bluuebunny/crossref_metadata_2025_split huggingface dataset:
European Society of Cardiology 0/1-hour algorithm (high-sensitivity cardiac troponin T) performance across distinct age groups
Authors: Millard Marissa J , Ashburn Nicklaus P , Snavely Anna C , Hashemian Tara , Supples Michael , Allen Brandon , Christenson Robert , Madsen Troy , McCord James , Mumma Bryn , Stopyra Jason , Wilkerson Richard Gentry , Mahler Simon A 
Published: March 2024

BackgroundTo determine if the European Society of Cardiology 0/1-hour (ESC 0/1-h) algorithm with high-sensitivity cardiac troponin T (hs-cTnT) meets the ≥99% negative predictive value (NPV) safety threshold for 30-day cardiac death or myocardial infarction (MI) in older, middle-aged and young subgroups.MethodsWe conducted a subgroup analysis of adult emergency department patients with chest pain prospectively enrolled from eight US sites (January 2017 to September 2018). Patients were stratified into rule-out, observation and rule-in zones using the hs-cTnT ESC 0/1-h algorithm and classified as older (≥65 years), middle aged (46–64 years) or young (21–45 years). Patients had 0-hour and 1-hour hs-cTnT measures (Roche Diagnostics) and a History, ECG, Age, Risk factor and Troponin (HEART) score. Fisher’s exact tests compared rule-out and 30-day cardiac death or MI rates between ages. NPVs with 95% CIs were calculated for the ESC 0/1-h algorithm with and without the HEART score.ResultsOf 1430 participants, 26.9% (385/1430) were older, 57.4% (821/1430) middle aged and 15.7% (224/1430) young. Cardiac death or MI at 30 days occurred in 12.8% (183/1430). ESC 0/1-h algorithm ruled out 35.6% (137/385) of older, 62.1% (510/821) of middle-aged and 79.9% of (179/224) young patients (p<0.001). NPV for 30-day cardiac death or MI was 97.1% (95% CI 92.7% to 99.2%) among older patients, 98.4% (95% CI 96.9% to 99.3%) in middle-aged patients and 99.4% (95% CI 96.9% to 100%) among young patients. Adding a HEART score increased NPV to 100% (95% CI 87.7% to 100%) for older, 99.2% (95% CI 97.2% to 99.9%) for middle-aged and 99.4% (95% CI 96.6% to 100%) for young patients.ConclusionsIn older and middle-aged adults, the hs-cTnT ESC 0/1-h algorithm was unable to reach a 99% NPV for 30-day cardiac death or MI unless combined with a HEART score.Trial registration numberNCT02984436.
Impact of NOTCH1 expression in primary breast adenoid cystic carcinoma
Authors: Salem Alireza , Wu Yun , Ding Qingqing , Middleton Lavinia P 
Published: March 2024

AimsAdenoid cystic carcinoma (AdCC) originates from salivary-type like glands in the head and neck, lung, and breast. AdCC shows chromosomal translocation, resulting inMYB::NFIBfusion and overexpression of MYB. Recently, NOTCH1 pathway alteration has been recognised in a subset of patients with salivary gland AdCC and has been shown to be associated with poor survival. In this study, we investigated the correlation of NOTCH1 pathway alteration with the clinical outcome of patients with primary breast AdCC by examining NOTCH1 immunoreactivity in attempts to better predict clinical outcomes.MethodsWe identified 25 cases of breast AdCC, reviewed the clinical outcome and performed immunohistochemical (IHC) staining for NOTCH1 on FFPE sections.ResultsIHC evaluation of NOTCH1 expression in 25 cases of primary breast AdCCs revealed a positive correlation between NOTCH1 expression and primary tumour size. All cases with NOTCH1 expression were greater than 15 mm in size at presentation but only 50% of NOTCH1 negative tumours were greater than 15 mm. We demonstrated a positive correlation between NOTCH1 positive AdCCs and recurrence/metastases. 63.6% of NOTCH1 positive AdCCs had either metastases or recurrence. On the contrary, only 21.5% of NOTCH1 negative AdCCs had recurrence or metastases. AdCCs with NOTCH1 positivity correlated with inferior relapse free survival (median 33 vs 129 months).ConclusionsOur study demonstrates that in patients with breast AdCC, overexpression of NOTCH1 ≥20% is associated with larger tumour size and aggressive clinical outcomes. Importantly, NOTCH1 inhibitors may have potential therapeutic effect in patients with breast AdCC.
Flow failure assessment for dams and embankments
Authors: Stark Timothy D. , Jung Hyunil , Lin Jiale 
Published: March 2024

