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Fever is a hallmark of malaria. Several studies have linked febrile temperatures to reduced parasite viability, but also to increased cytoadhesion, a key driver of pathology. However, different mechanisms have been proposed to cause changes in cytoadhesion and parasite sensitivity to heat. Here, we demonstrate that exposure of Plasmodium falciparum-infected red blood cells (iRBCs) to physiologically relevant febrile heat stress (39 °C), derived from patient data, enhances cytoadhesion through increased trafficking of the major virulence factor PfEMP1 to the iRBC surface. This phenomenon is not limited to PfEMP1 and common laboratory strains, as it extends to the surface nutrient channel PSAC in four clinical isolates of diverse geographic origin. The increased surface protein display occurs without changes in overall protein expression or parasite developmental progression. Using phosphoproteomics and proximity labelling, we find that elevated temperature also increases trafficking and phosphorylation of exported proteins into the RBC. Enhanced export is likely reliant on the presence of a transmembrane domain as shown by NanoLuc reporter assays. Collectively, our results indicate that febrile temperatures commonly experienced during infection can accelerate protein export, likely at the parasitophorous vacuole. This enhanced export following heat stress is relevant because increased cytoadhesion could influence disease severity through earlier iRBC sequestration and elevated bound parasite mass. A fever usually indicates that the body is fighting an infection. In malaria, parasites infect red blood cells, and high temperature is a common symptom. Fever may slow parasite growth, but it may also increase levels of a parasite protein called PfEMP1 on the surface of infected cells. PfEMP1 makes these cells sticky, helping them attach to blood vessel walls and avoid removal by the spleen. This adhesion can worsen disease by blocking small blood vessels, including those in the brain. If the fever increases this stickiness, it could worsen symptoms. However, previous studies used to vary temperatures, leading to conflicting results. Jones et al. tested whether a common fever temperature (39 °C) affects PfEMP1 levels and cell adhesion. Using infected human red blood cells, they found that 39 °C increases both adhesion to proteins found on blood vessel walls and the number of cells displaying PfEMP1 on their surface. To investigate the process behind this increase, they used techniques to measure the activity of proteins and their interactions with other human proteins. They showed that heat accelerates the export of certain parasite proteins to the red blood cell surface, including PfEMP1 and likely others, without increasing overall protein levels or parasite growth. These findings suggest that fever may accelerate the surface export of certain parasite proteins, which unintentionally help infected cells adhere more strongly and earlier to blood vessels, potentially worsening the disease. However, further work is needed to confirm this in more realistic settings and to link it directly to disease severity in patients.

This study presents an innovative approximate optimal controller for variable-span morphing aircraft (MA), where the mapping relationship between aerodynamic parameters and deformation parameters is unknown. The foundation of our approach relies on two core observations: unknown dynamic models for MA have a common representation across different morphing scenarios, while the specific morphing condition lies in a collection of adaptive linear parameters. Guided by this dual-layer decomposition, a novel meta-learning (MetaL) training structure with an adversarial optimization framework is leveraged to extract common invariant features from offline flight data. At the same time, we incorporate the squeeze-and-excitation (SE) network, a novel architectural unit, into the MetaL training process, aiming to enhance the network's representational capability through dynamic recalibration of channel features. Regarding the new deformation situations encountered during the online process, online data are collected to update the common features via a continual learning method, and a concurrent learning (ConcL)-based methodology is introduced to update the linear coefficients. Utilizing the identified dynamical model, a model-based reinforcement learning (RL) framework is formulated to address optimal control problems of MA. By employing nonsmooth Lyapunov stability analysis, it is demonstrated that continuously updating the weights allows the implemented control strategies to converge to a neighborhood of the optimal strategies. Furthermore, numerical simulations are performed to validate the effectiveness of the proposed methodology.

