bluuebunny/crossref_metadata_2025_split huggingface dataset:
From dome to duplex: Convergent gravitational collapse explains coeval intracratonic doming and nappe tectonics, central Australia
Authors: Ibrahim Youseph , Rey Patrice F. , Whitney Donna L. , Teyssier Christian , Roger Françoise , Bosse Valérie , Cenki Bénédicte 
Published: January 2024

Abstract
In central Australia, an apparently coeval gneiss dome (Entia Dome) developed adjacent to a thrust belt (Arltunga Nappe Complex) within an intracratonic setting. Here we employ a combination of fieldwork, geochronology, and numerical modeling to investigate the structure and tectonic evolution of these features. We present a structural model linking an extensional domain comprising the Entia Dome, across a transitional zone containing the Bruna décollement zone and the Illogwa shear zone, into a contractional zone comprising thrusts and duplexes of the Arltunga Nappe Complex. Supported by numerical modeling, we propose a tectonic model in which the dome and nappe complex formed synchronously because of the convergent gravitational collapse of the 30–40-km-deep Paleozoic Harts Range rift.
Supplemental Material: Structure and provenance of the Cretaceous Pingshanhu Basin in the Hexi Corridor: Implications for Mesozoic tectonics in the northern Tibetan Plateau
Authors: Wu Chen , al. et 
Published: January 2024

<p>Table S1: Detailed results of detrital zircon U-Pb analyses for sandstone samples from Pingshanhu Basin. Table S2: Summary of geochronology results for magmatic rocks in the Qilian Shan and the Alxa block. </p>
Doxapram for apnoea of prematurity and neurodevelopmental outcomes at age 5–6 years
Authors: Tréluyer Ludovic , Zana-Taieb Elodie , Jarreau Pierre-Henri , Benhammou Valérie , Kuhn Pierre , Letouzey Mathilde , Marchand-Martin Laetitia , Onland Wes , Pierrat Véronique , Saade Lauren , Ancel Pierre Yves , Torchin Héloïse 
Published: January 2024

ObjectiveTo assess the long-term neurodevelopmental impact of doxapram for treating apnoea of prematurity.DesignSecondary analysis of the French national cohort study EPIPAGE-2. Recruitment took place in 2011. A standardised neurodevelopmental assessment was performed at age 5–6 years. A 2:1 propensity score matching was used to control for the non-randomised assignment of doxapram treatment.SettingPopulation-based cohort study.PatientsAll children born before 32 weeks’ gestation alive at age 5–6 years.InterventionsBlind and standardised assessment by trained neuropsychologists and paediatricians at age 5–6 years.Main outcome measuresNeurodevelopmental outcomes at age 5–6 years assessed by trained paediatricians and neuropsychologists: cerebral palsy, developmental coordination disorders, IQ and behavioural difficulties. A composite criterion for overall neurodevelopmental disabilities was built.ResultsThe population consisted of 2950 children; 275 (8.6%) received doxapram. Median (IQR) gestational age was 29.4 (27.6–30.9) weeks. At age 5–6 years, complete neurodevelopmental assessment was available for 60.3% (1780 of 2950) of children and partial assessment for 10.6% (314 of 2950). In the initial sample, children receiving doxapram had evidence of greater clinical severity than those not treated. Doxapram treatment was associated with overall neurodevelopmental disabilities of any severity (OR 1.43, 95% CI 1.07 to 1.92, p=0.02). Eight hundred and twenty-one children were included in the 2:1 matched sample. In this sample, perinatal characteristics of both groups were similar and doxapram treatment was not associated with overall neurodevelopmental disabilities (OR 1.09, 95% CI 0.76 to 1.57, p=0.63).ConclusionsIn children born before 32 weeks’ gestation, doxapram treatment for apnoea of prematurity was not associated with neurodevelopmental disabilities.
Impact of socioeconomic status on presentation, care quality and outcomes of patients attended by emergency medical services for dyspnoea: a population-based cohort study
Authors: Zhou Jennifer , Nehme Emily , Dawson Luke , Bloom Jason , Smallwood Natasha , Okyere Daniel , Cox Shelley , Anderson David , Smith Karen , Stub Dion , Nehme Ziad , Kaye David 
Published: January 2024

