bluuebunny/crossref_metadata_2025 huggingface dataset:
A hybrid SARIMA-Prophet model for predicting historical streamflow time-series of the Sobat River in South Sudan
Authors: Kenyi Manzu Gerald Simon , Yamamoto Kayoko
Published: August 2024

Accurate river streamflow forecasting is pivotal for effective water resource planning, infrastructure design, utilization, optimization, and flood planning and warning. Streamflow prediction remains a difficult task due to several factors such as climate change, topography, and lack of observed data in some cases. This paper investigates and evaluates the individual performances of the seasonal auto-regressive integrated moving average (SARIMA) and Prophet models in forecasting the streamflow of the Sobat River and proposes a hybrid SARIMA-Prophet model to leverage the strengths of both approaches. Using the augmented Dickey-Fuller (ADF) and the Kwiatkowski-Phillips-Schmidt-Shin (KPSS) tests, the flow of the Sobat River was found to be stationary. The performance of the models was then assessed based on their residual errors and predictive accuracy using the mean absolute error (MAE), root mean squared error (RMSE), and coefficient of determination (R2). Residual analysis and prediction capabilities revealed that Prophet slightly edged SARIMA in terms of prediction efficacy; however, both models struggled to effectively capture extreme values, resulting in significant overestimations and slight underestimations. The hybrid SARIMA-Prophet model significantly reduced residual variability, achieving a lower MAE of 4.047 m3/s, RMSE of 6.17 m3/s, and a higher R2 of 0.92 than did the SARIMA (MAE: 5.39 m3/s, RMSE: 8.70 m3/s, R2: 0.85) and Prophet (MAE: 5.35 m3/s, RMSE: 8.32 m3/s, and R2: 0.86) models. This indicates that the hybrid model handles both long-term patterns and short-term fluctuations more effectively than the individual models. The findings of the present study highlight the potential of hybrid SARIMA-Prophet models for streamflow forecasting in terms of accuracy and reliability, thus contributing to more effective water resource management and planning, particularly in the Sobat River.
The Value of Drilling—A Chance-Constrained Optimization Approach
Authors: Jeuken Rick , Forbes Michael
Published: August 2024

Managing uncertainty is a core challenge in mine planning. Mine planners often represent various planning variables, such as equipment performance and geological parameters, as random variables due to inherent uncertainties. This paper looks at geological uncertainty and its impact on mine planning. Some traditional approaches to manage this uncertainty include using conditional simulations or mathematical programming in the planning process. Drilling additional holes, despite its cost, is a common method to reduce uncertainty using additional samples to reduce deposit variance. In this paper, we first outline an ore blending optimization model which uses chance-constrained programming to manage property limit risk when selecting the order of ore feed into a processing facility. In coal mining, in tactical planning horizons, the order of coal seam removal is usually predetermined, allowing a blending model to ensure optimal feed properties. Using chance-constrained programming allows us to blend the uncertainties from geological models to maximize plant output while adhering to property constraints. We use the chance-constrained blending model to determine the value of additional information from infill drilling. The model prioritizes drilling locations that reduce uncertainty and improve blending outcomes. A case study on a coking coal mine in Queensland, Australia, demonstrates the model’s application, highlighting significant improvements in blending by reducing the variance of high-quality blocks. The study concludes that targeting high-quality blocks for variance reduction can better accommodate lower-quality material, offering a more valuable approach than the traditional focus of reducing uncertainty in low-quality blocks. This approach provides insights for improving mine planning strategies and showcases the potential of chance constraints in optimizing ore blending under uncertainty.
Aggregate Stability and Aggregate-Associated Organic Matter along a Soil Chronosequence on the Galápagos Archipelago
Authors: Chittamart Natthapol , Mentler Axel , Rechberger Maria V. , Gerzabek Martin H. , Zehetner Franz
Published: August 2024

