bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Machine Learning to Predict Cloud Turbulent Entrainment‐Mixing Processes
Authors: Gao Sinan , Lu Chunsong , Zhu Jiashan , Li Yabin , Liu Yangang , Zhao Binqi , Hu Sheng , Liu Xiantong , Lv Jingjing 
Published: August 2024

AbstractDifferent turbulent entrainment‐mixing mechanisms between clouds and environment are essential to cloud‐related processes; however, accurate representation of entrainment‐mixing in weather/climate models still poses a challenge. This study exploits the use of machine learning (ML) to address this challenge. Four ML (Light Gradient Boosting Machine [LGB], eXtreme Gradient Boosting, Random Forest, and Support Vector Regression) are examined and compared. It is found that LGB performs best, and thus is selected to understand the impact of entrainment‐mixing on microphysics using simulation data from Explicit Mixing Parcel Model. Compared with traditional parameterizations, the trained LGB provides more accurate microphysical properties (number concentration and cloud droplet spectral dispersion). The partial dependences of predicted microphysics on features exhibit a strong alignment with physical mechanisms and expectations, as determined by the interpreting method, thus overcoming the limitations of the “black box” scheme. The underlying mechanisms are that the smaller number concentration and larger spectral dispersion correspond to more inhomogeneous entrainment‐mixing. Specifically, number concentration after entrainment‐mixing is positively correlated with adiabatic number concentration and liquid water content affected by entrainment‐mixing, and inversely correlated with adiabatic volume mean radius. Spectral dispersion after entrainment‐mixing is negatively correlated with liquid water content affected by entrainment‐mixing, turbulent dissipation rate and relative humidity of entrained air. Sensitivity analysis further suggests that number concentration is mainly determined by cloud microphysical properties whereas spectral dispersion is influenced by both cloud microphysical properties and environmental variables. The results indicate that the LGB scheme has the potential to enhance the representation of entrainment‐mixing in weather/climate models.
Crustal Structure of the Northeast South China Sea Rifted Margin
Authors: Rodrigues de Vargas Mateus , Tugend Julie , Mohn Geoffroy , Kusznir Nick , Liang‐Fu Lin 
Published: August 2024

AbstractWe investigate the crustal structure of the Northeastern (NE) South China Sea (SCS) rifted margin to constrain its crustal thickness and basement nature with implications for the Mesozoic and Cenozoic evolution of the SCS. First‐order interfaces interpreted from seismic reflection data were integrated into a 3D gravity inversion scheme to determine Moho depth and crustal thickness variations. A joint inversion of seismic and gravity data allowed us to determine crustal density variations along 2D profiles. The distal margin of the NE SCS is divided into two distinct crustal domains: the Southern Rift System (SRS), and the Southern High (SH). The SRS shows an extremely thinned crust on top of which thick Cenozoic sequences are observed. It is separated from the oceanic crust (∼6–8 km thick) by the SH, a comparatively thicker crustal domain (∼10–15 km thick) with significant magmatic additions. The distal NE SCS margin formed during the Cenozoic rifting of the SCS. The SH likely corresponds to a polygenic piece of crust, recording polyphase magmatic activity since the Mesozoic, with potentially significant activity during Cenozoic post‐rift time. The NE SCS margin is conjugate to Palawan whose basement is considered to be part of the exotic Luconia microcontinent that collided with Eurasia during the Late Cretaceous. Basement similarities between Palawan and the SH are highlighted, suggesting that the latter might also be part of Luconia. Our results suggest that the docking/suture zone between Eurasia and Luconia might have acted as a preferred zone for the Cenozoic rift development.
A Robust Multi‐Objective Pressure Sensor Placement Method for Burst Detection in Water Distribution Systems
Authors: Du Kun , Yu Jinxin , Zheng Feifei , Xu Wei , Savic Dragan , Kapelan Zoran 
Published: August 2024

