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464 papers

Persistent Delirium in the Elderly: A Case Report and Review of Multifactorial Contributors and Management Challenges.

Salisbury T. · Jun 25, 2026

Introduction This case describes persistent delirium exceeding 18 months with prominent paranoid delusions in a 72-year-old woman with chronic hyponatremia, poststroke epilepsy, and alcohol use disorder. It highlights diagnostic and pharmacologic management challenges when standard agents carry prohibitive risks. Patient’s main concerns and important clinical findings A 72-year-old woman with a history of left hemispheric hemorrhagic stroke, poststroke epilepsy, and chronic alcohol use presented with acute confusion. Laboratory evaluation revealed severe hyponatremia (Na 122 mmol/L). Clinical findings included persecutory delusions, severe agitation with dangerous behaviors (attempting to leave moving vehicles, stabbing attempt), anxiety, insomnia, and fluctuating cognitive status with return to baseline between episodes. EEG demonstrated epileptiform discharges and generalized encephalopathy. Divalproex sodium levels at presentation were supratherapeutic (up to 127 mcg/mL). There was no evidence of prior dementia or progressive cognitive decline. Primary diagnoses interventions and outcomes The primary diagnosis was persistent delirium with multifactorial etiology. Interventions included hyponatremia correction, transition from divalproex to lacosamide, and initiation of mirtazapine, which was selected for its lower hyponatremia risk compared to other antidepressants, lower seizure risk compared to antipsychotics, and low deliriogenic potential. Sleep and anxiety improved with partial agitation reduction, though delirium persisted. Over 18 months, paranoid delusions evolved from episodic to continuous, creating treatment adherence barriers. Conclusion This case underscores the potential for exceptionally prolonged delirium in medically complex older adults, diagnostic complexity in differentiating persistent delirium from ictal-related psychosis and other conditions, and individualized pharmacotherapy considerations. Early multidisciplinary intervention, capacity assessments, and caregiver support are critical.

Medicine

Severe Pediatric Snakebite With Coagulopathy and Compartment Syndrome: Conservative Management With Plasma Exchange.

Al Muqbel ZM et al. · Jun 25, 2026

Snakebite envenomation is a global public health concern, and hemotoxic bites can lead to severe coagulopathy, microangiopathic hemolytic anemia, and compartment syndrome. We describe a previously healthy 6-year-old boy who presented with progressive left lower limb swelling, discoloration, and bleeding from intravenous cannula sites following a snakebite sustained in rural Pakistan, consistent with severe hemotoxic envenomation. Despite antivenom and transfusion support, he developed persistent venom-induced consumption coagulopathy with hypofibrinogenemia, markedly prolonged clotting times, thrombocytopenia, and features of microangiopathic hemolytic anemia. Severe limb swelling raised concern for compartment syndrome; however, fasciotomy was deferred due to the high risk of bleeding in the setting of uncontrolled coagulopathy. Transferred to Bahrain, he underwent five sessions of therapeutic plasma exchange, initiated due to ongoing clinical and laboratory deterioration, resulting in stabilization of hematologic parameters, resolution of limb swelling, and preservation of limb function. This case highlights the role of plasma exchange in children unresponsive to conventional therapy and demonstrates that conservative management of suspected compartment syndrome may be feasible when surgical intervention carries significant risk, underscoring the importance of early recognition and multidisciplinary care in complex pediatric envenomation.

Biochemistry, Genetics and Molecular Biology

Evaluating Source-Based Large Language Models for Preclinical Dermatology Education: Comparative Study.

