bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic rate and osmoregulation in desert spring amphipods
Authors: Burns McKenna P.A. , Schaeffer Paul J. , Berg David J. 
Published: November 2022

Desert springs contain many endemic taxa and are of conservation concern due to anthropogenic activities that are expected to increase environmental salinity. Understanding the nature of osmoregulation is necessary to predict how non-vagile aquatic organisms will respond to changes. In the Chihuahuan Desert, the amphipod genus Gammarus Fabricius, 1775 is composed of two lineages. These lineages have species that currently inhabit springs ranging from 0.4 to 7.8 parts per thousand (ppt). All Gammarus in this region are of conservation concern because each is endemic to a single spring system. We exposed individuals of Gammarus colei Walters, Cannizzaro, and Berg in Walters, Cannizzaro, Trujillo and Berg, 2020 and Gammarus seideli Cannizzaro, Walters and Berg, 2018 species occupying low-salinity springs, to the range of salinities found in the Chihuahuan Desert. We measured metabolic rates as [Formula: see text] to examine the energetic cost of osmoregulation. We also measured the hemolymph osmolality of G. colei and compared that with the isosmotic line to determine the degree of osmoregulation. Neither species increased its metabolic rate across increasing salinities. However, G. colei showed an increase in hemolymph osmolality. Despite the divergence (∼66 million years ago) between the two lineages, it appears their physiological tolerances have converged, suggesting that both lineages may be able to persist when exposed to moderate salinity changes.
$$\varLambda (1405)$$ mediated triangle singularity in the $$K^-d\rightarrow p\varSigma ^-$$ reaction
Authors: Feijoo A. , Molina R. , Dai L. R. , Oset Eulogio 
Published: November 2022

AbstractWe study for the first time the $$p\varSigma ^-\rightarrow K^-d$$

p

Σ
-

→

K
-

d

and $$K^-d\rightarrow p\varSigma ^-$$

K
-

d
→
p

Σ
-

reactions close to threshold and show that they are driven by a triangle mechanism, with the $$\varLambda (1405)$$

Λ
(
1405
)

, a proton and a neutron as intermediate states, which develops a triangle singularity close to the $${\bar{K}}d$$

K

¯

d

threshold. We find that a mechanism involving virtual pion exchange and the $$K^-p\rightarrow \pi ^+\varSigma ^-$$

K
-

p
→

π
+

Σ
-

amplitude dominates over another one involving kaon exchange and the $$K^-p\rightarrow K^-p$$

K
-

p
→

K
-

p

amplitude. Moreover, of the two $$\varLambda (1405)$$

Λ
(
1405
)

states, the one with higher mass around 1420 MeV, gives the largest contribution to the process. We show that the cross section, well within measurable range, is very sensitive to different models that, while reproducing $${\bar{K}}N$$

K

¯

N

observables above threshold, provide different extrapolations of the $${\bar{K}}N$$

K

¯

N

amplitudes below threshold. The observables of this reaction will provide new constraints on the theoretical models, leading to more reliable extrapolations of the $${\bar{K}}N$$

K

¯

N

amplitudes below threshold and to more accurate predictions of the $$\varLambda (1405)$$

Λ
(
1405
)

state of lower mass.
Higgs-boson visible and invisible constraints on hidden sectors
Authors: Biekötter Thomas , Pierre Mathias 
Published: November 2022

AbstractWe investigate the impact of interactions between hidden sectors and the discovered Higgs boson $$h_{125}$$

h
125

, allowing for additional invisible decay channels of $$h_{125}$$

h
125

. We perform $$\chi ^2$$

χ
2

-fits to the measurements of the Higgs-boson cross sections as a function of the invisible branching ratio and different combinations of coupling modifiers, where the latter quantify modifications of the couplings of $$h_{125}$$

h
125

compared to the predictions of the Standard Model. We present generic results in terms of exclusion limits on the coupling modifiers and the invisible branching ratio of $$h_{125}$$

h
125

. Additionally, we apply our results to a variety of concrete model realizations containing a hidden sector: dark matter within Higgs- and singlet-portal scenarios, models featuring (pseudo) Nambu–Goldstone bosons and two Higgs doublet extensions. One of the main conclusions of our work is that in a wide class of models the indirect constraints resulting from the measurements of the cross sections of $$h_{125}$$

