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Abstract: Diagnostic boundaries between immune thrombocytopenia (ITP) and other thrombocytopenic states, such as thrombocytopenic myelodysplastic syndromes, may be difficult to establish, and the detection of somatic mutations by next-generation sequencing (NGS) may be of aid. Here, we aimed at characterizing the prevalence and clinical significance of clonal hematopoiesis in ITP. In this multicentric retrospective observational study, we enrolled 167 adult patients with ITP, followed at 13 centers in Italy, United Kingdom, and the United States. Patients underwent NGS evaluation after a median of 3.6 years from ITP onset, and 83% had received at least 1 therapy line, for a median of 2 lines (range, 0-9); 51 of 167 patients (30%) had at least 1 mutation. After exclusion of germ line variants and polymorphisms, 31 of 167 (18.5%) were defined as having clonal hemopoiesis. Most commonly mutated genes were TET2, DNMT3A, SRSF2, and ASXL1 (median variant allele frequency, 29%); 19 of 31 patients (68%) had high-risk variants, and 8 had multiple mutations. Mutated patients were more frequently older males and showed a shorter time from first to second-line therapy, particularly with thrombopoietin receptor agonist (TPO-RA). Additionally, clonal hematopoiesis was associated with increased thrombotic risk (26% vs 8% in NGS-negative cases; P = .01), independently from TPO-RA exposure, though with an age effect. These data demonstrated the prevalence of clonal hematopoiesis in 18% of adult patients with ITP, which is associated with older age, relapsed/refractory disease, and high risk of thrombotic complications.

Abstract Aims Proteomic profiling offers an expansive approach to biomarker discovery and mechanistic hypothesis generation for LV remodelling, a critical component of heart failure (HF). We sought to identify plasma proteins cross‐sectionally associated with left ventricular (LV) size and geometry in a diverse population‐based cohort without known cardiovascular disease (CVD). Methods and results Among participants of the Multi‐Ethnic Study of Atherosclerosis (MESA), we quantified plasma abundances of 1305 proteins using an aptamer‐based platform at exam 1 (2000–2002) and exam 5 (2010–2011) and assessed LV structure by cardiac magnetic resonance (CMR) at the same time points. We used multivariable linear regression with robust variance to assess cross‐sectional associations between plasma protein abundances and LV structural characteristics at exam 1, reproduced findings in later‐life at exam 5, and explored relationships of associated proteins using annotated enrichment analysis. We studied 763 participants (mean age 60 ± 10 years at exam 1; 53% female; 19% Black race; 31% Hispanic ethnicity). Following adjustment for renal function and traditional CVD risk factors, plasma levels of 3 proteins were associated with LV mass index at both time points with the same directionality (FDR

The evolution of Connected Vehicles (CVs) has introduced significant advancements in both in-vehicle and vehicle-edge platforms, creating a highly connected ecosystem. These advancements, however, have heightened exposure to cybersecurity risks. This work reviews emerging security challenges in the CV ecosystem from a new perspective, focusing on the integration of in-vehicle platforms such as the infotainment system and vehicle-edge platforms. By analyzing case studies such as Android Automotive, Message Queuing Telemetry Transport (MQTT), and the Robot Operating System (ROS), we identify the primary security threats, including malware attacks, data manipulation, and Denial of Service (DoS) attacks. The discussion extends to privacy concerns and the lack of trust-building mechanisms in CVs, highlighting how these gaps can be exploited. To mitigate these risks, we retrieve solutions drawn from the broader field of Internet of Things (IoT) security research, including Multi-Factor Authentication (MFA) and trust-based systems. The proposed framework aims to increase the trustworthiness of devices within the CV ecosystem. Finally, we identify future research directions in adaptive mechanisms and cross-domain security.

