搜索结果：Rogue

Patients with T1 nonmuscle-invasive bladder cancer (NMIBC) face substantial risks of recurrence and progression to muscle-invasive disease. However, current risk stratification tools rely on retrospective data with significant heterogeneity in the reporting of adverse pathological features. The ROGUE-1 registry was designed to address the unmet need for a clean, prospective dataset on primary T1 bladder cancer to enable accurate risk stratification and guide clinical decision-making. ROGUE-1 is a multicentric, international, prospective registry enrolling 700 patients with a pathologically confirmed primary diagnosis of T1 bladder cancer across 18 urology centers in Europe and North America. All patients must have T1 disease confirmed at second-look transurethral resection of bladder tumor (TURB). Clinical, pathological, and epidemiological data are prospectively collected using an electronic case report form on the Castor electronic data capture platform. Central pathology review by expert genitourinary pathologists is performed for all specimens. An optional molecular component includes transcriptome analysis of formalin-fixed paraffin-embedded tumor specimens. The primary endpoints are therapy failure rates (recurrence, high-grade recurrence, and progression to muscle-invasive disease). Follow-up data are collected at 3-mo intervals. This is a protocol paper; no clinical results are reported. A key limitation is the observational design, which precludes treatment standardization across centers. The optional molecular component may result in variable specimen availability. ROGUE-1 will provide a prospective, multi-institutional dataset to improve risk stratification in T1 NMIBC and identify patients who may benefit from early aggressive treatment versus conservative management. ClinicalTrials.gov (NCT05792033).

This work presents a theoretical and numerical investigation of the modulational instability and rogue wave triplets of dust-acoustic waves in a dusty plasma composed of warm adiabatic dust grains with opposite polarity, q-nonextensive electrons, and nonthermal ions. The dynamics are modeled by deriving a nonlinear Schrödinger (NLS) equation using the reductive perturbation method. This equation leads to the growth rate of modulational instability of dust-acoustic waves. The analysis reveals that positively charged dust grains, the degree of electron nonextensivity, and the distribution of electrons (protons) on negatively (positively) charged dust grains critically influence the growth rate of instability. The ratio of dispersion to nonlinear coefficients in the NLS equation demarcates stable and unstable regions, distinguishing bright and dark solitons. This novel mechanism reveals a second stability regime in opposite polarity dusty plasma for the fast acoustic mode. We also explore the impacts of multiple physical parameters, which are sensitive in forming rogue wave triplets. These parameters result in three distinct peaks arranged in a triangular pattern, with unique rotational behavior that offers a new perspective on the dynamical behaviors of localized nonlinear waves. To validate the model, we benchmark the exact analytical solutions for rogue wave triplets with numerical results. This comparison demonstrates the accuracy of the model and provides deeper insight into nonlinear localized waves. This analysis has significant implications for rogue wave triplet formation in both space and laboratory plasma environments. These triplets may coalesce into super freak waves under specific conditions, particularly when key physical parameters approach zero.

A collaboration between ground and space observations unveils a rogue planet.

In this work, we study a prototypical, experimentally accessible scenario that enables the systematic generation of so-called high-order rogue waves in atomic Bose-Einstein condensates. These waveforms lead to significantly and controllably more extreme focusing events than the famous Peregrine soliton. In one spatial dimension, we showcase conclusive numerical evidence that our scheme generates the focusing behavior associated with the first four rogue waves from the relevant hierarchy. We then extend considerations to anisotropic two-dimensional and even three-dimensional settings, establishing that the scheme can generate second-order rogue waves despite the well-known limitation of finite-time blow up of focusing nonlinear Schrödinger equations.