Purpose: Soil aggregate stability is a crucial property affecting soil erodibility, water infiltration and carbon sequestration. This study aimed to determine ultrasonic aggregate stability (USAS) as well as solid and dissolved organic carbon (OC and DOC) associated with aggregate fractions of different aggregation strength and size in volcanic soils along an Andosol-Luvisol-Cambisol chronosequence on the Galápagos Islands. Methods: Aggregate stability was determined by ultrasonication at different energy levels, i.e. 20, 100, and 500 J mL− 1. OC was measured in different aggregate size fractions, i.e. macroaggregates (250–2000 μm), microaggregates (63–250 μm), and the fraction < 63 μm, and released DOC was determined. Results: Aggregate breakdown increased with ultrasonic energy input. The Andosol (short-range order minerals, high OC) had the highest aggregate stability among the studied soils. The OC contents in the stable macro- and microaggregates (at 20 J mL− 1) were highest in the Andosol (20.4 and 20.1%, respectively), followed by the Luvisol (11.6 and 10.8%, respectively) and the Cambisol (6.5 and 6.7%, respectively). The decreasing aggregate-associated OC stabilization with increasing soil age coincided with mineralogical changes from short-range order phases to high-activity clays to low-activity clays. The release of DOC during sonication was highest for the intermediate-aged soil (Luvisol) and mainly occurred at low and intermediate energy levels, while for the young soil (Andosol), released DOC steadily increased until the highest energy level. Conclusions: Our results imply that mineralogical/pedogenic changes over millennial time scales can make volcanic soils more susceptible to losses of OC by leaching and water erosion.
A Novel Stem Cell Model to Study Preeclampsia Endothelial Dysfunction
Authors: Wu Yanming , Sun Tianyanxin , Medina Pedro , Narasimhan Purnima , Stevenson David K. , Von Versen-Höynck Frauke , Armstrong Jennifer , Wu Joseph C. , Sayed Nazish , Winn Virginia D.
Published: August 2024

Preeclampsia is a common pregnancy complication affecting 5% to 7% of all pregnancies worldwide annually. While the pathogenesis is not fully understood, maternal endothelium dysfunction is thought to be a central component to preeclampsia development. Studies to dissect maternal endothelial dysfunction, particularly on a patient-specific basis, are hampered by limited access to systemic primary endothelial cells (ECs). The objective of this study was to establish a replenishable, patient-specific in vitro EC model to allow robust mechanistic studies to dissect endothelial dysfunction in preeclampsia. Induced pluripotent stem cells (iPSCs) from three women with a history of normotensive pregnancies were differentiated into ECs. The established ECs were exposed to pooled sera from normotensive pregnancies, preeclamptic pregnancies, normotensive postpartum for non-pregnant comparison and controls. Endothelial functions including nitric oxide (NO) release, cell migration, tube formation and viability were evaluated. Levels of NO release were significantly lower after incubation with preeclamptic sera compared to the fetal bovine serum (FBS) control, and normotensive and non-pregnant (postpartum) sera treatments were also lower than FBS but higher than preeclamptic sera treatments. Tube formation and cell migration were also impaired with preeclamptic sera compared to FBS controls. Cell viabilities remained unaffected by any sera treatment. Consistent outcomes were obtained across all three patient-specific lines treated with the same pooled sera. Establishment of patient-derived iPSC-ECs treated with pregnancy sera serves as a novel model to explore the interplay between individual maternal endothelial health and circulating factors that lead to endothelial dysfunction in preeclampsia.
Multiple sclerosis: a narrative overview of current pharmacotherapies and emerging treatment prospects
Authors: Olejnik Piotr , Roszkowska Zuzanna , Adamus Sylwia , Kasarełło Kaja
Published: August 2024

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by pathological processes of demyelination, subsequent axonal loss, and neurodegeneration within the central nervous system. Despite the availability of numerous disease-modifying therapies that effectively manage this condition, there is an emerging need to identify novel therapeutic targets, particularly for progressive forms of MS. Based on contemporary insights into disease pathophysiology, ongoing efforts are directed toward developing innovative treatment modalities. Primarily, monoclonal antibodies have been extensively investigated for their efficacy in influencing specific pathological pathways not yet targeted. Emerging approaches emphasizing cellular mechanisms, such as chimeric antigen receptor T cell therapy targeting immunological cells, are attracting increasing interest. The evolving understanding of microglia and the involvement of ferroptotic mechanisms in MS pathogenesis presents further avenues for targeted therapies. Moreover, innovative treatment strategies extend beyond conventional approaches to encompass interventions that target alterations in microbiota composition and dietary modifications. These adjunctive therapies hold promise as complementary methods for the holistic management of MS. This narrative review aims to summarize current therapies and outline potential treatment methods for individuals with MS.
Large deviations and fairness for a betting game with a constant ratio of capital
Authors: Nakata Toshio
Published: August 2024