Aims: The “2 to 10% strain rule” for fracture healing has been widely interpreted to mean that interfragmentary strain greater than 10% predisposes a fracture to nonunion. This interpretation focuses on the gap-closing strain (axial micromotion divided by gap size), ignoring the region around the gap where osteogenesis typically initiates. The aim of this study was to measure gap-closing and 3D interfragmentary strains in plated ovine osteotomies and associate local strain conditions with callus mineralization. Methods: MicroCT scans of eight female sheep with plated mid-shaft tibial osteotomies were used to create image-based finite element models. Virtual mechanical testing was used to compute postoperative gap-closing and 3D continuum strains representing compression (volumetric strain) and shear deformation (distortional strain). Callus mineralization was measured in zones in and around the osteotomy gap. Results: Gap-closing strains averaged 51% (mean) at the far cortex. Peak compressive volumetric strain averaged 32% and only a small tissue volume (average 0.3 cm3) within the gap experienced compressive strains > 10%. Distortional strains were much higher and more widespread, peaking at a mean of 115%, with a mean of 3.3 cm3 of tissue in and around the osteotomy experiencing distortional strains > 10%. Callus mineralization initiated outside the high-strain gap and was significantly lower within the fracture gap compared to around it at nine weeks. Conclusion: Ovine osteotomies can heal with high gap strains (> 10%) dominated by shear conditions. High gap strain appears to be a transient local limiter of osteogenesis, not a global inhibitor of secondary fracture repair. Cite this article: Bone Joint Res 2025;14(1):5–15.

Payment channel networks (PCNs) are a viable solution to the issue of blockchain scalability by offering off-chain transactions between two untrusted peers, without committing each transaction to the blockchain. The payment channel cannot be used when its deposit is depleted, which hinders the payment completion, such as it is overly utilized in one direction. However, they cannot migrate the deposit from one channel to another to facilitate payment completion when a depletion in the channel deposit arises. This limitation arises from the basic design assumption of payment channels, i.e., each channel is independent from others. To overcome this limitation, this paper proposes PaySwitch, inspired by the traditional network switch, to enable connecting multiple payment channels through one PaySwitch smart contract. PaySwitch is designed to enable any peer in the PaySwitch to dynamically reallocate the deposits in their payment channels while maintaining the independence of each other to ensure the trustworthiness of the channel. This paper presents the security definition of PaySwitch and formally proves its security using the UC-framework. To demonstrate the feasibility of PaySwitch, this paper applies it to several routing algorithms. The experimental results show that PaySwitch is capable of improving the transaction success rate and throughput compared with the traditional payment channel based approaches.

Abstract Group A Streptococcus (Strep A) is a human-exclusive bacterial pathogen killing annually more than 500,000 patients, and no current licensed vaccine exists. Strep A bacteria are highly diverse, but all produce an essential, abundant, and conserved surface carbohydrate, the Group A Carbohydrate, which contains a rhamnose polysaccharide (RhaPS) backbone. RhaPS is a validated universal vaccine candidate in a glycoconjugate prepared by chemical conjugation of the native carbohydrate to a carrier protein. We engineered the Group A Carbohydrate biosynthesis pathway to enable recombinant production using the industry standard route to couple RhaPS to selected carrier proteins within Escherichia coli cells. The structural integrity of the produced recombinant glycoconjugate vaccines was confirmed by Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Purified RhaPS glycoconjugates elicited carbohydrate-specific antibodies in mice and rabbits and bound to the surface of multiple Strep A strains of diverse M-types, confirming the recombinantly produced RhaPS glycoconjugates as valuable vaccine candidates.

Abstract Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries. The data were collected between November 2022 and August 2023 as part of the global Many Labs study “Trust in Science and Science-Related Populism” (TISP). The questionnaire contained comprehensive measures for individuals’ trust in scientists, science-related populist attitudes, perceptions of the role of science in society, science media use and communication behaviour, attitudes to climate change and support for environmental policies, personality traits, political and religious views and demographic characteristics. Here, we describe the dataset, survey materials and psychometric properties of key variables. We encourage researchers to use this unique dataset for global comparative analyses on public perceptions of science and its role in society and policy-making.

