bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astronomically forced paleoclimate and sea-level changes recorded in the continental margin of the South China Sea over the past ~23 m.y.
Authors: Wei Xiaosong , Yan Detian , Wang Danlei , Fu Haijiao 
Published: February 2024

AbstractThe Earth has witnessed the emergence of continental-sized ice sheets, starting with Antarctica and gradually extending to both hemispheres over the past 40 million years. These ice accumulations have had a dramatic impact on both paleoclimate and sea level, substantially influencing sediment deposition in the continental margins. However, understanding sediment accumulation on an orbital scale in continental margins remains limited because of the scarcity of high-resolution, chronologically constrained sedimentary records. Here, we conducted a highly resolved cyclostratigraphic analysis based on natural gamma radiation (GR) series in depth domain at the continental margin of the South China Sea. We established a 22.8 m.y.-long high-resolution astronomical time scale spanning from the Miocene to the Quaternary by tuning the GR records to the global deep-sea benthic foraminifera carbon isotope curves and the 405 k.y. eccentricity cycles. The m.y.-scale sea-level changes since the Miocene were reconstructed through the sedimentary noise modeling of the 405-k.y.-tuned GR series. These reconstructions aligned with regional and global sea-level changes. The phase correlation between the filtered 1.2 m.y. cycles of sea-level change curves (dynamic noise after orbital tuning and ρ1 median models) from δ13Cbenthic and tuned GR series and the 1.2 m.y. obliquity amplitude modulation cycles revealed a shift from an anti-phase to an in-phase relationship across the middle Miocene climate transition (ca. 13.8 Ma), suggesting extensive expansion of the Antarctic ice sheet played a key role. In addition, a shift from an in-phase to an anti-phase relationship during the late Miocene (ca. 8 Ma and 5.3 Ma), indicating ephemeral expansion of the Arctic ice sheets or the changes in carbon cycle involving the terrestrial and deep ocean carbon reservoirs, might be the primary driver of eustatic changes. Furthermore, obliquity forcing and changes in meridional gradients in insolation that transported poleward flux of heat, moisture, and precipitation increased ice accumulation in both pole ice sheets and nonlinearly transferred high-latitude signals to low-latitude regions. This phenomenon is supported by the observation of strong obliquity signals in low latitude during global climate cooling interval. Our results suggest that m.y.-scale sea-level variations respond to astronomically induced climate change and ice sheet dynamics of both poles. This work contributes a highly resolved low-latitude geological archive to the future reconstruction of paleoclimate evolution on a global scale.
Nannofossil imprints across the Paleocene–Eocene thermal maximum
Authors: Slater Sam M. , Bown Paul R. , Jardine Phillip E. 
Published: February 2024

Abstract
The Paleocene–Eocene thermal maximum (PETM; ca. 56 Ma) geological interval records a marked decline in calcium carbonate (CaCO3) in seafloor sediments, potentially reflecting an episode of deep- and possibly shallow-water ocean acidification. However, because CaCO3 is susceptible to postburial dissolution, the extent to which this process has influenced the PETM geological record remains uncertain. Here, we tested for evidence of postburial dissolution by searching for imprint fossils of nannoplankton preserved on organic matter. We studied a PETM succession from the South Dover Bridge (SDB) core, Maryland, eastern United States, and compared our imprint record with previously published data from traditionally sampled CaCO3-preserved nannoplankton body fossils. Abundant imprints through intervals devoid of CaCO3 would signify that postburial dissolution removed much of the CaCO3 from the rock record. Imprints were recorded from most samples but were rare and of low diversity. Body fossils were substantially more numerous and diverse, capturing a more complete record of the living nannoplankton communities through the PETM. The SDB succession records a dissolution zone/low-carbonate interval at the onset of the PETM, through which nannoplankton body fossils are rare. No nannoplankton imprints were found from this interval, suggesting that the rarity of body fossils is unlikely to have been the result of postburial dissolution. Instead, our findings suggest that declines in CaCO3 through the PETM at the SDB location were the result of: (1) biotic responses to changes that were happening during this event, and/or (2) CaCO3 dissolution that occurred before lithification (i.e., in the water column or at the seafloor).
Buckle me up! A randomised controlled trial using a tablet-based emergency department intervention for child car safety education
Authors: Zhang Angela Yu , Leviter Julie , Baird Janette , Charles-Chauvet Danielle , Frackiewicz Laura M , Duffy Susan , Dessie Almaz 
Published: February 2024