暂无摘要（点击查看详情）

暂无摘要（点击查看详情）

暂无摘要（点击查看详情）

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction, impaired thrombopoiesis and a bleeding diathesis, with growing recognition of accompanying inflammatory and immunoregulatory disturbances. Despite the widespread use of corticosteroids, intravenous immunoglobulin (IVIG) and thrombopoietin receptor agonists (TPO-RAs), 30–50% of patients exhibit incomplete, unstable or transient platelet responses, underscoring a persistent unmet need for mechanism-informed therapeutic strategies. Current management paradigms remain largely focused on platelet count restoration rather than direct modulation of pathogenic platelet–immune crosstalk. Accumulating pre-clinical evidence, supported by limited clinical observations, implicates platelet glycoprotein VI (GPVI), a collagen receptor and immunothrombotic signalling hub, as a mechanistically relevant contributor to platelet hyperactivation, inflammatory amplification and aberrant platelet–leucocyte interactions in ITP. Experimental models indicate that GPVI-dependent signalling pathways can promote thromboinflammatory responses, facilitate immune cell engagement and influence platelet clearance dynamics, positioning GPVI as a plausible, albeit incompletely validated, therapeutic target. Emerging pre-clinical studies suggest that selective modulation of GPVI signalling may attenuate pathogenic platelet activation while preserving essential haemostatic function, thereby improving platelet survival and functional competence. This review integrates current insights into GPVI biology within the broader immunopathological landscape of ITP and evaluates innovative therapeutic concepts, including GPVI-targeted inhibitors deployed through nanocarrier systems, autologous platelet-mediated delivery and hydrogel-based protective platforms designed to enhance targeting precision and durability. We further discuss the rationale for combination strategies with established therapies and the potential utility of GPVI-linked biomarkers and platelet functional profiling to guide patient stratification. By reframing platelets as active immunoregulatory effectors rather than passive autoimmune targets, this review advances a mechanistic framework for next-generation, precision-oriented intervention in ITP. Although clinical validation remains limited, GPVI-centred strategies represent a rational and testable avenue for moving beyond symptomatic platelet augmentation towards disease-modifying immunothrombotic modulation.

暂无摘要（点击查看详情）

暂无摘要（点击查看详情）

Exportin-1 (XPO1/CRM1) is a validated target in hematologic malignancies best studied for its role in mediating nuclear export. In this issue of Blood Cancer Discovery, Barajas and colleagues reveal that UBTF tandem duplications found in acute myeloid leukemia complete a nuclear export sequence that enables a novel UBTF-XPO1 interaction, particularly at chromatin loci critical for leukemogenesis, thus raising the question: Could XPO1 inhibitors find new use in the UBTF-TD acute myeloid leukemia subtype? See related article by Barajas et al., p. 51.

Failure to resolve the neutrophilic inflammation during the innate immune response results in neutrophil accumulation in the airways. These cells exhibit prolonged survival, increased necrosis, and impaired phagocytic capacity. Paradoxically, despite reduced pathogen-clearing ability, neutrophils release serine proteases that drive the destruction of airway tissue. Their persistence in the lung chronically promotes a cycle of tissue damage, remodeling, and inflammation, leading to progressive pulmonary dysfunction. Recent discoveries in neutrophil dysregulation open up the possibility of developing more targeted, disease-specific therapies, potentially revolutionizing the treatment of diseases like cystic fibrosis, chronic obstructive pulmonary disease, bronchiectasis, and asthma, where current treatments remain largely generalized and ineffective. This review explores the complex relationship between neutrophil dysregulation and disease progression, highlighting the different roles that neutrophils play across various lung diseases, and will summarize current strategies to target key pathways. Understanding these pathways could inform the development of therapeutic strategies to effectively mitigate neutrophil-driven inflammation to improve the clinical outcome.

The eukaryotic translation initiation factor 3 (eIF3) is the largest and most complex initiation factor in eukaryotes, functioning as a central hub that integrates signals from cellular stress, metabolism, and developmental pathways to regulate mRNA translation. Recent advances have uncovered subunit-specific roles of eIF3 that extend beyond canonical cap-dependent translation to include specialized mechanisms such as selective mRNA recruitment, noncanonical cap recognition, and translation elongation. This review summarizes the current mechanistic understanding of the contribution of aberrant eIF3 activity to diverse disease processes, including oncogenesis, neurodevelopmental and neurodegenerative disorders, muscle pathology, and infectious disease. We evaluate therapeutic strategies aimed at modulating eIF3 function, including subunit-selective small molecules, RNA-based therapeutics, and CRISPR-based interventions. We discuss the therapeutic promise of both inhibitory approaches-targeting oncogenic or pathogen-hijacked eIF3-and restorative strategies to correct genetic loss-of-function in neurological disease. Finally, we outline key challenges and opportunities for clinical translation, including tissue-specific delivery, subunit selectivity, and the identification of predictive biomarkers. eIF3 emerges as a versatile and druggable node in translational control with broad relevance across human disease.