Abstract Background This study aims to investigate how pre-existing health status and social background contribute to excess mortality during the COVID-19 crisis in Belgium. Methods The study population consists of almost 1.4 million adult members of Solidaris, the second largest health insurance fund in Belgium. Pre-existing health status was identified using health care reimbursement data, including medication use. Social characteristics included a proxy for low socio-economic status, nationality of origin, and living arrangement. Excess mortality during the COVID-19 crisis was measured by computing the relative difference between all-cause mortality in 2020 or 2021 and the average yearly mortality in 2015–2019. Directly Standardised Mortality Rates (DSMRs) were calculated to investigate absolute mortality inequalities. Mortality Rate Ratios (MRRs) were computed using Poisson regression analyses to investigate relative mortality inequalities. Results DSMRs show that persons with no previous disease experienced significant excess mortality in 2020, like men with one, two or three diseases and women with various numbers of pre-existing diseases. Results by specific disease show heterogenous results. After adjusting for age, sex and social characteristics, persons with cancer experienced a significant mortality deficit of 17% in 2020 and of 9% in 2021. For persons with cancer and asthma or COPD, significant mortality deficits of 10% and 3% were observed in 2020 and 2021, respectively. Conclusion The study provides insights into the complex dynamics of mortality during the COVID-19 crisis, emphasising the need to consider individual-level information on pre-existing health and social background jointly.

Abstract Background Despite many years of investigation into mesenchymal stem cells (MSCs) and their potential for treating inflammatory conditions such as COVID-19, clinical outcomes remain variable due to factors like donor variability, different tissue sources, and diversity within MSC populations. Variations in MSCs’ secretory and proliferation profiles, and their proteomic and transcriptional characteristics significantly influence their therapeutic potency, highlighting the need for enhanced characterization methods to better predict their efficacy. This study aimed to evaluate the biological characteristics of MSCs from different tissue origins, selecting the most promising line for further validation in a K18-hACE2 mouse model of SARS-CoV-2 infection. Methods We studied nine MSC lines sourced from either bone marrow (hBMMSC), dental pulp (hDPMSC), or umbilical cord tissue (hUCMSC). The cells were assessed for their proliferative capacity, immunophenotype, trilineage differentiation, proteomic profile, and in vitro immunomodulatory potential by co-culture with activated lymphocytes. The most promising MSC line was selected for further experimental validation using the K18-hACE2 mouse model of SARS-CoV-2 infection. Results The analyzed cells met the minimum criteria for defining MSCs, including the expression of surface molecules and differentiation capacity, showing genetic stability and proliferative potential. Proteomic analysis revealed distinct protein profiles that correlate with the tissue origin of MSCs. The immunomodulatory response exhibited variability, lacking a discernible pattern associated with their origin. In co-culture assays with lymphocytes activated with anti-CD3/CD28 beads, all MSC lines demonstrated the ability to inhibit TNF-α, to induce TGF-β and Indoleamine 2,3-dioxygenase (IDO), with varying degrees of inhibition observed for IFN-γ and IL-6, or induction of IL-10 expression. A module of proteins was found to statistically correlate with the potency of IL-6 modulation, leading to the selection of one of the hUCMSCs as the most promising line. Administration of hUCMSC to SARS-CoV-2-infected K18 mice expressing hACE2 was effective in improving lung histology and modulating of a panel of cytokines. Conclusions Our study assessed MSCs derived from various tissues, uncovering significant variability in their characteristics and immunomodulatory capacities. Particularly, hUCMSCs demonstrated potential in mitigating lung pathology in a SARS-CoV-2 infection model, suggesting their promising therapeutic efficacy.

Abstract Background Apple breeding schemes can be improved by using genomic prediction models to forecast the performance of breeding material. The predictive ability of these models depends on factors like trait genetic architecture, training set size, relatedness of the selected material to the training set, and the validation method used. Alternative genotyping methods such as RADseq and complementary data from near-infrared spectroscopy could help improve the cost-effectiveness of genomic prediction. However, the impact of these factors and alternative approaches on predictive ability beyond experimental populations still need to be investigated. In this study, we evaluated 137 prediction scenarios varying the described factors and alternative approaches, offering recommendations for implementing genomic selection in apple breeding. Results Our results show that extending the training set with germplasm related to the predicted breeding material can improve average predictive ability across eleven studied traits by up to 0.08. The study emphasizes the usefulness of leave-one-family-out cross-validation, reflecting the application of genomic prediction to a new family, although it reduced average predictive ability across traits by up to 0.24 compared to 10-fold cross-validation. Similar average predictive abilities across traits indicate that imputed RADseq data could be a suitable genotyping alternative to SNP array datasets. The best-performing scenario using near-infrared spectroscopy data for phenomic prediction showed a 0.35 decrease in average predictive ability across traits compared to conventional genomic prediction, suggesting that the tested phenomic prediction approach is impractical. Conclusions Extending the training set using germplasm related with the target breeding material is crucial to improve the predictive ability of genomic prediction in apple. RADseq is a viable alternative to SNP array genotyping, while phenomic prediction is impractical. These findings offer valuable guidance for applying genomic selection in apple breeding, ultimately leading to the development of breeding material with improved quality.