A procedure is proposed to assess whether a liquefied strength should be applied to a zone of non-plastic silt, silty sand, and (or) clean sand in a static or seismic stability analysis to assess the flow failure potential of dams and slopes. The procedure consists of the following five main steps to assess flow failure potential: (1) assess static liquefaction potential of segments along a potential failure surface; (2) assess seismic liquefaction potential by calculating the factor of safety against liquefaction (FoSLiquefaction) for any amplitude of shaking in each segment; (3) if liquefaction is not triggered in any of these segments, assess the magnitude of shear-induced pore-water pressures due to seismic or vibratory events of any amplitude; (4) assign a liquefied strength to segment(s) that experience seismic liquefaction, i.e., FoSLiquefaction < 1 or significant pore-water pressure generation, i.e., total pore-water pressure ratio ≥ 0.7; and (5) conduct a post-triggering stability analysis to assess flow failure potential. This procedure is illustrated using the 1971 seismic permanent deformations of Upper San Fernando Dam and 2015 Fundão tailings dam failure.
CP violation in B decays: recent developments and future perspectives
Authors: Fleischer Robert 
Published: March 2024

AbstractCP violation in B decays provides a powerful tool to probe physics from beyond the Standard Model. A theoretical overview of recent developments of benchmark channels is given, ranging from non-leptonic to rare leptonic and semileptonic modes, opening up exciting perspectives for the future high-precision era of flavour physics and the pursuit of New Physics.
Nuclear isomers in medicine
Authors: Jensen Mikael 
Published: March 2024

AbstractOnly a small handful of nuclear isomers plays an important role in modern medicine. However, one single isomer (Tc-99m) is in terms of quantitative use almost the foundation of the medical application of radioactive compounds. This single isomer has driven the development of modern nuclear medicine over half a century. It is used for diagnostic imaging every day and all over the world. The nuclear and atomic physics basis for this is explained. The main areas of nuclear medicine (diagnostic single photon imaging, diagnostic positron emitter imaging and therapeutic use) are explained, and the few important isomers used in each category are exposed. Although nuclear medicine is evolving rapidly and making important gains in the management of oncological, cardiological and neurological diseases, new radionuclides and new isomers are rarely introduced. The medical use is confined to a narrow set of radionuclides close to the line of stability, and here, of course, the nuclear properties in general and the characteristics of the isomeric states are well known, and possible medical usage has been considered repeatedly. The nuclear isomers will probably keep their role, but from basic physics point of view, just as useful but trivial example of applied nuclear physics.
Data from Comparison of Neuropathy-Inducing Effects of Eribulin Mesylate, Paclitaxel, and Ixabepilone in Mice
Authors: Wozniak Krystyna M. , Nomoto Kenichi , Lapidus Rena G. , Wu Ying , Carozzi Valentina , Cavaletti Guido , Hayakawa Kazuhiro , Hosokawa Satoru , Towle Murray J. , Littlefield Bruce A. , Slusher Barbara S. 
Published: March 2024

<div>Abstract<p>Chemotherapy-induced neurotoxicity is a significant problem associated with successful treatment of many cancers. Tubulin is a well-established target of antineoplastic therapy; however, tubulin-targeting agents, such as paclitaxel and the newer epothilones, induce significant neurotoxicity. Eribulin mesylate, a novel microtubule-targeting analogue of the marine natural product halichondrin B, has recently shown antineoplastic activity, with relatively low incidence and severity of neuropathy, in metastatic breast cancer patients. The mechanism of chemotherapy-induced neuropathy is not well understood. One of the main underlying reasons is incomplete characterization of pathology of peripheral nerves from treated subjects, either from patients or preclinically from animals. The current study was conducted to directly compare, in mice, the neuropathy-inducing propensity of three drugs: paclitaxel, ixabepilone, and eribulin mesylate. Because these drugs have different potencies and pharmacokinetics, we compared them on the basis of a maximum tolerated dose (MTD). Effects of each drug on caudal and digital nerve conduction velocity, nerve amplitude, and sciatic nerve and dorsal root ganglion morphology at 0.25 × MTD, 0.5 × MTD, 0.75 × MTD, and MTD were compared. Paclitaxel and ixabepilone, at their respective MTDs, produced significant deficits in caudal nerve conduction velocity, caudal amplitude and digital nerve amplitudes, as well as moderate to severe degenerative pathologic changes in dorsal root ganglia and sciatic nerve. In contrast, eribulin mesylate produced no significant deleterious effects on any nerve conduction parameter measured and caused milder, less frequent effects on morphology. Overall, our findings indicate that eribulin mesylate induces less neuropathy in mice than paclitaxel or ixabepilone at equivalent MTD-based doses. <i>Cancer Res; 71(11); 3952–62. ©2011 AACR</i>.</p></div>
Data from Gliomagenesis Arising from Pten- and Ink4a/Arf-Deficient Neural Progenitor Cells Is Mediated by the p53-Fbxw7/Cdc4 Pathway, Which Controls c-Myc
Authors: Kim Hong Sug , Woolard Kevin , Lai Chen , Bauer Peter O. , Maric Dragan , Song Hua , Li Aiguo , Kotliarova Svetlana , Zhang Wei , Fine Howard A. 
Published: March 2024