BackgroundLow socioeconomic status (SES) has been linked to poor outcomes in many conditions. It is unknown whether these disparities extend to individuals presenting with dyspnoea. We aimed to evaluate the relationship between SES and incidence, care quality and outcomes among patients attended by emergency medical services (EMS) for dyspnoea.MethodsThis population-based cohort study included consecutive patients attended by EMS for dyspnoea between 1 January 2015 and 30 June 2019 in Victoria, Australia. Data were obtained from individually linked ambulance, hospital and mortality datasets. Patients were stratified into SES quintiles using a composite census-derived index.ResultsA total of 262 412 patients were included. There was a stepwise increase in the age-adjusted incidence of EMS attendance for dyspnoea with increasing socioeconomic disadvantage (lowest SES quintile 2269 versus highest quintile 889 per 100 000 person years, ptrend<0.001). Patients of lower SES were younger and more comorbid, more likely to be from regional Victoria or of Aboriginal or Torres Strait Islander heritage and had higher rates of respiratory distress. Despite this, lower SES groups were less frequently assigned a high acuity EMS transport or emergency department (ED) triage category and less frequently transported to tertiary centres or hospitals with intensive care unit facilities. In multivariable models, lower SES was independently associated with lower acuity EMS and ED triage, ED length of stay>4 hours and increased 30-day EMS reattendance and mortality.ConclusionLower SES was associated with a higher incidence of EMS attendances for dyspnoea and disparities in several metrics of care and clinical outcomes.
Predictors of good outcomes and mortality after thrombectomy for basilar artery occlusion within 12 hours of onset
Authors: Su Junfeng , Hu Xiaohui , Chen Li , Li Rui , Tao Chunrong , Yin Yamei , Liu Huanhuan , Tan Xianhong , Hou Siyang , Xie Sanpin , Huo Longwen , Zhu Yuyou , Gong Daokai , Hu Wei 
Published: January 2024

BackgroundPatients with acute basilar artery occlusion (ABAO) who undergo combined standard medical treatment (SMT) and endovascular thrombectomy (EVT) may still have unsatisfactory outcomes. This study was conducted to identify the factors that may impact their outcomes.MethodsWe retrospectively reviewed the data of all patients with ABAO combined with SMT and EVT in the endovascular treatment for acute basilar artery occlusion (ATTENTION) trial. A good outcome is defined as a modified Rankin Scale (mRS) score of 0–3, a poor outcome as mRS score of 4–6, and mortality as death at 90-day follow-up. The study analyzed various factors influencing the patients’ good outcomes and mortality.ResultsThe study included 221 patients (148 men and 73 women). Among these patients, 45.7% achieved an mRS score of 0–3, while the overall mortality rate was 37.1% (82/221). A good outcome was significantly associated with younger age (adjusted OR 0.96; 95% CI 0.93 to 0.99; P=0.019), a baseline posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) of 8–10 (adjusted OR 2.34; 95% CI 1.07 to 5.12; P=0.034), and post-procedure pc-ASPECTS of 8–10 (adjusted OR 1.40; 95% CI 1.07 to 1.84; P=0.013). Additionally, time from puncture to reperfusion (adjusted OR 2.02; 95% CI 1.2 to 3.41; P=0.008) and intracranial hemorrhage (adjusted OR 3.59; 95% CI 1.09 to 11.8; P=0.035) were associated with 90-day mortality.ConclusionsYounger age, baseline pc-ASPECTS of 8–10, and higher post-procedure pc-ASPECTS could effectively predict good outcomes for patients with ABAO undergoing EVT. Additionally, a prolonged time from puncture to reperfusion and intracranial hemorrhage can independently predict mortality.Trial registration numberNCT04751708.
A shadow study for a static dyonic black hole with a global monopole surrounded by perfect fluid
Authors: Aslam M. Israr , Saleem Rabia 
Published: January 2024