Perivascular epithelioid cell tumors (PEComas) are an uncommon group of mesenchymal neoplasms characterized by perivascular epithelioid cells that exhibit dual myomelanocytic differentiation. Due to their lack of a site-specific cell of origin, they may arise in a wide variety of anatomic locations. Although most cases are caused by sporadic mutations of TSC1, TSC2, or TFE3 genes, a subset are caused by germline mutations in patients with tuberous sclerosis complex. These genetic alterations lead to uncontrolled cell growth through overactivation of mammalian target of rapamycin, which is a critical therapeutic target for management of malignant PEComas. The authors provide a comprehensive review of PEComas, highlighting shared genetic, histopathologic, and imaging features across diverse anatomic sites, while also covering site-specific manifestations and potential imaging pitfalls. Common imaging features, such as avid enhancement and presence of fat, reflect their underlying tumor angiogenesis and adiposity within triphasic variants. Given the varied presentations and frequent imaging overlap of PEComas with more common tumors, radiologists play a crucial role in recognizing imaging features and clinical scenarios suggestive of PEComas, as management strategies often differ. ©RSNA, 2026 Supplemental material is available for this article.

The pathogenesis of IgA nephropathy is mediated by B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Telitacicept is a fusion protein that targets and neutralizes both BAFF and APRIL and, as such, might be effective in IgA nephropathy. We now report a prespecified interim analysis of a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, which enrolled adults with biopsy-proven IgA nephropathy and persistent proteinuria (protein level, &#x2265;1.0 g per day), despite appropriate supportive care. Patients were randomly assigned in a 1:1 ratio to receive subcutaneous once-weekly telitacicept (240 mg) or matching placebo. The primary end point was the geometric mean ratio of the 24-hour urinary protein-to-creatinine ratio at 39 weeks relative to baseline. Safety was also evaluated. A total of 318 patients were assigned to receive telitacicept or placebo (159 in each group). At week 39, the percentage change in the 24-hour urinary protein-to-creatinine ratio was -58.9% with telitacicept and -8.8% with placebo, which corresponded to a relative difference (based on the ratio of geometric mean reductions between the two groups) of -55.0% (95% confidence interval [CI], -61.3 to -47.6; P<0.001) in favor of active medication. The percentage change in the estimated glomerular filtration rate relative to baseline was -1.0% (95% CI, -3.2 to 1.2) with telitacicept and -7.7% (95% CI, -9.9 to -5.4) with placebo. Adverse events were more common with telitacicept than with placebo (in 89.3% vs. 78.6% of patients), although serious adverse events were less common (in 2.5% vs. 8.2%). No unexpected safety findings were reported with telitacicept. In patients with IgA nephropathy at high risk for progression, 39 weeks of treatment with telitacicept led to a greater reduction in the 24-hour urinary protein-to-creatinine ratio than placebo. (Funded by RemeGen; TELIGAN ClinicalTrials.gov number, NCT05799287.).

Pleomorphic adenoma (PA) is the most common benign salivary gland neoplasm detected by fine-needle aspiration (FNA). However, metaplastic changes within PA can complicate its cytologic interpretation. This study evaluates the impact of metaplasia on the FNA interpretation in a large, multi-institutional cohort. A two-armed study design was employed: one included 200 consecutive PA resections and the corresponding FNAs, and the second included 53 PA cases with known metaplastic features identified by cytologic or pathologic review. Histologic assessment revealed metaplasia in 16% of the 200 PA cases. Although the majority (83%) were cytologically classified as Neoplasm: Benign, indeterminate diagnoses were more common in cases with metaplasia (25%) than in those without (15.5%). Squamous metaplasia was frequently interpreted as indeterminate relative to other types of metaplasia, and a statistical trend was observed between the extent of metaplasia and indeterminate categorization. In the multicenter arm, FNA cases with metaplasia were more frequently interpreted as indeterminate compared to FNA cases without metaplasia (61.8% vs. 15.8%, p&#xa0;<&#xa0;.01). Metaplastic change in PA can pose diagnostic challenges. Although most FNA cases with limited metaplastic features are appropriately classified, extensive metaplasia is more likely to result in an indeterminate interpretation.