<div>Abstract<p>Glioblastoma multiforme is the most common type of primary malignant brain tumor and may arise from a cell with neural stem-like properties. Deregulation of the retinoblastoma, phosphoinositide-3 kinase (PI3K), and p53 pathways are molecular hallmarks of this disease. Recent work has shown that <i>p53</i><sup>−/−</sup><i>Pten<sup>−/−</sup></i> mice form gliomas in a c-Myc–dependent manner. To explore the role of the <i>INK4A/ARF</i> locus and <i>Pten</i> deletions in gliomagenesis, we generated <i>Pten<sup>−/−</sup>Ink4a/Arf<sup>−/−</sup></i> mouse neural stem cells (mNSC) and such cells were highly proliferative, self-renewing, relatively refractory to differentiation, and induced both low- and high-grade glioma formation <i>in vivo</i>. In contrast to <i>p53</i><sup>−/−</sup><i>Pten<sup>−/−</sup></i> mNSCs, however, <i>Pten<sup>−/−</sup>Ink4a/Arf<sup>−/−</sup></i> mNSCs do not express appreciable levels of c-Myc <i>in vitro</i>, although glioma stem cells derived from thesecells did. Sequencing of <i>Pten<sup>−/−</sup>Ink4a/Arf<sup>−/−</sup></i> mNSC–derived tumors revealed spontaneous mutations in <i>Tp53 in vivo</i> with subsequent downregulation of <i>Fbxw7</i>. Expression of p53 mutants in <i>Pten<sup>−/−</sup>Ink4a/Arf<sup>−/−</sup></i> mNSC or knockdown of Fbxw7 resulted in reexpression of c-Myc with enhanced <i>Pten<sup>−/−</sup>Ink4a/Arf<sup>−/−</sup></i> mNSC tumorigenecity. We propose that p53 mutations contribute to gliomagenesis by both allowing the overexpression of c-Myc through downregulation of Fbxw7 and by protecting against c-Myc–induced apoptosis. <i>Cancer Res; 72(22); 6065–75. ©2012 AACR</i>.</p></div>
A Histone Methylation–MAPK Signaling Axis Drives Durable Epithelial–Mesenchymal Transition in Hypoxic Pancreatic Cancer
Authors: Brown Brooke A. , Myers Paul J. , Adair Sara J. , Pitarresi Jason R. , Sah-Teli Shiv K. , Campbell Logan A. , Hart William S. , Barbeau Michelle C. , Leong Kelsey , Seyler Nicholas , Kane William , Lee Kyoung Eun , Stelow Edward , Jones Marieke , Simon M. Celeste , Koivunen Peppi , Bauer Todd W. , Stanger Ben Z. , Lazzara Matthew J. 
Published: March 2024

Abstract

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) plays a key role in tumor progression and response to therapy. The dense PDAC stroma causes hypovascularity, which leads to hypoxia. Here, we showed that hypoxia drives long-lasting epithelial–mesenchymal transition (EMT) in PDAC primarily through a positive-feedback histone methylation–MAPK signaling axis. Transformed cells preferentially underwent EMT in hypoxic tumor regions in multiple model systems. Hypoxia drove a cell autonomous EMT in PDAC cells, which, unlike EMT in response to growth factors, could last for weeks. Furthermore, hypoxia reduced histone demethylase KDM2A activity, suppressed PP2 family phosphatase expression, and activated MAPKs to post-translationally stabilize histone methyltransferase NSD2, leading to an H3K36me2-dependent EMT in which hypoxia-inducible factors played only a supporting role. Hypoxia-driven EMT could be antagonized in vivo by combinations of MAPK inhibitors. Collectively, these results suggest that hypoxia promotes durable EMT in PDAC by inducing a histone methylation–MAPK axis that can be effectively targeted with multidrug therapies, providing a potential strategy for overcoming chemoresistance.

