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Electrocardiographic (ECG) artifacts mimicking acute coronary syndrome (ACS) pose a risk of misdiagnosis and unnecessary procedures. While arterial pulsation artifacts are known to cause limb-lead ST-T changes adhering to the "single-limb lead exemption principle," their potential to induce specific repolarization abnormalities in precordial leads remains unreported. A 66-year-old woman presented with chest tightness. The initial ECG showed ST-segment elevation in leads III and aVF, depression in I and aVL, and a previously undescribed pattern of isolated mid-portion T-wave inversions in precordial leads V2-V6, with preserved initial T-wave morphology. Suspected ACS was reconsidered after a senior physician noted atypical features. The diagnosis of radial artery pulsation artifact was confirmed after repositioning the limb electrodes away from the radial pulse, which normalized all ECG abnormalities Coronary computed tomography angiography revealed only mild atherosclerosis, ruling out acute ischemia. To our knowledge, this case is the first to describe a previously unreported variant manifestation of arterial pulsation artifact featuring isolated mid-portion T-wave inversions in precordial leads. We propose a potential mechanism via propagation of limb-derived interference currents through the Wilson Central Terminal, combined with an electromechanical hypothesis. This pattern, especially when combined with the limb lead exemption principle (spared lead II localizing the source to the left arm), suggests a potential electrocardiographic sign for differentiating artifact from true pathology. We also propose a practical bedside approach integrating lead-specific analysis and electrode repositioning to prevent misdiagnosis.

In March and April of 2023, an outbreak of highly pathogenic avian influenza virus, H5N1 strain Eurasian lineage goose/Guangdong H5 clade 2.3.4.4b, resulted in at least 17 mortalities of free-ranging California condors (Gymnogyps californianus) in Arizona. Condors presented dead or with neurologic signs and lethargy. Infection resulted in multisystemic inflammation and necrosis that most consistently and severely affected the brain, spleen, and adrenal glands. Immunohistochemistry performed on tissues from a subset of condors labeled cells in multiple organ systems for influenza A virus, most abundantly in neurons, epithelial cells, and mononuclear inflammatory cells and often colocalized with areas of inflammation. Acute blunt force trauma, presumably from ground collision after falling from a height, was a common finding and indicated a rapidly debilitating disease course and neurologic impairment. Hepatic lead concentrations were relatively low with no concurrent incidences of acute lead toxicosis, an otherwise common cause of death in free-ranging California condors. Bone lead reflected long-term lead accumulation in several condors. Assessment of ingesta in 8 condors via morphologic hair identification showed a mix of consumed taxa, most commonly Bovidae. In summary, California condors, like other New World vultures (family Cathartidae), are highly susceptible to this strain of H5N1, and this should be taken into consideration when planning release, feeding, and morbidity and mortality responses.

Single-cell foundation models such as scGPT have been promoted as representations of gene regulation, but their advertised regulatory signal has been judged largely from attention weights, which are correlational. We ask a deliberately bounded question: whether direct interventions on scGPT gene tokens-causal with respect to the model's own computation-recover model-internal transcription-factor (TF)-target dependencies that align with curated references, whether that signal is robust, and whether it transfers to real perturbation responses. We separate these into two explicit validation axes and report both, including where the model-internal signal does not correspond to biological causality. On Tabula Sapiens kidney, lung, and immune subsets, plus an external Krasnow lung atlas and three CRISPR perturbation datasets (Adamson, Dixit, Shifrut), we ablate or swap TF token values inside scGPT and quantify changes in target-token readouts. Axis 1 (reference alignment): intervention scores are evaluated against curated TRRUST and DoRothEA references and against attention and coexpression baselines, with new robustness studies over cell count (120-500), positive/negative pair count, four negative-sampling designs, and four readout strategies (mean, L2, cosine, max). We trace component-level circuits via activation patching, and benchmark against twelve GRN inference methods including a neural-network baseline on a matched substrate, additionally giving the classical methods larger cell budgets to test the equal-information question. Axis 2 (perturbation transfer): scores are evaluated against CRISPR perturbation-derived edges under balanced labels and AUROC. On Axis 1, lung shows reproducible enrichment that is stable across cell count and survives all four negative-sampling designs (permutation p improving from 0.07 to 0.03 as cells grow from 120 to 500); kidney enrichment is significant at small samples but does not survive scaling (permutation p rising to 0.16 at 500 cells); immune is at baseline. Richer readouts (L2, cosine) recover signal the scalar mean compresses away, particularly in kidney. On the matched benchmark scGPT leads classical and neural baselines at the shared 120-cell budget, but the lead narrows as the classical methods are given more cells, confirming this is a signal-efficiency result, not general superiority. On Axis 2, balanced evaluation of all three CRISPR datasets, including the TF-screen Dixit data, yields AUROC ≈ 0.50: the model-internal signal does not predict real perturbation responses. scGPT encodes tissue-conditional, intervention-sensitive regulatory structure that is aligned with literature-curated TF-target edges (robustly in lung) but is representational rather than biologically causal: it does not transfer to perturbation outcomes. The pipeline is a practical mechanistic-audit toolkit for biological foundation models, and the gap between reference alignment and perturbation transfer is a concrete cautionary result for using such models in regulatory inference.

