bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic behavior, social optimization, and revenue maximization in queues with infinite servers
Authors: Su Yan , Li Junping
Published: November 2024

Motivated by the impact of emerging technologies on (toll) parks, this paper studies a problem of customers’ strategic behavior, social optimization, and revenue maximization for infinite-server queues. More specifically, we assume that a customer’s utility consists of a positive reward for receiving service minus a cost caused by the other customers in the system. In the observable setting, we show the existence, uniqueness, and expressions of the individual equilibrium threshold, the socially optimal threshold, and the optimal revenue threshold, respectively. Then, we prove that the optimal revenue threshold is smaller than the socially optimal threshold, which is smaller than the individual one. Furthermore, we also extend the cost functions to any finite polynomial function with nonnegative coefficients. In the unobservable setting, we derive the joining probabilities of individual equilibrium and optimal revenue. Finally, using numerical experiments, we complement our results and compare the social welfare and the revenue under these two information levels.
Transcatheter closure of a large aortopulmonary window using a Lifetech™ Konar-MF occluder device
Authors: Chaturvedi Kanupriya , Thakur Prashant , Gupta Sunil Kumar
Published: November 2024

Aortopulmonary window is a rare CHD, which comprises a communication between the ascending aorta and the pulmonary artery. The standard treatment of aortopulmonary window is surgical; however, few cases are amenable to closure via percutaneous intervention. We present a case of aortopulmonary window closure using Lifetech™ Konar-MF occluder device (Lifetech Scientific Co. Ltd., Shenzhen).
Linking heart and mind: development and evaluation of online information material on mental health disorders in children and adolescents with CHDs
Authors: Hejl Julie L. , Lau-Jensen Sara H. , Hjortdal Vibeke E. , Rask Charlotte U.
Published: November 2024

Psychiatric comorbidity is common in children and adolescents with CHDs. Early recognition and evidence-based treatments are crucial to prevent long-term consequences. To support early identification and reduce stigma, we 1) developed and 2) tested the usability and acceptability of online information material on common mental health disorders targeted healthcare professionals and affected families. Website content was shaped by insights from interviews with healthcare professionals across sectors, parents, and adolescents. Evaluations demonstrated promising acceptability and usability of the first prototype but indicated the need for improvements in specific aspects of content, navigation, and overall aesthetics.
Anticoagulation with warfarin for paediatric cardiac indications: a retrospective study
Authors: O’Brien Stephen T. , Duignan Sophie , Crumlish Kathleen , O’Donoghue Jacqueline , Franklin Orla , McMahon Colin J.
Published: November 2024

Warfarin is used as anticoagulation for children for a wide range of cardiac indications but carries the disadvantage of requiring international normalised ratio monitoring and dose adjustment. Management of warfarin therapy is challenging due to its narrow therapeutic window and is further complicated in children by dietary changes, frequent illnesses, and developing systems of metabolism and haemostasis.

A retrospective review was performed of patients’ medical records to assess the indication for warfarin use, percentage of international normalised ratio values in target range (%ITR), and frequency of phlebotomy.

Twenty-six patients were identified. The most common indication for warfarin use was in patients post-total cavo-pulmonary connection (n = 19, 73%). We demonstrated a variability in duration of warfarin therapy following total cavo-pulmonary connection (median of 11.1 months). Nineteen (73%) patients had used the CoaguChek machine for home measurement of international normalised ratio. The median frequency of phlebotomy for all indications was once every 10 days, and the median %ITR was 55.4 % (29.7–86.4%). Of note, the percentage under target range in the patients with mechanical mitral (n = 2) and aortic valves (n = 1) was found to be 23% and 33%, respectively.

These data demonstrate a high frequency of international normalised ratio values outside of the target range as seen in previous studies of warfarin in children. This necessitates frequent phlebotomy and dose changes, which can have a significant effect on the quality of life of these patients and their families highlighting the need to focus on quality improvement in the area of anticoagulation in paediatric cardiac patients.
The prefrontal cortex, but not the medial temporal lobe, is associated with episodic memory in middle-aged persons with HIV
Authors: Campbell Laura M. , Fennema-Notestine Christine , Sundermann Erin E. , Barrett Averi , Bondi Mark W. , Ellis Ronald J. , Franklin Donald , Gelman Benjamin , Gilbert Paul E. , Grant Igor , Heaton Robert K. , Moore David J. , Morgello Susan , Letendre Scott , Patel Payal B. , Roesch Scott , Moore Raeanne C.
Published: November 2024

Objective:

Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.

Design:

We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).

Results:

At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.