Background and objectivesCorrect child car restraint use significantly reduces risk of death and serious injury in motor vehicle crashes, but millions of US children ride with improper restraints. We created a tablet-based car restraint educational intervention using Computer Intervention Authoring Software (CIAS) and examined its impact on knowledge and behaviours among parents in the paediatric emergency department (PED).MethodsThis was a non-blinded, randomised controlled trial of parents of PED patients ages 0–12 years. Participants were evaluated for baseline car restraint knowledge and behaviour. The intervention group completed an interactive tablet-based module, while the control group received printed handouts on car restraint safety. After 1 week, both groups received a follow-up survey assessing changes in car restraint knowledge and behaviour. Logistic regressions determined predictors of knowledge retention and behavioural changes. Parents in the CIAS group were also surveyed on programme acceptability.Results211 parents completed the study with follow-up data. There was no significant difference in baseline car restraint knowledge (74.3% correct in intervention, 61.8% in control, p=0.15), or increase in follow-up restraint knowledge. Significantly more intervention-group caregivers reported modifying their child’s car restraint at follow-up (52.5% vs 31.8%,p=0.003), and 93.7% of them found CIAS helpful in learning to improve car safety.ConclusionParents had overall high levels of car restraint knowledge. Using CIAS led to positive behavioural changes regarding child car restraint safety, with the vast majority reporting positive attitudes towards CIAS. This novel, interactive, tablet-based tool is a useful PED intervention for behavioural change in parents.Trial registration numberNCT03799393.
Helmet utilisation and its associated factors among motorcyclists in northern Ghana: an analytical cross-sectional survey
Authors: Adjei Benjamin Noble , Nakua Emmanuel Kweku , Donkor Peter , Gyaase Daniel , Alhassan Mohammed Muhib , Amissah John , Osei Bonsu Emmanuel , Enuameh Yeetey , Mock Charles N 
Published: February 2024

BackgroundMotorcycle crashes are a major source of road traffic deaths in northern Ghana. Helmet use has been low. The last time it was formally assessed (2010), helmet use was 30.0% (34.2% for riders and 1.9% for pillion riders). We sought to determine the current prevalence of helmet use and its associated factors among motorcyclists in northern Ghana.MethodsCross-sectional observations of motorcycle helmet use were conducted among 3853 motorcycle riders and 1097 pillion riders in the Northern Region at 12 different locations near intersections, roundabouts and motorcycle bays. Modified Poisson regression was used to assess the factors associated with helmet use.ResultsThe prevalence of helmet use was 22.1% overall: 26.7% among motorcycle riders and 5.7% among pillion riders. On the multivariable regression analysis, the prevalence of helmet use among motorcycle riders was 69% higher during the day compared with the night, 58% higher at weekend compared with weekday, 46% higher among males compared with females, but it was 18% lower on local roads compared with highways, 67% lower among young riders compared with the elderly and 29% lower when riding with pillion rider(s).ConclusionDespite small increases in motorcycle helmet use among pillion riders, helmet use has declined overall over the past decade. Immediate actions are needed to promote helmet use among motorcyclists in northern Ghana. This calls for a multisectoral approach to address the current low helmet use, targeting young riders, female riders, pillion riders, evening riding and riding on local roads.
Firearm manufacturing and imports in the USA and their association to firearm homicides in Central America and the Caribbean, 1991–2019
Authors: Weigend Vargas Eugenio , Hans Zainab , Wiebe Douglas J , Goldstick Jason E 
Published: February 2024

