Acute generalized exanthematous pustulosis associated with human parvovirus B19 infection.Juliette COURSIER1 Aymeric HENNEMANN1, Léa MALINOWSKI3, Quentin LEPILLER4,Joséphine MOREAU1, François AUBIN1,21 Service de Dermatologie, Centre Hospitalier Universitaire, Besançon, France2 Université Franche Comté, Inserm 1098 RIGHT, Besançon, France3 Service de Maladies Infectieuses, Centre Hospitalier Universitaire, Besançon, France4 Laboratoire de Virologie, Centre Hospitalier Universitaire, Besançon, France

Background and Purpose: Hexokinase 2 (HK2) is a key enzyme linked to high tumor cell proliferation. Its inhibitors such as 3-bromopyruvic acid (3-BP) induce cancer cell death, highlighting HK2 modulation as potential anti-cancer treatment. However, standard chemotherapies often cause the emergence of cellular senescence, which goes along with cell metabolic reprogramming and treatment failure. This study explores whether targeting HK2 can induce cancer cell senescence and whether metabolic changes in senescent cancer cells are tied to the cellular HK2 status. Experimental Approach: The expression of hexokinase 1 (HK1) and HK2 was assessed using immunoblot and immunofluorescence analysis in cell lines and in primary murine breast cancer (BC) cells. The senescence inducing potential of HK2 inhibition, and the effect of chemotherapy-induced senescence on HK1 and HK2 expression was assessed. Cell-based approaches were complemented by analyzing single-cell RNA sequencing data from BC patients. Key Results: BC cell sensitivity to HK2 inhibition did not correlate with HK2 expression levels. Consistently, senescence was linked to a decrease in HK2, but an increase in HK1 expression. Moreover, genetic knockdown of HK2 induced senescence, indicating that a change in the HK2/HK1 ratio drives, rather than results from, cellular senescence. This shift in HK2/HK1 ratio was confirmed in single-cell RNA sequencing data of BC biopsies. Conclusion and Implications: Expressional shifts in the HK2/HK1 ratio may serve as a novel marker for BC cell senescence. While targeting HK2 shows promise in untreated cancers, senescence-inducing anti-cancer therapies may limit the effectiveness of HK2-targeted treatments in pre-treated cancer patients.

Key Clinical MessageThe coexistence of systemic and localized sclerosis in children and adolescents is a rare phenomenon, but it has been documented. This dual presentation can complicate diagnosis and management, as the systemic features may overshadow localized symptoms. Early recognition and a multidisciplinary approach are essential for optimizing outcomes in affected patients.

Background: to evaluate the clinical characteristics of children with cutaneous mastocytosis (CM), correlate with serum tryptase, disease severity and caregiver’s quality of life (QoL). Methods: a prospective study evolving children under 18 years old, with CM followed from Month/2021 to Month/2023. The severity of CM was assessed using the Scoring Cutaneous Mastocytosis Index (SCORMA) and serum tryptase levels, and the caregiver’s QoL applying the Family Dermatology Life Quality of Index (FDLQI-BRA). Results: Thirty two patients, mean age=29 months (range 3 to 171), 20 (62.5%) had maculopapular CM, 10 (31.2%) mastocytoma and 2 (6.3%) diffuse CM. There were signs and/or symptoms in 25 cases (78.1%). Pruritus occurred in 19 (59.4%) and was more common in patients with maculopapular CM (p = 0.04). Serum tryptase levels were higher in patients with pruritus compared to asymptomatic individuals (p = 0.03). A weak correlation was observed between the SCORMA score and serum tryptase (r = 0.25). Caregiver’s QoL was a median of 7.0 (IIQ = 2.5 – 9.0), ranging from 0.0 to 21.0, and for 17 (53.1%) families, the impact on QoL was very severe or severe. Conclusion: pediatric mastocytosis was benign, serum tryptase levels were higher in symptomatic patients, and the disease had a negative impact on caregiver’s QoL.

This letter proposes a Per-Unit modeling standard (PUMS) for simplified calculations in grid-forming converter (GFMC) systems, which can improve and simplify the modeling process. The proposed PUMS can solve the bottlenecks and difficulties of calculation, caused by the upper limits of calculation in MATLAB, while developing large-scale grid-integration of GFMC. Besides, the proposed PUMS is well matched with actual value modeling. And the switching modeling is compared by the average model with coincidence to verify effectiveness. Finally, modeling and analysis are validated by simulations and experiments.