Conclusions:

Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.
An Economic Assessment of the EU–Japan Economic Partnership Agreement with Realistic Preference Utilization Rates
Authors: Van der Vorst Camille
Published: November 2024

Recent years have seen an increased focus on the implementation of Preferential Trade Agreements (PTAs). While the number of PTAs has risen remarkably since early 2000, data on the utilization of preferential tariffs under these agreements point out that some businesses have not gained access to all the benefits that PTAs can provide. When utilization rates are low, the impact of the agreement will likely differ from what was anticipated by ex-ante economic research. This paper conducts a dynamic Computable General Equilibrium (CGE) analysis of the expected impact of the EU–Japan Economic Partnership Agreement and compares a scenario that includes realistic preference utilization data with a standard scenario where all tariff liberalization is assumed to be fully utilized by businesses. The results show considerable differences between the two scenarios and illustrate the need to make the inclusion of credible utilization data standard practice in the modelling of international trade.
Benefit-finding in children with advanced cancer and their parents
Authors: Siefring Emma , Olsavsky Anna L. , Schaefer Megan , Sutherland-Foggio Malcolm , Himelhoch Alexandra C. , Hill Kylie N. , Kenney Ansley E. , Humphrey Lisa , Olshefski Randal , Gerhardt Cynthia A.
Published: November 2024

Objectives

Although pediatric cancer often causes significant stress for families, most childhood cancer survivors are resilient and do not exhibit severe or lasting psychopathology. Research demonstrates some survivors may report benefit-finding or positive outcomes following this stressful life event. However, considerably less research has included families of children who are unlikely to survive their illness. Thus, this study investigated benefit-finding among parents and their children with advanced cancer, as well as associated demographic and medical factors.

Methods

Families (N = 72) of children with advanced cancer (ages 5–25) were recruited from a large pediatric hospital. Advanced cancer was defined as relapsed or refractory disease, an estimated prognosis of <60%, or referral to end-of-life care. Participants completed a demographic survey and the Benefit Finding Scale at enrollment.

Results

Children, mothers, and fathers reported moderate to high benefit-finding scores. Correlations between family members were weak and non-significant. Children reported significantly higher benefit-finding than fathers. Demographic and medical factors were not associated with benefit-finding in children, mothers, or fathers.

Significance of results

Families of children with advanced cancer reported moderate to high benefit-finding regardless of background or medical factors. Children identified benefits of their cancer experience independent of the experiences of their mothers and fathers. Larger studies should continue to examine factors associated with positive and negative outcomes in the context of childhood cancer to inform interventions.
Polycentric governance in collusive agreements
Authors: Schmal W. Benedikt
Published: November 2024

Collusive agreements in the form of corporate cartels are complex structures. The involved firms need to agree on terms that are legally not enforceable. However, the interplay between the involved firms in a collusive agreement, i.e., the governance dimension within a cartel, has received surprisingly low attention. Using a comprehensive OECD dataset of 191 cartels from 2012 to 2018, this paper empirically demonstrates how polycentric governance within a cartel may possibly contribute to understanding its stability. It may be beneficial for the duration and lower sanctions imposed by competition authorities, especially for large cartels. By that, the paper sheds new light on two aspects: the entangled governance structures of corporate cartels and the relevance of the concept of polycentricity beyond public administration.
Mutual coupling reduction of two-port dielectric resonator MIMO antenna using defected ground structure
Authors: Sharma Gouri Shankar , Gupta Anshul
Published: November 2024

This article focuses on reducing mutual coupling between the ports of dielectric resonator antenna (DRA) using defected ground structures (DGSs). The antenna has the dimension of 50 mm × 50 mm × 8.5 mm. The resonating element in the proposed two-port radiator consists of a cylindrical structure of alumina ceramic (ɛr = 9.8). The rectangular-shaped aperture is utilized to excite both of the resonating elements. The resonating ceramic elements acting as radiators are offset-fed to enhance the antenna’s coupling. Combining interdigital-shaped and semicircular arc-shaped DGSs improves isolation between two resonating elements, embodying the structural novelty. The measured operating frequency range of Port-1 and Port-2 is 5.19–6.7 and 5.15–6.68 GHz, resonating at 5.58 and 5.56 GHz, respectively. The measured mutual coupling between the two ports is −35.5 dB. The measured gain for Port-1 is depicted to be 5.5 dB. The presented multiple-input–multiple-output (MIMO) radiator in this article is an appropriate candidate for WLAN (5.25–5.35, 5.47–5.725, 5.725–5.85, 5.850–5.925 GHz) and WiMAX(5.5 GHz) applications. All the simulated and experimentally observed MIMO parameters of the radiator are discovered to be within optimal bounds.
Deep-blur: Blind identification and deblurring with convolutional neural networks
Authors: Debarnot Valentin , Weiss Pierre
Published: November 2024

We propose a neural network architecture and a training procedure to estimate blurring operators and deblur images from a single degraded image. Our key assumption is that the forward operators can be parameterized by a low-dimensional vector. The models we consider include a description of the point spread function with Zernike polynomials in the pupil plane or product-convolution expansions, which incorporate space-varying operators. Numerical experiments show that the proposed method can accurately and robustly recover the blur parameters even for large noise levels. For a convolution model, the average signal-to-noise ratio of the recovered point spread function ranges from 13 dB in the noiseless regime to 8 dB in the high-noise regime. In comparison, the tested alternatives yield negative values. This operator estimate can then be used as an input for an unrolled neural network to deblur the image. Quantitative experiments on synthetic data demonstrate that this method outperforms other commonly used methods both perceptually and in terms of SSIM. The algorithm can process a 512