Abstract Enhancement of security, personalization, and safety in advanced transportation systems depends on driver identification. In this context, this work suggests a new method to find drivers by means of a Random Forest model optimized using the osprey optimization algorithm (OOA) for feature selection and the salp swarm optimization (SSO) for hyperparameter tuning based on driving behavior. The proposed model achieves an accuracy of 92%, a precision of 91%, a recall of 93%, and an F1-score of 92%, significantly outperforming traditional machine learning models such as XGBoost, CatBoost, and Support Vector Machines. These findings show how strong and successful our improved method is in precisely spotting drivers, thereby providing a useful instrument for safe and quick transportation systems.

Abstract Unsustainable wild meat hunting poses a significant threat to wildlife and tropical forest ecosystems. While high levels of extraction linked to commercial trade have received significant attention, the sustainability of subsistence hunting by Indigenous Peoples in Africa has been less studied. Understanding how changing lifestyles, particularly the sedentarisation of former hunter-gatherers, have affected the use of forest resources is crucial for wildlife conservation and livelihoods. The spatial management of hunting through the establishment of no-take zones, which act as sources for adjacent hunting areas, offers promise for the sustainability of Indigenous livelihoods. We conducted an extensive camera trap study in hunting areas subject to source-sink dynamics used by 10 sedentarised Baka communities. We compared species richness, occupancy, abundance, and community composition to a relatively non-hunted reference area in the adjacent Dja Faunal Reserve. Subsistence hunting by the Baka had a limited impact on species richness but significantly altered community composition and the abundance of carnivores, seed dispersers and granivores. These changes highlight that even the spatial management of hunting may have consequences for the sustainability of hunting systems and the functional ecology of tropical forests.

Abstract Understanding the dynamic tumor immune microenvironment (TIME) is important in guiding immunotherapy. We have previously validated signatures predictive of checkpoint inhibitor efficacy which distinguish immunomodulatory, mesenchymal stem-like, and mesenchymal phenotypes. Here we use twenty tumor types (7162 samples) to identify potentially conserved immune biology within these TIME spaces, genes co-expressed across distinct cell types involved these immune processes, and the association of these signatures with ICI response. One signature, which contained multiple B-cell markers, was associated with immunotherapy efficacy in three cohorts, including IMvigor210. This signature of potentially conserved B-cell biology in co-infiltrated immune cell ecosystems had a more consistent association with outcome than comparable single cell type models and likely reflects a complex immunological response involving multilayered relationships between distinct immune effector cell types. These signatures were most highly expressed in tumors with prominent immune cell invasion, however there was consistent identification of infiltrate presence in relatively immune restricted cases. This suggests that these immune population signatures may identify conserved immune cell type co-infiltrate physiology of the TIME that best captures immune physiology with potential clinical utility.

Abstract Droplets exhibiting a myriad of shapes on surfaces are ubiquitous in both nature and industrial applications. In high-resolution manufacturing processes, e.g., semiconductor chips, precise control over wetting shapes is crucial for production accuracy. Despite the high demand for describing droplet wetting shapes and their transformations across a wide range of applications, a robust model for precisely depicting complex three-dimensional (3D) wetting droplet shapes on heterogeneous surfaces remains elusive. Herein, we fill this gap by developing a universal, high-precision model that accurately describes wetting shapes, including those with polygonal baselines and irregular footprints. Our model reveals the intricate wetting morphologies beyond the classic Young’s law and Cassie-Baxter-Wenzel models. Besides, it aligns quantitatively with physical simulations for various droplet volumes. This work provides a potential method to achieve highly complex morphologies of droplets via low-cost beforehand design of the surfaces, thereby opening up potential applications in 3D printing, printed electronics, and microfluidics.