This paper proposes a novel two-stage hybrid model that integrates the asymmetric conditional autoregressive range (AsyCARR) with long short-term memory (LSTM) models to forecast volatility. In the first stage, the Parkinson (PK) volatility estimates are fitted using the AsyCARR model to obtain the predicted volatilities. The residuals, defined as the deviations between the average lagged of observed PK estimates and the predicted volatilities, are obtained. In the second stage, the LSTM model is employed to train and forecast the residuals. The ultimate forecasted volatilities are obtained by combining the predicted residuals with the average lagged of PK. The main feature of the two-stage hybrid model lies in its ability to capture the asymmetric response of shocks to the conditional expectation of PK volatility while effectively handling the nonlinear residuals components. Moreover, this study investigates the feasibility of incorporating five distinct forms of residuals as an input variable respectively into the LSTM model to enhance forecasting accuracy. Empirical analyses demonstrate that this family of hybrid AsyCARR-LSTM models delivers outstanding performance in both in-sample fitting and out-of-sample forecasting across a comprehensive set of loss functions. Furthermore, the superiority of the hybrid AsyCARR-LSTM model in out-of-sample forecasting is validated through Hansen’s model confidence set test, based on heteroskedastic mean squared error, which confirms its statistical advantage over the CARR and AsyCARR models. Lastly, the findings indicate that the forecasting performance of hybrid models are influenced by the choice of residual forms.

Warming can release carbon from organic matter (OM) initially freeze-locked in circumarctic permafrost. The extent of this carbon release depends on OM reactivity. Our understanding of how OM reactivity varies across different terrestrial permafrost types and how it changes during transport from land to marine shelves remains limited. In this study, we measured bulk organic, isotopic and thermogravimetric properties as proxies of OM reactivity on various materials, including bulk deposits and water-soluble fractions (leachates) from terrestrial Holocene and Pleistocene permafrost, bulk surface sediments from the Laptev Sea, and sediment cores from the western Laptev Sea. Bulk OM from terrestrial Pleistocene permafrost exhibited lower reactivity compared to Holocene permafrost. Leachates from terrestrial Pleistocene permafrost displayed slightly higher OM reactivity and younger radiocarbon ages than their corresponding bulk fractions but these values remained lower than those of Holocene permafrost. On the eastern Laptev Sea shelf, a higher contribution of Pleistocene permafrost-derived OM resulted in relatively old radiocarbon ages and reduced OM reactivity in surface sediments compared to the central and western Laptev Sea shelf. A cross-shelf gradient in OM reactivity was observed in the central and western Laptev Sea, with a rapid decrease near the coast followed by a more gradual decline offshore. Downcore analyses revealed that this reduction in OM reactivity reflects primarily degradation during cross-shelf transport rather than after burial. Our results advance the understanding of OM reactivity differences between Pleistocene and Holocene permafrost, as well as changes in terrestrial permafrost OM reactivity during transport and after burial.

In this study, we analyze the ionospheric and thermospheric changes from three coronal mass ejections (CMEs) that triggered a composite geomagnetic storm on 4-5 November 2023 with two activity periods. The first CME arrival on 4 November resulted in moderate activity (SYM-H=-60 nT), while two CMEs that arrived on 5 November caused intense geomagnetic disturbances (SYMH=-188 nT). Using global observations of vertical total electron content (VTEC) and the normalized VTEC storm-time index, we examine ionospheric anomalies during these events. Additionally, we use satellite observations of thermospheric composition, temperature and density, along with ionosonde-derived estimations of the large-scale traveling ionospheric disturbances velocities. Our results show that initial ionospheric changes in both activity periods were driven by prompt penetration electric fields, leading to positive VTEC anomalies. However, the delayed effects were vastly different. Due to weak high-latitude heating, the negative phase in 4 November event was largely inhibited. In contrast, on 5 November, high-latitude thermospheric heating was significant and led to strong decreases in the O/N2 ratios and setup global disturbance winds, causing severe negative VTEC anomalies. Despite weaker overall effects in VTEC, the moderate 4 November event caused a much more pronounced degradation of the GNSS availability due to stronger auroral scintillations. Our results underscore the highly dynamic nature of the ionosphere-thermosphere system and showcase that even similarly driven and temporally close events can nevertheless produce markedly different ionospheric responses. Notably, events with weaker geomagnetic activity can pose greater hazard and need to be carefully monitored to mitigate their potential impacts.