This Article is a follow-up to a recent Gazette Article about a probabilistic betting game studied by Abdin et al. [1]. We examine the speed of convergence of the probability needed to investigate this game by giving concrete examples, using the large deviation, which is a valuable tool for estimating probabilities of repeated trials (see [2], [3, Chapter 6], [4, Section 5.11]). Moreover, to get a deep understanding of the game, we study fairness when it is repeated infinite times. Let us call it fairness in the sense of infinity, whose exact definition will be given in the final section.
Viva ‘Vis-viva’
Authors: Mahony John D.
Published: August 2024

Long live the vis-viva equation. There is sometimes more than one way of telling a story with the same ending, and this is particularly true in the field of applied mathematics where there are often different ways of obtaining the same result to a given problem, so that what might be lost or not appreciated in one approach can be found and appreciated in another. It is the purpose here to illustrate this by presenting a well-known example drawn from the field of orbital dynamics, namely the development of what is called the Vis-viva equation. This equation is simply an expression relating the square of the velocity of an orbiting object, for example a planet orbiting a sun, to orbit parameters and scientific constants. It is a standard workhorse equation that is used extensively today by orbit control specialists wishing to determine and affect velocities of spacecraft orbiting significantly larger masses, and it was developed from work carried out centuries ago by Gottfried Leibniz (1646 – 1716). The first story will simply acknowledge the equation and how it arose. The second story will present an alternative approach based on calculus, trigonometry, algebra and computations set against the backdrop of an ellipse geometry. This second story leads to the vis-viva equation in disguise, so to speak, and examples of the speeds of two planets, Earth and Mercury, orbiting the Sun will be discussed. Where relevant, the nomenclature of orbit dynamics will be acknowledged. The discussion will involve primarily a planet’s orbit velocity of translation and detailed considerations will not be given to effects due to its speed of rotation.
Escalating Wildfires in Siberia Driven by Climate Feedbacks Under a Warming Arctic in the 21st Century
Authors: Huang Xin , Xue Lian , Wang Zilin , Liu Yawen , Ding Ke , Ding Aijun
Published: August 2024

Siberian wildfire is of paramount importance in the carbon cycle and climate change as it is a major disturbance in the pan‐Arctic ecosystems. In recent decades, the Siberian wildfire regime has been shifting; however, less is known about its process‐based feedback mechanisms. By integrating in‐situ and satellite observational data sets as well as chemistry‐climate coupled modeling, we find that central Siberia has featured the most prominent wildfire escalation during the past two decades, which is closely related to hydrological drought with decreasing rainfall and drying soil under a fast‐warming Arctic. Furthermore, fire‐emitted aerosols compound the increasing wildfires via serving as cloud condensation nuclei and suppressing precipitation, forming self‐amplifying feedback. As the Arctic warming is projected to continue, wildfires are estimated to more than double by the end of this century. This work highlights the great importance of fire risk management based on a fundamental scientific understanding of the complex climate system.
Integrated Spectral and Compositional Analysis for the Lunar Tsiolkovskiy Crater
Authors: Tognon Gloria , Zambon Francesca , Carli Cristian , Massironi Matteo , Giacomini Lorenza , Pozzobon Riccardo , Salari Giulia , Tosi Federico , Combe Jean‐Philippe , Fonte Sergio
Published: August 2024

Remote sensing observations represent the primary means in the production of geologic maps of planetary surfaces. However, they do not provide the same level of detail as Earth's geologic maps, which rely also on field observations and laboratory analyses. Color‐derived basemaps can help to bridge this gap by highlighting peculiar surface and compositional properties. Here, we analyzed the spectral properties of the lunar Tsiolkovskiy crater through the definition of spectral units summarizing the information enclosed by a set of selected spectral parameters. We then performed a compositional analysis of the newly derived spectral units that helped us in discriminating the presence and relative abundance of the main mineralogical phases on the Moon. As a final step, we produced a geo‐stratigraphic map of the Tsiolkovskiy crater integrating in a single mapping product both morphologic, stratigraphic and compositional information. The basaltic infilling of the crater is distinguished by three spectral units associated with distinct effusive events presenting a different composition. On the central peak, plagioclase and olivine suggest the presence of Mg‐suite rocks from the lower crust. The continuous ejecta deposits are mostly characterized by impact melts and shocked materials rich in glass or agglutinates related to more mature terrains from which occasionally appear fresher anorthositic and gabbroic outcrops exposed by the inward sliding of the crater walls. Overall, the geo‐stratigraphic map allows inferring compositional variations associated with the different morpho‐stratigraphic units, which clarify and elaborate on the compositional heterogeneities within the lunar crust and the Tsiolkovskiy crater, and its geologic evolutionary history.
The Effect of Drying Boreal Lakes on Plants, Soils, and Microbial Communities in Lake Margin Habitats
Authors: Patil Vijay P. , McFarland Jack W. , Wickland Kimberly P. , Manies Kristen , Winterstein Mark , Hollingsworth Teresa N. , Euskirchen Eugénie S. , Waldrop Mark P.
Published: August 2024