Abstract Background Polypharmacy (i.e., treatment with ≥ 5 drugs) is common in patients with atrial fibrillation (AF) and has been associated with suboptimal management and worse outcomes. Little is known about how prescribed drug patterns affect management and prognosis in patients with AF. Methods Based on data from the prospective global GLORIA-AF Registry Phase III (recruiting patients with AF and CHA2DS2-VASc score ≥ 1), we performed a latent class analysis to identify treatment patterns based on 14 drug classes including cardiovascular (CV) and non-CV drugs. We analysed associations with oral anticoagulant (OAC) use and risk of a composite primary outcome (all-cause death and major adverse cardiovascular events (MACE)) and secondary outcomes. Results Among 21,245 patients (mean age 70.2 ± 10.3 years, 44.9% females), we identified 6 patterns: i) Low Medicated pattern (18.3%); ii) Hypertension pattern (21.1%); iii) Heart Failure pattern (20.0%); iv) CV Prevention pattern (21.0%); v) Mixed Morbidity pattern (4.5%); and vi) High Medicated pattern (15.0%). All groups had higher odds of OAC use vs the Low Medicated pattern, with highest prevalences in the Heart Failure pattern (OR [95%CI]: 2.17 [1.90–2.48]) and the High Medicated pattern (OR [95%CI]: 2.08 [1.77–2.44]). Over 3-year follow-up, Heart Failure, Mixed Morbidity and High Medicated patterns were associated with higher risk of the primary composite outcome (aHR [95%CI]: 1.32 [1.14–1.53]; 1.45 [1.17–1.80] and 1.35 [1.14–1.60], respectively). Similar results were observed for all-cause mortality. Conclusions In patients with AF, different treatment patterns can be identified. Each pattern was associated with unique OAC use and long-term clinical outcomes.

Abstract Background To identify the prognosis of Japanese patients with collecting duct carcinoma (CDC). Methods We used a hospital-based cancer registry data in Japan to extract CDC cases that were diagnosed in 2013, histologically confirmed, and determined the first course of treatment. We further investigated treatment modalities and estimated overall survival (OS) by the Kaplan–Meier method. Results A total of 61 CDC patients were identified. The 5-year OS rate for all CDC patients who were diagnosed in Japan during 2013 was 23.6% (95% CI: 15.0–37.4), with a median OS of 14 months (95% CI: 12–24). The 5-year OS rate for CDC patients at stages I, III, and IV were 53.0% (95% CI: 29.9–94.0), 35.7% (95% CI: 19.8–64.4), and 3.4% (95% CI: 0.5–23.7), respectively. Noteworthy, the 1-year OS for stage IV patients was 27.6% (95% CI: 0.5–23.7) and the median OS was only 5 months (95% CI: 4–12). We further examined the OS for advanced disease according to treatment modalities. The median OS of patients who undertook chemotherapy alone was significantly shorter than patients who undertook surgery alone for advanced disease (4 months [95% CI: 4-NA] vs. 15 months [95% CI: 13–68]; p

Abstract Background Africa’s involvement in clinical trials remains very low. Although the crucial role of training initiatives in building clinical trial capacity in Africa has been documented, current efforts fall short as they lack alignment with local contexts. This study aimed to design, develop, implement, and evaluate an innovative clinical trial operations training program for Africa. Methods We developed ClinOps, a novel 10-week clinical trial operations training program for study coordinators in Africa to enhance their expertise in four fundamental areas: designing, conducting, managing, and reporting clinical trials. To streamline the learning process, we used cloud-based applications that minimize the need for software installations while maximizing student engagement. VoiceThread facilitated interactive content that could be accessed offline. Moodle, an open-source learning management system, offered a platform for sharing learning tools, mentorship, and rubric-driven competency assessments, including quizzes, forums, tutorials, and group assignments. We utilized Zoom for live tutorials and mentoring as required. Effectiveness of the program was evaluated through quantitative pre- and post-surveys, qualitative end-course evaluations, and a comprehensive monitoring and evaluation framework. The pre- and post-surveys measured changes in trainees’ confidence in clinical trial domains and leadership and coordination skills. End-course evaluations gathered feedback on the course content, organization, technology, and instructional methods. We used Wilcoxon rank test to analyze pre- and post-survey scores and thematic analysis to analyze the qualitative data. Results In the initial cohort, 88 study coordinators from 19 countries participated, including 56 (64%) females, with 57 (65%) actively employed as study coordinators during the training, and 85 (97%) possessing prior experience in clinical trial roles. Among these, 71 (81%) successfully completed the course, with 69 (97%) also completing the post-course assessment. Post-training scores demonstrated substantial improvement compared to pre-training scores in each competency area, including in designing (pre-post training median score = 3.6 vs. 4.6, median difference = 1.0, 95% CI 0.8–1.1, p