Lin FJ et al. · Jun 25, 2026

Background Large language models (LLMs) have gained increasing popularity in medical education, with evidence supporting their educational value when framed through the lens of cognitive load theory. Source-based LLMs, which explicitly ground responses in user-uploaded material via retrieval-augmented generation algorithms, may offer additional educational value by using student-developed materials to conceptualize new areas of learning within a familiar framework. This has applications for areas like medical education in dermatology, which could benefit from inclusive sources and enhanced education to alleviate health care gaps. However, no prior studies have examined whether the inclusion of student-authored notes alters the response characteristics of a source-based LLM when responding to medical questions. Objective This study aims to conduct an observational, comparative performance evaluation study assessing the accuracy, response reproducibility, and intermodel response similarity of freely available LLMs on text-only step 1 dermatology questions, and to explore whether providing extensive student-generated notes to a source-based LLM alters these performance characteristics. Methods In December 2024, 4 LLMs were evaluated: NotebookLM (NLM) with uploaded preclerkship study guides (NLM w/ Notes), NLM with an uploaded blank sheet of paper (NLM w/o Notes), ChatGPT-4o Mini, and Google Gemini 1.5 Flash. Each model completed 3 trials of 121 text-based United States Medical Licensing Examination (USMLE) step 1 dermatology questions from the AMBOSS question bank. They were evaluated for overall majority-consensus accuracy, accuracy by question difficulty, intertrial reproducibility, and agreement in answer choice selection between models. Differences were analyzed through a Cochran Q omnibus test and subsequent pairwise McNemar tests with Benjamini-Hochberg correction. Response reproducibility and intermodel agreement were analyzed through Fleiss κ statistics with 95% CI. Results ChatGPT-4o Mini achieved the highest overall majority-consensus accuracy (102/121, 84.3%). NLM w/ Notes demonstrated the highest intertrial reproducibility (Fleiss κ=0.927, 95% CI 0.875-0.978) and strong performance on lower-difficulty questions but comparatively reduced accuracy on higher-difficulty items. NLM w/o Notes exhibited significantly higher omission rates (38/363, 10.5% vs ≤7/363, 1.92% for other models) than other tested LLMs. Sensitivity analysis excluding omissions increased NLM w/o Notes' accuracy from 66.9% (81/121) to 77.8% (77/99), matching NLM w/ Notes' accuracy of 74.4% (90/121). Intermodel agreement was significantly higher between NLM w/ Notes and ChatGPT-4o Mini compared to NLM w/o Notes and Gemini 1.5 Flash. Conclusions Provision of student-generated notes substantially increased response reproducibility in a source-based LLM, likely reflecting consistent retrieval of similar source excerpts across trials. However, note-grounding appeared to constrain performance on higher-difficulty questions, suggesting a retrieval-augmented generation algorithm retrieval error when question stems excluded characteristic "keywords" present in lower-difficulty items. The results highlight potential challenges of a student-level, cognitive load theory-grounded educational LLM that must deal with notes not curated by experts, balance source use and internal reasoning, and meaningfully appraise uploaded sources to assess a student's individual learning gaps.

Social Sciences

Role of the nonhelical tailpiece of myosin-II in regulating filament architecture and function.

Wang K et al. · Jun 25, 2026

Mammalian nonmuscle myosin-II isoforms (NM-IIA, NM-IIB, and NM-IIC) each contain a nonhelical tailpiece (NHT) at their C terminus. Stop-codon mutations in the NHT of NM-IIA are linked to diseases such as macrothrombocytopenia. However, the role of the NHT in NM-II filament assembly and function remains poorly understood. Here, we show that NM-II isoforms lacking the NHT, including disease-associated NM-IIA truncations, form enlarged bipolar filaments with reduced bare zones. NHT length emerges as a key determinant of filament size. Moreover, NM-IIA NHT truncations generate stress fibers composed of enlarged bipolar filaments that exhibit reduced FRAP recovery and an increased tendency to aggregate, resulting in impaired cell migration. We further provide in vivo evidence that NM-IIA assembles into bipolar filaments in the absence of RLC phosphorylation, a property enhanced by NHT deletion. Together, these findings establish the NHT as a critical regulator of NM-II filament architecture, dynamics, and function and provide mechanistic insight into NM-IIA NHT-associated diseases.

Medicine

DNA damage complexity as a predictor of cell survival: a microscopic Monte Carlo-based modeling framework for photon, proton and carbon ion irradiation.

Qi M et al. · Jun 25, 2026

Objective. Biological effect of charged particles characterized by cell surviving fraction (SF) depends on physical factors such as particle type, dose, beam quality descriptors, e.g. linear energy transfer or lineal energy. Driven by the crucial role of DNA double-strand breaks (DSBs) as indicators of cellular responses to ionizing radiation, this study aims to develop a cell-specific SF model based on the initial DSBs of varying complexities applicable to photon, proton, and carbon-ion irradiations across the investigated beam qualities. Approach. Microscopic Monte Carlo simulations were used to calculate DSBs for experiments measuring SF of H460 and H1437 lung cancer cells irradiated by proton (dose-mean lineal energyy¯d2.0-20.0 keV µ m -1 ), carbon ions (y¯d18.6-87.9 keV µ m -1 ) and reference 137 Cs photon beam. We modeled SF as a third-order polynomial function of DSBs of various complexities with two, three, and more strand breaks. The function was determined by a data fitting process. Main Results. For each cell line, a single model was able to accurately describe SF in experiments under all 19 irradiation conditions with different particle types andy¯dvalues. Root mean square errors were 0.218 for H460 cells and 0.170 for H1437 cells. When applying the model to a proton spread-out-Bragg-peak case, calculated relative biological effectiveness at SF = 0.1 were 1.01-1.42 for the H460 cells and 1.03-1.65 for the H1437 cells depending on the depth. Significance. We successfully developed an SF model using DSBs of various complexities as input variables. The model provides a unified description of photon, proton, and carbon-ion irradiations across investigated beam qualities.

