bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PL03-02: When to intervene along the breast cancer continuum?
Authors: Hwang E. Shelley 
Published: April 2023

Abstract
Advances in epidemiology and cancer biology have clearly established that the group of diseases currently deemed “cancers” in fact encompasses many conditions with enormous variation in biologic behavior. Decades of cancer screening have preferentially diagnosed early, asymptomatic, indolent lesions. This trend will only increase as screening technologies become ever more sensitive, leading to an epidemic of overtreatment in completely asymptomatic individuals. The treatment of many of these conditions often has uncertain benefit on cancer mortality, while coming at the clear cost of treatment-related morbidity. Multi-omic testing plays a role in refining treatment recommendations based upon risk of progression. Genomic profiling of accurately annotated longitudinal case control datasets have provided insights into breast lesions termed “ductal carcinoma in situ” (DCIS), which are thought to be precursors to invasion and metastases. Both transcriptomics as well spatially resolved proteomic characterization of DCIS have uncovered novel biology of the epithelial cells that make up DCIS, as well as the heterogeneous precancer ecosystems which can be either permissive or inhibitory for invasion. Recent work has uncovered a clonal evolution pathway characterized by multiclonal invasion, and has helped to build risk stratification tools to refine treatment recommendations. In addition to molecular characterization, risk modeling may yield insights about which patients derive greatest benefit from intervention. For asymptomatic tumors at low risk of cancer progression, there may be little to no benefit to treatment, whereas for more high-risk lesions, progression to invasion and metastasis may be rapid and deadly. Given the lead-time between the development of precancer and progression to invasive disease, there may also be a case for tailoring intervention of screen detected cancer by age and the presence of competing comorbidities. The decision of whether and when to intervene for screen-detected cancers will require a multidisciplinary effort including expertise in cancer biology, mathematical modeling, psychology, health policy, decision science and communication, as well as thoughtful engagement from patients and health care providers to identify the optimal time to intervene along the cancer progression continuum.
Citation Format: E. Shelley Hwang. When to intervene along the breast cancer continuum?. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr PL03-02.
Abstract PL03-04: Forecasting pancreatic carcinogenesis through spatial multi-omics
Authors: Fertig Elana Judith 
Published: April 2023

Abstract
This talk presents a hybrid computational and experimental strategy to uncover interactions between neoplastic cells and the microenvironment during pancreatic carcinogenesis. As pancreatic cancer develops, it forms a complex microenvironment of multiple interacting cells. The microenvironment of advanced pancreatic cancer includes a dense composition of cells, such as macrophages and fibroblasts, that are associated with immunosuppression. New single-cell and spatial molecular profiling technologies enable unprecedented characterization of the cellular and molecular composition of the microenvironment. These technologies provide the potential to identify candidate therapeutics to intercept immunosuppression in pancreatic cancer. Inventing new mathematical approaches in computational biology are essential to uncover mechanistic insights from high-throughput data for these precision interception strategies. Here, we demonstrate how converging technology development, machine learning, and mathematical modeling can relate the pancreatic precancer microenvironment to carcinogenesis and therapeutic response. Combining genomics with mathematical modeling provides a forecast system that can yield computational predictions to anticipate when and how the cancer is progressing for therapeutic selection. This mathematical forecast system will empower a new predictive oncology paradigm, which selects therapeutics to intercept the pathways that would otherwise cause future cancer progression.
Citation Format: Elana Judith Fertig. Forecasting pancreatic carcinogenesis through spatial multi-omics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr PL03-04.
Abstract PL05-02: To the tumor and beyond: Tales of a holistic miRNA delivery vehicle
Authors: Kasinski Andrea L. 
Published: April 2023

