bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A014: Transcriptional regulation of basal leader cell identity during collective breast cancer invasion
Authors: Doak Andrea E. , Qu Rose , Cheung Kevin J. 
Published: January 2023

Abstract
An early step in breast cancer progression is invasion of tumor cells into surrounding tissues. In many breast cancers, particularly ductal carcinomas, this invasion is accomplished by tumor cells migrating as a cohesive group. This often involves cells that take on heterogeneous roles as either leader or follower cells. Studies in common mouse and human breast cancer models have established that leader cells express high levels of keratin-14 (K14) and other basal epithelial markers. The presence of these K14+ cells promote metastasis and predict poor prognosis. The molecular mechanisms regulating K14+ leader cell identity and the methods for targeted depletion of these cells remain obscure. Here we performed time-sampled single cell RNA-sequencing in 3D type I collagen-embedded tumor organoids isolated from the MMTV-PyMT luminal B model of breast cancer. 11 distinct cellular transcriptional states were identified, and through correlation with K14 expression and invasive strand formation we classified one of the states as leader cells. Having confirmed the leader cell cluster markers spatially localize to the invasive front, we next asked which transcription factors were enriched, reasoning that transcription factors could be master regulators of leader cell fate. Three different shRNAs targeting ten genes were systematically evaluated for their effects on collective invasion and keratin-14 transcription. Each transcription factor was designated as either an invasion promoter or invasion suppressor depending on the correlation between transcription factor expression and organoid invasion. Studies are ongoing investigating the impact of invasion-promoting and invasion-suppressing transcription factors on cellular transcriptional states and metastatic dissemination in-vivo. We propose that targeting invasion-suppressing pathways could be combined with therapies that specifically target and eliminate K14+ invasive cells. To this end, we have identified multiple candidate druggable targets and specific surface markers expressed in K14+ invasive cells.
Citation Format: Andrea E. Doak, Rose Qu, Kevin J. Cheung. Transcriptional regulation of basal leader cell identity during collective breast cancer invasion [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A014.
Abstract B038: Remodeling the extracellular matrix environment and establishing distinct immune cell profiles enables the formation of brain metastasis in non-small cell lung cancer adenocarcinoma
Authors: Wang Albert R. , Brown Jared , Baschnagel Andrew , Buehler Darya , Kendziorski Christina , Iyer Gopal 
Published: January 2023

Abstract
Dissemination of tumor cells from the primary site of the lung to distant sites in non-small cell lung cancer (NSCLC) is poorly understood. With distinct mutation signatures in patients, altering pathways is critical to preventing tumor cell dissemination to distant sites. Towards this, we characterized 21 "trios" patient-matched brain metastases (BrM), primary tumors (LT), and normal samples (LN), revealing a pattern of extracellular matrix remodeling which suppressed immune cell infiltration. Our objectives were to (i) determine if clinically sampled primary lung tumors encode gene expression patterns distinct from normal tissue, suggestive of increased tumor invasiveness including brain metastasis, and (ii) determine the biologic underpinning of immune-suppressive information carryover from primary lung tumor to brain metastasis. Transformation of the normal lung cells to primary tumor cells suggested a breakdown in ECM axes primarily governed by upregulation of collagen (COL1A1, COL1A2, COL3A1, COL10A1), fibronectin (FN1), and matrix metalloproteinases (MMP7, MMP9, MMP11, MMP12, MMP13, MMP14) genes. Collectively, the primary tumor cells used MMPs to break down the main components of lung ECM and reorganized collagen and fibronectin in the tumor microenvironment to facilitate migration and invasion. Migration and subsequent cell adhesion in the brain microenvironment revealed upregulation of neural cell adhesion molecule (NCAM1) and phosphoprotein 1 (SPP1). These changes in ECM profiles between LT and BrM signify primary tumor cells' adaptation in the brain microenvironment. Further computational deconvolution revealed reduced HLA class II gene expression (HLA-DMA, HLA-DOB, HLA-DPA1, HLA-DPB1, HLA-DQA2, HLA-DQB2, HLA-DRA) correlated with lower CIBERSORTx enrichment scores of immune cell populations in BrM. Overall, using the matched sequencing information, we will present the underlying signaling gradients that dictate dissemination of primary lung tumor cells to the brain environment in the background of altered ECM environment using cellular models harboring EGFR, KRAS, and ALK driver mutations.
Citation Format: Albert R. Wang, Jared Brown, Andrew Baschnagel, Darya Buehler, Christina Kendziorski, Gopal Iyer. Remodeling the extracellular matrix environment and establishing distinct immune cell profiles enables the formation of brain metastasis in non-small cell lung cancer adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B038.
Abstract B040: Leader cells mediate tumor engraftment and promote immunosuppression to drive ovarian cancer progression in vivo
Authors: Wilson Amy L. , Doran Brittany R. , Basri Bashirah , Moffitt Laura R. , Plebanski Magdalena , Stephens Andrew N. , Bilandzic Maree 
Published: January 2023