AbstractBursts in water distribution systems (WDSs) lead to water wastage and negative environmental impacts. Optimizing pressure sensor placement (PSP) for effective burst detection is crucial for prompt response and adverse event mitigation. While many optimization methods are available for this purpose, their resulting PSP strategies often exhibit large variability caused by background noise or metering accuracy, representing low robustness. This consequently hinders the wide application of existing PSP methods for burst detection in WDSs. This study proposes a novel multi‐objective PSP method aimed at maximizing burst detection while minimizing the number of sensors. Within this method, a new threshold metric is introduced to quantify the minimum detectable burst outflow across all pipes. The metric has the key advantage of taking into account the fact that the relative magnitude of the detectable threshold for different pipes is independent of noise, thereby addressing the low robustness issue. The proposed method is applied to three WDSs, and results show that it can consistently achieve robust optimal PSP strategies across diverse noise conditions. Comprehensive comparisons between the proposed method and the other benchmark approaches are conducted using five metrics, including detection performance and layout characteristics. These comparisons reveal the properties of each optimization method and show how detection performance is affected by various placement features. It is anticipated that the proposed method can be useful in engineering practice due to its great robustness in determining the optimal PSP strategies for burst detection in WDSs compared to other alternatives.
Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community
Authors: Cuglievan Branko , Kantarjian Hagop , Rubnitz Jeffrey E. , Cooper Todd M. , Zwaan C. Michel , Pollard Jessica A. , DiNardo Courtney D. , Kadia Tapan M. , Guest Erin , Short Nicholas J. , McCall David , Daver Naval , Nunez Cesar , Haddad Fadi G. , Garcia Miriam , Bhalla Kapil N. , Maiti Abhishek , Catueno Samanta , Fiskus Warren , Carter Bing Z. , Gibson Amber , Roth Michael , Khazal Sajad , Tewari Priti , Abbas Hussein A. , Bourgeois Wallace , Andreeff Michael , Shukla Neerav N. , Truong Danh D. , Connors Jeremy , Ludwig Joseph A. , Stutterheim Janine , Salzer Elisabeth , Juul-Dam Kristian L. , Sasaki Koji , Mahadeo Kris M. , Tasian Sarah K. , Borthakur Gautam , Dickson Samantha , Jain Nitin , Jabbour Elias , Meshinchi Soheil , Garcia-Manero Guillermo , Ravandi Farhad , Stein Eytan M. , Kolb E. Anders , Issa Ghayas C. 
Published: August 2024

AbstractAberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell transplant physicians have united their expertise to explore the potential of menin inhibitors in pediatric leukemia treatment internationally. Our efforts aim to provide a comprehensive clinical overview of menin inhibitors, integrating preclinical evidence and insights from ongoing global clinical trials. Additionally, we propose future international, inclusive, and efficient clinical trial designs, integrating pediatric populations in adult trials, to ensure broad access to this promising therapy for all children and adolescents with menin-dependent leukemias.
Giant Kerr nonlinearity of terahertz waves mediated by stimulated phonon polaritons in a microcavity chip
Authors: Huang Yibo , Lu Yao , Li Wei , Xu Xitan , Jiang Xinda , Ma Ruobin , Chen Lu , Ruan Ningjuan , Wu Qiang , Xu Jingjun 
Published: August 2024

AbstractOptical Kerr effect, in which input light intensity linearly alters the refractive index, has enabled the generation of optical solitons, supercontinuum spectra, and frequency combs, playing vital roles in the on-chip devices, fiber communications, and quantum manipulations. Especially, terahertz Kerr effect, featuring fascinating prospects in future high-rate computing, artificial intelligence, and cloud-based technologies, encounters a great challenge due to the rather low power density and feeble Kerr response. Here, we demonstrate a giant terahertz frequency Kerr nonlinearity mediated by stimulated phonon polaritons. Under the influences of the giant Kerr nonlinearity, the power-dependent refractive index change would result in a frequency shift in the microcavity, which was experimentally demonstrated via the measurement of the resonant mode of a chip-scale lithium niobate Fabry-Pérot microcavity. Attributed to the existence of stimulated phonon polaritons, the nonlinear coefficient extracted from the frequency shifts is orders of magnitude larger than that of visible and infrared light, which is also theoretically demonstrated by nonlinear Huang equations. This work opens an avenue for many rich and fruitful terahertz Kerr effect based physical, chemical, and biological systems that have terahertz fingerprints.
Child maltreatment as a transdiagnostic risk factor for the externalizing dimension: a Mendelian randomization study
Authors: Konzok Julian , Gorski Mathias , Winkler Thomas W. , Baumeister Sebastian E. , Warrier Varun , Leitzmann Michael F. , Baurecht Hansjörg 
Published: August 2024