Abstract
Like the challenges and skepticism that faced the antibody therapeutics field over a decade ago, RNA therapeutics is facing the same. And, like the antibody therapeutics field, we are beginning to realize the clinical impact of RNA therapeutics amiss these challenges. This is most clearly highlighted with the recent approval of mRNA vaccines to prevent against SARS-CoV-2 and the first FDA approved RNAi drugs targeted to the liver. Unfortunately, RNA-based drugs targeted to cancer cells is lagging behind, even with countless years of work that has revealed the power of using RNAi for treating oncological diseases. Lack of success in this space is attributed to inability to deliver RNAi safely and effectively. A successful delivery agent requires multiple features. First, the agent must deliver the RNA specifically to the intended cells. Second, the agent must have a large therapeutic window, meaning that toxicity, if observed, should occur at doses that are orders of magnitude higher than the therapeutic dose. Third, if delivery of the RNA is by way of a specific ligand and receptor pair, as is the case herein, the RNA must successfully escape the endosome. Simply swelling the endosome is not enough if noncovalent interactions between the ligand and the receptor cannot be disrupted. Fourth, the RNA should include appropriate stabilizing modifications to increase intracellular half-life that will reduce dosing and cost. Through hard work and dedication in this space, we have come up with an inclusive, easily synthesized, intramolecular molecule that achieves all of these essential features. Moreover, the ligand used to achieve successful delivery is also being evaluated for imaging tumors localized in the central nervous system. Here, the challenges we face, the hurdles we have overcome, and the barriers that still remain to achieve success in revealing the clinical potential of miRNA as anti-cancer therapeutics will be presented.
Citation Format: Andrea L. Kasinski. To the tumor and beyond: Tales of a holistic miRNA delivery vehicle. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr PL05-02.
Supplementary Table S2 from Chemoprevention with Cyclooxygenase and Epidermal Growth Factor Receptor Inhibitors in Familial Adenomatous Polyposis Patients: mRNA Signatures of Duodenal Neoplasia
Authors: Delker Don A. , Wood Austin C. , Snow Angela K. , Samadder N. Jewel , Samowitz Wade S. , Affolter Kajsa E. , Boucher Kenneth M. , Pappas Lisa M. , Stijleman Inge J. , Kanth Priyanka , Byrne Kathryn R. , Burt Randall W. , Bernard Philip S. , Neklason Deborah W. 
Published: April 2023

<p>Endpoint only comparisons 3.	Endpoint only comparisons (with all polyps, all 20 samples) a.	Drug normal to polyp b.	Placebo normal to polyp 4.	Endpoint only excluding polyps < 50% tumor purity a.	Drug normal to polyp b.	Placebo normal to polyp</p>
Supplementary Table S1 from Chemoprevention with Cyclooxygenase and Epidermal Growth Factor Receptor Inhibitors in Familial Adenomatous Polyposis Patients: mRNA Signatures of Duodenal Neoplasia
Authors: Delker Don A. , Wood Austin C. , Snow Angela K. , Samadder N. Jewel , Samowitz Wade S. , Affolter Kajsa E. , Boucher Kenneth M. , Pappas Lisa M. , Stijleman Inge J. , Kanth Priyanka , Byrne Kathryn R. , Burt Randall W. , Bernard Philip S. , Neklason Deborah W. 
Published: April 2023

<p>Endpoint versus baseline comparisons: List of genes differentially regulated at 1.5 fold (includes 2.0 fold). 1.	Endpoint v baseline (with all polyps) a.	Normal tab i.	Drug normal v baseline ii.	Placebo normal v baseline b.	Polyp tab i.	Drug polyp v baseline ii.	Placebo polyp v baseline 2.	Endpoint v baseline excluding polyps < 50% tumor purity a.	Polyp tab i.	Drug polyp v baseline ii.	Placebo polyp v baseline</p>
Using Neural Networks to Learn the Jet Stream Forced Response from Natural Variability
Authors: Connolly Charlotte , Barnes Elizabeth A. , Hassanzadeh Pedram , Pritchard Mike 
Published: April 2023