Following the introduction of antiretroviral therapy (ART), the prognosis after being diagnosed with HIV infection has changed from a universally fatal disease to a largely manageable chronic condition. Despite these advances, opportunistic infections remain a central challenge, particularly in individuals with declining CD4 T-cell counts. The authors review the pathologic conditions unique to patients living with HIV infection at various levels of disease progression, based on CD4 cell thresholds, and examine how radiologic patterns at CT can guide differential diagnoses in the post-ART age. A CT pattern-based radiologic approach-such as consolidation, ground-glass opacities, cavitation, and nodularity-enables radiologists to distinguish between typical bacterial infections, opportunistic fungal or mycobacterial processes, and less common viral causes in addition to their many mimics. Immune reconstitution inflammatory syndrome (IRIS) further complicates the diagnostic algorithm, as newly reconstituted immune activity after initiation of ART can unmask previously subclinical infections or worsen known ones. The overlapping clinical and imaging features of IRIS with opportunistic disease underscore the need for vigilant monitoring and a nuanced interpretation of radiologic findings. Additionally, lymphadenopathy in patients living with HIV infection is a common CT finding with a broad differential diagnosis, which can be narrowed if one is attuned to certain characteristics useful in differentiating underlying disease. In this comprehensive overview, the authors highlight the critical role of using CD4 cell counts with a pattern-based approach to interpreting radiologic studies in optimizing care for people living with HIV infection. &#xa9;RSNA, 2026 Supplemental material is available for this article.

Understanding toilet avoidance and stool withholding at school is essential, as this can adversely affect children's health and well-being. To assess the prevalence of toilet avoidance and stool withholding at school, and to explore the differences of withholding behavior by gender and geographic location of the school, identify reasons for withholding, and describe physical symptoms and health care utilization. This cross-sectional study used an online questionnaire developed by experts from Amsterdam University Medical Center and the Dutch Digestive Health Fund. Children aged 8 to 16 years from primary schools (aged 8-12 years) and high schools (aged 13-16 years) were recruited by Verian, an external research agency, through a nationwide online panel in the Netherlands. In July 2024, school-aged children completed the questionnaire. The primary outcomes were the prevalence of stool withholding, reasons for withholding, gastrointestinal symptoms, and health care utilization. Secondary outcomes included differences between gender and geographic location of the school, children's reasons for avoiding school toilets, and toilets' perceived cleanliness. To assess potential differences in withholding behavior according to gender and geographic location, a Cochran-Armitage test was performed. A total of 1000 children, 518 aged 8 to 12 years (264 [51.0%] male) and 482 aged 13 to 16 years (234 [48.5%] male) completed the questionnaire. Stool withholding was reported by 265 primary school children (51.2%) and 344 high school children (71.4%), with no significant differences by gender or geographic location. Hygiene and privacy concerns were the most commonly reported reasons for withholding stool with 610 (84.3%) of children accounting for hygiene and 574 (79.3%) citing privacy concerns, and 410 (41.0%) of children rated school toilet cleanliness as insufficient. Abdominal pain was frequently reported (365 of 724 [50.4%]) and 15 of 336 primary school children (4.5%) experienced fecal incontinence. Overall, 42 primary school children (12.5%) had consulted a physician for symptoms related to withholding. In this cross-sectional study, toilet avoidance and stool withholding at school were common among both primary and high school children, mostly due to hygiene and privacy concerns. Improving school toilet facilities may reduce withholding behavior, gastrointestinal symptoms, and related physician visits, thereby supporting children's physical, psychological, and educational well-being.