$ \times $

512 image under a second on a consumer graphics card and does not require any human interaction once the operator parameterization has been set up.1
A muscle synergies-based controller to drive a powered upper-limb exoskeleton in reaching tasks
Authors: Penna Michele Francesco , Giordano Luca , Tortora Stefano , Astarita Davide , Amato Lorenzo , Dell’Agnello Filippo , Menegatti Emanuele , Gruppioni Emanuele , Vitiello Nicola , Crea Simona , Trigili Emilio
Published: November 2024

This work introduces a real-time intention decoding algorithm grounded in muscle synergies (Syn-ID). The algorithm detects the electromyographic (EMG) onset and infers the direction of the movement during reaching tasks to control a powered shoulder–elbow exoskeleton. Features related to muscle synergies are used in a Gaussian Mixture Model and probability accumulation-based logic to infer the user’s movement direction. The performance of the algorithm was verified by a feasibility study including eight healthy participants. The experiments comprised a transparent session, during which the exoskeleton did not provide any assistance, and an assistive session in which the Syn-ID strategy was employed. Participants were asked to reach eight targets equally spaced on a circumference of 25 cm radius (adjusted chance level: 18.1%). The results showed an average accuracy of 48.7% after 0.6 s from the EMG onset. Most of the confusion of the estimate was found along directions adjacent to the actual one (type 1 error: 33.4%). Effects of the assistance were observed in a statistically significant reduction in the activation of Posterior Deltoid and Triceps Brachii. The final positions of the movements during the assistive session were on average 1.42 cm far from the expected ones, both when the directions were estimated correctly and when type 1 errors occurred. Therefore, combining accurate estimates with type 1 errors, we computed a modified accuracy of 82.10±6.34%. Results were benchmarked with respect to a purely kinematics-based approach. The Syn-ID showed better performance in the first portion of the movement (0.14 s after EMG onset).
Several Mechanisms Drive the Heterogeneity in Browning Across a Boreal Stream Network
Authors: Zhu Xudan , Berninger Frank , Chen Liang , Larson Johannes , Sponseller Ryan A. , Laudon Hjalmar
Published: November 2024

Over the past few decades, many catchments in Northern hemisphere have experienced increases in dissolved organic carbon (DOC) concentrations, resulting in a brownish color of the water, known as aquatic browning. Several mechanisms have been proposed to explain browning, but consensus regarding the relative importance of recovery from acid deposition, climate change, and land management remains elusive. To advance our understanding of browning mechanisms, we explored DOC trends across 13 nested boreal catchments, leveraging concurrent hydrological, chemical, and terrestrial ecosystem data to quantify the contributions of different drivers on observed trends. We first identified the related environmental factors, then attributed the individual trends of DOC to potential drivers across space and time. Our results showed that all catchments exhibited increased DOC trends from 2003 to 2021, but the DOC response rates differed by five‐fold. No single mechanism could fully explain the browning; instead, sulfate deposition, climate‐related factors, and site properties jointly controlled the variation in DOC trends. Specifically, the long‐term increases in DOC were primarily driven by recovery from sulfate deposition, followed by increases in terrestrial productivity, temperature, and discharge. However, catchment area and landcover type also regulated the response rate of DOC to these drivers, creating spatial heterogeneity in browning among sub‐catchments despite similar deposition and climate forcing. Interestingly, browning has weakened in the last decade as sulfate deposition has fully recovered and other current drivers are insufficient to sustain the long‐term increases. Our results highlight that multifaceted, spatially structured, and nonstationary drivers must be accounted for to predict future DOC changes.
Ionospheric Disturbances Observed Over the Peruvian Sector During the Mother's Day Storm (G5‐Level) on 10–12 May 2024
Authors: Singh Ram , Scipión Danny E. , Kuyeng Karim , Condor Percy , De La Jara Cesar , Velasquez Juan Pablo , Flores Roberto , Ivan Edwar , Souza Jonas R. , Migliozzi Michael
Published: November 2024

This article presents the recent extreme and rare G5‐level geomagnetic storm (Mother's Day Storm) effects on the equatorial and low‐latitude ionosphere observed at the Peruvian sector by the Jicamarca (11.9°S, 76.8°W, magnetic dip 1°N) incoherent scatter radar and associated instruments. This storm was produced by multiple Earth‐directed coronal mass ejections, which generated significant modifications in the Earth's magnetic field, leading to the Sym‐H of ∼−518 nT. On the dayside, due to the strong eastward penetration electric field, vertical plasma drift and equatorial electrojet (EEJ) enhanced for 2–3 hr and remained consistent at values of ∼95 m/s and 260 nT between 1700 and 1900 UT (1200 and 1400 LT). At the same time, vertical E  B plasma drift uplifted the equatorial ionosphere, producing the dusk‐side super plasma fountain and transferring electron density to higher latitudes. A huge increase (∼1,325%) in electron density (from 11 to 142 TECu) is observed at low and mid‐latitudes from ∼20°S to 50°S between 2000 and 0400 UT (1500–2300 LT). The strong westward penetration electric field suppressed pre‐reversal enhancement, leading to downward plasma drift (∼−96 m/s) at around 2400 UT (1900 LT). Overnight, vertical plasma drift fluctuated between ±90 m/s, and the combined effect of penetration and disturbance dynamo electric fields caused a significant increase (∼530 km) in ionospheric virtual height. In the main and early recovery phase, consistent short‐ and long‐duration electric field disturbances persisted for approximately 30 hr, with periods of ∼48 and 90 min.
Lower‐Hybrid Wave‐Induced Plasma Mixing Related to Kelvin‐Helmholtz Vortices During Southward IMF
Authors: Blasl K. A. , Settino A. , Nakamura R. , Hasegawa H. , Nakamura T. K. M. , Hosner M.
Published: November 2024