h
125

provide substantially stronger constraints on the invisible Higgs-boson branching ratio compared to the direct limits obtained from searches for the invisible decay of $$h_{125}$$

h
125

. However, we demonstrate that the presence of an invisible decay mode of $$h_{125}$$

h
125

can also open up parameter space regions which otherwise would be excluded as a result of the indirect constraints. As a byproduct of our analysis, we show that in light of the new results from the LZ collaboration a fermionic DM candidate within the simplest Higgs-portal scenario is ruled out under standard assumptions.
Taphonomy of bivalve skeletal remains as a means of detecting changes in oxygen depletion and recognizing ancient upwelling environments
Authors: Edelman-Furstenberg Yael 
Published: November 2022

Abstract
Bivalve shells from shelf and slope environments of the Benguela upwelling system were examined for their state of preservation for the first time, and were used to test whether their preservation is a proxy for spatially variable seafloor taphonomic conditions that lead to different degrees of time averaging. Distinctive shell damage-profiles show increasing shell damage further from the centre of the upwelling cells affected by anoxic conditions (opal and organic-rich) and towards the carbonate- and phosphate-rich facies (with slower sedimentation rates at the margins of the cells. Discrete taphofacies range from a very low damage profile (opal and organic-rich, facies 1) to very high damage (phosphate, facies 3), with elevated numbers of rounded, fragmented and bored shells as well as very little associated sedimentary matrix. This gradient in taphofacies is associated with a gradient from census assemblages with low damage to (within-habitat time-averaged) assemblages in carbonate and (environmentally-condensed) phosphate facies of moderate and higher species richness that are associated with increasing time averaging. This pattern follows the upwelling facies gradient of high opal and organic matter in areas of most intense upwelling cells and outward to aerated but food-abundant carbonate-rich seafloors and spatially coexisting phosphorite-rich concentrations. Thus, the taphonomic gradient ranges from stressful, oxygen-depleted seafloor environment under upwelling regimes that limit metazoan predators and borers (and thus minimize destruction), to well-oxygenated seafloors with increased predators and micro-boring animals that all foster post-mortem shell destruction. The rarity of encrusters is a conspicuous feature of these facies across the whole gradient that may reflect temporary recurrence of oxygen-depleting conditions even at the carbonatic and phosphatic facies. The state of preservation of these shells can serve as a modern analogue for identifying similar settings in the geological record but also for Anthropocene settings affected by eutrophication and expanding oxygen minimum zones. Molluscan taphofacies with unusually low levels of skeletal damage from borers and encrusters can thus represent sensitive proxies of conditions affected by Anthropocene deoxygenation and eutrophication.
Truncal Dynamics May Trump: Serial ctDNA to Predict Early Therapeutic Response
Authors: Eluri Madhulika , Kopetz Scott , Parseghian Christine M. 
Published: November 2022

Summary
Promising utility of using serial ctDNA in metastatic colorectal cancer to both refine patient selection, reduce toxicity due to chemotherapy, and to evaluate emerging resistance mechanisms may lead the way to novel therapeutic strategies. However, important questions remain in validating its use as a predictive biomarker of treatment response.
See related article by Vidal et al., p. 379
Abstract A024: Prognostic effects of different TP53 mutations in pancreatic ductal adenocarcinoma
Authors: Arbelaez Carlos M. Mejia , Shan Xining , Robert Tseng , Robert Marie E. , Ma Xiaomei , Escobar-Hoyos Luisa F. 
Published: November 2022