Abstract
Observational studies suggest that child maltreatment increases the risk of externalizing spectrum disorders such as attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), antisocial personality disorder (ASPD), and substance use disorder (SUD). Yet, only few of such associations have been investigated by approaches that provide strong evidence for causation, such as Mendelian Randomization (MR). Establishing causal inference is essential given the growing recognition of gene-environment correlations, which can confound observational research in the context of childhood maltreatment. Evaluating causality between child maltreatment and the externalizing phenotypes, we used genome-wide association study (GWAS) summary data for child maltreatment (143,473 participants), ADHD (20,183 cases; 35,191 controls), CD (451 cases; 256,859 controls), ASPD (381 cases; 252,877 controls), alcohol use disorder (AUD; 13,422 cases; 244,533 controls), opioid use disorder (OUD; 775 cases; 255,921 controls), and cannabinoid use disorder (CUD; 14,080 cases; 343,726 controls). We also generated a latent variable ‘common externalizing factor’ (EXT) using genomic structural equation modeling. Genetically predicted childhood maltreatment was consistently associated with ADHD (odds ratio [OR], 10.09; 95%-CI, 4.76–21.40; P = 1.63 × 10−09), AUD (OR, 3.72; 95%-CI, 1.85–7.52; P = 2.42 × 10−04), and the EXT (OR, 2.64; 95%-CI, 1.52–4.60; P = 5.80 × 10−04) across the different analyses and pleiotropy-robust methods. A subsequent GWAS on childhood maltreatment and the externalizing dimension from Externalizing Consortium (EXT-CON) confirmed these results. Two of the top five genes with the strongest associations in EXT GWAS, CADM2 and SEMA6D, are also ranked among the top 10 in the EXT-CON. The present results confirm the existence of a common externalizing factor and an increasing vulnerability caused by child maltreatment, with crucial implications for prevention. However, the partly diverging results also indicate that specific influences impact individual phenotypes separately.
Brain volumes and cortical thickness and associations with cognition in children born extremely preterm
Authors: Kvanta Hedvig , Padilla Nelly , Nosko Daniela , Mårtensson Gustaf , Broström Lina , de Gamarra-Oca Lexuri Fernández , Bolk Jenny , Ådén Ulrika 
Published: August 2024

Abstract
Background
Children born extremely preterm (EPT) have altered brain volumes and cortical thickness and lower cognition than children born at term. Associations between these have remained largely unexplored, due to the lack of studies focusing on children born EPT.

Methods
Children underwent brain magnetic resonance imaging (MRI) at term and/or 10 years and cognitive assessments at 12 years. The study comprised of 42 children born EPT and 29 term-born controls with cognitive data and MRI data at 10 years, 25 children born EPT had MRI data at term age and 20 had longitudinal MRI data.

Results
Cognition was positively associated with brain volumes at 10 years, but negatively associated with cortical thickness at 10 years. Most associations between term age brain volumes and cognitive outcomes were non-significant for children born EPT. Growth from term to 10 years in children born EPT was not associated with cognition. Insular volume was positively associated with cognition in children born EPT.

Conclusion
Imaging assessments at 10 years had similar associations to cognition in children born EPT and term-born controls. Insular volume could be a biomarker for cognitive outcome. Associations between brain volumetric growth and cognition require further investigation.

Impact

This study investigated brain volumes, volumetric growth, and cortical thickness in children born extremely preterm, who have rarely been studied exclusively, and compared the data with term-born controls.

In both groups, brain volumes at 10 years were positively associated with cognitive outcome at 12 years, but cortical thickness at 10 years was negatively associated with cognitive outcome at 12 years. Volumetric growth from term age to 10 years was not associated with cognitive outcome in the subset of children born extremely preterm with longitudinal data.