Abstract
Two distinct features of anthropogenic climate change, warming in the tropical upper troposphere and warming at the Arctic surface, have competing effects on the midlatitude jet stream’s latitudinal position, often referred to as a “tug-of-war.” Studies that investigate the jet’s response to these thermal forcings show that it is sensitive to model type, season, initial atmospheric conditions, and the shape and magnitude of the forcing. Much of this past work focuses on studying a simulation’s response to external manipulation. In contrast, we explore the potential to train a convolutional neural network (CNN) on internal variability alone and then use it to examine possible nonlinear responses of the jet to tropospheric thermal forcing that more closely resemble anthropogenic climate change. Our approach leverages the idea behind the fluctuation–dissipation theorem, which relates the internal variability of a system to its forced response but so far has been only used to quantify linear responses. We train a CNN on data from a long control run of the CESM dry dynamical core and show that it is able to skillfully predict the nonlinear response of the jet to sustained external forcing. The trained CNN provides a quick method for exploring the jet stream sensitivity to a wide range of tropospheric temperature tendencies and, considering that this method can likely be applied to any model with a long control run, could be useful for early-stage experiment design.
Effect of plant growth regulators DA-6 and COS on drought tolerance of pineapple through bromelain and oxidative stress
Authors: Huang XiaoKui , Rao GangShun , Peng XiaoDu , Xue YingBin , Hu HanQiao , Feng NaiJie , Zheng DianFeng 
Published: April 2023

Abstract
Background
Due to global warming, drought climates frequently occur on land, and despite being drought resistant, pineapples are still subjected to varying degrees of drought stress. Plant growth regulators can regulate the stress tolerance of plants through hormonal effects. This experiment aims to investigate the regulatory effects of different plant growth regulators on Tainong- 16 and MD-2 Pineapple when subjected to drought stress.

Results
In this experiment, we examined the regulatory effects of two different plant growth regulators, sprayed on two pineapple varieties: MD-2 Pineapple and Tainong-16. The main component of T1 was diethyl aminoethyl hexanoate (DA-6) and that of T2 is chitosan oligosaccharide (COS). An environment similar to a natural drought was simulated in the drought stress treatments. Then, pineapples at different periods were sampled and a series of indicators were measured. The experimental results showed that the drought treatments treated with T1 and T2 plant growth regulators had a decrease in malondialdehyde, an increase in bromelain and antioxidant enzyme indicators, and an increase in phenotypic and yield indicators.

Conclusion
This experiment demonstrated that DA-6 and COS can enhance the drought resistance of pineapple plants to a certain extent through bromelain and oxidative stress. Therefore, DA-6 and COS have potential applications and this experiment lays the foundation for further research.
Early symptoms preceding post-infectious irritable bowel syndrome following COVID-19: a retrospective observational study incorporating daily gastrointestinal symptoms
Authors: Yamamoto Ryo , Yamamoto Asako , Masaoka Tatsuhiro , Homma Koichiro , Matsuoka Tadashi , Takemura Ryo , Wada Michihiko , Sasaki Junichi ,   Keio Donner Project, Kanai Takanori , Amagai Masayuki , Saya Hideyuki , Nishihara Hiroshi 
Published: April 2023

Abstract
Background
Intestinal microinflammation with immune dysfunction due to severe acute respiratory syndrome coronavirus 2 reportedly precipitates post-infectious irritable bowel syndrome. This study aimed to elucidate potential risk factors for subsequent development of irritable bowel syndrome, hypothesizing that it is associated with specific symptoms or patient backgrounds.

Methods
This single-center retrospective observational study (2020–2021) included adults with confirmed coronavirus disease requiring hospital admission and was conducted using real-world data retrieved from a hospital information system. Patient characteristics and detailed gastrointestinal symptoms were obtained and compared between patients with and without coronavirus disease-induced irritable bowel syndrome. Multivariate logistic models were used to validate the risk of developing irritable bowel syndrome. Moreover, daily gastrointestinal symptoms during hospitalization were examined in patients with irritable bowel syndrome.

Results
Among the 571 eligible patients, 12 (2.1%) were diagnosed with irritable bowel syndrome following coronavirus disease. While nausea and diarrhea during hospitalization, elevated white blood cell count on admission, and intensive care unit admission were associated with the development of irritable bowel syndrome, nausea and diarrhea were identified as risk factors for its development following coronavirus disease, as revealed by the adjusted analyses (odds ratio, 4.00 [1.01–15.84] and 5.64 [1.21–26.31], respectively). Half of the patients with irritable bowel syndrome had both diarrhea and constipation until discharge, and constipation was frequently followed by diarrhea.

