases, respectively) and increases in pericytes and fibroblasts in preleukemic BM compared to WT (2.7 and 3.5-fold increase, respectively). Unlike what is observed in full-blown AML, we found an increase in CD55+ fibroblasts resulting from increased proliferation (13% vs 6% cell cycling, P=0.0016). Importantly, co-culture assays found that CD55+ BM fibroblasts expanded LSCs at increased levels over normal HSCs (83+/-7.5 vs 57+/-10.1, P=0.0006). Downregulation of several collagen genes (Col1a1, Col1a2, Col3a1, Col4a1, and Col6a1, P&lt; 0.05) was found in these preleukemic CD55+ fibroblasts, suggesting that remodeling of the extracellular matrix might be an important mechanism by which these CD55+ fibroblast remodel the normal BMM and promote leukemogenesis. Furthermore, sequencing of full-blown leukemic BM niche cells have identified several key differences in the BM architecture, suggesting that the preleukemic BM is indeed distinct from full-blown leukemic BM and is important for disease initiation and progression, and not disease maintenance.
Citation Format: Chinmayee Goda, Rohan Kulkarni, Alexander Rudich, Malith Karunasiri, Yaphet Bustos, Sadie Chidester, Ozlen Balcioglu, Elizabeth AR Garfinkle, Bethany Mundy-Bosse, Elaine R Mardis, Guido Marcucci, Ramiro Garzon, Katherine Miller, Adrienne M Dorrance. Identification of the unique preleukemic bone marrow niche in acute myeloid leukemia [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P07.
Abstract P23: RHOA inactivation subverts IFN-γ response and promotes antigen escape in CAR-T resistant diffuse large B-cell lymphoma
Authors: Newsam Austin D , Coughlin Caroline A , Goretsky Yitzhar E , Alaoui Abdessumad Y , Tsai Daniel E , Coffey David G , Sondhi Anya K , Roberts Evan R , Gallego Natalia Campos , Manara Paola , Bilbao Daniel , Ziccheddu Bachisio , Spiegel Jay Y , Jain Michael D , Locke Frederick L , Alderuccio Juan P , Maura Francesco , Schatz Jonathan H 
Published: March 2024

Abstract
CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies have shown breakthrough responses for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), however, over half of patients still progress. Whole genome sequencing of CAR-T treated patients revealed RHOA (3p21.31) deletions highly enriched in patients with poor responses (p = 0.0013). RHOA is altered in approximately 25% of newly diagnosed DLBCL, yet no work has comprehensively defined its role in lymphoma biology or immune resistance. We created RHOA loss-of-function (LoF) cell lines and performed RNA-sequencing followed by drug viability assays to interrogate pathways of dependence in RHOA deficient DLBCL. We also created immunocompetent models of RHOA deficient lymphoma in vivo and conducted single-cell RNA sequencing to assess the resulting lymphoma microenvironments. CAR-T cells were engineered and used to challenge RHOA LoF tumors in vitro. Upon discovering highly upregulated gene sets involving PI3K/AKT/mTOR signaling, we employed drug viability assays and established a critical reliance on AKT signaling in RHOA LoF cell lines. Upregulated AKT was found to suppress JAK2-STAT1 mediated (IFN-γ) signaling and this effect was reversed with PI3K inhibition. Single-cell transcriptomics of RHOA deficient mouse lymphomas revealed decreased Cd8a expression and increased Cd4 expression of T-cells (p = 0.09 and p = 0.028, respectively), suggesting an immunosuppressive microenvironment as a result of abolished IFN-γ mediated immunorecognition. RHOA deficient cell lines were also found to downregulate surface CD19 expression (p &lt; 0.0001) and demonstrated significantly decreased CAR-T cell killing in vitro (p = 0.0005). Future experiments will challenge RHOA deficient immunocompetent tumors in vivo with and without PI3K inhibitors to assess efficacy of combinatorial therapy.
Citation Format: Austin D Newsam, Caroline A Coughlin, Yitzhar E Goretsky, Abdessumad Y Alaoui, Daniel E Tsai, David G Coffey, Anya K Sondhi, Evan R Roberts, Natalia Campos Gallego, Paola Manara, Daniel Bilbao, Bachisio Ziccheddu, Jay Y Spiegel, Michael D Jain, Frederick L Locke, Juan P Alderuccio, Francesco Maura, Jonathan H Schatz. RHOA inactivation subverts IFN-γ response and promotes antigen escape in CAR-T resistant diffuse large B-cell lymphoma [abstract]. In: Proceedings of the Blood Cancer Discovery Symposium; 2024 Mar 4-6; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2024;5(2_Suppl):Abstract nr P23.
Comparison of Transcatheter Edge-to-Edge Mitral Valve Repair for Primary Mitral Regurgitation Outcomes to Hospital Volumes of Surgical Mitral Valve Repair
Authors: Grayburn Paul A. , Mack Michael J. , Manandhar Pratik , Kosinski Andrzej S. , Sannino Anna , Smith Robert L. , Szerlip Molly , Vemulapalli Sreekanth 
Published: March 2024