Medicine

Organ-Dependent Antioxidant, Redox-Modulating, and Lifespan Effects of Galanthus elwesii Extracts in Drosophila melanogaster.

Ertan O et al. · Jun 25, 2026

Galanthus elwesii is a pharmaceutically valuable Amaryllidaceae species known for its diverse bioactive metabolites; however, the relationship between its phytochemical profile, antioxidant capacity, and in vivo biological effects remains poorly understood. In this study, aerial (APE) and belowground (BPE) parts were extracted using water, methanol, and ethanol, and evaluated through a combined in vitro and in vivo approach. Total phenolic and flavonoid contents were quantified, and antioxidant activities were assessed via DPPH radical-scavenging and Fe 2+ metal-chelation assays, including IC 50 determination. The in vivo effects of selected extracts were investigated in Drosophila melanogaster through larval toxicity and developmental survival assays, adult lifespan analysis, and oxidative stress biomarkers (TAS, TOS, and OSI). Phytochemical composition and antioxidant activity exhibited strong organ- and solvent-dependent variability, with belowground extracts generally demonstrating higher phenolic content and stronger radical-scavenging and metal-chelating capacities. In vivo, most extracts showed low-to-moderate developmental toxicity at selected concentrations, while certain belowground extracts significantly extended lifespan at subtoxic doses. Oxidative status measurements revealed reduced TOS and OSI levels alongside maintained or increased TAS, indicating effective suppression of oxidative stress rather than direct antioxidant action. Correlation analysis revealed moderate negative correlations between phenolic/flavonoid content and antioxidant activity, although these relationships did not reach statistical significance. Overall, these findings suggest that G. elwesii extracts exert organ-dependent phytochemical and bioactivity profiles and may act as in vivo redox modulators associated with improvements in oxidative balance and lifespan-related parameters.

Chemistry

Photosynthetic Behavior of Wheat in Reclaimed Fly Ash Amended Soil-Probed by MINI-PAM (Photosynthetic Yield Analyzer).

Piparia C et al. · Jun 25, 2026

Fly ash (FA) management is a global environmental concern. Although FA has been widely studied as a soil amendment to improve crop growth and productivity, its utilization remains limited due to the presence of toxic heavy metals (HMs). Reclamation of FA using tolerant plant species is a sustainable strategy to mitigate adverse environmental effects and improve its suitability as a soil mulcher. However, studies evaluating the use of reclaimed fly ash (RFA) as a soil amendment remain limited. In the present study, wheat was cultivated under six conditions: T1 (normal soil, NS; control), T2 (fresh fly ash, FFA), T3 (RFA), and mixtures of RFA and NS at ratios of 1:1 (T4), 1:2 (T5), and 1:3 (T6). Prior to sowing, 12 targeted HMs were quantified using inductively coupled plasma-mass spectrometry (ICP-MS). To assess the photosynthetic behavior of wheat, chlorophyll fluorescence parameters, including Fv/fm (variable to maximum chlorophyll fluorescence), Y(II) (effective quantum yield of photosystem II), Y(NPQ) (quantum yield of regulated non-photochemical energy dissipation), and Y(NO) (quantum yield of non-regulated energy dissipation), were measured with a pulse-amplitude-modulated chlorophyll fluorometer (MINI-PAM). Results showed that Fv/fm and Y(II) were highest in T1, followed by T6, whereas Y(NPQ) and Y(NO) were lowest in T6, followed by T1. Spearman's correlation analysis revealed that Cr (chromium), Mn (manganese), Ni (nickel), Cu (copper), and Zn (zinc) were positively correlated with Fv/fm and Y(II) ( p p < 0.001); opposite trends were observed for Y(NPQ) and Y(NO). Although heavy metal concentrations remained below established critical thresholds, even sub-threshold variations influenced physiological performance. Overall, these findings highlight the potential of reclaimed fly ash as a soil amendment for sustainable wheat cultivation.