Heterotopic ossification (HO) is a frequent complication in persons with spinal cord injury (SCI). This condition leads to limitations in movement and to abnormal posture, which can impair sitting and bed positioning and may result in pressure ulcers. Surgery is considered when HO causes severe limitations due to joint obstruction caused by the ossification. However, the defect left after resection is often extensive and may create significant dead spaces that can lead to seroma or hematoma formation if not adequately filled, increasing the risk of infection and prolonged hospitalization, and extended antibiotic therapy. We report five cases of large HO treated with resection followed by muscle flap reconstruction to eliminate all dead spaces. All patients were male, with a median age of 44 years old; 3 patients were paraplegic and 2 tetraplegics; 3 patients presented with AIS A and 2 with AIS B. All HOs were in the trochanteric region and involve the hip joint, with a mean defect size of 9,6 × 39,7 × 9,4 cm. After HO resection the defects were filled with a rectus femoris muscle flap. In two cases we observed a seroma that was drained, and the defect was filled with another muscle flap (vastus lateralis and semimembranosus). In all reported cases, following muscle flap positioning, no seromas or hematomas were observed. We believe that this reconstructive technique can be beneficial in such cases and may become part of our standard approach to HO resection.

Environmental illusions (e.g., shadows, reflections, and tire marks) are naturally existing yet overlooked phenomena in real-world driving environments. They can disturb visual perception, leading to misinterpretation of the scene and posing serious safety risks to autonomous driving (AD) systems. However, existing researches largely overlook these phenomena, leaving a critical gap. To address this issue, we study AD robustness through the lane perception perspective, a fundamental task supporting core functions like cruise control and lane centering. We focus on two representative models: conventional lane detection (LD) and vision-language model-based systems (ADVLMs). In this work, we introduce the first benchmark, LanEvil++, for evaluating the robustness of lane perception under environmental illusions. LanEvil++ encompasses 14 types of illusions and leverages the CARLA simulator to generate 94 high-fidelity, fully controllable 3D scenes, yielding a dataset of 90,292 annotated images, 1,596 video clips, and 41,855 visual question answering pairs. Extensive evaluations demonstrate that environmental illusions substantially degrade the performance of state-of-the-art LD methods. On average, LD models experience a 5.27% drop in Accuracy and a 10.49% decline in F1-score, while ADVLMs show a 2.03% reduction in GPT-score and a 0.75% drop in Language-score. Among all illusions, shadows emerge as the most disruptive factor, reducing accuracy by up to 7.20%. Furthermore, closed-loop simulations using OpenPilot and LMDrive reveal that these illusions can lead to incorrect driving decisions, underscoring their real-world implications. Complementary real-world case studies highlight safety-critical failures in actual traffic scenes. To enhance robustness, we propose the Multimodal Illusion Defense Approach (MIDA), which uses hard examples to improve illusion resistance. MIDA achieves substantial gains under challenging conditions, boosting robustness by 4.23% on LD models and 3.82% on ADVLMs. We hope this work brings greater attention to the threats posed by environmental illusions and motivates the development of more robust AD systems. Part of our dataset and demos can be found at the https://tianyuan2001.github.io/lanevilpp.github.io/.