Decadal scale lake drying in interior Alaska results in lake margin colonization by willow shrub and graminoid vegetation, but the effects of these changes on plant production, biodiversity, soil properties, and soil microbial communities are not well known. We studied changes in soil organic carbon (SOC) and nitrogen (N) storage, plant and microbial community composition, and soil microbial activities in drying and non‐drying lakes in the Yukon Flats National Wildlife Refuge. Historic changes in lake area were determined using Landsat imagery. Results showed that SOC storage in drying lake margins declined by 0.13 kg C m−2 yr−1 over 30 years of exposure of lake sediments, with no significant change in soil N. Lake drying resulted in an increase in graminoid and shrub aboveground net primary production (ANPP, +3% yr−1) with little change in plant functional composition. Increases in ANPP were similar in magnitude (but opposite in sign) to losses in SOC over a 30‐year drying trend. Potential decomposition rates and soil enzyme activities were lower in drying lake margins compared to stable lake margins, possibly due to high salinities in drying lake margin soils. Microbial communities shifted in response to changing plant communities, although they still retained a legacy of the previous plant community. Understanding how changing lake hydrology impacts the ecology and biogeochemistry of lake margin terrestrial ecosystems is an underexamined phenomenon with large impacts to landscape processes.
A Real‐Time Prediction System of the Intensity of Solar Energetic Proton Events Based on a Solution of the Diffusion Equation
Authors: Zhang Y. , Wang Y. , Li X. , Zuo P. B.
Published: August 2024

In this study, based on solar energetic particle (SEP) events classification and a solution of the diffusion equation, we present an efficient system, HITSEP, to predict the intensities in different energy channels (P4 15.0–44.0 MeV, P5 40.0–80.0 MeV, and P6 80.0–165.0 MeV) of energetic proton events observed by GOES spacecraft. The system can predict the rising phase (especially the peak time and peak intensity) of the energetic proton events using only a small amount of data at the beginning of the solar energetic proton events. Among the events that meet the conditions for the use of our prediction system from 2003 to 2017, for P4, P5, and P6 channels, the median Warning Times are 3.70, 2.52, and 1.69 hr; the median Error of the Intensity for events are 0.43, 0.23, 0.34 orders of magnitude; the median Error of the Peak Time for events are 2.53, 0.55, 0.43 hr, respectively. Our system is based on physical mechanisms and has a high accuracy in forecasting the peak intensity with a strict definition of the error. The HITSEP system has huge potential to apply in the space weather forecast. The application of the HITSEP system in space weather forecasting is very promising.
Tracer Velocity Versus Bedload Velocity: Derivation of the Unsteady Virtual Bedload Velocity From Decelerating Tracers
Authors: Klösch M. , Pessenlehner S. , Gmeiner P. , Habersack H.
Published: August 2024

During rest periods, bedload tracers can be buried, while transport can move them to locations with different bed shear stresses or a different riverbed composition. This affects the mobility of the tracers compared to that of the bedload at the location where the tracers were seeded and has so far limited the explanatory power of field tracer studies on the virtual bedload velocity. This paper proposes a method to assess both the unsteady virtual tracer velocity and the unsteady virtual bedload velocity from field tracer studies. First, the virtual bedload velocity was conceptualized as the velocity of a relay run and contrasted with the velocity of the decelerating runs of bedload tracers. Then, a regression method for deriving the unsteady virtual velocity of bedload tracers was extended to account for tracer slowdown by including a corresponding function of the distance traveled. Finally, data from 65 bedload tracers in the Upper Drava River with very‐high‐frequency (VHF) transmitters were used for method testing. By linking the measured tracer mobility to the hydraulics and bed surface grain size near the seeding location, it was possible to determine the unsteady bedload velocity function as the unsteady tracer velocity function at a travel distance of zero. The tracer travels exhibited increasing slowdown effects with increasing tracer grain size, probably due to the dominant role of advection effects at the study site. The derivation of the bedload velocity ensures comparability to laboratory results and between tracer studies.
Effect of Tropical Cyclone Intensity on the Relationship Between Hydrometeor Distribution and Rapid Intensification by GPM GMI
Authors: Leng Yuankang , Liu Rui , Zhu Peijun , Zhang Honglei
Published: August 2024