Breast cancer is the most common cancer and the leading cause of mortality among Brazilian women. Once the tumor is detected, prompt treatment is essential to improve prognosis and reduce both the physical and psychological suffering of the patient and her family. However, access to oncology treatment varies across regions, with disparities remaining significant. Primary health care holds great potential for promoting breast cancer screening and early detection. However, the impact of primary care networks on access to treatment is still underexplored. This study examines the effect of primary health care team availability on breast cancer notification rates and the average waiting time for surgical treatment in Brazilian municipalities, using a panel of public health indicators from 2015 to 2023. The results indicate that, while waiting times have decreased across all regions, inequalities persist, especially in the North. Specifically, increasing the availability of primary health care teams leads to higher breast cancer notification rates in the North, Northeast, and Center-West regions, and reduces surgical waiting times in the Northeast and South. These findings underscore regional health disparities and the critical role of primary care in ensuring timely diagnosis and treatment of breast cancer.

Centuries of barley (Hordeum vulgare) domestication and selection has resulted in reduced genetic diversity in modern cultivars, limiting breeder’s options to select desirable traits. Barley landraces, heirloom varieties and wild relatives are substantially more variable and can be exploited to reintroduce favourable genes and alleles. Five doubled haploid populations were phenotyped for net form net blotch (NFNB) disease, caused by the pathogen Pyrenophora teres f. teres, at three growth stages. Major, moderate and minor effect quantitative trait loci (QTLs) associated with NFNB resistance were detected on six of the seven barley linkage groups, with percentages of explained variance (PEV) ranging from less than ten to over 70%. Previously established major (PEV > 50%) and moderate (PEV 10 - 40%) effect QTLs on 3H and 6H were detected against the Australian isolate used, as well as moderate and minor QTLs (PEV < 10%) distributed on 2H, 3H, 4H and 5H. Differences in effect sizes of individual QTL were apparent between growth stages, tapering up towards heading or down from seedlings, together with growth stage-specific and synergistic QTL. Several of these QTL represent novel sources of resistance which may be combined for durable NFNB resistance.

Onycholysis in a patient with hyperthyroidismAuthors affiliationBaraka Alphonce1,2 Edson Lufunyo31Department of internal medicine, Benjamin Mkapa Hospital, Dodoma, Tanzania2Department of internal Medicine, University of Dodoma, Dodoma, Tanzania3Department of Endocrinology, Benjamin Mkapa Hospital, Dodoma, Tanzania*Corresponding authorBaraka AlphonceP.O Box 11088, Dodoma1 Tiba street, 41218, Dodoma, TanzaniaEmail: alphonncebaraka@gmail.com

Chiral γ-amino acids are among the most valuable and ubiquitous structural units in natural products, pharmaceuticals and many physiologically active compounds. Herein, we demonstrate a convenient synthetic approach to chiral γ-amino acid structures via an asymmetric aryl-aminoalkylation of alkenes enabled by a dual photoredox/nickel catalysis. Taking advantage of the mild and redox-neutral condition, high levels of enantiocontrol of α-carbonyl benzylic stereocenters are obtained. Experimental and computational mechanistic studies were performed to gain insights into the mechanism and origin of enantioselectivity. The results reveal that the reaction follows a Ni(0)/Ni(I)/Ni(III)/Ni(I) catalytic cycle and C‒X bond oxidative addition is the enantiodetermining step.

Title:Squamous cell carcinoma of the sigmoid colon: A rare late presentation of metastatic urothelial cancer of the bladderAuthors: Hamzah Shariff MD1, Ghazal Ghafari, DO, MPH2, Zachary Hoffer, MD, PhD2, Danyall Saeed3, Anila Mahesh MD4, Kishore Kumar MD51 Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania2 Department of Clinical and Laboratory Pathology, Geisinger Medical Center, Danville, Pennsylvania3 Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania4 Department of Internal Medicine, Geisinger Wyoming Valley Medical Center, Wilkes Barre, Pennsylvania5 Department of Gastroenterology, Geisinger Wyoming Valley Medical Center, Wilkes Barre, Pennsylvania

This study investigates the application of Convolutional Neural Networks (CNNs) for the automated classification of Meso-Cenozoic foraminifera from the West African margin, with a focus on planktonic, benthic, and agglutinated taxa. Three training datasets comprising 11,378 images were used to train CNN models for microfossil detection, genus-level, and species-level identification. Genus-level classification (72.4%) outperformed species-level identification (50.2%), as it reduced misclassifications from morphological variability and post-mortem degradation in closely related species. The genus-level CNN performed well for genera with distinct morphological features, such as Muricohedbergella sp. and Heterohelix sp., but struggled with Subbotina spp. and Dicarinella spp. due to shared morphological traits and diagenetic alterations. For benthic foraminifera, Nummulites sp. was easily identified, while Gavelinella sp. posed significant challenges. These results highlight the potential of CNNs for high-throughput classification, while also revealing limitations particularly for taxa with high morphological variability or diagenetic changes. The findings have important implications for biostratigraphy, suggesting that CNNs can enhance genus-level classification in biostratigraphic applications. Further advancements such as multi-view imaging and expanded training datasets could enhance the CNN performance. The integration of CNNs with traditional biostratigraphic methods could enhance the temporal resolution of foraminiferal biostratigraphy, further advancing both the classification process and the understanding of paleoenvironmental conditions.