Abstract Introduction The technical development of ultrasound devices based on silicon chips has revolutionized ultrasound examinations, leading to the implementation of these portable handheld devices (PUD) in different medical fields. However, training on these devices is necessary to assure appropriate use and ensure valid results. While training programs for the use of conventional standard ultrasound devices (SUD) have been described, no training program for these handheld devices has been developed thus far. Methods A training program for obstetric ultrasound examination was modified through the addition of an extra module focusing on the use of these PUDs. After the module the students had to attend an OSCE in which their skills of using the PUD and the SUD were tested and analyzed by applying the agreement rate, the intraclass correlation coefficient (ICC) and Bland–Altman plots. Furthermore, the students’ ultrasound results were compared with those of trained physicians by employing the one-sample Student's t-test. After the OSCE, the students answered a survey regarding their experience and their expected use of these devices. Result An agreement of one hundred percent was reached for basic parameters such as fetal position, placental position, fetal heartbeat and for the classification of the amniotic fluid. The ICC showed a good to moderate agreement between the results of fetal biometry achieved by SUD and PUD. The T-test results confirmed a high reliability between the physicians’ results and the students’ results, independent of the used device. The students remarked a good handling of the ultrasound devices and supported the use in their future specialties. Discussion The reliability between the examinations using the SUD and PUD were high but lower than the results observed for trained physicians. Therefore, the implementation of an additional module for portable ultrasound teaches the students to reliably examine basic obstetric parameters and provides a solid basis for further training and improvement of ultrasound skills in use of PUD.

Abstract Background Testicular torsion (TT) is the abnormal twisting of the spermatic cord leading to strangulation of the testis. Any non-traumatic acute scrotal pain in adolescents and young adults is considered TT until proven otherwise. It is a urological emergency. The diagnosis is clinically based on symptoms and signs that raise a high index of suspicions. Scrotal exploration is necessary, which will provide diagnostic certainty and allow treatment. Methods This study aimed to assess the clinical predictors of TT. This was a retrospective cross-sectional study of patients aged 15 years and older who underwent surgical exploration for suspected TT from January 2005 to December 2021 at Teaching Hospital Yalgado Ouedraogo (Burkina Faso). We compared the demographic data and clinical findings of patients according to the intraoperative diagnosis. Results In total, 135 scrotal explorations were performed for suspected TT. The average age of the patients was 24.56 years. TT was found in 123 cases (91.11%), epididymo-orchitis in 8 cases (5.93%) and in 4 cases (2.96%) no abnormality was found. Scrotal swelling and elevation of the testicle were more common in TT than in other cases (p

Abstract While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro—a new group-II intron-encoded RT—to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and three mouse tissues and show that, while the landscape of modifications is highly variable throughout the tRNA sequence framework, it is stabilized for modifications that are required for reading of the genetic code. The coordinated changes have fundamental importance for development of tRNA modifications in protein homeostasis.

Abstract Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases. Uncommon BC presentations like male, inflammatory and pregnancy-related BC pose challenges. Emerging therapeutic strategies targeting genetic alterations or immune microenvironment are being explored.

Abstract Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p

Abstract Background High-field magnetic resonance imaging (MRI) is a powerful diagnostic tool but can induce unintended physiological effects, such as nystagmus and dizziness, potentially compromising the comfort and safety of individuals undergoing imaging. These effects likely result from the Lorentz force, which arises from the interaction between the MRI's static magnetic field and electrical currents in the inner ear. Yet, the Lorentz force hypothesis fails to explain observed eye movement patterns in healthy adults fully. This study explores these effects and tests whether the Lorentz force hypothesis adequately explains magnetic vestibular stimulation. Methods We developed a mathematical model integrating computational fluid dynamics, fluid-structure interaction solvers, and magnetohydrodynamic equations to simulate the biomechanical response of the cristae ampullares. Using high-resolution micro-CT data of the human membranous labyrinth, we ensured anatomical accuracy. Experimental validation involved measuring horizontal, vertical, and torsional slow-phase eye movements in healthy subjects exposed to varying magnetic field intensities and head positions. Results Our model accurately replicates observed nystagmus patterns, predicting slow-phase eye velocities that match experimental data. Results indicate that Lorentz force-induced stimulation of individual cupulae explains variability in eye movements across different magnetic field intensities and head orientations. Conclusions This study empirically supports the Lorentz force hypothesis as a valid explanation for magnetic vestibular stimulation, offering new insights into the effects of high-field MRI on the vestibular system. These findings provide a foundation for future research and improved clinical practices.