Abstract
Epithelial ovarian cancer (EOC) is most frequently diagnosed at an advanced stage, and is characterized by its high recurrence rate and almost-universal acquisition of chemoresistance. Metastasis of EOC is driven by heterogenous spheroids that passively disseminate throughout the peritoneal cavity, promoting tumor spread and recurrence. We previously identified a sub-population of highly motile and invasive “Leader cells” (LCs) that express the basal epithelial protein KRT14 as an absolute determinant of invasive potential. We demonstrated KRT14 knockout in EOC cells does not impact viability or proliferation, however completely ablates their ability to invade through Matrigel in 2D and 3D format in vitro. Although a role for LCs in mesothelial clearance and invasion has been established, these mechanisms remain poorly understood. Here we show a critical role for KRT14+ LCs in immunosuppression and tumor-immune privilege in vivo. In the ID8 syngeneic EOC mouse model, tumor-specific LC (KRT14) loss (LCKO) impaired ovarian intrabursal primary tumor engraftment and subsequent metastatic spread. Immune phenotyping by flow cytometry revealed that mice bearing LCKO tumors displayed decreased proportions of immunosuppressive tumor-adjacent Tregs and M2 macrophages, and improved CD8+ T-cell/Treg ratios. Conversely, forced LC-overexpression (LCOE) in EOC tumors accelerated metastasis, and promoted tumor-immune evasion via upregulated secretion of suppressive chemokines including CCL22 and CCL5. In addition to their critical role in migration and invasion, the current study provides in vivo evidence that leader cells are mediators of immune suppression in ovarian cancer. This work supports the basis that defining novel strategies to target LCs to promote anti-tumor immunity and limit metastatic progression may be a useful strategy for improved epithelial ovarian cancer therapy.
Citation Format: Amy L. Wilson, Brittany R. Doran, Bashirah Basri, Laura R. Moffitt, Magdalena Plebanski, Andrew N. Stephens, Maree Bilandzic. Leader cells mediate tumor engraftment and promote immunosuppression to drive ovarian cancer progression in vivo [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B040.
Abstract B050: Reproducible and effective preclinical models of prostate cancer metastasis established with PDXs
Authors: Yin JuanJuan I. , Daryanani Asha , Alilin Aian , Lake Ross , Kelly Kathy 
Published: January 2023

Abstract
Metastatic castration resistant prostate cancer (mCRPC) is a lethal disease. Understanding the intricacy of this disease and developing targeted treatment is hampered by the lacking of clinically relevant animal models. LuCaP patient-derived xenografts (PDXs), established from advanced metastatic prostate cancer, are a large cohort that encompass the molecular and cellular heterogeneity of mCRPC. We have established four prostate cancer metastasis models from three androgen receptor (AR) positive lines (LuCaP136, LuCaP167 and LuCaP23.1) and one AR negative line LuCap145.2. The three AR positive LuCap lines metastasized to vertebrae and long bones with differing bone-associated histology while the AR negative LuCap145.2 metastasize to brain and spinal cord. The bone metastasis phenotypes of the models encompass: osteolytic (LuCaP136), mixed bone destruction and new bone formation (LuCaP167), and a highly osteoblastic histology (LuCaP23.1). LuCap136 and LuCap167 also metasize to soft tissues including adrenal, kidney and liver. Castration responses were studied on LuCap136 and LuCap167 models. Although both models are castration resistant, LuCap136 model initially are sensitive to castration with decreased tumor progression, and AR down-regulated in the metastatic sites. In contrast, tumor progression was not affected after castration in LuCap167 model. AR and ARV7 were up-regulated in metastatic cells. In summary, the LuCap PDX lines have the capacity for systemic growth in clinically accurate metastatic sites. In addition, the two AR positive models show different castration response which may be driven by different pathways. Understanding the complexity of these pathways would guide optimal selection of drug combinations to achieve the best outcome for patients with mCRPC.
Citation Format: JuanJuan I. Yin, Asha Daryanani, Aian Alilin, Ross Lake, Kathy Kelly. Reproducible and effective preclinical models of prostate cancer metastasis established with PDXs [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B050.
Abstract IA025: About motifs, non-codingRNAs and metastases
Authors: Calin George A. 
Published: January 2023

