Giant cell arteritis (GCA) is a systemic vasculitis of medium- and large-sized arteries, most commonly presenting with headache, scalp tenderness, and, if untreated, can lead to visual loss from ischemic optic neuropathy. Although the most common ophthalmic manifestations of Giant Cell Arteritis are related to ocular ischemia, orbital involvement can occur and remains underrecognized. Fewer than 10 cases in the literature describe perioptic or retrobulbar infiltration, underscoring the uniqueness and diagnostic challenge of such presentations. 75-year-old male with past medical history of hypertension, benign prostatic hyperplasia status post transurethral resection, traumatic subdural hematoma (SDH), who presented with episodic left eye vision loss (central and peripheral vision), followed by acute altitudinal vision loss in the right eye for 1 week. He also complained of right-sided headaches s/p SDH and chronic joint pain, but denied any other constitutional symptoms. The neurological exam revealed significantly decreased right eye visual acuity with an altitudinal field defect, color desaturation, and grade 2 + disc edema. Labs revealed an erythrocyte sedimentation rate (ESR) of 21 mm/h (normal age-adjusted), and a C-reactive protein (CRP) of 1.9 mg/dL(elevated). Magnetic resonance imaging of the brain and orbits, with and without contrast, showed bilateral retrobulbar/perioptic soft-tissue infiltration and enhancement, suggestive of an inflammatory, infectious, or autoimmune process. Blood work showed normal thyroid function and negative rheumatological work-up. Spinal fluid studies were within normal limits except for mildly elevated protein (white-blood cell 3, red-blood cell 1, Protein 52, and Glucose 54, while serum glucose was 94). Temporal artery biopsy was positive for temporal arteritis. His hospital course was complicated by left eye episodic vision loss. High-dose IV steroids led to initial improvement and stabilization of symptoms at discharge, requiring oral steroid taper. 10 months later, he had persistent vision loss in the right eye at the follow-up visit and also suffered complications from chronic steroid use. This case highlights the challenges in diagnosing and treating GCA. Diagnostic delay can occur from under-recognition of atypical presentations. Neuroimaging provided important diagnostic value in this case; however, its routine role in diagnostic criteria requires validation in larger studies.
Surgical approaches for zygomaticomaxillary complex (ZMC) fractures have evolved toward minimizing cutaneous incisions while maintaining adequate exposure. Conventional approaches for frontozygomatic fixation, such as lateral brow or transconjunctival incisions with lateral extension, may result in visible scarring or periocular complications. Building on previous transconjunctival techniques, we applied an independent upper eyelid transconjunctival incision as a non-cutaneous approach for frontozygomatic fixation in selected ZMC tripod fractures. This retrospective comparative study included 27 patients with unilateral ZMC tripod fractures, of whom 12 underwent non-scar fixation using an upper eyelid transconjunctival approach, and 15 underwent fixation through preexisting periorbital traumatic lacerations. The surgical strategy consisted of initial reduction and fixation via an intraoral approach, followed by selective additional fixation of the frontozygomatic region when residual step deformity or instability was present. Preoperative and 6-month postoperative computed tomography and three-dimensional photogrammetry were used to evaluate bony and soft tissue intermalar height differences. Preoperative intermalar height differences were comparable between groups. At 6 months postoperatively, both groups showed marked improvement, with bony differences of -0.2 ± 1.2 mm and -0.4 ± 0.4 mm, and soft tissue differences of 0.0 ± 0.6 mm and -0.2 ± 0.7 mm in the non-scar and control groups, respectively, with no clinically meaningful between-group differences. No clinically significant approach-related ophthalmic complications were observed. The upper eyelid transconjunctival approach is a reliable non-cutaneous option for frontozygomatic fixation in selected ZMC tripod fractures, providing adequate exposure and stable fixation without visible scarring.