BackgroundFirearm manufacturing and imports grew in the US during the mid-2000s. We hypothesise those increases corresponded to increased international firearms trafficking and in turn were associated with increases in firearm homicides abroad.MethodsWe used the Global Burden of Disease database to quantify annual firearm and non-firearm homicide rates in Central American and Caribbean countries, 1991–2019. We obtained US firearm manufacturing and import data from the Bureau of Alcohol, Tobacco, Firearms and Explosives. We used two-way fixed effects regressions to estimate within-country associations between homicide rates (firearm and non-firearm) and US firearm manufacturing and imports.FindingsFirearm homicide rates in Central American and Caribbean countries increased from 8.38/100K population in 2004 to 17.55/100 K in 2012 and remained steady thereafter. Those surges coincided with increases in US firearm manufacturing/imports (from 4.99 million in 2004 to 13.12 million in 2012). Non-firearm homicides remained roughly constant from 1991 to 2019. Adjusted analysis showed that an annual increase of one million firearms manufactured/imported in the US corresponded to an annual increase of 1.42 (95% CI 0.62 to 2.21) firearm homicides per 100 K in Central American and Caribbean countries. The corresponding change for non-firearm homicides was −0.18 (95% CI −1.46 to 1.11). We found country-to-country variability in these effects.InterpretationIncreases in US firearm manufacturing/imports were associated with increases in firearm homicide rates in Central American and Caribbean countries but not associated with non-firearm homicides. The specificity to firearm homicides suggests possible international repercussions of increased firearm manufacturing and imports in the US implications are discussed.
Parental education and occupation in relation to childhood type 1 diabetes: nationwide cohort study
Authors: Lopez-Doriga Ruiz Paz , Tapia German , Bakken Inger J. , Håberg Siri E. , Gulseth Hanne L , Skrivarhaug Torild , Joner Geir , Stene Lars C 
Published: February 2024

BackgroundSocioeconomic status in the risk of developing type 1 diabetes seems inconsistent. We investigated whether risk of childhood-onset type 1 diabetes differed by parental education or occupation in a nationwide cohort.MethodsThis cohort study included all children born in Norway from 1974 to 2013. In individually linked data from nationwide population registries following children born in Norway up to 15 years of age, we identified 4647 with newly diagnosed type 1 diabetes during 15 381 923 person-years of follow-up.ResultsChildren of mothers with a master’s degree had lower risk of type 1 diabetes than children of mothers with completed upper secondary education only (adjusted incidence rate ratio, aIRR=0.82 95% CI: 0.70 to 0.95). There was no difference between upper secondary and lower secondary maternal education (aIRR=0.98, 95% CI: 0.89 to 1.08). Paternal education was not significantly associated with type 1 diabetes, lower secondary compared with upper secondary aIRR 0.96 (0.88–1.05) and master compared with upper secondary aIRR 0.93 (0.83–1.05). While maternal elementary occupation was associated with a lower risk of type 1 diabetes, specific maternal or paternal occupations were not.ConclusionsOur results suggested inverse U-shaped associations between maternal socioeconomic status and risk of type 1 diabetes. Non-linear associations may be part of the reason why previous literature has been inconsistent.
Transferring Causal Mechanism over Meta-representations for Target-Unknown Cross-domain Recommendation
Authors: Zhang Shengyu , Miao Qiaowei , Nie Ping , Li Mengze , Chen Zhengyu , Feng Fuli , Kuang Kun , Wu Fei 
Published: February 2024

Tackling the pervasive issue of data sparsity in recommender systems, we present an insightful investigation into the burgeoning area of non-overlapping cross-domain recommendation, a technique that facilitates the transfer of interaction knowledge across domains without necessitating inter-domain user/item correspondence. Existing approaches have predominantly depended on auxiliary information, such as user reviews and item tags, to establish inter-domain connectivity, but these resources may become inaccessible due to privacy and commercial constraints.
To address these limitations, our study introduces an in-depth exploration of Target-unknown Cross-domain Recommendation (CDR), which contends with the distinct challenge of lacking target domain information during the training phase in the source domain. We illustrate two critical obstacles inherent to Target-unknown CDR: the lack of an inter-domain bridge due to insufficient user/item correspondence or side information and the potential pitfalls of source-domain training biases when confronting distribution shifts across domains. To surmount these obstacles, we propose the CMCDR framework, a novel approach that leverages causal mechanisms extracted from meta-user/item representations. The CMCDR framework employs a vector-quantized encoder–decoder architecture, enabling the disentanglement of user/item characteristics. We posit that domain-transferable knowledge is more readily discernible from user/item characteristics, i.e., the meta-representations, rather than raw users and items. Capitalizing on these meta-representations, our CMCDR framework adeptly incorporates an attention-driven predictor that approximates the front-door adjustment method grounded in causal theory. This cutting-edge strategy effectively mitigates source-domain training biases and enhances generalization capabilities against distribution shifts. Extensive experiments demonstrate the empirical effectiveness and the rationality of CMCDR for target-unknown cross-domain recommendation.
Abstract A001: Transcriptomic and microRNA profiling revealed novel therapeutic targets for breast cancer subtypes
Authors: Elango Ramesh , Vishnubalaji Radhakrishnan , Rashid Sameera , Alajez Nehad 
Published: February 2024