We examine characteristics of the boundaries of 11 Kelvin‐Helmholtz vortex crossings observed by MMS on 23 September 2017 under southward IMF conditions. At both the leading and trailing edges, boundary regions of mixed plasma are observed together with lower‐hybrid wave activity. We found that thicker boundary regions feature a higher number of sub‐ion scale current sheets, of which only one shows clear reconnection signatures. Moreover, the lower‐hybrid waves along the vortex spine region are identified as an effective mechanism for plasma transport with an estimated diffusion coefficient of s. Comparisons with 3D simulations performed under the same conditions as the MMS event suggest that the extension of the boundary regions as well as the number of current sheets are related to different evolutionary stages of the vortices. Such observations can be explained by changes in the upstream magnetic field conditions.
Dissolved Nitrous Oxide and Methane in the Taiwan Strait: Distribution, Seasonal Variation, and Emission
Authors: Wang Xue , Zhan Liyang , Liu Jian , Wang Aijun , Zhang Jiexia , Chen Weicong , Wu Man , Wen Wenjian , Zhang Ruijie , Ye Wangwang
Published: November 2024

The global ocean plays an important role in the overall budgets of nitrous oxide (N2O) and methane (CH4), especially in continental estuaries and shelf areas. Four cruises were conducted between 2021 and 2022, covering the spring, summer, and fall seasons, to study the spatial and seasonal characteristics of N2O and CH4 distributions and emissions in the Taiwan Strait (TWS). The surface N2O and CH4 concentrations gradually decreased from the coast to the open sea, with maximum values (14.3 and 15.6 nmol L−1) occurring near the Jiulong and Minjiang estuaries, respectively. The mean surface N2O concentration (8.2 nmol L−1) was highest in the spring and approximately the same in the summer as in the fall. The mean surface concentrations of CH4 (8.8 nmol L−1) were greater in summer than in spring and fall, probably because of the high freshwater input in summer. Except for several stations in fall, surface waters were oversaturated with N2O and CH4 relative to the atmosphere in other seasons, and the TWS was a net source of atmospheric N2O and CH4 in the spring, summer, and fall. In situ production is the main source of N2O and CH4 in the TWS, with nitrification being the dominant mechanism of N2O production in the TWS. In contrast, physical influences (riverine inputs and water mass mixing) reshape the distributions of N2O and CH4. The annual emissions of N2O and CH4 from the TWS were estimated to be 0.9 × 10−3 ± 2.9 × 10−3 Tg yr−1 and 1.6 × 10−3 ± 3.0 × 10−3 Tg yr−1, respectively. Taken together, the TWS accounts for 0.025% of the surface area of the world's oceans and 0.022% ± 0.07% and 0.017% ± 0.033% of global oceanic N2O and CH4 emissions, respectively.
Using Explainable AI and Transfer Learning to Understand and Predict the Maintenance of Atlantic Blocking With Limited Observational Data
Authors: Zhang Huan , Finkel Justin , Abbot Dorian S. , Gerber Edwin P. , Weare Jonathan
Published: November 2024

Blocking events are an important cause of extreme weather, especially long‐lasting blocking events that trap weather systems in place. The duration of blocking events is, however, underestimated in climate models. Explainable Artificial Intelligence are a class of data analysis methods that can help identify physical causes of prolonged blocking events and diagnose model deficiencies. We demonstrate this approach on an idealized quasigeostrophic (QG) model developed by Marshall and Molteni (1993), https://doi.org/10.1175/1520‐0469(1993)050<1792:taduop>2.0.co;2. We train a convolutional neural network (CNN), and subsequently, build a sparse predictive model for the persistence of Atlantic blocking, conditioned on an initial high‐pressure anomaly. Shapley Additive ExPlanation (SHAP) analysis reveals that high‐pressure anomalies in the American Southeast and North Atlantic, separated by a trough over Atlantic Canada, contribute significantly to prediction of sustained blocking events in the Atlantic region. This agrees with previous work that identified precursors in the same regions via wave train analysis. When we apply the same CNN to blockings in the ERA5 atmospheric reanalysis, there is insufficient data to accurately predict persistent blocks. We partially overcome this limitation by pre‐training the CNN on the plentiful data of the Marshall‐Molteni model, and then using Transfer learning (TL) to achieve better predictions than direct training. SHAP analysis before and after TL allows a comparison between the predictive features in the reanalysis and the QG model, quantifying dynamical biases in the idealized model. This work demonstrates the potential for machine learning methods to extract meaningful precursors of extreme weather events and achieve better prediction using limited observational data.
Online Learning of Entrainment Closures in a Hybrid Machine Learning Parameterization
Authors: Christopoulos Costa , Lopez‐Gomez Ignacio , Beucler Tom , Cohen Yair , Kawczynski Charles , Dunbar Oliver R. A. , Schneider Tapio
Published: November 2024