This study analyzes hydrometeor evolution during rapid intensification (RI) and tropical cyclone (TC) intensity dependence using satellite data. Previous studies have suggested ice cloud water or non‐convective precipitation as a predictor of RI from different perspectives. However, few studies have focused on the impact of TC intensity or comprehensive comparisons to identify better indicators. During RI, hydrometeor contents in weak TCs increase over the entire region, whereas they increase mainly in the inner‐core region and decrease in advance in the outer‐core region for strong TCs. Hydrometeor contents in the inner‐core are higher in RI than in slow intensification, and their maxima location is related to TC intensity and intensification rate. Cloud water path (CWP) in the inner‐core region is most correlated with the intensification rate, especially in weak TCs. Therefore, the CWP can serve as a predictor of RI and can be applied to all TC intensities.
Dust Source Areas and Their Plume Extent Derived From Satellite Data Fields
Authors: AlNasser Faisal , Chehbouni Abdelghani , Entekhabi Dara
Published: August 2024

In this study, prominent dust source areas are identified along with their plume extent using high temporal frequency satellite observations. Hourly dust plume observations of the Dust Belt from geostationary‐orbit satellites are analyzed for the 2017‐12–2022‐11 period. To identify dust source areas and their extents, we back‐track plumes to their source, assessing source areas in terms of emission frequency, contribution, and plume extent patterns. This method advances over traditional source allocation techniques that rely on polar‐orbiting satellites based on a few daily passes and meteorological wind fields for backtracking. Our findings indicate that Boreal summer is the most intense season for most sources, except in the Southern Sahara, which experiences winterly winds. Our analysis also reveals significant contributions from regions within the Sahara that experience expansive but infrequent dust storms, highlighting the importance of considering both frequency and magnitude in understanding dust emissions.
Analysis of the Antarctic Marginal Ice Zone Based on Unsupervised Classification of Standalone Sea Ice Model Data
Authors: Day Noah S. , Bennetts Luke G. , O’Farrell Siobhan P. , Alberello Alberto , Montiel Fabien
Published: August 2024

The Antarctic marginal ice zone, the regularly wave‐affected outer band of the sea ice covered Southern Ocean, typically contains an unconsolidated ice cover comprised of smaller, thinner floes than the inner ice pack. Thus, it is a highly dynamic region and susceptible to rapid expansion and contraction, making it a focal area for understanding and predicting the response of Antarctic sea ice to a changing climate. This novel study uses unsupervised statistical clustering of sea ice data simulated by a global sea ice model (standalone CICE6 combined with a wave propagation module and prescribed ocean) to address the outstanding challenge of separating the marginal ice zone from the inner ice pack in sea ice data sets. The method identifies a marginal ice zone with the desired characteristics and floe size is shown to be the key variable in the classification. Simulated marginal ice zone widths are similar to those derived from satellite observations of wave penetration distances, but contrast with those using the standard 15%–80% areal sea ice concentration proxy, particularly during austral winter. The simulated marginal ice zone is found to undergo a seasonal transition due to new ice formation in winter, increased drift in spring, and increased rates of wave‐induced breakup and melting in summer. The understanding gained from the study motivates incorporation of wave and floe‐scale processes in sea ice models, and the methods are available for application to outputs from high‐resolution and coupled sea ice–ocean–wave models for more detailed studies of the marginal ice zone (in both hemispheres).
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

Different 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

We 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

Bursts 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

Aberrant 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

Optical 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.
Chiral liquid crystal elastomers advance light modulation
Authors: Ma Jiazhe , Yang Zhongqiang
Published: August 2024

Chiral liquid crystal elastomers, as soft photonic materials, enable dynamic omnidirectional tuning of circularly polarized reflection wavelength and function as an effective medium for full-color circularly polarized luminescence, showing promise for advanced photonic applications.
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

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

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

Alzheimer’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

This 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

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

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.