Sports-related oral and maxillofacial trauma exhibits distinct injury mechanisms depending on the type of sport; however, comprehensive analyses integrating these characteristics remain limited. This study aimed to elucidate the clinical features of sports-related oral and maxillofacial trauma. This single-center retrospective study included 1615 patients (mean age 41.04 years; 64.8% male) treated between 2012 and 2025 in Shimane University Hospital, Department of Oral and Maxillofacial Surgery/Maxillofacial Trauma Center, Shimane, Japan. Among them, 239 (14.8%) had sports-related injuries and were significantly younger and more frequently male (p < 0.001). Multivariable analysis showed that nasal bone (odds ratio [OR] 5.900, 95% confidence interval [CI] 3.309-10.521), orbital wall (OR: 8.044, 95% CI: 4.664-13.874), zygomatic and zygomatic arch (OR: 3.239, 95% CI: 1.455-7.213), and naso-orbito-ethmoidal fractures (OR: 6.507, 95% CI: 1.971-21.483), as well as contusions (OR: 2.601, 95% CI: 1.385-4.885), were positively associated, whereas mucosal lacerations (OR: 0.485, 95% CI: 0.290-0.811) and referral from dental/medical clinics (OR: 0.312, 95% CI: 0.178-0.546) were negatively associated (all p < 0.01). However, panfacial fractures occurred less frequently. Sports-related trauma was primarily associated with nasal, orbital wall, zygoma and zygomatic arch, and naso-orbito-ethmoidal fractures. These findings indicate that sports-related oral and maxillofacial trauma is characterized by distinct and predominantly midfacial fracture patterns.
PurposeRestrictive strabismus is a major cause of diplopia and impaired quality of life in thyroid eye disease (TED), but its clinical and imaging characteristics remain incompletely understood. This study investigated the clinical and magnetic resonance imaging (MRI) characteristics of TED patients with restrictive strabismus at initial presentation.MethodsAmong 5,234 TED patients treated between 2009 and 2024, 339 patients (6.5%) with clinically confirmed restrictive strabismus and supportive MRI findings were retrospectively included. Restrictive strabismus was confirmed primarily by positive forced duction testing with limitation of ocular rotations. Clinical characteristics, thyroid function, Clinical Activity Score (CAS), NOSPECS classification, strabismus type, and orbital MRI findings were analyzed. Contrast-enhanced orbital MRI, including T1-weighted and fat-suppressed T2-weighted sequences, was used to evaluate extraocular muscle enlargement, inflammation, and edema.ResultsPatients with active extraocular muscles had higher CAS scores than those with stable muscles (P < 0.01). Monocular-onset patients showed higher CAS and NOSPECS scores (both P < 0.01). Hyperthyroid patients had higher NOSPECS scores than euthyroid patients (P < 0.01). Longer disease duration before presentation was associated with smaller muscle area, less inflammation, and reduced edema, whereas higher CAS scores correlated with larger muscle area and more severe edema.ConclusionsTED patients with restrictive strabismus were predominantly male and commonly showed binocular involvement and hyperthyroidism. Inferior rectus involvement was the most common imaging finding, especially in vertical strabismus. Orbital MRI may help evaluate extraocular muscle activity and guide strabismus surgery timing.
Lateral canthotomy is a commonly used adjunctive technique to the transconjunctival approach in the so-called "swinging lower eyelid" procedure to enhance orbital exposure. Despite its widespread use, the closure phase remains sparsely detailed in the literature, although it is critical for accurate restoration of the lateral canthal anatomy and prevention of eyelid malposition. This technical note details a step-by-step method for lateral canthotomy closure designed to achieve anatomic reconstitution of the native canthal architecture while preserving the exposure benefits of canthotomy. The protocol emphasizes identification and sequential reattachment of the inferior limb of the lateral canthal tendon. Key anatomical landmarks, technical pearls, and common pitfalls are highlighted to enhance reproducibility and facilitate surgical teaching. This standardized closure approach may improve consistency in surgical practice and provide a framework for future studies correlating closure techniques with functional and aesthetic outcomes.