Conclusions
While irritable bowel syndrome was rarely diagnosed following coronavirus disease, nausea and diarrhea during hospitalization precede the early signs of irritable bowel syndrome following coronavirus disease.
Interrelationship between muscle fitness in childhood and bone mineral density in adulthood: mediation analysis of muscle fitness in adulthood
Authors: Barbosa Cynthia Correa Lopes , da Costa Julio Cesar , Romanzini Catiana Leila Possamai , Batista Mariana Biagi , Blasquez-Shigaki Gabriela , Fernandes Rômulo Araújo , Martinho Diogo V. , Oliveira Tomás , Ribeiro Luís P. , Coelho-e-Silva Manuel João , Ronque Enio Ricardo Vaz 
Published: April 2023

Abstract
Background
This study was aimed to examine the relationship between muscular fitness indicators in childhood and areal bone mineral density (aBMD) in adulthood and to verify whether the relationship is mediated by performance on muscular fitness indicators in adulthood.

Methods
A sample of 138 healthy adults (69 males; 22.3 years) were followed after a previous assessment at the age of 7–10 years. Stature, body mass and muscular fitness indicators (handgrip strength, standing long jump and sit-ups tests) were assessed in childhood and adulthood. Additionally, total body, upper limbs, lower limbs, right femoral neck and lumbar spine aBMD was assessed in adulthood using dual X-ray absorptiometry. Analysis included descriptive statistics; t-test or Mann-Whitney U-test for comparison between males and females, multiple linear regression for the prediction aBMD from muscular fitness indicators in childhood, mediation analysis of the respective muscular fitness indicators in adulthood and the relationship between muscular fitness indicators in childhood and aBMD.

Results
Males were stronger compared to females regarding muscular fitness indicators in childhood and adulthood, and presented higher mean values for aBMD in adulthood, except for lumbar spine (p < 0.05). Regression analysis revealed that some muscular fitness indicators in childhood showed significant positive relationship with bone health indicators in adulthood, such as: handgrip strength and total body aBMD (β = 0.005; R2 = 0.35; p = 0.040) and upper limbs aBMD (β = 0.005; R2 = 0.55; p = 0.019); and sit-ups test was a significant predictors of lumbar spine BMD (β = 0.003; R2 = 0.06; p = 0.039). Mediation analysis pointed out the following: adulthood handgrip strength mediated relationships between childhood handgrip strength and total aBMD (indirect effect (IE) = 0.0025; 95%CI = 0.0005–0.0048), and upper limbs aBMD (IE = 0.0040; 95%CI = 0.0017–0.0069).

Conclusions
Muscular fitness indicators in childhood showed significant relationship with bone health indicators in adulthood and the sit-ups test in childhood had direct effect on lumbar spine aBMD in adulthood. Adulthood handgrip strength mediated the relationship between childhood handgrip strength and total body and upper limb aBMD, pointing out that muscular fitness in childhood may be a aBMD determinant in adulthood, especially when higher muscle fitness performance is maintained in adulthood.
Pulmonary function in a cohort of heart-healthy individuals from Northern Sweden—a comparison with discordant reference values
Authors: Erelund Sofia , Karp Kjell , Arvidsson Sandra , Johansson Bengt , Sundström Nina , Wiklund Urban 
Published: April 2023

Abstract
Background
Dynamic spirometry is an important investigation to differentiate between impaired and normal lung function. This study aimed to evaluate the results of lung function testing in a cohort of subjects from Northern Sweden without any known heart or pulmonary disease. Our focus was to compare with two reference materials that have showed differences in the age-dependency of lung function in Swedish subjects.