This work integrates machine learning into an atmospheric parameterization to target uncertain mixing processes while maintaining interpretable, predictive, and well‐established physical equations. We adopt an eddy‐diffusivity mass‐flux (EDMF) parameterization for the unified modeling of various convective and turbulent regimes. To avoid drift and instability that plague offline‐trained machine learning parameterizations that are subsequently coupled with climate models, we frame learning as an inverse problem: Data‐driven models are embedded within the EDMF parameterization and trained online in a one‐dimensional vertical global climate model (GCM) column. Training is performed against output from large‐eddy simulations (LES) forced with GCM‐simulated large‐scale conditions in the Pacific. Rather than optimizing subgrid‐scale tendencies, our framework directly targets climate variables of interest, such as the vertical profiles of entropy and liquid water path. Specifically, we use ensemble Kalman inversion to simultaneously calibrate both the EDMF parameters and the parameters governing data‐driven lateral mixing rates. The calibrated parameterization outperforms existing EDMF schemes, particularly in tropical and subtropical locations of the present climate, and maintains high fidelity in simulating shallow cumulus and stratocumulus regimes under increased sea surface temperatures from AMIP4K experiments. The results showcase the advantage of physically constraining data‐driven models and directly targeting relevant variables through online learning to build robust and stable machine learning parameterizations.
Characterizing Subsurface Structures From Hard and Soft Data With Multiple‐Condition Fusion Neural Network
Authors: Cui Zhesi , Chen Qiyu , Luo Jian , Ma Xiaogang , Liu Gang
Published: November 2024

Accurately inferring realistic subsurface structures poses a considerable challenge due to the impact of morphology on flow and transport behaviors. Traditional subsurface characterization relies on two primary types of data: hard data, derived from direct subsurface measurements, and soft data, encompassing remotely sensed geophysical information and its interpretation. Existing deep‐learning‐based methodologies predominantly focus on the transition from multiple observations to subsurface structures. However, implicit non‐linear correlations among diverse data sources often remain underutilized, leading to potential bias and errors. In this study, we introduce a multiple‐condition fusion network (MCF‐Net) to characterize subsurface structures based on both hard and soft data. To harness the full potential of multiple‐source subsurface observations, two distinct neural networks extract implicit features from hard and soft data. The integration of these features is achieved through multiple‐condition fusion blocks, designed to capture representative characteristics. These blocks are also adept at reconstructing heterogeneous structures and facilitating hydrological parameterization. MCF‐Net exhibits accuracy in estimating subsurface structures across various types of subsurface observations. Experimental results underscore the utility and superiority of MCF‐Net in applications of hydrogeological modeling.
Comparing stem cell mobilization with chemotherapy and cytokine (G-CSF) versus cytokine alone in myeloma patients (MOCCCA): a randomized phase II, open-label, non-inferiority trial
Authors: Jeker Barbara , Thalmann Laura , Bacher Ulrike , Nilius Henning , Rhyner Gaëlle , Sökler Martin , Soltermann Susanne , Winkler Annette , Vorburger Corinne , Daskalakis Michael , Hoffmann Michèle , Pabst Thomas
Published: November 2024

In fit patients with newly diagnosed myeloma, high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is considered standard of care. For mobilization of CD34+ cells for ASCT, combined cytotoxic chemotherapy and G-CSF is commonly used. However, the importance of cytostatic chemotherapy for reliable mobilization remains unclear. This prospective randomized phase II non-inferiority trial compared G-GSF only (G) compared to standard chemotherapy/G-CSF (CG) for CD34+ mobilization. The primary endpoint was a less than 15% difference in successful stem cell collection ( ≥ 5.0 × 106 CD34+ cells/kg b.w. in a single day collection procedure without additional stimulation with plerixafor) with the G regimen. 136 patients were 1:1 randomized. With an 18% difference in favor of the CG therapy, the non-inferiority margin was not maintained (95% CI 1%, 34%, p = 0.04). The median total CD34+ yield was 9.99 × 106/kg b.w. in CG patients and 7.42 × 106/kg b.w. in patients with G-CSF alone (p < 0.001). Ultimately, 130 (96%) patients proceeded to HDCT with ASCT. There were no differences in adverse events, hematologic engraftment, quality of life, or pain perception between the groups. Our data indicate that G-CSF only is inferior to chemotherapy with G-CSF for peripheral CD34+ stem cell mobilization. Trial registration SNCTP #: SNCTP000002952; Trials.gov #: NCT03442673.
NINJ1: Bridging lytic cell death and inflammation therapy
Authors: Shen Jinze , Chen Ruixiu , Duan Shiwei
Published: November 2024