Respiratory diseases are increasingly prevalent among children, significantly impacting their growth, development, and quality of life. In recent years, respiratory rehabilitation has emerged as a vital therapeutic approach, demonstrating positive effects in alleviating symptoms of pediatric respiratory diseases, improving lung function, and enhancing overall quality of life. This review provides a comprehensive overview of the advancements in the application of respiratory rehabilitation in children with respiratory conditions, exploring the underlying theoretical foundations, commonly utilized methods, and recent research findings. The aim is to offer guidance for clinical practice and highlight the importance of integrating respiratory rehabilitation into the management of pediatric respiratory diseases.

Communication follows the path of least friction. For any message with required fidelity, agents choose the feasible method that minimizes perceived effort across encoding, transmission, and decoding. Automated encoding collapses the encode term while meeting fidelity, making writing optional for transmission and valuable chiefly where it improves content quality or satisfies legitimacy constraints. This paper states the least-friction law, explains the perceived–actual effort gap, identifies where manual writing remains efficient, offers falsifiable predictions, and notes the zero-encoder limit where transmission friction vanishes. The result is a general decision rule for communication that is independent of any particular technology.

Transnational crime networks that traffic in cocaine and gold increasingly affect the forests and peoples of the Amazon. How international demand, trafficking, and impacts on Amazonian forests have changed, however, remains underexplored. We show that, annually, cocaine metabolite concentration in European sewage increased by 17% since 2011, while in the Brazilian Amazon cocaine seizures and gold royalties recently rose by ~50%, and forest loss in Peru since 2004 grew by 31% for every tenfold increase in coca cultivation. Forest loss is ~9X larger in the Amazon than elsewhere in Peru, and departments bordering Brazil record higher forest loss per unit of coca cultivation and high recent losses (2019-2023). During this period, transnational networks of violent non-state actors (VNSAs) consolidated control over borders and triple borders, fostering environmental degradation. We also explore scenarios of cocaine decriminalization and falling demand, and find neither necessarily curbs conservation impacts, as markets can bifurcate into legal and illegal portions, as gold does today, and traffickers can pivot to other activities. Instead, disarticulating VNSAs is essential for Amazon conservation. Therefore, robust, transnationally coordinated law enforcement and sustainable, legal economic alternatives are indispensable to protect Amazonian peoples and ecosystems.

Fungus-animal symbioses have evolved countless times across the tree of life. While the stability of these mutualistic or parasitic interkingdom interactions often depends on optimized nutrient exchange, we lack a framework to explore whether animal-derived nutrients are optimal for fungal symbionts. We propose that this conceptual gap has constrained studies of how fungus-animal symbioses achieve ecological success as well as predictions about whether they will remain evolutionarily stable over time. We use Nutritional Geometry (NG) to harness nutritional niche theory and identify the crucial fundamental and realized nutritional niche dimensions of fungi that mediate symbiotic stability. We hypothesize that the dimensions of fungal nutritional niches are governed by their symbiotic role (mutualist vs. pathogen), degree of animal host control over nutritional competition (monoculture vs. polyculture), and breadth of host associations (specialist vs. generalist). We then show how these NG predictions can be rigorously tested integrating cleverly designed NG experiments with recent technological advances. We propose that this general theory can provide powerful niche-based insights into phenomena ranging from coevolutionary arms races to the potential emergence of economically important pathogens.

This study employs mesoscale simulations using the Weather Research and Forecasting model to investigate wind-farm blockage phenomena over a six-month period in the North Atlantic Ocean. The impact of atmospheric stratification and associated gravity waves on blockage effects is assessed, unencumbered by the presence of nearby land. Simulations reveal the formation of gravity waves at specific times, particularly evident in vertical velocity at hub height. Blockage analysis indicates no significant stratification effects on farm blockage above a Froude number of 10 and increased blockage below a Froude number of 5. Different turbine layouts yield similar results, highlighting the Froude number as a key indicator of gravity wave effects on wind farm aerodynamics. This study underscores the negative impact of stratification effects, driven by gravity waves, on wind farm production, reducing efficiency of additional 3% during approximately 5% of operational time.