Methods
The study population consisted of 285 healthy adults (148 males, 52%) between 20–90 years of age. The subjects had been randomly selected from the population register for inclusion in a study investigating cardiac function in heart-healthy subjects, but were also assessed with dynamic spirometry. At least seven percent reported smoking. Sixteen subjects presented with pulmonary functional impairments and were excluded from the current study. The sex-specific age-dependency in lung volumes was estimated using the LMS model, where non-linear equations were derived for the mean value (M), the location (L) or skewness, and the scatter (S) or coefficient of variation. This model of the observed lung function data was compared with reference values given by the original LMS model published by the Global Lung Initiative (GLI), and with the model from the recent Obstructive Lung Disease In Norrbotten (OLIN) study, where higher reference values were presented for Swedish subjects than those given by the GLI model.

Results
No differences were found in the age-dependency of pulmonary function between the LMS model developed in the study and the OLIN model. Although the study group included smokers, the original GLI reference values suggested significantly lower normal values of FEV1 (forced expiratory volume) and FVC (forced vital capacity), and consequently fewer subjects below the lower limit of normality, than both the rederived LMS and OLIN models.

Conclusions
Our results are in line with previous reports and support that the original GLI reference values underestimate pulmonary function in the adult Swedish population. This underestimation could be reduced by updating the coefficients in the underlying LMS model based on a larger cohort of Swedish citizens than was available in this study.
Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia
Authors: Tan Yue , Shan Lingling , Zhao Liping , Deng Biping , Ling Zhuojun , Zhang Yanlei , Peng Shuixiu , Xu Jinlong , Duan Jiajia , Wang Zelin , Yu Xinjian , Zheng Qinlong , Xu Xiuwen , Tian Zhenglong , Zhang Yibing , Zhang Jiecheng , Chang Alex H. , Feng Xiaoming , Pan Jing 
Published: April 2023

Abstract
Background
Donor-derived CD7-directed chimeric antigen receptor (CAR) T cells showed feasibility and early efficacy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL), in a previous phase I trial report, at a median follow-up of 6.3 months. Here we report long-term safety and activity of the therapy after a 2-year follow-up.

Methods
Participants received CD7-directed CAR T cells derived from prior stem cell transplantation (SCT) donors or from HLA-matched new donors after lymphodepletion. The target dose was 1 × 106 (± 30%) CAR T cells per kg of patient weight. The primary endpoint was safety with efficacy secondary. This report focuses on the long-term follow-up and discusses them in the context of previously reported early outcomes.

Results
Twenty participants were enrolled and received infusion with CD7 CAR T cells. After a median follow-up time of 27.0 (range, 24.0–29.3) months, the overall response rate and complete response rate were 95% (19/20 patients) and 85% (17/20 patients), respectively, and 35% (7/20) of patients proceeded to SCT. Six patients experienced disease relapse with a median time-to-relapse of 6 (range, 4.0–10.9) months, and 4 of these 6 patients were found to have lost CD7 expression on tumor cells. Progression-free survival (PFS) and overall survival (OS) rates 24 months after treatment were respectively 36.8% (95% CI, 13.8–59.8%) and 42.3% (95% CI, 18.8–65.8%), with median PFS and OS of respectively 11.0 (95% CI, 6.7–12.5) months and 18.3 (95% CI, 12.5–20.8) months. Previously reported short-term adverse events (< 30 days after treatment) included grade 3–4 cytokine release syndrome (CRS; 10%) and grade 1–2 graft-versus-host disease (GVHD; 60%). Serious adverse events reported > 30 days after treatment included five infections and one grade 4 intestinal GVHD. Despite good CD7 CAR T-cell persistence, non-CAR T and natural killer cells were predominantly CD7-negative and eventually returned to normal levels in about half of the participants.

Conclusions
In this 2-year follow-up analysis, donor-derived CD7 CAR T-cell treatment demonstrated durable efficacy in a subset of patients with r/r T-ALL. Disease relapse was the main cause of treatment failure, and severe infection was a noteworthy late-onset adverse event.

Trial registration

ChiCTR2000034762.
Nonnegative nontrivial solutions for a class of $p(x)$-Kirchhoff equation involving concave-convex nonlinearities
Authors: Chu Changmu , He Zhongju 
Published: April 2023

AbstractIn this paper, we study the existence of a class of $p(x)$
p
(
x
)
-Kirchhoff equation involving concave-convex nonlinearities. The main tools used are the perturbation technique, variational method, and a priori estimation.