AbstractIn this paper, we mainly study the shadow and observable features of a dyonic black hole (DBH) with a global monopole surrounded by perfect fluid under various profiles of accretions. We investigate the influence of model parameters on the observational signatures and space-time structure of black holes (BHs). We observe that the value of $$b_{ps}$$

b

ps

increases with the increasing values of $$\alpha $$
α
and $$\eta $$
η
, while it decreases with the increasing values of the electromagnetic parameter. We found that the corresponding regions and the observed specific intensities of the direct, lensing and photon ring emissions dramatically changed according to the variation of BH state parameters. It is noticed that the total observed flux is dominated by the direct emission and the lensing ring makes a small contribution while the photon ring makes a negligible contribution due to its exponential narrowness, even the photon ring intersects the thin plane more than three times to pick up a larger intensity. Assuming the spherically symmetric accretion disk, it is found that due to the Doppler effect of infalling motion, shadows of infalling accretion are found to be darker as compared to static ones. However, the size and position of the DBH shadows do not change in both cases, implying that the BH’s shadow size depends on the geometric space-time and the shadow’s luminosities rely on the accretion flow models. Finally, the discussion is done analytically and numerically, and ray-tracing methods are adopted to obtain the proper visualizations.
Interaction between Continuous Pack-Years Smoked and Polygenic Risk Score on Lung Cancer Risk: Prospective Results from the Framingham Heart Study
Authors: Duncan Meredith S. , Diaz-Zabala Hector , Jaworski James , Tindle Hilary A. , Greevy Robert A. , Lipworth Loren , Hung Rayjean J. , Freiberg Matthew S. , Aldrich Melinda C. 
Published: January 2024

Abstract

Background:
Lung cancer risk attributable to smoking is dose dependent, yet few studies examining a polygenic risk score (PRS) by smoking interaction have included comprehensive lifetime pack-years smoked.

Methods:
We analyzed data from participants of European ancestry in the Framingham Heart Study Original (n = 454) and Offspring (n = 2,470) cohorts enrolled in 1954 and 1971, respectively, and followed through 2018. We built a PRS for lung cancer using participant genotyping data and genome-wide association study summary statistics from a recent study in the OncoArray Consortium. We used Cox proportional hazards regression models to assess risk and the interaction between pack-years smoked and genetic risk for lung cancer adjusting for European ancestry, age, sex, and education.

Results:
We observed a significant submultiplicative interaction between pack-years and PRS on lung cancer risk (P = 0.09). Thus, the relative risk associated with each additional 10 pack-years smoked decreased with increasing genetic risk (HR = 1.56 at one SD below mean PRS, HR = 1.48 at mean PRS, and HR = 1.40 at one SD above mean PRS). Similarly, lung cancer risk per SD increase in the PRS was highest among those who had never smoked (HR = 1.55) and decreased with heavier smoking (HR = 1.32 at 30 pack-years).

Conclusions:
These results suggest the presence of a submultiplicative interaction between pack-years and genetics on lung cancer risk, consistent with recent findings. Both smoking and genetics were significantly associated with lung cancer risk.

Impact:
These results underscore the contributions of genetics and smoking on lung cancer risk and highlight the negative impact of continued smoking regardless of genetic risk.
Abstract A054: PP2A activation alters macropinosome processing in pancreatic cancer cells leading to metabolic stress and cancer cell death
Authors: Baral Garima , Pfeffer Claire M. , Doraivel Indiraa , Allen-Petersen Brittany L. 
Published: January 2024