Blastocystis sp. is the most common enteric protist colonizing a wide range of host and is characterized by wide genotypic diversity. Heat Shock Protein 70 (HSP70), a common stress-response protein has been associated with increased proliferation in Blastocystis sp. under thermal stress. However, the extent of HSP70 genetic variation and its link to thermostability remains unexplored. Our study aims to elucidate HSP70 gene variants among different Blastocystis sp. subtypes, analyze their responses to thermal stress, and evaluate their protease activity following the thermal stress. Heat Shock Protein 70 gene from eighteen Blastocystis sp. isolates of varying subtype - ST1, ST3, ST4, ST6, and ST7 - were amplified, sequenced and phylogenetically analyzed. The cells were then subjected to thermal stress at 42&#xb0;C for 24 hours and the cell viability was monitored for seven days. Protease activity in solubilized antigens (SA) from purified Blastocystis sp. cells was evaluated following exposure to thermal stress. Phylogenetic analysis revealed two distinct clades: ST4 and ST7 (Clade 1) which are mostly thermotolerant, while ST1, ST3, and ST6 (Clade 2) exhibited lower tolerance. Total protease activity was similar across subtypes, suggesting need for further sub-class specific analysis. Our findings suggests that thermal stress adaptation is subtype dependent and may be influenced by HSP70 variation. This insight highlights the importance of HSP70 as a potential molecular marker for stress adaptation in Blastocystis sp. and underscore the need for deeper investigation of its functional role in parasite persistence and pathogenic potential.

Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised children. Pediatric data are limited, and treatment guidelines often rely on adult studies. This study aimed to assess clinical characteristics and treatment outcomes of pediatric IA. We conducted a retrospective cohort study of pediatric patients (0-18&#xa0;years) diagnosed with IA at a tertiary center in T&#xfc;rkiye between 2010 and 2022. Data on demographics, underlying conditions, Aspergillus species, antifungal susceptibility, treatment regimens, and outcomes were analyzed. Survival analysis was performed using Kaplan-Meier curves. Fifty-five children met criteria for proven (69%) or probable (31%) IA after excluding 22 possible cases. Median age was 8.6&#xa0;years; mortality did not differ significantly by age, sex, or underlying condition. Hematologic malignancies were the most common comorbidity (35%). Aspergillus fumigatus was the predominant species (57%), and no antifungal resistance was detected. Classical risk factors; central venous catheter use (53%), neutropenia (51%), and recent chemotherapy (35%) were frequent but showed no association with mortality. Lung involvement was the most common presentation (71%), followed by sinus (31%) and central nervous system involvement (13%). Thirty-day mortality was 11%, 12-week mortality was 20% (11/55), and overall mortality reached 29%. Pediatric IA remains associated with substantial morbidity and mortality, although outcomes in this cohort were more favorable than those reported in many prior pediatric series. No single clinical, microbiological, or radiological factor reliably predicted mortality, underscoring the complexity of risk stratification. Early diagnosis and timely antifungal therapy remain essential, and multicenter prospective studies are needed to optimize treatment approaches.

Cholinergic deficiency is a hallmark neurotransmitter abnormality in Alzheimer's disease (AD) that has traditionally been addressed with cholinesterase inhibitors. In severe AD, butyrylcholinesterase (BuChE) becomes the dominant cholinesterase, suggesting a potential therapeutic target. (-)-N1,N8-bisnorcymserine tartrate (BNC) is a selective BuChE inhibitor designed to address this unmet need. We conducted a phase I, single-center, randomized, double-blind, placebo-controlled, ascending single oral dose clinical trial to evaluate the safety, tolerability, and pharmacokinetics of BNC in 30 healthy volunteers. There were no adverse events (AEs) grade 2 or above or any serious adverse events (SAEs). Most events were mild and self-limited, the most common being asymptomatic bradycardia and headache. The mean AUClast (SD) was 120.98 h&#x2217;ng/mL (74.30) for the 40 mg dose, 148.20 h&#x2217;ng/mL (99.43) for the 80 mg dose, and 196.33 h&#x2217;ng/mL (91.74) for the 120 mg dose. Accordingly, median tmax (range) and mean Cmax (SD) were 1.8 (1.0-5.0) hr and 13.94 (7.64) ng/mL for the 40 mg dose, 1.8 (1.5-5.0) hr and 18.54 (6.44) ng/mL for the 80 mg dose, and 2 (1.0-4.5) hr and 20.93 (5.00) ng/mL for the 120 mg dose. The mean half-life of BNC ranged from 5.5 to 7 h. BNC was safe and well tolerated when administered as a single oral dose of up to 120 mg. This first-in-human, phase I study permits further investigation of this drug as a potential symptomatic treatment for AD. ClinicalTrials.gov, NCT01747213.