Abstract
MicroRNA and other short or long non-codingRNAs alterations are involved in the initiation, progression and metastases of human cancer. The main molecular alterations are represented by variations in gene expression, usually mild and with consequences for a vast number of target protein coding genes. The causes of the widespread differential expression of non-codingRNAs in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the processing machinery. MicroRNA and other short or long non-codingRNAs expression profiling of human tumors has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify non-codingRNAs that may represent downstream targets of activated oncogenic pathways or that are targeting protein coding genes involved in cancer. Recent studies proved that miRNAs and non-coding ultraconserved genes are main candidates for the elusive class of cancer predisposing genes and that other types of non-codingRNAs participate in the genetic puzzle giving rise to the malignant phenotype. These discoveries could be exploited for the development of useful markers for diagnosis and prognosis, as well as for the development of new RNA-based cancer therapies.
Citation Format: George A. Calin. About motifs, non-codingRNAs and metastases [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr IA025.
High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis
Authors: Cortese Nina , Carriero Roberta , Barbagallo Marialuisa , Putignano Anna Rita , Costa Guido , Giavazzi Fabio , Grizzi Fabio , Pasqualini Fabio , Peano Clelia , Basso Gianluca , Marchini Sergio , Colombo Federico Simone , Soldani Cristiana , Franceschini Barbara , Di Tommaso Luca , Terracciano Luigi , Donadon Matteo , Torzilli Guido , Kunderfranco Paolo , Mantovani Alberto , Marchesi Federica 
Published: January 2023

AbstractPatients with colorectal liver metastasis (CLM) present with heterogenous clinical outcomes and improved classification is needed to ameliorate the therapeutic output. Macrophages (Mϕ) hold promise as prognostic classifiers and therapeutic targets. Here, stemming from a single-cell analysis of mononuclear phagocytes infiltrating human CLM, we identified two Mϕ markers associated with distinct populations with opposite clinical relevance. The invasive margin of CLM was enriched in pro-inflammatory monocyte-derived Mϕ (MoMϕ) expressing the monocytic marker SERPINB2, and a more differentiated population, tumor-associated Mϕ (TAM), expressing glycoprotein nonmetastatic melanoma protein B (GPNMB). SERPINB2+ MoMϕ had an early inflammatory profile, whereas GPNMB+ TAMs were enriched in pathways of matrix degradation, angiogenesis, and lipid metabolism and were found closer to the tumor margin, as confirmed by spatial transcriptomics on CLM specimens. In a cohort of patients, a high infiltration of SERPINB2+ cells independently associated with longer disease-free survival (DFS; P = 0.033), whereas a high density of GPNMB+ cells correlated with shorter DFS (P = 0.012) and overall survival (P = 0.002). Cell–cell interaction analysis defined opposing roles for MoMϕ and TAMs, suggesting that SERPINB2+ and GPNMB+ cells are discrete populations of Mϕ and may be exploited for further translation to an immune-based stratification tool. This study provides evidence of how multi-omics approaches can identify nonredundant, clinically relevant markers for further translation to immune-based patient stratification tools and therapeutic targets. GPNMB has been shown to set Mϕ in an immunosuppressive mode. Our high dimensional analyses provide further evidence that GPNMB is a negative prognostic indicator and a potential player in the protumor function of Mϕ populations.
denúncia do racismo e a contestação da democracia racial pela imprensa negra nos primórdios do futebol paulistano
Authors: Abrahão Bruno Otávio de Lacerda , Oliveira George Roque Braga , Soares Antonio Jorge Gonçalves 
Published: January 2023