Abstract
The majority of pancreatic ductal adenocarcinoma (PDAC) patients present with late-stage, metastatic disease that is often resistant to therapeutics, resulting in the lowest survival rate of all major cancers. Metabolic rewiring in response to oncogenic signals plays a critical role in PDAC cell survival, tumor growth, and metastasis. In contrast to normal epithelial cells, these metabolic alterations make PDAC tumors dependent on glutamine for survival, highlighting a unique metabolic vulnerability that can be therapeutically exploited. However, during times of nutrient stress, PDAC cells can circumvent this vulnerability by engulfing extracellular fluids to replenish amino acids, including glutamine, in a process called, macropinocytosis. Macropinocytosis occurs downstream of oncogenic KRAS, a small GTPase that is almost universally mutated in PDAC patients. The inhibition of macropinocytosis in vivo reduces PDAC tumor growth, underscoring the importance of this pathway to cancer cell survival. However, the signaling mechanisms that regulate this process and the contribution of macropinocytic signaling to aggressive cancer phenotypes remains poorly understood. Protein phosphatase 2A (PP2A) is a heterotrimeric complex that regulates a wide variety of cell signaling pathways, including KRAS, and is commonly deregulated in human PDAC tumors. Recently, PP2A has been implicated as an important regulator of macropinocytosis, but the mechanism by which this occurs is unknown. We demonstrate that the genetic loss of the specific PP2A subunit, B56a, accelerates the formation of KRAS-driven pancreatic lesions in an in vivo mouse model, implicating this subunit as a critical negative regulator of KRAS phenotypes during PDAC progression. Here, we show that acute PP2A-B56a activation prevents the fusion of macropinosomes with lysosomes, robbing PDAC cells of critical metabolic nutrients and driving cell death. Consistent with these findings, PP2A activation also reduces glutamine levels and suppresses oxidative phosphorylation. Finally, we determined that PP2A activating compounds can function synergistically with metabolic inhibitors, supporting a new therapeutic strategy in this aggressive and deadly cancer. Together, our results implicate PP2A as a critical suppressor of PDAC metabolic plasticity and highlight the use of PP2A activating compounds to prevent PDAC nutrient scavenging.
Citation Format: Garima Baral, Claire M. Pfeffer, Indiraa Doraivel, Brittany L. Allen-Petersen. PP2A activation alters macropinosome processing in pancreatic cancer cells leading to metabolic stress and cancer cell death [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A054.
Abstract A094: LIN28B/HMGA2 axis accelerates PDA by promoting oncogenic protein synthesis
Authors: Dobersch Stephanie , Cavendar Sarah , Yamamoto Naomi , Boila Liberales Debraj , Wladyka Cindy , Roudier Martine , Notta Faiyaz , Eisenman Robert , Hsieh Andrew , Kugel Sita 
Published: January 2024

Abstract
Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is projected to be the second leading cause of cancer deaths in the United States by 2030. Molecular characterization studies have described two major transcriptional subsets, called 'classical’ and ‘basal’. Basal PDAs (~25% of PDAs) have the worst overall survival and are the only class to act as an independent poor prognostic factor. The imminent entry of KRAS inhibitors into the clinic to treat PDA is poised to change this, but genetic experiments have predicted that the basal subtype of pancreatic cancer will be intrinsically resistant to these inhibitors. Therefore, there is an urgent need to understand basal PDA development and identify its unique vulnerabilities. We have discovered that the expression of the oncofetal RNA-binding protein LIN28B and its downstream target, the chromatin protein and high-mobility group (HMG) AT-hook 2 (HMGA2), are highly expressed in the basal subtype of PDA. We find LIN28B dramatically accelerates KRAS-driven PDA and acts as a potent oncogene in genetically engineered mouse models (GEMMs) of PDA. We find that HMGA2, downstream of LIN28B, controls cell growth and orchestrates the pathogenesis of basal PDA by hijacking a precise node of mRNA translation machinery. This raises the intriguing possibility that the aberrant activation of HMGA2 increases mRNA translation and may be one mechanism by which PDA attains the highly aggressive basal phenotype. Mechanistically, we observed that loss of HMGA2 results in decreased phosphorylation of S6K and EIF4B. Interestingly, this was independent of changes in MTOR activity. Loss of function studies using siRNA or inhibitors against PP2A restored pS6K and pEIF4B levels, and mRNA translation when HMGA2 was lost. It is known that reduction in pEIF4B levels leads to a reduction in mRNA translation of difficult-to-transcribe transcripts, such as the MYC oncogene. Indeed, loss of HMGA2 leads to a dramatic reduction in MYC protein levels but no changes to transcription or protein stability. Thus, our work has unveiled a new axis in LIN28B/HMGA2 high basal PDA that controls mRNA translation independent of MTOR, is reliant on PP2A, and controls cell growth through MYC translation. This work has the potential to identify innovative therapeutic strategies to combat this deadly subtype of PDA.
Citation Format: Stephanie Dobersch, Sarah Cavendar, Naomi Yamamoto, Liberales Debraj Boila, Cindy Wladyka, Martine Roudier, Faiyaz Notta, Robert Eisenman, Andrew Hsieh, Sita Kugel. LIN28B/HMGA2 axis accelerates PDA by promoting oncogenic protein synthesis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A094.
Abstract A103: Developing small molecules to disrupt IL-17RB and MLK4 interaction for pancreatic cancer treatment
Authors: Chen I-Chih , Ko Yi-Ling , Huang Ching-Hsuan , Lee Jiin-Horng , Lo Yung-Cheng , Hu Chun-Mei 
Published: January 2024