Abstract
Numerous studies suggested breast cancer (BC) from the Middle East and North Africa (MENA) to be presented at younger age with advanced tumor grade, suggesting underlying biological differences. Given the limited transcriptomic profiling data on BC from the MENA region, we performed mRNA and microRNA (miRNA) transcriptomic profiling on a local cohort of BC (n=96) from Qatar. Our data revealed the differentially expressed genes and miRNAs in relation to BC molecular subtypes (HR+, HER2+, HER2+HR+, and TNBC), tumor grade (high vs low), patients’ age (young (≤ 40) vs old (&gt; 40)), and ethnicity (MENA vs non-MENA). Our data revealed close similarity between TNBC and HER2+, while the transcriptome of HER2+HR+ tumor was similar to that from HR+ tumors. Integrated network analysis identified complex miRNA-mRNA regulatory networks in each BC molecular subtype, in high vs low grade tumors, in tumors from young vs old, and in tumors from MENA vs non-MENA, thus implicating miRNA-mediated gene regulation as an key mechanism in shaping the transcriptome of BC. Integration of our transcriptomic data with CRISPR-Cas9 functional screen data and the Drug-Gene Interaction Database identified numerous dependencies and therapeutic vulnerabilities for each BC molecular subtype. Among those, CDC123 was functionally validated as potential therapeutic target for TNBC. Survival analyses identified mRNA and miRNA-based signatures predicative of relapse free survival (RFS), which were validated in larger BC cohorts. Our data provides comprehensive transcriptomic profiling and unraveled the miRNA-mRNA regulatory networks in BC patients from the region and identified numerous actionable gene targets, employing integrated approach. Findings from the current study have potential implications to improve the current standard-of-care for BC from the MENA as well as patients from other ethnicities.
Citation Format: Ramesh Elango, Radhakrishnan Vishnubalaji, Sameera Rashid, Nehad Alajez. Transcriptomic and microRNA profiling revealed novel therapeutic targets for breast cancer subtypes [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A001.
Abstract A033: Nuclear EGFR as a regulator of the tumor microenvironment
Authors: Escoto Angelica 
Published: February 2024

Abstract
Overexpression of the Epidermal Growth Factor Receptor (EGFR) is observed in all subtypes of breast cancer and is associated with large tumor size, poor differentiation, and poor clinical outcomes. However, the role of EGFR in driving the disease remains unclear, as EGFR-targeted antibodies and tyrosine kinase inhibitors fail to work effectively in breast cancer patients with EGFR overexpression. A possible explanation for therapeutic resistance is the role of intracellular EGFR, where retrograde trafficking of EGFR to the nucleus results in EGFR functioning directly as a transcriptional cofactor, regulating the expression of genes that promote tumor growth, metastasis, and an immune suppressive microenvironment. Our goal is to understand how targeting nuclear EGFR impacts this microenvironment. Using a novel therapeutic peptide (cSNX1.3) that targets retrograde trafficking of EGFR, we discovered that inhibiting retro-translocation of EGFR elicited an immune response as demonstrated by the secretion of inflammatory cytokines. Using RNA-Seq analysis, we detected an increase in the expression of cytokine receptors and natural killer (NK) cell ligands, such as RAET1 and AICL. We demonstrated that this active immune microenvironment is not observed when we treat with the EGFR kinase inhibitor Erlotinib, indicating a nuclear EGFR-specific outcome. Studies from tumor-bearing WAP-TGFα transgenic mice (an EGFR-dependent model of breast cancer) found the presence of NK cells and the expression of their activating ligands and receptors, IL-33 and SLAM7, respectively, in the tumor microenvironment. We hypothesize that nuclear EGFR is suppressing the expression of inflammatory cytokines, receptors, and ligands important for activation and recruitment of NK cells, thereby allowing immune evasion and ultimately progression of the disease. Future studies will investigate the potential to combine nuclear EGFR inhibitors with immunotherapies to activate the tumor immune microenvironment and promote optimal therapeutic efficacy.
Citation Format: Angelica Escoto. Nuclear EGFR as a regulator of the tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A033.
Abstract A047: Gamma Aminobutyric Acid Subunit Pi (GABRP) Promotes Breast Cancer Metastasis to the Brain
Authors: Packard Rebecca 
Published: February 2024