Framing control policies to mitigate the impact of invasive plants on indigenous biodiversity within the Sustainable Development Goals (SDG) framework is the primary objective of this work. Using reported ecological dynamics of the invasive species _Lantana camara_, we develop a minimal three-species network model, where each node follows generalized Lotka-Volterra (GLV) dynamical equations. Employing Lie algebra and network control theory, we establish the model’s controllability and accessibility criteria. Through nonlinear optimization programming, we derive sustainable policies for controlling abundances of _Lantana camara_. We also have used Shannon entropy as an indicator to assess the sustainability of these optimal policies. The analysis of the sensitivity measured using this technique reveals that the control strategy is critically dependent on the ratio of the intrinsic growth rates of the _Lantana camara_ and the control plant. Thus, we get a modular algorithmic decision support mechanism for designing control policies to manage _Lantana camara_ abundances. KEYWORDS: Lantana camara; Generalized Lotka-Volterra; Shannon entropy; Sustainable development goals; Sensitivity analysis.

The rising incidence of mosquito-borne diseases poses a public health challenge worldwide. However, local-scale interactions among vectors, hosts, and the environment remain poorly understood. We leveraged historical, multi-source data to assess mosquito-borne disease transmission risk in Mediterranean humanized wetlands, examining mosquito vectors, avian hosts for West Nile virus (WNV), and human hosts for dengue, Zika, and chikungunya. Mosquito activity peaked between June and October. Aedes albopictus was predominant in urban areas, while Culex species were more prevalent in rural and natural environments. The spatial patterns of avian host communities influenced the potential amplification and dilution of the WNV enzootic cycle. High-risk areas for WNV circulation were identified near urban edges, particularly adjacent to rice fields and wetlands where mosquitoes and reservoir hosts overlapped. These findings emphasize the importance of targeted mosquito surveillance and mitigation strategies in urban centers and surrounding rural landscapes to effectively reduce the risk of mosquito-borne diseases.

Late spring frosts (LSF) pose ecological and economic risks, yet their changing frequency and extent under climate warming remain unclear. Using 1220 observations from 304 French oak populations (1997–2021), we developed and validated a model to simulate LSF damage. Our results reveal a long-term decline in LSF frequency (-0.22% yr⁻¹) and extent (-0.34% yr⁻¹) from 1961 to 2021, driven by a faster advancement of the last frost day (-0.28 days yr⁻¹) than budburst (-0.21 days yr⁻¹). However, regional variations emerge, with continental areas experiencing increased frost damage extent despite reduced frequency. These findings underscore the importance of considering both LSF frequency and extent when assessing frost risks in a warming climate, providing a comprehensive framework for future ecological and economic evaluations of LSF impacts.

We evaluated the effectiveness of drone-based survey protocols combined with an AI count model relative to traditional ground-based visual surveys for counting sage-grouse at leks. Drone-induced flushing of sage-grouse from leks occurred in 16% of flight attempts. Point-of-interest (POI) flight profiles outperformed linear flight profiles in counting accuracy for both AI and manual methods. POI flights provided more images and a larger field of view, resulting in counts similar to traditional ground-based visual (GBV) lek surveys, while linear flights consistently produced undercounts. Our custom AI counter (INDECS) yielded counts of sage-grouse similar to manual counts in POI surveys, but not in linear surveys. When integrated into modified N-mixture models, drone surveys with POI profiles yielded precise estimates of detection probabilities and abundance for all survey methods that resulted in similar inference to GBV surveys. Our results suggest that AI-enhanced drone surveys, particularly with POI flight profiles, offer a promising alternative to traditional surveys with reduced bias and improved consistency in sage-grouse population monitoring.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major cause of ischemic stroke. Between 91% and 100% of cardiogenic thrombi are in the left atrial appendage (LAA), and the morphology of the LAA might be associated with the formation of LAA thrombus (LAAT). This review provides a detailed discussion of the LAA’s anatomy and the LAAT’s diagnosis. It focuses on analyzing the role of LAA morphology in blood stasis, morphological abnormality, and hypercoagulable states. Accurate evaluation of the morphology of the LAA can assist with risk stratification in patients with AF. The commonly used LAA morphological evaluation indicators must be more comprehensive and objective. Recently, new imaging protocols allow for LA morphological remodeling and fibrosis assessment, which has been demonstrated to correlate with assessing the individual’s risks of thromboembolic events and practical imaging of patients with LAAT.