Significance:
Integrated regulation of histone methylation and MAPK signaling by the low-oxygen environment of pancreatic cancer drives long-lasting EMT that promotes chemoresistance and shortens patient survival and that can be pharmacologically inhibited.
See related commentary by Wirth and Schneider, p. 1739
ACSL4-Mediated Membrane Phospholipid Remodeling Induces Integrin β1 Activation to Facilitate Triple-Negative Breast Cancer Metastasis
Authors: Qiu Yuxiang , Wang Xing , Sun Yan , Jin Ting , Tang Rui , Zhou Xinyue , Xu Ming , Gan Yubi , Wang Rui , Luo Haojun , Liu Manran , Tang Xi 
Published: March 2024

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and has a poor prognosis and a high propensity to metastasize. Lipid metabolism has emerged as a critical regulator of tumor progression and metastasis in other cancer types. Characterization of the lipid metabolic features of TNBC could provide important insights into the drivers of TNBC metastasis. Here, we showed that metastatic TNBC tumors harbor more unsaturated phospholipids, especially long-chain polyunsaturated fatty acids, at the sn-2 position of phosphatidylcholine and phosphatidylethanolamine compared with primary tumors. Metastatic TNBC tumors upregulated ACSL4, a long-chain polyunsaturated acyl-CoA synthetase that drives the preferential incorporation of polyunsaturated fatty acids into phospholipids, resulting in the alteration of membrane phospholipid composition and properties. Moreover, ACSL4-mediated phospholipid remodeling of the cell membrane induced lipid-raft localization and activation of integrin β1 in a CD47-dependent manner, which led to downstream focal adhesion kinase phosphorylation that promoted metastasis. Importantly, pharmacologic inhibition of ACSL4 suppressed tumor growth and metastasis and increased chemosensitivity in TNBC models in vivo. These findings indicate that ACSL4-mediated phospholipid remodeling enables TNBC metastasis and can be inhibited as a potential strategy to improve the efficacy of chemotherapy in TNBC.

Significance:
ACSL4 upregulation in triple-negative breast cancer alters cell membrane phospholipid composition to increase integrin β1 activation and drive metastasis, indicating that targeting ACSL4 could potentially block metastasis and improve patient outcomes.
Data from Inhibiting WEE1 and IKK-RELA Crosstalk Overcomes TNFα Resistance in Head and Neck Cancers
Authors: Hu Zhengbo , Viswanathan Ramya , Cheng Hui , Chen Jianghong , Yang Xinping , Huynh Angel , Clavijo Paul , An Yi , Robbins Yvette , Silvin Christopher , Allen Clint , Ormanoglu Pinar , Martin Scott , Cornelius Shaleeka , Saleh Anthony , Chen Zhong , Van Waes Carter , Morgan Ethan L. 
Published: March 2024

<div>Abstract<p>TNFα is a key mediator of immune and radiotherapy-induced cytotoxicity, but many cancers, including head and neck squamous cell carcinomas (HNSCC), display TNF resistance due to activation of the canonical IKK–NF-κB/RELA pro-survival pathway. However, toxicities associated with direct targeting of the canonical pathway point to the need to identify mechanism(s) contributing to TNFα resistance and synthetic lethal targets to overcome such resistance in cancer cells. Here, RNAi screening for modulators of TNFα–NF-κB reporter activity and cell survival unexpectedly implicated the WEE1 and CDC2 G<sub>2</sub>–M checkpoint kinases. The IKKα/β-RELA and WEE1-CDC2 signaling pathways are activated by TNFα and form a complex in cell lines derived from both human papillomavirus (−) and (+) subtypes of HNSCC. WEE1 inhibitor AZD1775 reduced IKK/RELA phosphorylation and the expression of NF-κB–dependent pro-survival proteins Cyclin D1 and BCL2. Combination of TNFα and AZD1775 enhanced caspase-mediated apoptosis <i>in vitro</i>, and combination treatment with radiotherapy and AZD1775 potentiated inhibition of HNSCC tumor xenograft growth <i>in vivo</i>, which could be significantly attenuated by TNFα depletion. These data offer new insight into the interplay between NF-κB signaling and WEE1-mediated regulation of the G<sub>2</sub>–M cell-cycle checkpoint in HNSCC.</p>Implications:<p>Inhibiting WEE1 and IKK-RELA crosstalk could potentially enhance the effects of therapies mediated by TNFα with less systemic immune suppression and toxicity than observed with direct interruption of IKK-NF-κB/RELA signaling.</p></div>
Infants Infer Social Relationships Between Individuals Who Engage in Imitative Social Interactions
Authors: Kudrnova Vanessa , Spelke Elizabeth S. , Thomas Ashley J. 
Published: March 2024

