bluuebunny/crossref_metadata_2025_split huggingface dataset:
The complete chloroplast genome of Persicaria perfoliata and comparative analysis with four medicinal plants of Polygonaceae
Authors: Huo Ziting , Xu Wenbo , Guo Huijun , Yang Peng , Zhang Qianwen , Lu Xu , Wang Long 
Published: May 2022

Polygonaceae is a large family of medicinal herbs that includes many species used as traditional Chinese medicine, such as Per sicaria per foliata. Here, we sequenced the complete chloroplast genome of P. per foliata using Illumina sequencing technology with the purpose of providing a method to facilitate accurate identification. After being annotated, the complete chloroplast genome of P. per foliata was compared with those of Fagopyrum tataricum, Per sicaria chinensis, Fagopyrum dibotrys, and Fallopia multiflora. The complete chloroplast genome of P. per foliata is 160 730 bp in length, containing a small single-copy region of 12 927 bp, a large single-copy region of 85 433 bp, and a pair of inverted repeat regions of 62 370 bp. A total of 131 genes were annotated, including 8 rRNA genes, 34 tRNA genes, and 84 protein-coding genes. Forty-two simple sequence repeats and 55 repeat sequences were identified. Mutational hotspot analyses indicated that five genes ( matK, ndhF, ccsA, cemA, and rpl20) could be selected as candidates for molecular markers. Moreover, phylogenetic analysis showed that all the Polygonaceae species formed a monophyletic clade, and P. per foliata showed the closest relationship with P. chinense. The study provides valuable molecular information to accurately identify P. per foliata and assist in its development and application.
Wormholes and holography: an introduction
Authors: Kundu Arnab 
Published: May 2022

AbstractWormholes are intriguing classical solutions in General Relativity, that have fascinated theoretical physicists for decades. In recent years, especially in Holography, gravitational Wormhole geometries have found a new life in many theoretical ideas related to quantum aspects of gravity. These ideas primarily revolve around aspects of quantum entanglement and quantum information in (semi-classical) gravity. This is an introductory and pedagogical review of Wormholes and their recent applications in Gauge-Gravity duality and related ideas.
Actomyosin contractility requirements and reciprocal cell–tissue mechanics for cancer cell invasion through collagen-based channels
Authors: Beunk Lianne , Bakker Gert-Jan , van Ens Diede , Bugter Jeroen , Gal Floris , Svoren Martin , Friedl Peter , Wolf Katarina 
Published: May 2022

Abstract
The interstitial tumor microenvironment is composed of heterogeneously organized collagen-rich porous networks as well as channel-like structures and interfaces which provide both barriers and guidance for invading cells. Tumor cells invading 3D random porous collagen networks depend upon actomyosin contractility to deform and translocate the nucleus, whereas Rho/Rho-associated kinase-dependent contractility is largely dispensable for migration in stiff capillary-like confining microtracks. To investigate whether this dichotomy of actomyosin contractility dependence also applies to physiological, deformable linear collagen environments, we developed nearly barrier-free collagen-scaffold microtracks of varying cross section using two-photon laser ablation. Both very narrow and wide tracks supported single-cell migration by either outward pushing of collagen up to four times when tracks were narrow, or cell pulling on collagen walls down to 50% of the original diameter by traction forces of up to 40 nN when tracks were wide, resulting in track widths optimized to single-cell diameter. Targeting actomyosin contractility by synthetic inhibitors increased cell elongation and nuclear shape change in narrow tracks and abolished cell-mediated deformation of both wide and narrow tracks. Accordingly, migration speeds in all channel widths reduced, with migration rates of around 45-65% of the original speed persisting. Together, the data suggest that cells engage actomyosin contraction to reciprocally adjust both own morphology and linear track width to optimal size for effective cellular locomotion.

Graphic abstract
Abstract A029: Identification of tumor microenvironment components in patient-derived pancreatic ductal adenocarcinoma organoids
Authors: Gao Mei , Bailey Charles J. , Harper Megan M. , Cavnar Michael J. , Pandalai Prakash , Qasem Shadi A. , Kim Joseph 
Published: May 2022

Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is highly drug resistant with no change in therapeutic approach for the last decade. The PDAC tumor microenvironment (TME) is highly desmoplastic and associated with altered treatment response. Our group previously identified 9 distinct cell types in human PDAC tumors using single-cell RNA-sequencing, demonstrating a diverse TME. However, the TME of in vitro organoid PDAC models remains underexplored. We initiated characterization of the TME from PDAC patient derived organoids (PDOs) to establish a working model for accurate drug sensitivity testing. Methods: We performed immunofluorescence (IF) staining on whole-mount early passage (&lt;P4) PDO lines and corresponding paraffin-embedded primary PDAC specimens to evaluate for activated cancer-associated fibroblasts (CAFs) using antibodies against α-smooth muscle actin (α-SMA) and fibroblast activated protein (FAP); and to evaluate for T-regulatory (Treg) cells with antibodies against interleukin-2 receptor α (IL-2Rα) and forkhead box protein P3 (FOXP3). Results: CAFs promote an immunosuppressive TME in PDAC and have recently been subclassified into inflammatory fibroblasts and myofibroblasts, which can both restrain and promote tumor progression. In this study, we identified three distinct subtypes of CAFs in PDOs, which are consistent with the subtypes found in matched clinical tumor specimens: α-SMA+, which has been reported to be indicative of pancreatic stellate cell activation and associated with increased desmoplasia; FAP+, which influences cancer cell motility, invasion, and cycle progression, extracellular matrix deposition, and angiogenesis within the TME; and α-SMA+/FAP+, which is a myofibroblast subtype. We additionally identified Treg populations in PDOs with peripheral IL-2Rα and central FOXP3 expression in the organoid spheres. Tregs have previously been shown to be overexpressed in the PDAC TME, making this finding clinically relevant. Conclusions: In this preliminary study, we show that PDAC PDOs demonstrate TME components that mirror primary tumor specimens, including CAFs and Tregs. The demonstration of a tumor-matched, immunocompetent TME in PDAC PDOs provides a more clinically relevant in vitro tumor model for patient-matched drug sensitivity testing.
Citation Format: Mei Gao, Charles J. Bailey, Megan M. Harper, Michael J. Cavnar, Prakash Pandalai, Shadi A. Qasem, Joseph Kim. Identification of tumor microenvironment components in patient-derived pancreatic ductal adenocarcinoma organoids [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A029.
Abstract A039: Transcriptomic analysis of canine osteosarcoma from a precision medicine perspective reveals limitations of differential gene expression studies
Authors: Nance Rebecca L. , Cooper Sara , Starenki Dmytro , Wang Xu , Sandey Maninder , Koehler Jey , Agarwal Payal , Matz Brad , Lindley Stephanie , Smith Annette , Smith Ashley , Bergman Noelle , Smith Bruce F. 
Published: May 2022

Abstract
Despite significant advances in cancer diagnosis and treatment, osteosarcoma (OSA), an aggressive primary bone tumor, has eluded attempts at improving patient survival for many decades. Spontaneously occurring OSA in the dog shares remarkably similar clinical, histological, and molecular characteristics and therefore serves as an excellent model for the disease. The difficulty in managing OSA lies in its extreme genetic complexity, drug-resistance, and heterogeneity, making it improbable that a single-target treatment would be beneficial for the majority of affected individuals. Precision medicine seeks to fill this gap by addressing the intra- and inter-tumoral heterogeneity to improve patient outcome and survival. Characterization of differentially expressed genes (DEGs) provides insight into the phenotype and can be useful for informing appropriate therapies as well as development of novel treatments. To identify relevant DEGs, RNA profiles of primary tumor should be contrasted with that of normal tissue derived from the same cell-of-origin as the tumor prior to chemotherapy, as convoluted drug-resistant pathways make interpretation difficult. Traditional DEG analysis combines patient data to derive statistically inferred genes that are dysregulated in the group; however, the results from this approach are not necessarily consistent across individual patients, thus contradicting the basis of precision medicine. In this preliminary study, we use transcriptomic sequencing of RNA isolated from primary canine OSA tumor and patient-matched normal bone from seven dogs prior to chemotherapy to identify DEGs in the group. We then evaluate the universality of these changes in transcript levels among patients by deriving individual-level fold-change values using strict filtering parameters. The results from this study can be useful for reframing our perspective of transcriptomic analysis from a precision medicine perspective by identifying variations in DEGs among individuals.
Citation Format: Rebecca L. Nance, Sara Cooper, Dmytro Starenki, Xu Wang, Maninder Sandey, Jey Koehler, Payal Agarwal, Brad Matz, Stephanie Lindley, Annette Smith, Ashley Smith, Noelle Bergman, Bruce F. Smith. Transcriptomic analysis of canine osteosarcoma from a precision medicine perspective reveals limitations of differential gene expression studies [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A039.
Abstract IA012: Aging, tissue ecology, and the evolution of cancer within us
Authors: DeGregori James , Pham-Danis Catherine , Rozhok Andrii I , Evans Edward J. , Marongiu Fabio , Scarborough Hannah , Henry Curtis J. 
Published: May 2022