Insular volume may be a potential biomarker for cognitive outcome in children born extremely preterm.
Recent advances in Alzheimer’s disease: mechanisms, clinical trials and new drug development strategies
Authors: Zhang Jifa , Zhang Yinglu , Wang Jiaxing , Xia Yilin , Zhang Jiaxian , Chen Lei 
Published: August 2024

AbstractAlzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate and diverse, stemming from a combination of factors such as aging, genetics, and environment. Our current understanding of AD pathologies involves various hypotheses, such as the cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, and abnormal autophagy. Nonetheless, unraveling the interplay among these pathological aspects and pinpointing the primary initiators of AD require further elucidation and validation. In the past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available drugs primarily offer symptomatic relief and often accompanied by undesirable side effects. However, recent approvals of aducanumab (1) and lecanemab (2) by the Food and Drug Administration (FDA) present the potential in disrease-modifying effects. Nevertheless, the long-term efficacy and safety of these drugs need further validation. Consequently, the quest for safer and more effective AD drugs persists as a formidable and pressing task. This review discusses the current understanding of AD pathogenesis, advances in diagnostic biomarkers, the latest updates of clinical trials, and emerging technologies for AD drug development. We highlight recent progress in the discovery of selective inhibitors, dual-target inhibitors, allosteric modulators, covalent inhibitors, proteolysis-targeting chimeras (PROTACs), and protein-protein interaction (PPI) modulators. Our goal is to provide insights into the prospective development and clinical application of novel AD drugs.
Disparities in time to treatment with oral antimyeloma medications
Authors: Gasoyan Hamlet , Anwer Faiz , Kovach Jeffrey D. , Casacchia Nicholas J. , Wang Ming , Valent Jason , Halpern Michael T. , Rothberg Michael B. 
Published: August 2024

AbstractThis retrospective cohort study used Taussig Cancer Center’s Myeloma Patient Registry to identify adults with multiple myeloma diagnosed between January 2017-December 2021. Electronic health records data captured time from diagnosis to initial prescription fill for oral antimyeloma medications and initiation of facility administered or oral antimyeloma treatment. We identified 720 patients with a mean age at diagnosis of 67 years ±11; 55% were male, 77% White, 22% Black, 1% other races, covered by private insurance (36%), traditional Medicare (29%), Medicare Advantage (25%), and Medicaid (8.3%). Over a third of patients (37%) resided in an area in the most disadvantaged area deprivation index (ADI) quartile. The median available follow-up was 765 days. Seventy-five percent of the cohort filled an oral antimyeloma medication prescription (excluding corticosteroids), with a median time to fill of 28 days (IQR, 15–61). In the multivariable Cox regression model, Black race (vs. White, adjusted hazard ratio [aHR], 0.61, 95% CI, 0.42–0.87), older age at diagnosis (aHR per 1 year, 0.97, 95% CI, 0.95–0.98), diagnosis during an inpatient admission (aHR, 0.63, 95% CI, 0.43–0.92), and estimated glomerular filtration rate ≤29 ml/min/1.73 m2 (vs. ≥60, aHR, 0.46, 95% CI, 0.29–0.73) were negatively associated with prescription fill for oral antimyeloma medication at 30 days, while insurance type and ADI were not significant predictors.
Pre-treatment magnetic resonance imaging in anal cancer: large-scale evaluation of mrT, mrN and novel staging parameters
Authors: Sekhar Hema , Kochhar Rohit , Carrington Bernadette , Kaye Thomas , Tolan Damian , Malcomson Lee , Saunders Mark P. , Sperrin Matthew , Sebag-Montefiore David , van Herk Marcel , Renehan Andrew G. 
Published: August 2024

Abstract
Background
In patients with squamous cell carcinoma of the anus (SCCA), magnetic resonance (MR) imaging is recommended for pre-treatment staging prior to chemo-radiotherapy (CRT), but large-scale evaluation of its staging performance is lacking.

Methods
We re-characterised pre-treatment MRs from 228 patients with non-metastatic SCCA treated consecutively by CRT (2006–2015) at one UK cancer centre. We derived TN staging from tumour size (mrTr) and nodal involvement (mrN), and additionally characterised novel beyond TN features such as extramural vascular invasion (mrEMVI) and tumour signal heterogeneity (mrTSH). Primary outcomes were 5-year overall survival (OS) and 3-year loco-regional failure (LRF). Time-to-event analyses used Kaplan-Meier estimates; Hazard Ratios (HRs) with confidence intervals (CIs) were derived from Cox models.