NINJ1, a critical transmembrane protein in inflammation, governs diverse biological processes. Recent breakthroughs revealed NINJ1’s structural basis for plasma membrane rupture, which is directly linked to lytic cell death. This discussion explores NINJ1’s functions, focusing on its pivotal role in lytic cell death regulation and the latest advancements in targeted therapeutic interventions.
Antiseizure medication use during pregnancy and children’s neurodevelopmental outcomes
Authors: Madley-Dowd Paul , Ahlqvist Viktor H. , Forbes Harriet , Rast Jessica E. , Martin Florence Z. , Zhong Caichen , Barry Ciarrah-Jane S. , Berglind Daniel , Lundberg Michael , Lyall Kristen , Newschaffer Craig J. , Tomson Torbjörn , Davies Neil M. , Magnusson Cecilia , Rai Dheeraj , Lee Brian K.
Published: November 2024

The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23–4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05–1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01–1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate.
Metallaphotocatalytic triple couplings for modular synthesis of elaborate N-trifluoroalkyl anilines
Authors: Zhou Ting , Zhang Zhong-Wei , Nie Jing , Kwong Fuk Yee , Ma Jun-An , Cheung Chi Wai
Published: November 2024

The integration of trifluoromethyl groups and three-dimensional quaternary carbon moieties into organic molecules has emerged as a prominent strategy in medicinal chemistry to augment drug efficacy. Although trifluoromethyl (hetero)aromatic amines and derivatives are prevalent frameworks in pharmaceuticals, the development of trifluoromethyl-embedded, intricately structured alkyl amine scaffolds for medicinal research remains a significant challenge. Herein, we present a metallaphotoredox multicomponent amination strategy employing 3,3,3-trifluoropropene, nitroarenes, tertiary alkylamines, and carboxylic acids. This synthetic pathway offers notable advantages, including the accessibility and cost-effectiveness of starting materials, high levels of chemo- and regioselectivity, and modularity. Furthermore, this approach enables the synthesis of a broad spectrum of aniline compounds featuring both trifluoromethyl group and distal quaternary carbon motifs along the aliphatic chains. The accelerated access to such elaborate N-trifluoroalkyl anilines likely involves three sequential radical-mediated coupling events, providing insightful implications for the retrosynthesis of potential compounds in organic synthesis and drug discovery.
Surface superconductivity in the topological Weyl semimetal t-PtBi2
Authors: Schimmel Sebastian , Fasano Yanina , Hoffmann Sven , Besproswanny Julia , Corredor Bohorquez Laura Teresa , Puig Joaquín , Elshalem Bat-Chen , Kalisky Beena , Shipunov Grigory , Baumann Danny , Aswartham Saicharan , Büchner Bernd , Hess Christian
Published: November 2024

Topological superconductivity is a promising concept for generating fault-tolerant qubits. Early experimental studies looked at hybrid systems and doped intrinsic topological or superconducting materials at very low temperatures. However, higher critical temperatures are indispensable for technological exploitation. Recent angle-resolved photoemission spectroscopy results have revealed that superconductivity in the type-I Weyl semimetal—trigonal PtBi2 (t-PtBi2)—is located at the Fermi-arc surface states, which renders the material a potential candidate for intrinsic topological superconductivity. Here we show, using scanning tunnelling microscopy and spectroscopy, that t-PtBi2 presents surface superconductivity at elevated temperatures (5 K). The gap magnitude is elusive: it is spatially inhomogeneous and spans from 0 to 20 meV. In particular, the large gap value and the shape of the quasiparticle excitation spectrum resemble the phenomenology of high-Tc superconductors. To our knowledge, this is the largest superconducting gap so far measured in a topological material. Moreover, we show that the superconducting state at 5 K persists in magnetic fields up to 12 T.
SAGA1 and MITH1 produce matrix-traversing membranes in the CO2-fixing pyrenoid
Authors: Hennacy Jessica H. , Atkinson Nicky , Kayser-Browne Angelo , Ergun Sabrina L. , Franklin Eric , Wang Lianyong , Eicke Simona , Kazachkova Yana , Kafri Moshe , Fauser Friedrich , Vilarrasa-Blasi Josep , Jinkerson Robert E. , Zeeman Samuel C. , McCormick Alistair J. , Jonikas Martin C.
Published: November 2024