Abstract
Why do we get cancer? Why is cancer highly associated with old age? Of course, aging is associated with the accumulation of more mutations, and some of these mutations can contribute to cancer phenotypes. But we now understand that carcinogenesis is much more complex than originally appreciated. In particular, there are tissue environmental forces that both impede and promote cancer evolution. Just as organismal evolution is known to be driven by environmental changes, cellular (somatic) evolution in our bodies is similarly driven by changes in tissue environments, whether caused by the normal process of aging, by lifestyle choices or by extrinsic exposures. Environmental change promotes selection for new phenotypes that are adaptive to the new context. In our tissues, aging or insult-driven alterations in tissues drives selection for adaptive mutations, and some of these mutations can confer malignant phenotypes. We have been using mouse models of cancer initiation, mathematical models of cellular evolution, and analyses of human tissue samples to better understand the evolutionary forces that control somatic cell evolution and thus cancer risk. We have shown that aging and inflammation dependent changes in tissue environments dramatically dictate whether cancer-causing mutations are advantageous to stem cells in our tissues, starting the cells down the path to cancer. Our studies have focused on cancer initiation within the hematopoietic system and the lung. These studies have also uncovered molecular explanations for mutation-driven adaptation to aged and inflammatory tissue environments. In all, these studies indicate that strategies to prevent or treat cancers will need to incorporate interventions that alter tissue microenvironments.
Citation Format: James DeGregori, Catherine Pham-Danis, Andrii I Rozhok, Edward J. Evans, Fabio Marongiu, Hannah Scarborough, Curtis J. Henry. Aging, tissue ecology, and the evolution of cancer within us [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA012.
Abstract IA013: Genetic heterogeneity and tumor microenvironment in glioblastoma
Authors: Walentynowicz Kacper A. , Engelhardt Dalit , Yadav Shreya , Onubogu Ugoma , Salatino Roberto , Vincentelli Cristina , McDonald Thomas O. , Michor Franziska , Janiszewska Michalina 
Published: May 2022

Abstract
Glioblastoma (GBM), the most aggressive brain tumor, remains an unmet medical need. Despite aggressive chemotherapy, radiation and surgery, only 5.6% of patients survive beyond 5 years post-diagnosis. Targeted approaches have not been successful in this tumor type due to the extreme heterogeneity of GBM. Mosaic amplification of oncogenes suggests that multiple genetically distinct clones are present in each tumor. However, little is known about how different subpopulations of GBM cells interact with each other or with the surrounding tumor microenvironment (TME). To address this, we employed spatial protein profiling coupled with single-cell spatial maps of fluorescence in situ hybridization (FISH) for key oncogenes frequently amplified in GBM. Our analysis spanned 3-4 areas from 17 formalin-fixed paraffin-embedded (FFPE) GBM cases, 96 sub-regions of interest and total of 35,843 single nuclei. Digital spatial profiling for 79 protein markers associated with GBM biology, TME and neurobiology revealed high intra-tumor variability of vasculature, between distinct regions of the same tumor biopsy. The single-cell FISH signal quantification allowed us to classify tumors based on the relative frequency of cells harboring co-occurring of EGFR and CDK4 amplifications. Tumors with low odds ratio for EGFR and CDK4 co-amplification in a cell had a significantly higher EGFR copy number in cells harboring this amplification. Cell-to-cell variation in EGFR copy number was also much higher in these tumors, suggesting a possibility for extrachromosomal origin of this amplification. Interestingly, the tumors with high frequency of cells harboring co-amplification of EGFR and CDK4 exhibit higher infiltration by CD163+ immunosuppressive macrophages. Our results suggest that high throughput assessment of genomic alterations at the single cell level could provide a measure for predicting the immune state of GBM.
Citation Format: Kacper A. Walentynowicz, Dalit Engelhardt, Shreya Yadav, Ugoma Onubogu, Roberto Salatino, Cristina Vincentelli, Thomas O. McDonald, Franziska Michor, Michalina Janiszewska. Genetic heterogeneity and tumor microenvironment in glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA013.
Abstract IA014: Insights from comparative oncology
Authors: Maley Carlo 
Published: May 2022

Abstract
Comparative biology facilitates the exploration of the major factors that determine cancer susceptibility and resistance. We are only at the beginning of exploring the solutions that nature has found to the problem of preventing cancer, and the weaknesses that have evolved, leaving some animals exceptionally vulnerable to particular types of cancers. Some cancer defenses appear to be cell-intrinsic, such as the propensity of elephant cells to apoptose when they suffer DNA damage. Other defenses appear to depend on the environment, such as the invasion suppressive effects of fibroblasts of some species discovered by Wagner and his colleagues. I will review our early data on patterns of cancer prevalence across species and our initial results supporting Peto’s paradox but showing that contrary to our predictions, life history factors do not seem to explain patterns of cancer prevalence across species.
Citation Format: Carlo Maley. Insights from comparative oncology [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA014.
Abstract IA026: Charting genotype to phenotype maps of tumorigenesis
Authors: Curtis Christina 
Published: May 2022