BACKGROUND:
Transcatheter edge-to-edge mitral valve (MV) repair (TEER) is an effective treatment for patients with primary mitral regurgitation at prohibitive risk for surgical MV repair (MVr). High-volume MVr centers and high-volume TEER centers have better outcomes than low-volume centers, respectively. However, whether MVr volume predicts TEER outcomes remains unknown. We hypothesized that high-volume MV surgical centers would have superior risk-adjusted outcomes for TEER than low-volume centers.

METHODS:
We combined data from the American College of Cardiology/Society of Thoracic Surgeons Transcatheter Valve Therapy registry and the Society of Thoracic Surgeons adult cardiac surgery database. MVr was defined as leaflet resection or artificial chords with or without annuloplasty and was evaluated as a continuous variable and as predefined categories (<25, 25–49, and ≥50 MV repairs/year). A generalized linear mixed model was used to evaluate risk-adjusted in-hospital/30-day mortality, 30-day heart failure readmission, and TEER success (mitral regurgitation ≤2+ and gradient <5 mm Hg).

RESULTS:

The study comprised 41 834 patients from 500 sites of which 332 (66.4%) were low, 102 (20.4%) intermediate, and 66 (13.2%) high-volume surgical centers (
P
<0.001). TEER success was 54.6% and was not statistically significantly different across MV surgical site volumes (
P
=0.4271). TEER mortality at 30 days was 3.5% with no significant difference across MVr volume on unadjusted (
P
=0.141) or adjusted (
P
=0.071) analysis of volume as a continuous variable. One-year mortality was 15.0% and was lower for higher MVr volume centers when adjusted for clinical and demographic variables (
P
=0.027). Heart failure readmission at 1 year was 9.4% and was statistically significantly lower in high-volume centers on both unadjusted (
P
=0.017) or adjusted (
P
=0.015) analysis.

CONCLUSIONS:
TEER can be safely performed in centers with low volumes of MV repair. However, 1-year mortality and heart failure readmission are superior at centers with higher MVr volume.
Design of a Stem Cell–Based Therapy for Ependymal Repair in Hydrocephalus Associated With Germinal Matrix Hemorrhages
Authors: Rodriguez-Perez Luis M. , Ojeda-Pérez Betsaida , López-de-San-Sebastián Javier , García-Bonilla María , González-García Marcos , Fernández-Muñoz Beatriz , Sánchez-Pernaute Rosario , García-Martín María L. , Domínguez-Pinos Dolores , Cárdenas-García Casimiro , Jiménez Antonio J. , Paez-Gonzalez Patricia 
Published: March 2024

BACKGROUND:
In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells.

METHODS:

GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student
t
or Wilcoxon-Mann-Whitney
U
test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively.

RESULTS:
PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 [forkhead box J1] transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema).

CONCLUSIONS:
In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.
A Novel Alignment-based Approach for PARSEVAL Measuress
Authors: Jo Eunkyul Leah , Park Angela Yoonseo , Park Jungyeul 
Published: March 2024

Abstract
We propose a novel method for calculating PARSEVAL measures to evaluate constituent parsing results. Previous constituent parsing evaluation techniques were constrained by the requirement for consistent sentence boundaries and tokenization results, proving to be stringent and inconvenient. Our new approach handles constituent parsing results obtained from raw text, even when sentence boundaries and tokenization differ from the preprocessed gold sentence. Implementing this measure is our evaluation by alignment approach. The algorithm enables the alignment of tokens and sentences in the gold and system parse trees. Our proposed algorithm draws on the analogy of sentence and word alignment commonly used in machine translation (MT). To demonstrate the intricacy of calculations and clarify any integration of configurations, we explain the implementations in detailed pseudo-code and provide empirical proof for how sentence and word alignment can improve evaluation reliability.
Lesion-symptom Mapping of Acceptability Judgments in Chronic Poststroke Aphasia Reveals the Neurobiological Underpinnings of Receptive Syntax
Authors: Fahey Danielle , Fridriksson Julius , Hickok Gregory , Matchin William 
Published: March 2024