Self-sustained oscillators are emerging as key physical elements for neuromorphic electronics, providing a hardware route to emulate the spiking dynamics of biological neurons. As conventional computing architectures struggle with power dissipation and parallel processing limitations, oscillatory devices offer a means to reproduce the brain's remarkable efficiency-performing adaptive and nonlinear tasks with minimal energy consumption. This review provides a unified synthesis of the diverse families of self-oscillating systems developed across physics, chemistry, and electronic engineering. We classify oscillators according to their operational mechanisms, distinguishing those driven by negative differential resistance (NDR) instabilities from those sustained by active-feedback amplifiers. Their common behavior is described within a nonlinear dynamical framework that links materials, electronic response, and the emergence of limit cycles in phase space. We discuss how these devices-ranging from electrochemical and memristive oscillators to transistor-based and hybrid architectures-can be modeled, measured, and coupled to form complex networks. Particular attention is given to the experimental identification of active elements and impedance signatures that reveal self-oscillation. By bridging device physics, nonlinear dynamics, and neuromorphic computing, this review outlines a coherent foundation for designing scalable, energy-efficient oscillatory systems that connect the physical principles of chemical and electronic oscillators with the computational logic of the brain.

Hookworm disease is one of the tropical neglected diseases that significantly impacts human health to varying degrees. Hookworms produce various proteins to facilitate host invasion and immune evasion. Despite available treatments, reinfection is common, underscoring the need for effective vaccines. However, the complexity of the hookworm's life cycle poses a challenge in understanding the immune response in the vaccine candidates. Reverse vaccinology (RV) offers a powerful approach to understand the immune response by using various bioinformatics tools. This study begins by identifying hookworm antigens capable of inducing host immune responses, followed by docking analysis with different dendritic cell (DC) receptors to investigate the immunological response of antigenic peptides and further correlated to the immunogenicity findings in clinical trial. Necator americanus GlutathioneS-Transferase-1 (Na-GST-1), a known immunogenic protein from Necator americanus, was selected for docking due to its strong antigenic properties. Fifteen DC receptors were evaluated against Na-GST-1, of which seven receptors (TLR2, TLR3, TLR4, TLR7, DEC-205, CD206, and CD36) exhibited stronger predicted interactions, as indicated by stronger binding affinities with Na-GST-1 utilizing various immunoinformatic tools. These receptors are associated with the mediation of Th1/Th2 immune responses, suggesting a potential correlation between docking affinity and the predicted immunogenicity of Na-GST-1. Overall, this study provides valuable insights into DC receptor-antigen interactions and demonstrate a computational approach for assessing the potential of hookworm antigens to engage DC receptors, thereby supporting rational hookworm vaccine design. These findings support the application of early in silico strategies for advancing vaccine candidates against hookworm infection and strengthening control efforts for neglected tropical diseases.

Quality-adjusted life-years (QALYs) are the predominant health benefit measure used in health technology assessment. In response to legal and policy constraints on the use of QALYs in some jurisdictions, alternative outcome measures, such as equal value life-years and health years in total, have been proposed. However, there is limited illustration of how these alternative measures behave when applied to common health economic model structures. Three stylized oncology economic models, reflecting typical features of published cost-effectiveness analyses, were used to examine how alternative outcome measures re-express identical underlying survival and health-related quality-of-life inputs. Outcomes based on QALYs were compared with those based on life-years, equal value life-years, and health years in total for renal cell carcinoma, chronic myeloid leukemia, and non-small cell lung cancer. Incremental health years in total were consistently larger than incremental QALYs (13-46% higher). The relationship between life-years and QALYs varied across indications (from 63% lower to 43% higher). When applied to identical model inputs, alternative outcome measures primarily re-express existing information rather than incorporate additional dimensions of health benefit. Differences relative to QALYs reflect alternative weighting of survival and health-related quality-of-life effects and depend on the balance between these components. These findings highlight the need for careful interpretation of alternative measures when used alongside QALYs in economic evaluation.