Abstract Psychological states influence our happiness and productivity; however, estimates of their impact have historically been assumed to be limited by the accuracy with which introspection can quantify them. Over the last two decades, studies have shown that introspective descriptions of psychological states correlate with objective indicators of cognition, including task performance and metrics of brain function, using techniques like functional magnetic resonance imaging (fMRI). Such evidence suggests it may be possible to quantify the mapping between self-reports of experience and objective representations of those states (e.g., those inferred from measures of brain activity). Here, we used machine learning to show that self-reported descriptions of experiences across tasks can reliably map the objective landscape of task states derived from brain activity. In our study, 194 participants provided descriptions of their psychological states while performing tasks for which the contribution of different brain systems was available from prior fMRI studies. We used machine learning to combine these reports with descriptions of brain function to form a ‘state-space’ that reliably predicted patterns of brain activity based solely on unseen descriptions of experience (N = 101). Our study demonstrates that introspective reports can share information with the objective task landscape inferred from brain activity.

This article presents the results of morphological studies, as well as comparisons and phylogenetic analyzes of sequences of four arbuscular mycorrhizal fungi (AMF, phylum Glomeromycota): Dominikia indica, Dominikia indica strain 211, Isolate 517, and Isolate 524. Dominikia indica strain 211 was previously characterized only by sequences of the 45S nuc rDNA region (= 18S, partial, ITS-1-5.8S-ITS2, 28S, partial) and the rpb1 gene (without any morphological data) that were deposited in GenBank under the incorrect name “Dominikia indica strain 211”. Its 45S sequences differed from the original D. indica sequences and, consequently, resulted in erroneous phylogenetic classification of this species. Isolate 517 and Isolate 524 slightly differed in morphology from Macrodominikia compressa (formerly D. compressa) and Microkamienskia perpusilla (formerly Kamienskia perpusilla), respectively. Microkamienskia perpusilla was originally found in a maritime dune site of Italy in 2009 and not yet reported from any other habitat in the world. Our sequence comparisons and analyses showed that D. indica represents a new genus, here created under the name Delicatispora gen. nov. with De. indica comb. nov., and Dominikia indica strain 211 is a new species, described as Dominikia paraminuta sp. nov. These analyses also indicated that Isolate 517 is conspecific to M. compressa and confirmed the correctness of the transfer of D. compressa by other AMF researchers to Macrodominikia gen. nov. with M. compressa comb. nov. Morphological studies of our M. compressa specimens grown in culture showed that the original description of this species is incomplete and, therefore, the description was emended. Phylogenetic analyses of Isolate 524 proved its conspecificity to Mk. perpusilla and thus revealed its second site of occurrence, i.e., the coastal dunes of the Hel Peninsula in northern Poland.

Introduction Few studies have investigated the relationship between cytokines and dizziness in elderly individuals.