A Imprensa Negra surgiu em São Paulo nos primeiros anos do Século XX como um coletivo que abordava a questão racial em seu contexto econômico, político e cultural. Tais veículos provocaram o debate através das discussões sobre a estrutura de poder, os modelos de organização social e cultural e as formas de reconhecimento e status ao descortinarem as tentativas de negação destas iniquidades sociais. Diante desta constatação, o objetivo deste artigo é analisar a denúncia de episódios de discriminação racial e a contestação do mito identitário de democracia racial no futebol paulistano do início do Século XX através das publicações da Imprensa Negra. Como fonte utilizamos seus jornais disponibilizados nos microfilmes da Biblioteca Nacional. Após lermos as matérias que tematizavam o esporte, selecionamos duas que se ocuparam de repercutir o preconceito e a discriminação racial no futebol paulistano naquele contexto. No período analisado, podemos observar que no futebol de São Paulo ocorria a inclusão em determinados espaços e exclusão em outros, o que impedia a efetivação de relações democratizadas e proporcionava a reprodução das contradições do racismo na sociedade. Concluiu-se que havia tensão entre a coexistência da denúncia do racismo e o louvor da democracia racial nos primórdios do futebol de São Paulo.
Association of Eating and Sleeping Intervals With Weight Change Over Time: The Daily24 Cohort
Authors: Zhao Di , Guallar Eliseo , Woolf Thomas B. , Martin Lindsay , Lehmann Harold , Coughlin Janelle , Holzhauer Katherine , Goheer Attia A. , McTigue Kathleen M. , Lent Michelle R. , Hawkins Marquis , Clark Jeanne M. , Bennett Wendy L. 
Published: January 2023

Background
We aim to evaluate the association between meal intervals and weight trajectory among adults from a clinical cohort.

Methods and Results

This is a multisite prospective cohort study of adults recruited from 3 health systems. Over the 6‐month study period, 547 participants downloaded and used a mobile application to record the timing of meals and sleep for at least 1 day. We obtained information on weight and comorbidities at each outpatient visit from electronic health records for up to 10  years before until 10 months after baseline. We used mixed linear regression to model weight trajectories. Mean age was 51.1 (SD 15.0) years, and body mass index was 30.8 (SD 7.8) kg/m
2
; 77.9% were women, and 77.5% reported White race. Mean interval from first to last meal was 11.5 (2.3) hours and was not associated with weight change. The number of meals per day was positively associated with weight change. The average difference in annual weight change (95% CI) associated with an increase of 1 daily meal was 0.28 kg (0.02–0.53).

Conclusions
Number of daily meals was positively associated with weight change over 6 years. Our findings did not support the use of time‐restricted eating as a strategy for long‐term weight loss in a general medical population.
The Vojvodina Gallery: Biographical Portraits of Four Jewish Cultural Workers
Authors: Ungar Olga 
Published: January 2023

Abstract
The article introduces four cultural workers of Jewish origin from Vojvodina, who were portrayed in the publication Vojvodina Gallery (1927). This unique biographical portrait gallery of influential people living at that time in the Vojvodina region, served as a starting point for this study. Vojvodina’s Jews were well represented in this publication; out of the three hundred and six individuals about sixty (or twenty percent of all entries) were of Jewish origin. Without the existence of the Vojvodina Gallery some of them would almost have been completely forgotten. Rediscovery of this publication is a reminder of the “lost generation” of Jews whose lives and careers were cut short by the Holocaust. The four personalities presented in this essay shed light on different aspects of Jewish cultural activities in Vojvodina: fine arts, literature, charitable work, and Jewish scholarship.
Quantum Computers for Weather and Climate Prediction: The Good, the Bad, and the Noisy
Authors: Tennie F. , Palmer T. N. 
Published: January 2023