Abstract
Approximately, 70% of pancreatic ductal adenocarcinomas (PDACs) have mutations in the TP53 gene; however, it is still unknown if gain- or loss- of function mutations in TP53 provide differential prognostic value to guide therapy. To fill this gap, we assessed the potential effect of wild-type, missense (gain-of-function) and truncating (loss-of-function) TP53 mutations in patient survival, in two independent clinical cohorts (The Cancer Genome Atlas cohort=141, and the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets cohort=376 PDACs). We employed multivariable Cox proportional hazards regression models adjusting for patient demographic (age at diagnosis, sex, race/ethnicity) and tumor characteristics (presence of distant metastasis at diagnosis). Additionally, we conducted stratified analyses by the status of “druggable” (DNA repair gene mutations) and other driver mutations (SMAD4 and CDKN2A genes). We found that PDACs with missense TP53 mutations were associated with a worse patient survival compared to tumors with wild-typeTP53 (HR = 1.47, 95% CI: 1.00-2.17; p=0.051). Similarly, patients with truncating mutations in TP53 had a trend to worse OS (HR=1.11, 95% CI, 0.70-1.76; p=0.654) compared to patients with wild-type TP53, however, these associations were not significant. Furthermore, we found that mutations in DNA repair genes, SMAD4 and CDKN2A genes did not show any prognostic value. Our findings suggest that molecular characterization of specific TP53 mutations may help to determine differences in patient prognosis and potentially guide future clinical management of patients.
Citation Format: Carlos M. Mejia Arbelaez, Xining Shan, Tseng Robert, Marie E. Robert, Xiaomei Ma, Luisa F. Escobar-Hoyos. Prognostic effects of different TP53 mutations in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A024.
Abstract A027: Validation of an early-stage pancreatic cancer classification model using 5-Hydroxymethylation profiles in plasma-derived cell-free DNA
Authors: Bergamaschi Anna , Haan David , Collins Micah , Guler Gulfem , Peters Melissa , Gigliotti Lauren , Chowdhury Shimul , Volkmuth Wayne , Levy Samuel 
Published: November 2022

Abstract
Background: Pancreatic cancer outcomes are poor, mostly due to the detection of cancer at late stages. Early-detection enables prompt initiation of treatment and has been reported to significantly improve outcomes. We have developed a novel sequencing-based epigenomics technology for cancer early-detection that enriches 5-hydroxymethylcytosine (5hmC) loci in cell-free DNA (cfDNA), and via machine learning algorithms, enables the detection of pancreatic cancer. Method: Whole-blood was obtained from a training cohort of 660 individuals (consisting of 132 pancreatic cancers (PaCa) and 528 non-cancers) and a validation cohort of 593 individuals (consisting of 86 PaCa and 507 non-cancers). cfDNA was isolated from plasma and 5hmC and whole-genome libraries were sequenced. Logistic regression algorithms were employed using 5hmC feature sets combined with physical characteristics to optimally partition cancers from non-cancers. Results: We trained and cross-validated a binomial logistic-regression model on PaCa and non-cancer samples. Cross validation of the training model yielded an overall sensitivity of 65.9%, early-stage (stage I-II) sensitivity of 57.1% and a specificity of 98%. The model was further validated on an independent set and yielded an overall sensitivity of 64%, early-stage sensitivity of 64.7% and a specificity of 98%. Conclusion: Our results demonstrate that plasma-derived cfDNA 5hmC profiles enable the detection of PaCa in early-stage disease providing a valuable tool especially for those individuals at high risk. A larger clinical study (NODMED: NCT05188586) is underway to validate the test in a high-risk population that would most benefit from early-detection.
Citation Format: Anna Bergamaschi, David Haan, Micah Collins, Gulfem Guler, Melissa Peters, Lauren Gigliotti, Shimul Chowdhury, Wayne Volkmuth, Samuel Levy. Validation of an early-stage pancreatic cancer classification model using 5-Hydroxymethylation profiles in plasma-derived cell-free DNA [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A027.
Abstract A041: Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for monitoring disease burden in patients with pancreatic cancer
Authors: Halder Kuntal , Jameson Gayle , Borazanci Erkut , Vrana Amber , Cridebring Derek , Von Hoff Daniel , Han Haiyong 
Published: November 2022