Depression in dementia with Lewy bodies (DLB) is a common neuropsychiatric symptom associated with reduced quality in life. Structural, functional and neurochemical abnormalities in glutamatergic and GABAergic neurotransmission are implicated in the pathophysiology of depression, showing changes in regions involved in emotional processing, including the subgenual cingulate cortex (sgACC), which shows pathological changes in DLB. Using post-mortem tissue from DLB patients and controls, we assessed synaptic and neurochemical changes within the sgACC in relation to depression in DLB. We identified a reduction of layer V GABAergic neurones in depressed DLB cases, potentially indicating reduced inhibition of layer V pyramidal neurons, leading to altered excitation. High-resolution confocal imaging demonstrated a significantly increased volume of presynaptic glutamatergic synapses containing phosphorylated α-synuclein (s129) in DLB cases, and specifically in depressed DLB cases, potentially as a compensatory response to the accumulation of pathological s129. GABAergic synapses containing s129 were enlarged in both DLB groups showing no depression specific changes. Selective reductions in glutamatergic and GABAergic receptors were seen in depressed DLB cases, suggesting a role in the pathophysiology of depression in DLB, that may prove amenable to therapy with fast-acting antidepressants. Interactions with serotonergic and dopaminergic innervation were observed, where preserved 5HT3B receptor and calbindin characterised non-depressed DLB patients. In depressed DLB cases, this may lead to reduced inhibition of lower layer pyramidal neurones due to reduced dopaminergic coupling and enhanced excitatory activity within the cingulate. Overall, our findings suggest altered excitatory and inhibitory neurotransmission may contribute to the development of depression in DLB.

Electrical synchrony is a key determinant of cardiac function and a fundamental component in the success of cardiac resynchronization therapy (CRT). Despite its importance, its definition remains imprecise and its assessment is largely based on indirect and non-standardized electrocardiographic parameters, such as QRS duration and morphology, which do not consistently reflect true electrical dyssynchrony or predict response to therapy. This narrative review explores the current understanding of cardiac electrical synchrony, highlighting the limitations of conventional evaluation methods and the heterogeneity of results observed in different clinical scenarios, including conduction disorders, heart failure, and device-based therapies. Special emphasis is placed on Synchromax®, a novel non-invasive tool that enables real-time assessment of electrical synchrony through cross-correlation analysis of surface electrocardiographic leads. This method provides reproducible, operator-independent measurements and allows classification of patients into different synchrony patterns. Clinical applicability spans pre-implant evaluation, intra-procedural guidance for optimal lead positioning, and post-implant optimization of pacing strategies. Furthermore, it offers new insights into the pathophysiology of conduction disturbances and supports the ongoing shift toward physiological pacing approaches. The ability to objectively measure electrical synchrony may represent a paradigm shift in cardiac electrophysiology, improving patient selection, guiding therapeutic decisions, and potentially reducing the rate of non-response to CRT. Integrating new tools for synchrony assessment into clinical practice could contribute to a more individualized and effective approach to cardiac pacing and resynchronization.

Hyperkalemia is a common complication of kidney disease and incidence increases as kidney function declines. Renin-angiotensin system blockade, which improves renal and cardiovascular outcomes, increases the risk of hyperkalemia. Unfortunately, hyperkalemia often leads to discontinuation of these medications, which can increase adverse outcomes. Treatment of chronic hyperkalemia includes diet and pharmacologic interventions. However, the association of dietary potassium intake with serum potassium levels is weak and does not consider important internal and external balance factors that affect serum levels. Traditional dietary interventions that limit dietary potassium lead to a restrictive diet that limits fruits and vegetables, whole-grains, and plant-based proteins. This restrictive approach may unnecessarily limit dietary quality and variety in a population already at risk for poor nutritional status and complications of chronic kidney disease (CKD). The management of hyperkalemia requires a comprehensive, individualized approach that moves beyond blanket dietary restriction. The objective of this review is to describe the role of diet and pharmacological approaches to manage hyperkalemia, highlighting newer dietary approaches.

Somatic mutations involving the canonical exon 10 hotspots of the thrombopoietin receptor gene (MPL) are established drivers in myeloproliferative neoplasms (MPNs), whereas the significance of rare, atypical variants remain unclear. We investigated the relevance of three uncommon MPL variants affecting residues Y591 and R592. Among a multicenter cohort with myeloid neoplasms undergoing next-generation sequencing (NGS), eight individuals harbouring MPL p.Y591D, p.Y591H, or p.R592Q variants were identified. Clinical data were integrated with a comprehensive literature review, in silico pathogenicity prediction, and structural bioinformatics modelling of the MPL-JAK2 complex. Clinically, these variants were observed across heterogeneous myeloid disorders and consistently co-occurred with canonical driver mutations in MPN cases. Certain patients with Y591 substitutions seem to exhibit aggressive disease phenotypes and/or suboptimal responses to JAK-inhibitors, whereas R592Q cases showed variable outcomes influenced by co-mutational profiles. Computational predictors yielded discordant pathogenicity assessments. Structural modeling indicated that these substitutions induce minor local rearrangement and do not significantly disrupt the overall MPL-JAK2 complex assembly. However, the Y591 substitutions may lead to loss of critical regulatory motifs by removing a key phosphorylation-dependent docking site and disrupting the YXXφ motif, potentially leading to receptor hypersensitivity to thrombopoietin. Regarding pathogenicity classification, the p.R592Q substitution should be considered as a variant of uncertain significance (VUS), whereas the Y591 alterations may be categorized either as VUS or as "likely oncogenic" depending on the chosen framework. Crucially, current evidence indicates that MPL p.Y591D, p.Y591H, and p.R592Q variants do not act as primary oncogenic drivers but may function only as disease modifiers.