Abstract
Disagreements persist regarding the neural basis of syntactic processing, which has been linked both to inferior frontal and posterior temporal regions of the brain. One focal point of the debate concerns the role of inferior frontal areas in receptive syntactic ability, which is mostly assessed using sentence comprehension involving complex syntactic structures, a task that is potentially confounded with working memory. Syntactic acceptability judgments may provide a better measure of receptive syntax by reducing the need to use high working memory load and complex sentences and by enabling assessment of various types of syntactic violations. We therefore tested the perception of grammatical violations by people with poststroke aphasia (n = 25), along with matched controls (n = 16), using English sentences involving errors in word order, agreement, or subcategorization. Lesion data were also collected. Control participants performed near ceiling in accuracy with higher discriminability of agreement and subcategorization violations than word order; aphasia participants were less able to discriminate violations, but, on average, paralleled control participants discriminability of types of violations. Lesion-symptom mapping showed a correlation between discriminability and posterior temporal regions, but not inferior frontal regions. We argue that these results diverge from models holding that frontal areas are amodal core regions in syntactic structure building and favor models that posit a core hierarchical system in posterior temporal regions.
Patient Characteristics and the Extent to Which Clinicians Involve Patients in Decision Making: Secondary Analyses of Pooled Data
Authors: Keij Sascha M. , Branda Megan E. , Montori Victor M. , Brito Juan P. , Kunneman Marleen , Pieterse Arwen H. 
Published: March 2024

Background The occurrence of shared decision making (SDM) in daily practice remains limited. Various patient characteristics have been suggested to potentially influence the extent to which clinicians involve patients in SDM. Objective To assess associations between patient characteristics and the extent to which clinicians involve patients in SDM. Methods We conducted a secondary analysis of data pooled from 10 studies comparing the care of adult patients with (intervention) or without (control) a within-encounter SDM conversation tool. We included studies with audio(-visual) recordings of clinical encounters in which decisions about starting or reconsidering treatment were discussed. Main Measures In the original studies, the Observing Patient Involvement in Decision Making 12-items (OPTION12 item) scale was used to code the extent to which clinicians involved patients in SDM in clinical encounters. We conducted multivariable analyses with patient characteristics (age, gender, race, education, marital status, number of daily medications, general health status, health literacy) as independent variables and OPTION12 as a dependent variable. Results We included data from 1,614 patients. The between-arm difference in OPTION12 scores was 7.7 of 100 points ( P < 0.001). We found no association between any patient characteristics and the OPTION12 score except for education level ( p = 0.030), an association that was very small (2.8 points between the least and most educated), contributed mostly by, and only significant in, control arms (6.5 points). Subanalyses of a stroke prevention trial showed a positive association between age and OPTION12 score ( P = 0.033). Conclusions Most characteristics showed no association with the extent to which clinicians involved patients in SDM. Without an SDM conversation tool, clinicians devoted more efforts to involve patients with higher education, a difference not observed when the tool was used. Highlights Most sociodemographic patient characteristics show no association with the extent to which clinicians involve patients in shared decision making. Clinicians devoted less effort to involve patients with lower education, a difference that was not observed when a shared decision-making conversation tool was used. SDM conversation tools can be useful for clinicians to better involve patients and ensure patients get involved equally regardless of educational background.
Correlation between endometriosis and migraine features: Results from a prospective case-control study
Authors: Selntigia Aikaterini , Exacoustos Caterina , Ortoleva Camille , Russo Consuelo , Monaco Giulia , Martire Francesco Giuseppe , Rizzo Giuseppe , Della-Morte David , Mercuri Nicola Biagio , Albanese Maria 
Published: March 2024

Background Endometriosis and migraine frequently coexist, but only a limited number of studies have focused on their mutual association. The aim of our study was to investigate, in untreated women with comorbid endometriosis/adenomyosis and migraine, the correlation between headache features and endometriotic subtypes and their possible relationship with pain severity and disease disability. Methods Fifty women affected by endometriosis/adenomyosis and migraine matched (1:2) with 100 patients with endometriosis alone and 100 patients with only migraine were recruited and underwent pelvic ultrasound imaging and neurological examination. Results Severe adenomyosis, posterior and anterior deep infiltrating endometriosis (p = 0.027, p = 0.0031 and p = 0.029, respectively) occurred more frequently in women with migraine. Dysmenorrhea was the most commonly reported symptom in women with endometriosis and migraine and the mean VAS scores of all typical endometriotic symptoms were significantly higher in the presence of comorbidity. Women with both migraine and endometriosis reported significant higher pain intensity (p = 0.004), higher monthly migraine days (p = 0.042) and increased HIT 6-scores (p = 0.01), compared with those without endometriosis. Conclusions Our results demonstrated that the co-occurrence of migraine in untreated women with endometriosis is associated with more severe gynecological infiltrations and correlated with increased pain intensity and disease disability. Trial Registration: Protocol number 119/21