Abstract
Pancreatic cancer is a highly lethal disease that is often diagnosed at a late stage, when it has metastasized to other organs. Several therapeutic options have been shown to be effective at significantly shrinking the tumor and improving survival. Unfortunately, very few of these treatments lead to the total disappearance of tumor and therefore require changes to the treatment strategy. One of the challenges is rapidly identifying if a treatment works or when it stops working so patients can be switched to another regimen. Currently, the best blood-based marker for tracking disease burden in patients with pancreatic cancer is CA19-9. Unfortunately, 15-20% of pancreatic cancer patients do not have elevated levels of this marker with a disproportionate number of non-CA19-9 elevated cases being African American and Hispanic patients. In addition, changes in this marker do not always correlate with disease burden since there are other factors that can change CA19-9 levels. In this study, we have identified two blood extracellular vesicle (EV) based protein markers THBS2 (Thrombospondin 2) and ALPPL2 (Alkaline phosphatase, placental-like 2) that aid in monitoring pancreatic cancer disease burden in both CA19-9 secretors and non-secretors. We found that the number of THBS2+ or ALPPL2+ EVs was significantly higher in serum samples from patients with pancreatic cancer than those from healthy controls. The level of THBS2+ or ALPPL2+ EVs in patients with pancreatic cancer correlated with a patient's response to treatment. In patients who have elevated CA19-9, the level of THBS2+ or ALPPL2+ EVs correlates with the changes in CA19-9 upon treatment. In CA19-9 negative patients, the level of THBS2+ EVs or ALPPL2+ EVs correlates with the tumor size changes (RECIST response) upon treatment. Hence, EVs containing THBS2 or ALPPL2 can potentially serve as additional and more informative biomarkers for monitoring disease burden in patients with pancreatic cancer regardless of their CA19-9 status. This work was supported by the Flinn Foundation and the HonorHealth Research Institute).
Citation Format: Kuntal Halder, Gayle Jameson, Erkut Borazanci, Amber Vrana, Derek Cridebring, Daniel Von Hoff, Haiyong Han. Extracellular vesicle based ALPPL2 and THBS2 as biomarkers for monitoring disease burden in patients with pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A041.
Abstract A074: Developing a novel in vivo model of pancreatic ductal adenocarcinoma using primary tumor samples and humanised mouse models
Authors: Fulton Alexander J. P. , Saeb-Parsy Kourosh , Basu Bristi 
Published: November 2022

Abstract
Pancreatic cancer (PDAC) remains one of the most lethal malignancies due to its late diagnosis and poor response to treatment. Preclinical models reflecting the uniquely complex structure of PDAC cells and the surrounding tumor microenvironment (TME) are required to ensure translational results. PDAC organoids, ex vivo 3D models of primary tumor cells, form an exciting preclinical model that reflects the complexity of PDAC. Tumor organoids co-cultured with stromal and immune cells have been previously explored in vitro but have thus far remained limited in any in vivo capacity. We therefore aimed to establish and characterize in vitro co-cultured PDAC organoids using primary human PDAC tumor samples plus autologous peripheral or splenic lymphocytes. Subsequent preliminary in vivo models have been established by engrafting co-cultured PDAC organoids and PDAC cancer associated fibroblasts into immunocompromised mice. The pilot data assessed retention, growth kinetics and metastatic potential and will subsequently form the foundation for comparable experiments using autologous humanized mouse models. This humanized mouse model, consisting of autologous human malignant, stromal and immune compartments, will add to the existing repertoire of preclinical models by more closely representing the entire tumor volume. In vitro and in vivo data compared to other preclinical models. Additional preliminary therapeutic response data may provide translational value and warrant further evaluation.
Citation Format: Alexander J. P. Fulton, Kourosh Saeb-Parsy, Bristi Basu. Developing a novel in vivo model of pancreatic ductal adenocarcinoma using primary tumor samples and humanised mouse models [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A074.
Abstract A078: Inhibition of precancerous transformation via drug-induced p53 activation
Authors: Twardowski Jennifer J. , Heist Thomas I. , Mello Stephano S. 
Published: November 2022

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer deaths in the US and has a 5-year survival rate of less than 10%. This low survival rate is largely due to low rates of early detection and the lack of treatments capable of inhibiting disease progression. Risk factors for PDAC include smoking, alcohol abuse, and pancreatitis. Pancreatic injury associated with pancreatitis is characterized by inflammation, fibrosis, and acinar cell death. Surviving acinar cells undergo acinar-to-ductal metaplasia (ADM), a regenerative process in which cells dedifferentiate, proliferate, and then redifferentiate into acinar cells. Recurrent pancreatic injury can sustain ADM and preclude redifferentiation, resulting in exocrine insufficiency and the formation of precursor lesions known as pancreatic intraepithelial neoplasia (PanIN). PanIN lesions harbor activating mutations in the MAP kinase pathway protein Kras, and can transform into PDAC after acquiring inactivating mutations in tumor suppressor p53. The lack of treatment options for pancreatitis patients reinforces the need for strategies that could resolve pancreatic damage and stop disease progression. Towards this end, we have recently shown that drug-induced activation of p53 in mouse models of pancreatitis preserves acinar cells, reduces the proliferation of PanIN lesions, and lowers levels of MAP kinase phosphorylation. We have also observed p53 activation during embryonic development of the pancreas, specifically in exocrine progenitor cells that commit to the acinar fate, suggesting a novel role of p53 in pancreatic differentiation. Based on our findings, we hypothesize that p53 activation can signal for the differentiation of acinar cells, and restrain PanIN proliferation through the suppression of MAP kinase signaling. Our studies will define the role of p53 in pancreatic differentiation and the potential of pharmacological p53 activation for the treatment for pancreatitis and prevention of PDAC.
Citation Format: Jennifer J. Twardowski, Thomas I. Heist, Stephano S. Mello. Inhibition of precancerous transformation via drug-induced p53 activation [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A078.
Abstract B008: Lipocalin-2 expression modulates ferroptosis in pancreatic ductal adenocarcinoma
Authors: Grisanti Valentina Pita , Dangel Andrew W. , Pietrzak Maciej , Hite Amy , Cruz-Monserrate Zobeida 
Published: November 2022