Abstract
Cancers often arise from a mutated cell that undergoes premalignant clonal expansion, all the while accruing additional mutations. These somatic mutations accumulate and spread in phenotypically normal tissues prior to apparent morphological changes, with aneuploidy and driver gene mutations often preceding cancer diagnosis by years. Identifying the causes of malignant transformation requires characterization of abnormal molecular phenotypes that precede this event in a tissue-specific manner. However, repeated sampling of healthy tissue or pre-neoplasia is not practical. Critically, neither the order of somatic alterations nor the clonal dynamics that precede malignant transformation can be reliably inferred from genomic sequencing of established tumors. New approaches are therefore needed to characterize pre-neoplastic clonal evolution. Here we model this occult process via CRISPR/dCas9 engineering of human epithelial organoids, followed by multi-year experimental evolution. Through longitudinal genome sequencing, transcriptional profiling and lineage tracing, we define causal relationships between common initiating genetic lesions and resulting phenotypes. The resultant data illuminate evolutionary constraints and barriers to malignant transformation with implications for early detection and risk stratification.
Citation Format: Christina Curtis. Charting genotype to phenotype maps of tumorigenesis [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA026.
Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS
Authors: Goh Charlene E. , Bohn Bruno , Marotz Clarisse , Molinsky Rebecca , Roy Sumith , Paster Bruce J. , Chen Ching‐Yuan , Rosenbaum Michael , Yuzefpolskaya Melana , Colombo Paolo C. , Desvarieux Moïse , Papapanou Panos N. , Jacobs David R. , Knight Rob , Demmer Ryan T. 
Published: May 2022

Background

The enterosalivary nitrate–nitrite–nitric oxide (NO
3
–NO
2
–NO) pathway generates NO following oral microbiota‐mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross‐sectionally.

Methods and Results

This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO
2
, NO, or ammonia [NH
3
]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation‐to‐depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic
Z
score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic
Z
score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH
3
summary ratio was inversely associated with a −0.10 (false discovery rate
q
=0.003) lower composite cardiometabolic
Z
score in simple adjusted models. Higher NH
3
summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate
q
=0.04) higher composite cardiometabolic
Z
score.

Conclusions
Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.
Invasive Hemodynamic Predictors of Survival in Patients With Mitral Stenosis Secondary to Mitral Annular Calcification
Authors: El Sabbagh Abdallah , Nishimura Rick A. , Eleid Mackram F. , Pislaru Sorin V. , Pellikka Patricia A. , Rihal Charanjit S. , Guerrero Mayra , Hodge David O. , Miranda William R. 
Published: May 2022

Background
The aim of this study was to establish prognostic hemodynamic parameters in patients with mitral stenosis secondary to mitral annular calcification.

Methods and Results

A retrospective cohort of 105 patients undergoing transseptal catheterization for hemodynamic evaluation of mitral annular calcification–related mitral stenosis between 2004 and 2020 was studied. Mitral valve gradient (MVG) and mitral valve area (MVA; calculated by the Gorlin formula) were measured using direct left atrial and left ventricular pressures. The median age of the patients was 70.3 years (58.4–76.7 years), and 53.3% were women. The median MVA was 1.7 cm
2
(1.3–2.3 cm
2
) and MVG was 7.3 mm Hg (5.3–10.3 mm Hg); left ventricular end‐diastolic pressure was 17.6±28.3 mm Hg. During a median of 2.1 years (0.7–4.5 years), there were 63 deaths; 1‐ and 5‐year survival were 76% and 40%, respectively. There was no association between left ventricular end‐diastolic pressure and survival. After adjusting for age and comorbidities, both MVA (hazard ratio [HR], 0.50 per cm
2
; 95% CI, 0.34–0.73) and MVG (HR, 1.1 per mm Hg; 95% CI, 1.05–1.20) were independent predictors of death. Atrial fibrillation was also independently associated with mortality. When added to a combined model, MVA remained associated with death (HR, 0.51 per cm
2
; 95% CI, 0.33–0.79) while MVG was not.

Conclusions
In patients with mitral annular calcification–related mitral stenosis, survival was poor. MVA and MVG were independently associated with death, but MVA was a better predictor of outcomes.