Earth and Planetary Sciences

Vaccination against tumour endothelial marker Robo4 inhibits tumour growth.

Escobar-Riquelme F et al. · Jun 25, 2026

Introduction Targeting tumour antigens is a major challenge in cancer-immunotherapy. We use active vaccination to induce antibodies targeting self-antigen Robo4, which is selectively expressed on tumour vascular endothelium, and supports vascular development. Our previous work showed that a conjugate of Robo4 with a foreign carrier protein induced autoantibodies specific to Robo4, which inhibited angiogenesis and tumour growth. Methods To translate the vaccine protocol to exploit a carrier protein used in routine human vaccination schedules, the well-characterized, non-toxic fragment C of tetanus toxin (TTc) was selected as the carrier protein. Recombinant protein Robo4-TTc (R4-TTc) was produced by Robo4 genetically linked to TTc. Results Priming with the carrier TTc followed by boost with Robo4-TTc (R4-TTc) efficiently induces strong antibody responses to Robo4 and inhibits tumour growth in LLC1 and 4T1 tumour models. The growth inhibition was correlated with anti-Robo4 IgG1 titres. Furthermore, decreased vessel formation and increased immune cell infiltration in tumours from R4-TTc vaccinated mice in the absence of detectable adverse effects on health. Conclusion The data indicate that this vaccination strategy remodels tumour vessels and probably promotes immunogenic pathway activation, therefore repressing tumour growth.

Medicine

Compact on-chip fluorescence microscope for dynamic imaging of cellular processes and biomimetic systems.

Khoubafarin S et al. · Jun 25, 2026

Real-time and High-throughput fluorescence imaging is essential for probing dynamic cellular behavior in biomimetic and tissue-on-chip systems. While fluorescence microscopy provides high sensitivity and subcellular resolution, the intrinsic heterogeneity of these engineered tissues requires imaging multiple regions to obtain representative biological information. Meeting this need typically demands mechanical scanning systems, which add both hardware and software complexity and substantially increase cost. Here, we developed a compact and low-cost on-chip fluorescence microscopy platform that integrates a two-dimensional microlens substrate directly onto a complementary metal-oxide-semiconductor sensor to achieve high resolution and signal-to-noise ratio (SNR). Excitation light is delivered laterally through a prism to induce total internal reflection, effectively rejecting background illumination and allowing only fluorescence emission to reach the detector. The system's optical geometry was optimized using analytical modeling and numerical simulations to maximize photon collection and SNR. Using this optimized system, we first demonstrated its capability at the cellular level by capturing drug-induced oxidative stress and rapid intracellular signaling dynamics in BT-20 breast cancer cells. Once we were successfully able to monitor these dynamic processes, we next applied the system to biomimetic models. In a microfluidic tumor-endothelial co-culture, we visualized the passage of small molecules, nanoparticles, and ions across the endothelial barrier under controlled flow conditions. Integration with microfluidic co-culture systems further demonstrated its ability to study complex interactions within tumor microenvironments. By combining simplicity, sensitivity, and compatibility with biomimetic platforms, this on-chip fluorescence microscope enables wide-field monitoring of cellular dynamics across large populations, allowing observation of cell-to-cell variability and supporting applications in drug screening, cellular signaling studies, and tissue-on-chip research.

Engineering

Advancing health equity for Roma people in Romania.

Matache M et al. · Jun 25, 2026

Over the past few decades, scholars in the humanities and social sciences have increasingly interrogated the histories and legacies of violence against Romani people through critical, decolonial, feminist, and anti-racist lenses. Building on this body of research, this article examines continuities of anti-Roma racism in a specific place, Romania, and how they can help reproduce and shape health outcomes and inequities today. Using a critical analysis of Romanian laws, policies, literature, and public discourse, we propose the right to a remedy for past collective injustices faced by historically oppressed and racialized populations as a pathway to the full realization of the right to health in places marked by continuous collective injustices. We argue that the realization of the right to health must be understood and addressed beyond equal access and protections against violations of the right to health; it also requires addressing the legacies and persistence of anti-Roma racism and its long-term impacts on health, well-being, and quality of life, as well as addressing other enduring oppressions.

Health Professions