Abstract
Background: Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the US. Lipocalin 2 (LCN2) is upregulated in PDAC patients and promotes inflammation and tumor growth. LCN2 regulates iron levels, which are dysregulated in tumors as cancer cells uptake increased iron to support growth. High iron levels can lead to ferroptosis, an iron-catalyzed form of cell death that relies on the oxidation of poly-unsaturated fatty acids (PUFAs). Ferroptosis is usually inhibited in cancer to prevent cell death and promote tumor growth. Therefore, LCN2 expression might influence ferroptosis outcomes in PDAC. Objective: To determine whether LCN2 inhibits ferroptosis and whether modulating LCN2 levels and other targets can be leveraged as treatments to induce ferroptosis in PDAC. Methods: Lcn2 expression was deleted via CRISPR in a mouse PDAC cell line (mKPC) to generate control Lcn2+/+ and Lcn2-/- mKPC cells. Gene expression changes were analyzed with RNA sequencing. Human and mouse PDAC cells were treated with a ferroptosis inducer, LCN2 blockade, and various PUFAs. Treatment effects on cell proliferation and lipid peroxidation were measured via 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay and BODIPY 581/591 C11 staining respectively. Gene expression of ferroptosis markers (SLC7A11, GPX4, and SLC11A2) and LCN2 were measured via RT-qPCR. Results: Deletion of Lcn2 in mKPC cells significantly decreased the expression of genes involved in ferroptosis-inhibiting antioxidant synthesis. Ferroptosis induction upregulated Lcn2 expression in PDAC cells and decreased the viability of mKPC Lcn2-/- and human PDAC cells, but not mKPC Lcn2+/+ or human pancreatic duct epithelial cells. LCN2 blockade treatment to PDAC cells modulated the expression SLC7A11, GPX4, and SLC11A2, key enablers and inhibitors of the ferroptosis antioxidant pathway. Conclusions: Ferroptosis decreases proliferation of PDAC cells, which might be mediated by LCN2 expression. LCN2 modulation has potential to induce ferroptosis and delay PDAC growth. Future studies will determine whether a combination approach with LCN2 modulation could induce ferroptosis in PDAC. Acknowledgments: This research is supported by the OSU Pelotonia Fellowship Program and the NCI R01CA223204.
Citation Format: Valentina Pita Grisanti, Andrew W. Dangel, Maciej Pietrzak, Amy Hite, Zobeida Cruz-Monserrate. Lipocalin-2 expression modulates ferroptosis in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B008.
Abstract B027: Three-dimensional genomic analysis of human pancreatic intraepithelial neoplasia (PanIN) reveals striking multifocality and genetic heterogeneity
Authors: Braxton Alicia M. , Kiemen Ashley , Karchin Rachel , Jiao Yuchen , Wu Pei-Hsun , Hruban Ralph H , Wirtz Denis , Wood Laura D. 
Published: November 2022

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Short Talks from Proffered Abstracts section (PR007) of the Conference Proceedings.
Citation Format: Alicia M. Braxton, Ashley Kiemen, Rachel Karchin, Yuchen Jiao, Pei-Hsun Wu, Ralph H Hruban, Denis Wirtz, Laura D. Wood. Three-dimensional genomic analysis of human pancreatic intraepithelial neoplasia (PanIN) reveals striking multifocality and genetic heterogeneity [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B027.