Abstract
Infants are born into rich social networks and are faced with the challenge of learning about them. When infants observe social interactions, they make predictions about future behavior, but it is not clear whether these predictions are based on social dispositions, social relationships, or both. The current studies (N = 188, N = 90 males) address this question in 12-month-old infants and 16- to 18-month-old toddlers who observe social interactions involving imitation. In Studies 1 and 3, infants and toddlers expected that imitators, compared to non-imitators, would respond to their social partners’ distress. Likewise, they expected the targets of imitation, compared to non-targets, to respond to their partner’s distress. In Study 2, these expectations did not generalize to interactions with a new partner, providing evidence that infants learned about the relationships between individuals as opposed to their dispositions. In Study 3, infants did not make predictions about responses to laughter, suggesting that infants see imitation as indicative of a specific kind of social relationship. Together, these results provide evidence that imitative interactions support infants’ and toddlers’ learning about the social relationships connecting unknown individuals.
Generative Ensemble Deep Learning Severe Weather Prediction from a Deterministic Convection-Allowing Model
Authors: Sha Yingkai , Sobash Ryan A. , Gagne David John 
Published: March 2024

Abstract
An ensemble postprocessing method is developed for the probabilistic prediction of severe weather (tornadoes, hail, and wind gusts) over the conterminous United States (CONUS). The method combines conditional generative adversarial networks (CGANs), a type of deep generative model, with a convolutional neural network (CNN) to postprocess convection-allowing model (CAM) forecasts. The CGANs are designed to create synthetic ensemble members from deterministic CAM forecasts, and their outputs are processed by the CNN to estimate the probability of severe weather. The method is tested using High-Resolution Rapid Refresh (HRRR) 1–24-h forecasts as inputs and Storm Prediction Center (SPC) severe weather reports as targets. The method produced skillful predictions with up to 20% Brier skill score (BSS) increases compared to other neural-network-based reference methods using a testing dataset of HRRR forecasts in 2021. For the evaluation of uncertainty quantification, the method is overconfident but produces meaningful ensemble spreads that can distinguish good and bad forecasts. The quality of CGAN outputs is also evaluated. Results show that the CGAN outputs behave similarly to a numerical ensemble; they preserved the intervariable correlations and the contribution of influential predictors as in the original HRRR forecasts. This work provides a novel approach to postprocess CAM output using neural networks that can be applied to severe weather prediction.

Significance Statement
We use a new machine learning (ML) technique to generate probabilistic forecasts of convective weather hazards, such as tornadoes and hailstorms, with the output from high-resolution numerical weather model forecasts. The new ML system generates an ensemble of synthetic forecast fields from a single forecast, which are then used to train ML models for convective hazard prediction. Using this ML-generated ensemble for training leads to improvements of 10%–20% in severe weather forecast skills compared to using other ML algorithms that use only output from the single forecast. This work is unique in that it explores the use of ML methods for producing synthetic forecasts of convective storm events and using these to train ML systems for high-impact convective weather prediction.
Deep Winter Mixed Layer Anchored by the Meandering Antarctic Circumpolar Current: Cross-Basin Variations
Authors: Song Zihan , Xie Shang-Ping , Xu Lixiao , Zheng Xiao-Tong , Lin Xiaopei , Geng Yu-Fan 
Published: March 2024

Abstract
A deep winter mixed layer forms north of the Antarctic Circumpolar Current (ACC) in the Indo-Pacific sectors, while the mixed layer depth (MLD) is shallow in the Atlantic. Using observations and a global atmospheric model, this study investigates the contribution of surface buoyancy flux and background stratification to interbasin MLD variations. The surface heat flux is decomposed into broad-scale and frontal-scale variations. At the broad scale, the meandering ACC path is accompanied by a zonal wavenumber-1 structure of sea surface temperature (SST) with a warmer Pacific than the Atlantic; under the prevailing westerly winds, this temperature contrast results in larger surface heat loss facilitating deeper MLD in the Indo-Pacific sectors than in the Atlantic. In the Indian sector, the intense ACC fronts strengthen surface heat loss compared to the Pacific. The surface freshwater flux pattern largely follows that of evaporation and reinforces the heat flux pattern, especially in the southeast Pacific. A diagnostic relationship is introduced to highlight the role of ACC’s sloping isopycnals in setting a weak submixed layer stratification north of ACC. This weak stratification varies in magnitude across basins. In the Atlantic and western Indian Oceans where the ACC is at a low latitude (∼45°S), solar heating, intrusions of subtropical gyres, and energetic mesoscale eddies together maintain relatively strong stratification. In the southeast Pacific, in comparison, the ACC reaches the southernmost latitude (56°S), far away from the subtropical front. This creates weaker stratification, allowing deep mixed layers to form, aided by surface buoyancy loss.