This review summarizes recent insights into the roles of the circadian clock in regulating cancer hallmarks, with a focus on its impact on the tumor microenvironment, and highlights the translational promise of circadian-informed strategies for cancer therapy. The circadian clock is a 24-hour biological timekeeping system that aligns physiological processes with cyclic environmental cues, such as light-dark cycles. Disruptions of circadian rhythms caused by lifestyle factors, including shift work, irregular sleep patterns, and jet lag, can lead to physiological dysregulation and increased risk of various diseases including cancer, positioning the circadian clock as both a critical driver of tumorigenesis and a potential target for chronotherapies. This review provides a comprehensive overview of circadian regulation in tumorigenesis across diverse cancer types by framing its role according to established cancer hallmarks, with particular emphasis on how the circadian system shapes immune cell dynamics within the tumor microenvironment to modulate tumor progression and immune surveillance. We further discuss recent preclinical and clinical advances in chronotherapy, highlighting how aligning therapeutic interventions with biological rhythms can enhance treatment efficacy, including responses to immunotherapy. By integrating mechanistic insights with translational applications, this review bridges circadian biology and oncology, providing a framework for future chronobiology-based cancer therapies.

Expanded CNS CD8+ T cell clones in MS can recognize EBV antigens, linking antiviral immunity to ongoing CNS pathology.

This case report describes a rare instance of simultaneous typhoid hepatitis and splenic abscess in a 27-year-old immunocompetent male from India. The patient presented with high fever, jaundice, abdominal pain, and vomiting, and was mimicking acute viral hepatitis or disseminated tuberculosis finally diagnosed with Salmonella typhi infection following extensive diagnostic & therapeutic evaluations. Despite the seriousness of hepatic and splenic involvement, especially in the absence of underlying immunodeficiency, the patient responded well to appropriate antibiotic therapy. The report highlights the diagnostic challenges and clinical significance of atypical typhoid complications, emphasizing the importance of timely recognition and treatment to improve outcomes. In India, infection with Salmonella typhi, causing typhoid fever, is quite common. This may sometimes mimic other infectious diseases, complicating the diagnosis and management of these patients. Typhoid fever is a multisystem illness transmitted by the Feco-oral route, primarily through contaminated water and undercooked food, caused by Salmonella typhi and Salmonella paratyphi. It carries an important health concern, especially in tropical and developing countries. [1], [2] The gastrointestinal complications related to Salmonella typhi infection are Ileal perforation/ulceration, and may lead to obstruction and have been commonly reported. [1] Apart from that, involvement of the liver and spleen in typhoid fever is a serious concern. Here we are representing a case that presented with typhoid hepatitis and typhoid splenic abscess.

暂无摘要（点击查看详情）

A 78-year-old male with a history of ischemic heart disease with prior myocardial infarction, severe left ventricular systolic dysfunction, and a device-related implantable cardioverter defibrillator (DR ICD) was admitted following a road traffic accident due to a sudden loss of control of the vehicle following a syncope. Initial investigations ruled out acute coronary syndrome and did not point to neurological causes. Device interrogation revealed the presence of pacemaker-mediated tachycardia (PMT), but since the episode trigger had been programmed off, it was not possible to determine when they occurred, how long they lasted, or their rate. However, atrial threshold testing promptly provoked a PMT. The induced PMT led to a tachycardia of 130 bpm, causing severe symptomatic hypotension with a mean blood pressure falling below 50 mmHg. This could be easily reproduced several times. Given the patient's severe left ventricular systolic dysfunction and the absence of any overt alternative explanation, the PMT likely triggered the syncope preceding the car accident. Management focused on reprogramming the DR ICD. The most critical adaptation was a mode switch from DDD to DDIR to prevent atrial tracking, effectively terminating PMT episodes. A prolongation of the postventricular atrial refractory period (PVARP) was not possible due to the very slow VA conduction. The follow-up revealed no other episodes of PMT and the patient no longer experiences episodes of presyncope or syncope. This report highlights the potential for PMTs to induce severe hemodynamic instability and syncope, underscoring the importance of meticulous device evaluation.