To evaluate the effect of saline boost injections on angiographic contrast. Angiographic examinations were performed using a SIEMENS ArtisQ Celling (VD11E) system with syngo Workplace (VD20B) and a PRESS DUO elite autoinjector (Nemoto Kyorindo, Tokyo). Standard injection parameters, assuming non-selective angiography from the abdominal aortic bifurcation to the common femoral artery, were 5.0 mL/s for 2.0&#xa0;s. Five boost conditions were assessed: injection speed of 5.0, 7.0, and 10.0 mL/s with total volumes of 5.0, 10.0, and 15.0 mL (1.0-3.0&#xd7; standard), and 7.0 and 10.0 mL volumes corresponding to the amount delivered within 1.0&#xa0;s. Time-enhancement curves (TECs) were generated from identical regions of interest placed in the proximal, middle, and distal portions of a vascular phantom to measure maximum signal intensity and enhancement duration. Additional quantitative analysis was performed using iFlow color-coded maps. Changes in the saline-flush boost volume resulted in minor differences compared with the baseline TECs. At a boost speed of 7.0 mL/s, maximum signal intensity increased by 7.2%, 8.1%, and 7.0% in the proximal, middle, and distal segments. At 10.0 mL/s, increases were 11.5%, 11.3%, and 11.1%, respectively. On iFlow analysis, the reference time-to-peak significantly shortened at 10.0 mL/s-3.49, 4.01, and 4.17&#xa0;s-compared with 3.68, 4.22, and 4.26&#xa0;s at baseline (p&#x2009;<&#x2009;0.01). Boosting double-speed saline injection improved the efficiency of contrast agent delivery to distal regions. Further improvements in injection efficiency may reduce the required amount of contrast agent and the number of frames.

BackgroundSepsis affects an estimated 166 million people annually. Short-term survival has been the primary focus of research to date, yet individuals who survive acute sepsis face substantial long-term challenges, including chronic illness, physical disability, cognitive impairment, chronic organ dysfunction, cardiovascular events, and psychological disorders. These complications contribute to personal economic hardship, high healthcare utilization, frequent rehospitalization, and significant mortality rates.ObjectivesWe aimed to identify and summarize key interventions for sepsis survivors' post-hospital discharge - including physical rehabilitation, psychological care, provider assessments, monitoring, medication, and education - and to identify gaps in current evidence to elucidate future research priorities.MethodsA systematic scoping review was completed across five databases, supplemented with hand searching. Two reviewers independently screened and extracted data. Eligible studies focused on adult survivors of sepsis, where interventions were implemented after discharge from acute care, and included any research design.ResultsThirteen studies with four follow-up papers were included. Five reported on the impact of simultaneous intervention protocols, four on physical rehabilitation alone, and two on provider assessment and follow-up. The final two focused on psychological care, and pharmacotherapy. Mortality and readmission rates were the most common outcomes measured; satisfaction with care services, mental health outcomes, and cardiovascular event incidence were also evaluated. Qualitative study data was limited. Four studies mentioned intervention costs, but none completed a cost-benefit analysis. Based on a limited pool of evidence, protocolized multi-intervention approaches, provider assessment and follow-up, and physical rehabilitation show some promise in reducing hospital readmissions and improving long-term survival from sepsis. No interventions positively impacted sepsis survivors' mental health. Further, no studies evaluating educational interventions alone were identified.ConclusionsThis review highlights the need for more comprehensive, multidisciplinary post-sepsis care interventions. Future research should focus on patient education, mental health support, and cost-effectiveness analyses to inform evidence-based post-sepsis care strategies.

Cognitive impairments are common in absence epilepsy, yet the neural basis of these deficits remains largely unknown. Communication between the thalamic reuniens nucleus and the prefrontal cortex is critical for flexible behavior. Here, we identify a disruption of this pathway in mice with absence epilepsy. This dysfunction leads to impaired cognitive flexibility and altered cortical inhibition, linking seizure-related thalamic activity to prefrontal network imbalance. Notably, targeted stimulation of the thalamic-prefrontal pathway alleviates both seizure occurrence and cognitive deficits. These findings reveal a shared circuit mechanism underlying epileptic and cognitive symptoms, pointing to new strategies for intervention.