Abstract West Africa, the largest cocoa‐producing region globally, has experienced significant deforestation in recent decades, leading countries to implement large‐scale agroforestry policies; however, most studies on farmers' adoption of agroforestry fail to consider the social (Who?), historical (When?), geographical (Where?), and ecological (What?) factors that influence their motivations to value trees. Drawing from a sample of 150 farmers responsible for the management of 12,096 trees, we quantified the motivations of farmers for 10 material and immaterial uses of trees and used a Bayesian modelling framework to explore the relative importance of the 4 W framework in explaining general motivations, specific to each use, as well as the varying levels of specialization in tree management strategies among farmers. The distribution of use values by category shows that the highest values are associated with (i) agronomic uses (such as shade for cocoa trees and soil fertilization), (ii) food for human consumption, (iii) social purposes, and (iv) medicinal uses. All four aspects of the 4 W framework significantly contribute to understanding farmers' deep motivations, while the influence of each 4 W determinant varies based on the specific material and immaterial uses being considered. The level of specialization or diversification in cocoa farmers' motivations is significantly influenced by their knowledge of tree species and cocoa tree density, with knowledgeable farmers exhibiting greater diversification, while higher cocoa tree density and the presence of remnant trees lead to more specialized strategies that hinder agroforestry adoption. From a political perspective, it is urgent that stakeholders involved in the promotion of agroforestry consider all dimensions of the farmer‐field system. The diversity of farmers' life histories (Who), of cultivated landscapes (Where), of field systems (What), and of time trajectories (When) present both constraints and opportunities with which farmers must contend to transition to much‐desired agroforestry systems. Read the free Plain Language Summary for this article on the Journal blog.

Abstract In response to mounting wildfire risks, land managers across the country will need to dramatically increase proactive wildfire management (e.g. fuel and forest health treatments). While human communities vary widely in their vulnerability to the impacts of fire, these discrepancies have rarely informed prioritizations for wildfire mitigation treatments. The ecological values and ecosystem services provided by forests have also typically been secondary considerations. To identify locations across the conterminous US where proactive wildfire management is likely to be effective at reducing wildfire severity and to yield co‐benefits for vulnerable communities and ecological values, we developed a set of spatial models that estimated wildfire mitigation potential (based on wildfire hazard and biophysical forest conditions) and either included or excluded information on vulnerable human communities, ecological values and ecosystem services. We then compared areas with high wildfire mitigation potential alone to refined ‘focal areas’ that overlaid social and ecological considerations to quantify the potential benefits of targeted wildfire mitigation treatments. Inclusion of social and ecological considerations substantially increased representation of vulnerable communities and ecological values in focal areas relative to the model that considered wildfire alone. For instance, restoration in these refined focal areas would cover 28% greater imperilled species richness, 45% greater water importance and 26% more families falling below the poverty line. By examining overlap between our refined focal areas and U.S. Forest Service top ranked firesheds (a prominent existing wildfire prioritization scheme), we show that our analysis can help to target wildfire mitigation efforts within firesheds to areas with particularly high social vulnerability and/or ecological value, providing an important compliment to a prioritization scheme based largely on risk to structures. Our results highlight the importance of considering ecological and social factors when implementing wildfire mitigation treatments and provide actionable guidance for integrating these considerations into existing prioritizations. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Ecosystem services (ES) are benefits people receive from nature. To sustain these benefits, we need to spatially connect communities benefitting from specific ES with landscape features that generate the ES. A variety of process‐based models support ES assessments by estimating the biophysical supply of ES that comes from landscapes. However, less attention has been given to how ES flow from landscapes to beneficiary groups. A ‘serviceshed’ is defined as the spatial area that provides an ecosystem service to beneficiaries at a specific location—thus connecting people to the landscapes and seascapes upon which they depend through ES flows. In this article, we propose a general framework to empirically define serviceshed boundaries. Using publicly available data, we apply this framework to two provisioning and two regulating services (1) agricultural and fishing livelihoods and (2) pollination and coastal flood control, respectively, in Canada. We find that agricultural fields of different types and sizes contribute livelihood value to 85% of the communities in the agricultural landscape, and fishing grounds of different sizes contribute to 24% of the communities in the fishing study area. On average, communities with a lower proportion of agricultural labour are associated with larger fields, whilst larger fishing grounds were associated with communities with a greater percentage of their population in fisheries, showing how different ES can have varied relationships with beneficiary communities. For regulating services, we find 66% of pollinator‐supplying areas are within the serviceshed of farming communities. Natural habitats and agricultural land account for 72% and 28% of this serviceshed area, respectively. Our models suggest also that 26% of saltmarshes are within the serviceshed of flood‐prone communities and most coastal communities in our study area benefit from saltmarshes, especially from those without dykes. We demonstrate how serviceshed mapping, when integrating social and ecological information, can be useful in multiple decision contexts. Servicesheds can help planners and managers better design zoning restrictions, restoration activities to benefit communities, or subsidy programmes to replace the value of ES lost due to climate change or land use development. Read the free Plain Language Summary for this article on the Journal blog.