Abstract
Over the past few years, quantum computers and quantum algorithms have attracted considerable interest and attention from numerous scientific disciplines. In this article, we aim to provide a nontechnical yet informative introduction to key aspects of quantum computing. We discuss whether quantum computers one day might become useful tools for numerical weather and climate prediction. Using a recently developed quantum algorithm for solving nonlinear differential equations, we integrate a simple nonlinear model. In addition to considering the advantages that quantum computers have to offer, we shall also discuss the challenges one faces when trying to use quantum computers for real-world problems involving “big data,” such as weather prediction.
Efficacy and safety of cyclosporine-based regimens for primary immune thrombocytopenia: a systematic review and meta-analysis
Authors: Li Xiaojing , Zhu Wenwei , Bao Jizhang , Li Jiekai , Zhou Yongming 
Published: January 2023

Objective To conduct a meta-analysis assessing the efficacy and safety of cyclosporine-based combinations for primary immune thrombocytopenia (ITP). Methods Randomized controlled clinical trials were collected by systematically searching databases (PubMed®, MEDLINE®, EMBASE, The Cochrane Library, China National Knowledge Infrastructure) from inception to June 2022. All studies included patients with ITP who received cyclosporine-based regimens. We performed comprehensive analyses of the overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, relapse rate, platelet count, and adverse drug reaction (ADR) rate. Results Seven studies (n = 418) were ultimately included. According to a fixed-effects model, cyclosporine-based combinations improved the ORR and CR rate and reduced the relapse rate. The ADR rate was not increased in the cyclosporine-based combination group. Cyclosporine-based regimens effectively increased the platelet count. Subgroup analysis illustrated that cyclosporine-based combinations were linked to higher ORRs in both children (odds ratio [OR] = 5.74, 95% confidence interval [CI] = 1.79–18.41) and adults (OR = 5.46, 95% CI = 2.48–12.02) and a higher CR rate in adults (OR = 2.97, 95% CI = 1.56–5.63). Conclusion Cyclosporine exhibited efficacy in the treatment of ITP without increasing the risk of ADRs.
Cryopreservation of two species of the multicellular volvocine green algal genus Astrephomene
Authors: Nozaki Hisayoshi , Mori Fumi , Tanaka Yoko , Matsuzaki Ryo , Yamashita Shota , Yamaguchi Haruyo , Kawachi Masanobu 
Published: January 2023

Abstract
Background
Astrephomene is an interesting green algal genus that, together with Volvox, shows convergent evolution of spheroidal multicellular bodies with somatic cells of the colonial or multicellular volvocine lineage. A recent whole-genome analysis of A. gubernaculifera resolved the molecular-genetic basis of such convergent evolution, and two species of Astrephomene were described. However, maintenance of culture strains of Astrephomene requires rapid inoculation of living cultures, and cryopreserved culture strains have not been established in public culture collections.

Results
To establish cryopreserved culture strains of two species of Astrephomene, conditions for cryopreservation of the two species were investigated using immature and mature vegetative colonies and two cryoprotectants: N,N-dimethylformamide (DMF) and hydroxyacetone (HA). Rates of cell survival of the A. gubernaculifera or A. perforata strain after two-step cooling and freezing in liquid nitrogen were compared between different concentrations (3 and 6%) of DMF and HA and two types of colonies: immature colonies (small colonies newly released from the parent) and mature colonies (large colonies just before daughter colony formation). The highest rate of survival [11 ± 13% (0.36–33%) by the most probable number (MPN) method] of A. gubernaculifera strain NIES-4017 (established in 2014) was obtained when culture samples of immature colonies were subjected to cryogenic treatment with 6% DMF. In contrast, culture samples of mature colonies subjected to 3% HA cryogenic treatment showed the highest “MPN survival” [5.5 ± 5.9% (0.12–12%)] in A. perforata. Using the optimized cryopreservation conditions for each species, survival after freezing in liquid nitrogen was examined for six other strains of A. gubernaculifera (established from 1962 to 1981) and another A. perforata strain maintained in the Microbial Culture Collection at the National Institute for Environmental Studies (MCC-NIES). We obtained ≥0.1% MPN survival of the A. perforata strain. However, only two of the six strains of A. gubernaculifera showed ≥0.1% MPN survival. By using the optimal cryopreserved conditions obtained for each species, five cryopreserved strains of two species of Astrephomene were established and deposited in the MCC-NIES.

Conclusions
The optimal cryopreservation conditions differed between the two species of Astrephomene. Cryopreservation of long-term-maintained strains of A. gubernaculifera may be difficult; further studies of cryopreservation of these strains are needed.