Chlorophyll is central to the capture of light energy but also contributes to pigmentation of plant products such as fruit. Bagging treatments are widely used to enhance chlorophyll degradation and to improve the visual quality of fruit such as apples, pears, and peaches. In this study, a bagging treatment of kiwifruit Actinidia chinensis (cultivar Jinshi; "JS") accelerated flesh chlorophyll degradation. RNA-seq analysis indicated that AcFBA2, which encodes a fructose-1,6-bisphosphate aldolase (FBA) enzyme, and AcRBCS1, encoding Rubisco small subunit (RBCS), both in the Calvin cycle, were significantly downregulated. Knockout of either gene resulted in leaf yellowing in kiwifruit, accompanied by severe damage to chloroplast structure. Further experiments indicated that AcFBA2 and AcRBCS1 could form a protein complex, which also occurred in orthologous Arabidopsis enzymes. Additionally, we identified two HSF transcription factors, AcHSFB2a and AcHSFA7a, which bind to the promoters of AcFBA2 and AcRBCS1, respectively, and repress their expression, thereby promoting yellowing of kiwifruit flesh. Transient overexpression of AcHSFB2a or AcHSFA7a could reduce chlorophyll content in tobacco leaves. In summary, an unexpected physical interaction between two key Calvin cycle enzymes (FBA and RBCS) was shown in kiwifruit and Arabidopsis, and downregulation of these two genes by bagging treatment and genome editing could lead to de-greening. Transcriptional regulation by AcHSFB2a and AcHSFA7a suggests a potential regulatory network linking HSF transcription factors with photosynthesis and chlorophyll degradation.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM) and remains a major cause of visual impairment and blindness in adults. Accumulating evidence indicates that DR is not merely a microvascular disorder, but a complex neurovascular disease driven by long-standing hyperglycemia, metabolic dysregulation, oxidative stress, chronic inflammation, neurodegeneration, and impaired neurovascular coupling. Mitochondria are central regulators of cellular energy metabolism and redox homeostasis, and mitochondrial dysfunction is increasingly recognized as a pivotal mechanism linking hyperglycemia-induced metabolic abnormalities to retinal neurovascular unit injury. Under persistent hyperglycemic conditions, excessive glucose flux and metabolic overload promote mitochondrial reactive oxygen species (ROS) overproduction, mitochondrial DNA (mtDNA) damage, impaired oxidative phosphorylation, mitochondrial fusion-fission imbalance, defective mitochondrial biogenesis, dysregulated mitophagy, metabolic reprogramming, and epigenetic alterations. These abnormalities lead to ATP depletion, inflammatory amplification, and activation of multiple forms of programmed cell death, including apoptosis, ferroptosis, pyroptosis, necroptosis, and poly(ADP-ribose) polymerase 1 (PARP1)-dependent cell death. Mitochondrial injury affects retinal endothelial cells, pericytes, Muller cells, microglia, retinal ganglion cells, photoreceptors, and retinal pigment epithelial cells in a cell-type-specific manner, ultimately contributing to blood-retinal barrier disruption, capillary occlusion, neurovascular coupling impairment, retinal neurodegeneration, and progression from non-proliferative to proliferative DR. This review summarizes recent advances in mitochondrial dysfunction in DR, focusing on oxidative stress, mtDNA injury, mitochondrial metabolic reprogramming, mitochondrial dynamics, mitochondrial biogenesis, mitophagy, epigenetic regulation, mitochondria-associated cell death, and neurovascular unit dysfunction. Emerging mitochondria-targeted therapeutic strategies, including mitochondrial antioxidants, modulation of mitochondrial biogenesis and dynamics, mitophagy regulation, mtDNA protection, ferroptosis and inflammasome inhibition, epigenetic intervention, are also discussed. A deeper understanding of mitochondrial mechanisms may provide new therapeutic targets and translational opportunities for DR prevention and treatment.