Abstract
Nearly 40% of pancreatic cancer overexpressed pro-inflammatory Interleukin-17 receptor B (IL-17RB), and this signal pathway plays an essential role in promoting tumorigenesis and metastasis. Targeting the initial event of IL-17B/IL-17RB oncogenic signaling by disrupting IL-17RB-MLK4 interaction represents an excellent strategy for treating pancreatic cancer. To develop specific and effective small molecule disruptors, we have established a high-throughput screening (HTS) method using pY447 IL-17RB signal-based assay to identify blockers inhibiting IL-17B/IL-17RB oncogenic signaling. Three FDA-approved drugs were found to inhibit IL-17B-induced pY447 of IL-17RB signaling after screening 2560 FDA-approved drugs and 11000 TKI-related compounds. These drugs are more effective than the original loop peptide in inhibiting soft agar colony formation and spheroid formation of pancreatic tumor cells. Furthermore, we identified Drug H, which was not an anticancer drug before, could efficiently and specifically disrupt the interaction between IL-17RB and MLK4. Oral administration of Drug H can significantly suppress pancreatic tumor growth and metastasis and extend the life of mice with pancreatic tumors. Combining Drug H with gemcitabine treatment also showed synergistic effects in suppressing pancreatic tumor growth and metastasis. These data suggest Drug H may be a promising lead compound for disrupting IL-17RB/MLK4 and treating pancreatic cancer.
Citation Format: I-Chih Chen, Yi-Ling Ko, Ching-Hsuan Huang, Jiin-Horng Lee, Yung-Cheng Lo, Chun-Mei Hu. Developing small molecules to disrupt IL-17RB and MLK4 interaction for pancreatic cancer treatment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A103.
Abstract C068: Construction of preclinical study model for optimal anticancer drug selection using PDX model in pancreatic cancer
Authors: Tanaka Ryota , Kimura Kenjiro , Tani Naoki , Eguchi Shimpei , Kageyama Ken , Kushiyama Shuhei , Kurihara Shigeaki , Kinoshita Masahiko , Nishio Kohei , Shinkawa Hiroji , Ohira Go , Yamamoto Akira , Ishizawa Takeaki 
Published: January 2024

Abstract
Background: Translational research using the patient-derived xenograft (PDX) model is progressing rapidly and is also becoming widespread in pancreatic cancer research. Since PDX models retain the characteristics and the heterogeneity of the primary tumor, PDX models can be reflected in the effectiveness of the anticancer drug in human. The purpose of this study was to establish the PDX library of pancreatic cancer for preclinical study. Methods: The tissues of the pancreatic cancer were obtained from patients who underwent surgery at our hospital. Two PDX models were established using immunodeficient rats. One case was effective in gemcitabine plus nab-paclitaxel (GnP) therapy, and the other was ineffective in GnP therapy in preoperative treatment. 5-FU, CPT-11, L-OHP, GEM, and CDDP were administered to these PDX models once a week for 3 weeks. The primary endpoint was tumor shrinkage. Results: GEM was effective in PDX model in a case in which GnP therapy was effective in the clinical setting, in contrast, GEM was ineffective in PDX model in a case in which GnP was ineffective in the clinical setting. This result was correlated with actual clinical practice. Conclusions: In this study, single anticancer drug tests were performed on PDX models using immunodeficient rats. The efficacy of anticancer drugs was correlated with the clinical setting, indicating that our PDX models might be useful as a preclinical study model. We are currently conducting multi anticancer drug studies.
Citation Format: Ryota Tanaka, Kenjiro Kimura, Naoki Tani, Shimpei Eguchi, Ken Kageyama, Shuhei Kushiyama, Shigeaki Kurihara, Masahiko Kinoshita, Kohei Nishio, Hiroji Shinkawa, Go Ohira, Akira Yamamoto, Takeaki Ishizawa. Construction of preclinical study model for optimal anticancer drug selection using PDX model in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C068.