Approximately one-third of global CO2 assimilation is performed by the pyrenoid, a liquid-like organelle found in most algae and some plants. Specialized pyrenoid-traversing membranes are hypothesized to drive CO2 assimilation in the pyrenoid by delivering concentrated CO2, but how these membranes are made to traverse the pyrenoid matrix remains unknown. Here we show that proteins SAGA1 and MITH1 cause membranes to traverse the pyrenoid matrix in the model alga Chlamydomonas reinhardtii. Mutants deficient in SAGA1 or MITH1 lack matrix-traversing membranes and exhibit growth defects under CO2-limiting conditions. Expression of SAGA1 and MITH1 together in a heterologous system, the model plant Arabidopsis thaliana, produces matrix-traversing membranes. Both proteins localize to matrix-traversing membranes. SAGA1 binds to the major matrix component, Rubisco, and is necessary to initiate matrix-traversing membranes. MITH1 binds to SAGA1 and is necessary for extension of membranes through the matrix. Our data suggest that SAGA1 and MITH1 cause membranes to traverse the matrix by creating an adhesive interaction between the membrane and matrix. Our study identifies and characterizes key factors in the biogenesis of pyrenoid matrix-traversing membranes, demonstrates the importance of these membranes to pyrenoid function and marks a key milestone toward pyrenoid engineering into crops for improving yields.
The mechanical and sensory signature of plant-based and animal meat
Authors: St. Pierre Skyler R. , Darwin Ethan C. , Adil Divya , Aviles Magaly C. , Date Archer , Dunne Reese A. , Lall Yanav , Parra Vallecillo María , Perez Medina Valerie A. , Linka Kevin , Levenston Marc E. , Kuhl Ellen
Published: November 2024

Eating less meat is associated with a healthier body and planet. Yet, we remain reluctant to switch to a plant-based diet, largely due to the sensory experience of plant-based meat. Food scientists characterize meat using a double compression test, which only probes one-dimensional behavior. Here we use tension, compression, and shear tests–combined with constitutive neural networks–to automatically discover the behavior of eight plant-based and animal meats across the entire three-dimensional spectrum. We find that plant-based sausage and hotdog, with stiffnesses of 95.9 ± 14.1 kPa and 38.7 ± 3.0 kPa, successfully mimic their animal counterparts, with 63.5 ± 45.7 kPa and 44.3 ± 13.2 kPa, while tofurky is twice as stiff, and tofu is twice as soft. Strikingly, a complementary food tasting survey produces in nearly identical stiffness rankings for all eight products (ρ = 0.833, p = 0.015). Probing the fully three-dimensional signature of meats is critical to understand subtle differences in texture that may result in a different perception of taste. Our data and code are freely available at https://github.com/LivingMatterLab/CANN
Population structure and selective signature analysis of local sheep breeds in Xinjiang, China based on high-density SNP chip
Authors: Li Yanhao , Li Xiaopeng , Han Zhipeng , Yang Ruizhi , Zhou Wen , Peng Yuwei , He Jianzhong , Liu Shudong
Published: November 2024

The frigid and droughty climate of Xinjiang in China has given rise to unique indigenous sheep breeds with robust adaptability and resistance. To investigate the genetic mechanism of adaptability of Xinjiang sheep to the local extreme environment, we conducted population genetic structure analyses for three native Xinjiang sheep breeds: Altay sheep (ALT), Bashbay Sheep (BSBC), and Duolang sheep (DLC), as well as two foreign sheep breeds: Suffolk and Dorset, using the Ovine Infinium HD SNP BeadChip(680 K). Our findings revealed distinct genetic and evolutionary histories between Xinjiang and foreign sheep breeds. Principal Component Analysis (PCA) and phylogenetic tree effectively differentiate these five sheep breeds based on their geographical origins, and the domestication level of Xinjiang sheep is comparatively lower than that of foreign sheep breeds. Furthermore, by utilizing three selective signature methods, namely Fixation Index (Fst), Cross Population Extended Haplotype Homozygosity Test (XP-EHH), and Nucleotide Diversity (π), we have successfully identified 22 potential candidate genes. Among these genes, there are TBXT, PDGFD, and VEGFA, which are closely related to tail type and lipid metabolism; VIL1, SLC11A1, and ZBTB46, which are associated with immune function; and candidate genes such as BNC1, HDAC1, and BMP5, which impact sheep reproductive traits. This study establishes a foundation for conserving and utilizing local sheep germplasm resources in Xinjiang and provides molecular insights into the genetic mechanisms governing sheep adaptation to extreme cold and arid environments.
Peak alpha frequency is linked to visual temporal attention in 6-month-olds
Authors: Arioli Martina , Mattersberger Matteo , Hoehl Stefanie , Brzozowska Alicja
Published: November 2024

The temporal resolution of adults’ visual attention has been linked to the frequency of alpha-band oscillations in electroencephalogram (EEG) signal, with higher Peak Alpha Frequency (PAF) being associated with better visual temporal processing skills. However, relatively less is known about neural mechanisms underlying individual differences in the temporal resolution of visual attention in infancy. This study investigated the role of PAF in visual temporal processing in early infancy. In a sample of 6-month-old infants (n = 62) we examined the relationship between PAF extracted from resting-state EEG, and saccadic latencies in a predictive cueing task where the appearance of a reward was predicted by higher or lower frequency of two flickering objects. Results showed that higher PAF was associated with shorter saccadic latencies in a condition with higher differences between the two flickering frequencies, speaking for the involvement of PAF in visual temporal attention in early development. Additionally, we found that infants were generally faster to orient to the reward in trials where both peripheral stimuli were flickering at relatively lower frequencies, roughly corresponding to the theta frequency band. Our findings support theoretical accounts highlighting the role of PAF in visual attention processing and extend this framework to early infancy.
Landscape patterns in stand-replacing disturbances across the world’s forests
Authors: Acil Nezha , Sadler Jonathan P. , Senf Cornelius , Suvanto Susanne , Pugh Thomas A. M.
Published: November 2024