Results
With a median follow up of 60.9 months, 5-year OS was 74%. Poor OS was associated with increasing mrT (HR: 1.12 per cm [95% CI: 1.07–1.33]), nodal positivity (HR 2.08 [95% CI 1.23–3.52]) and mrEMVI (HR 3.66 [95% CI: 1.88–7.41]). 3-year LRF rate was 16.5%. Increased LRF was associated with increasing mrT (HR: 1.43 per cm [95% CI: 1.26–1.63]), nodal positivity (HR 2.70 [95% CI 1.39–5.24]) and mrTSH (HR 2.66 [95% CI 1.29–5.48]).

Conclusions
In SCCA, the study demonstrates that mrT and mrN stages are prognostic, while mrEMVI and mrTSH may be novel prognostic factors.
Infections and their prognostic significance before diagnosis of chronic lymphocytic leukemia, non-Hodgkin lymphoma, or multiple myeloma
Authors: Packness Esben , Davidsson Olafur Birgir , Rostgaard Klaus , Andersen Michael Asger , Rotbain Emelie Curovic , Niemann Carsten Utoft , Brieghel Christian , Hjalgrim Henrik 
Published: August 2024

Abstract
Background
Immunodeficiency is a shared feature of B cell malignancies. The risk of infections and their prognostic significance after diagnosis are well characterized, but, conversely, less is known about prediagnostic infections in these domains.

Methods
In matched case-control analyzes, using Danish nationwide registers, we assessed the rate of prediagnostic infections in chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma (DLBCL), multiple myeloma (MM), follicular lymphoma (FL), marginal zone lymphoma (MZL), and lymphoplasmacytic lymphoma (LPL). Survival analyzes of data from clinical registers were then used to determine the effect of infections in the year preceding diagnosis on overall survival. To yield results for as many patients as possible, antimicrobial prescriptions were used as surrogates for infections.

Results
The nationwide and clinical registers comprised 30,389 patients, accumulating 213,649 antimicrobial prescriptions, and 18,560 patients accumulating 107,268 prescriptions, respectively. The relative risk of infections was increased up to 15 years prior to diagnosis of malignancy and markedly increased in the year just prior to diagnosis. More than two antimicrobials within one year prior to diagnosis were associated with significantly shorter overall survival, independently of known prognostic factors.

Conclusion
Patients with B cell-derived malignancies exhibit marked immunodeficiency several years prior to diagnosis such that different disease subtypes demonstrate both overlapping and distinct trends in infection risk preceding diagnosis. Moreover, multiple infections within the year preceding diagnosis are independently associated with shorter overall survival for all the examined malignancies.
Hexokinase HK3-mediated O-GlcNAcylation of EP300: a key regulator of PD-L1 expression and immune evasion in ccRCC
Authors: Zhang Wei , Zhao Enyang , Li Zhuolun , Liu Weiyang , Wang Jinpeng , Hou Wenbin , Zhang Nan , Yu Yang , Li Xuedong , You Bosen 
Published: August 2024

AbstractClear cell renal cell carcinoma (ccRCC) demonstrates enhanced glycolysis, critically contributing to tumor development. Programmed death-ligand 1 (PD-L1) aids tumor cells in evading T-cell-mediated immune surveillance. Yet, the specific mechanism by which glycolysis influences PD-L1 expression in ccRCC is not fully understood. Our research identified that the glycolysis-related gene (GRG) HK3 has a unique correlation with PD-L1 expression. HK3 has been identified as a key regulator of O-GlcNAcylation in ccRCC. O-GlcNAcylation exists on the serine 900 (Ser900) site of EP300 and can enhance its stability and oncogenic activity by preventing ubiquitination. Stably expressed EP300 works together with TFAP2A as a co-transcription factor to promote PD-L1 transcription and as an acetyltransferase to stabilize PD-L1 protein. Furthermore, ccRCC exhibits interactive dynamics with tumor-associated macrophages (TAMs). The uridine 5′-diphospho-N-acetylglucosamine (UDP-GlcNAc), which serves as a critical substrate for the O-GlcNAcylation process, facilitates TAMs polarization. In ccRCC cells, HK3 expression is influenced by IL-10 secreted by M2 TAMs. Our study elucidates that HK3-mediated O-GlcNAcylation of EP300 is involved in tumor immune evasion. This finding suggests potential strategies to enhance the efficacy of immune checkpoint blockade therapy.