Abstract
Triple negative breast cancer (TNBC) is an aggressive subset of breast cancer associated with poor prognosis. Although TNBC is only responsible for about 10-15% of breast cancer cases, it accounts for nearly 37% of mortalities. A main factor resulting in this poor prognosis is a higher risk of rapid relapse, which is distant metastasis or death within two years of diagnosis, compared to other breast cancer subsets. To begin to tease out mechanisms of this TNBC-specific rapid relapse, we analyzed differential expression between those tumors resulting in rapid relapse versus those tumors with delayed relapse. This analysis was completed in two independent microarray datasets and revealed a significant upregulation of gamma aminobutyric acid subunit pi (GABRP) mRNA in the TNBC tumors that rapidly relapsed. Previous work by us and others has revealed GABRP as a driver of aggressive behaviors in TNBC cell lines; however, its role in metastatic recurrence is still unclear. We have also observed a correlation between high GABRP mRNA and preferential metastatic progression to the brain. Thus, we hypothesized GABRP is a key mediator of metastasis in aggressive TNBCs, specifically in the establishment of brain metastases. To date, we have completed preliminary in vivo experimental metastasis studies of human breast cancer cells with and without GABRP expression where loss of GABRP reduces brain metastasis. Ongoing studies aim to test metastatic progression in a spontaneous metastasis in vivo model. We are also optimizing an antibody for biomarker screening in patients. Combined, our studies provide strong evidence that GABRP is a major driver of brain-specific metastases and subsequent poorer outcomes associated with TNBC, suggesting targeting GABRP has high therapeutic potential to reduce metastasis and mortality in TNBC patients.
Citation Format: Rebecca Packard. Gamma Aminobutyric Acid Subunit Pi (GABRP) Promotes Breast Cancer Metastasis to the Brain [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A047.
Abstract B002: The impact of mir-4728 on translation and pathway regulation in HER2-amplified breast cancer
Authors: Hafstad Völundur , Han Euisuk , Persson Helena 
Published: February 2024

Abstract
MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been implicated in cancer. Our research focuses on the miRNA mir-4728, which is located in an intron in the HER2 locus. The HER2 locus is amplified in approximately 15% of all breast tumors and is associated with a poor prognosis. Current therapeutic strategies for HER2-positive tumors involve targeted inhibition of the HER2 protein with monoclonal antibodies such as trastuzumab in combination with chemotherapy and surgery. However, if mir-4728 has a function independent of its host gene, targeting the HER2 protein alone may be insufficient. To investigate the role of mir-4728, we utilized antisense oligonucleotides to specifically block mir-4728 in a HER2-amplified breast cancer cell line, while leaving the protein receptor in tact. Polysome fractionation and ribosome profiling revealed that blocking the miRNA resulted in a substantial change in protein translation. We hypothesize that this effect may come as a result of mir-4728 being an indirect regulator of EIF4A, a key factor in the initiation of translation. In addition, we have observed changes in the synthesis of aromatase, a crucial enzyme in estrogen synthesis. These findings suggest that mir-4728 may play a role in the regulation of multiple pathways that contribute to cancer progression. Further investigation into this mechanism may provide valuable insight into the development of new therapeutic strategies for cancer treatment.
Citation Format: Völundur Hafstad, Euisuk Han, Helena Persson. The impact of mir-4728 on translation and pathway regulation in HER2-amplified breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B002.