The spatial imprint of forest disturbances, which can result from a variety of anthropogenic and natural causes, is important in shaping the form and function of the world’s forests. However, we lack a systematic assessment of how the forms of forest disturbances differ globally, which could help in sustainable forest policy and management initiatives to protect forest biomes. Here we produce a global-scale quantification of disturbance patch structures. Using indicators of magnitude, complexity and context, we found that the forms of stand-replacing disturbances can be classified into four broad patterns, whose spatial dominance varies across regions. Human activities were shown to introduce disturbance structures that are not naturally common, especially in the tropics. The consistency of these patterns across biomes outside intact forests suggests that a continuation of current dynamics may lead to a structural homogenization of the world’s forests, with potential consequences for forest ecology and functions. These results provide a greater understanding of the mechanisms governing forest dynamics and elucidating the causal agents of disturbances. This will be a key step towards building more reliable projections of future forest conditions, informing policymaking and ensuring the sustainability of forest management.
Mapping cellular stress and lipid dysregulation in Alzheimer-related progressive neurodegeneration using label-free Raman microscopy
Authors: Haessler Annika , Candlish Michael , Hefendehl Jasmin K. , Jung Nathalie , Windbergs Maike
Published: November 2024

Aβ plaques are a main feature of Alzheimer’s disease, and pathological alterations especially in their microenvironment have recently come into focus. However, a holistic imaging approach unveiling these changes and their biochemical nature is still lacking. In this context, we leverage confocal Raman microscopy as unbiased tool for non-destructive, label-free differentiation of progressive biomolecular changes in the Aβ plaque microenvironment in brain tissue of a murine model of cerebral amyloidosis. By developing a detailed approach, overcoming many challenges of chemical imaging, we identify spatially-resolved molecular signatures of disease-associated structures. Specifically, our study reveals nuclear condensation, indicating cellular degeneration, and increased levels of cytochrome c, showing mitochondrial dysfunction, in the vicinity of Aβ plaques. Further, we observe severe accumulation of especially unsaturated lipids. Thus, our study contributes to a comprehensive understanding of disease progression in the Aβ plaque microenvironment, underscoring the prospective of Raman imaging in neurodegenerative disorder research.
Effects of climate and forest development on habitat specialization and biodiversity in Central European mountain forests
Authors: Richter Tobias , Geres Lisa , König Sebastian , Braziunas Kristin H. , Senf Cornelius , Thom Dominik , Bässler Claus , Müller Jörg , Seidl Rupert , Seibold Sebastian
Published: November 2024

Mountain forests are biodiversity hotspots with competing hypotheses proposed to explain elevational trends in habitat specialization and species richness. The altitudinal-niche-breadth hypothesis suggests decreasing specialization with elevation, which could lead to decreasing species richness and weaker differences in species richness and beta diversity among habitat types with increasing elevation. Testing these predictions for bacteria, fungi, plants, arthropods, and vertebrates, we found decreasing habitat specialization (represented by forest developmental stages) with elevation in mountain forests of the Northern Alps – supporting the altitudinal-niche-breadth hypothesis. Species richness decreased with elevation only for arthropods, whereas changes in beta diversity varied among taxa. Along the forest developmental gradient, species richness mainly followed a U-shaped pattern which remained stable along elevation. This highlights the importance of early and late developmental stages for biodiversity and indicates that climate change may alter community composition not only through distributional shifts along elevation but also across forest developmental stages.
Ideal spin-orbit-free Dirac semimetal and diverse topological transitions in Y8CoIn3 family
Authors: Sato Manabu , Bouaziz Juba , Sumita Shuntaro , Kobayashi Shingo , Tateishi Ikuma , Blügel Stefan , Furusaki Akira , Hirayama Motoaki
Published: November 2024

Topological semimetals, known for their intriguing properties arising from band degeneracies, have garnered significant attention. However, the discovery of a material realization and the detailed characterization of spinless Dirac semimetals have not yet been accomplished. Here, we propose from first-principles calculations that the RE8CoX3 group (RE = rare earth elements, X = Al, Ga, or In) contains ideal spinless Dirac semimetals whose Fermi surfaces are fourfold degenerate band-crossing points (without including spin degeneracy). Despite the lack of space inversion symmetry in these materials, Dirac points are formed on the rotation-symmetry axis due to accidental degeneracies of two bands corresponding to different 2-dimensional irreducible representations of the C6v group. We also investigate, through first-principles calculations and effective model analysis, various phase transitions caused by lattice distortion or elemental substitutions from the Dirac semimetal phase to distinct topological semimetallic phases such as nonmagnetic linked-nodal-line and Weyl semimetals (characterized by the second Stiefel–Whitney class) and ferromagnetic Weyl semimetals.