F-box protein 32 (FBXO32), an E3 ubiquitin ligase, has been implicated in various cellular processes, but its role and regulatory network in DR-associated endothelial dysfunction are unclear. Here, we aimed to investigate the function of FBXO32 in high glucose (HG)-induced vascular endothelial cell injury and the underlying molecular mechanisms mediated by DNMT1 and Myc. Human retinal microvascular endothelial cells (HRMECs) were exposed to HG to mimic DR in vitro. The expression of FBXO32 and DNMT1 was detected by qRT-PCR and Western blot. Gain-of-function and loss-of-function experiments were performed to manipulate FBXO32, DNMT1, and Myc expression. Cell migration was evaluated by wound healing assay. Inflammatory cytokines (IL-1β, IL-6, TNF-α) were measured by ELISA. Glycolytic metabolism was assessed by detecting glucose consumption, lactate production, ATP level, and extracellular acidification rate (ECAR). Co-immunoprecipitation (Co-IP), ubiquitination assay, protein stability assay and GST pull down assay were used to verify the interaction between FBXO32 and Myc. Methylation-specific PCR (MSP) was performed to detect the methylation status of FBXO32 promoter. HG treatment significantly downregulated FBXO32 expression in HRMECs. Overexpression of FBXO32 inhibited HG-induced cell migration, inflammation (decreased IL-6 and TNF-α levels), and glycolytic metabolism (reduced glucose consumption, lactate production, ATP level, and ECAR). Treatment with 2-deoxy-D-glucose (2-DG), a glycolysis inhibitor, abolished the effects of FBXO32 overexpression on cell migration and inflammation, indicating that FBXO32 exerts its function by regulating glycolysis. The interaction between FBXO32 and Myc were confirmed by Co-IP assay and GST pull down assay. Ubiquitination and protein stability assays showed that FBXO32 promotes the ubiquitination and degradation of Myc, thereby reducing Myc protein stability. Overexpression of Myc reversed the inhibitory effects of FBXO32 on HG-induced cell migration, inflammation, and glycolysis. Furthermore, we identified DNMT1 as an upstream regulator of FBXO32. DNMT1 binds to the promoter region of FBXO32 and induces its methylation, leading to the downregulation of FBXO32. Knockdown of DNMT1 upregulated FBXO32 expression, inhibited HG-induced cell migration, inflammation, and glycolysis, while co-knockdown of DNMT1 and FBXO32 reversed these effects. Our findings demonstrate that DNMT1-mediated methylation downregulates FBXO32 expression in HG-induced vascular endothelial cells. FBXO32 inhibits HG-induced endothelial cell migration, inflammation, and glycolytic reprogramming by promoting the ubiquitination and degradation of Myc. This DNMT1-FBXO32-Myc regulatory axis provides a novel therapeutic target for the treatment of DR.
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Pain is included in the clinical activity score (CAS) as an indicator of inflammatory activity in Graves' orbitopathy (GO), yet its clinical relevance has not been systematically evaluated. We therefore investigated the relationship between pain, other inflammatory signs and quality of life (QoL), and assessed the effect of intravenous methylprednisolone (IVMP) treatment on pain perception in GO. In this prospective study, 40 patients with GO were assessed pre-treatment and 12 and 24 weeks after initiation of IVMP treatment. Pain was measured using numeric rating scale (NRS) scores for spontaneous retrobulbar pain, pain on eye movements and pain on touching the eye. QoL was evaluated using the TED-QOL and GO-QOL questionnaires. Pre-treatment NRS scores correlated with their corresponding CAS pain items, but not with the total 5-item CAS. Pre-treatment QoL correlated with spontaneous retrobulbar pain and pain on eye movements. In multivariate analysis, clinically meaningful improvement in pain on eye movements at 12 weeks independently predicted improvement in TED-QOL and GO-QOL appearance. At 24 weeks, improvement in pain on touching the eye independently predicted improvement in TED-QOL function. IVMP significantly reduced NRS pain scores at both follow-up visits. At 12 weeks, changes in total 5-item CAS correlated with changes in pain on eye movements and pain on touching the eye. Pain perception in GO is closely associated with QoL, both pre-treatment and in response to IVMP. Pain represents a clinically relevant, treatment-responsive component of GO, supporting the inclusion of pain items within the CAS.
Spatiotemporal optical vortices (STOVs) carrying transverse orbital angular momentum (OAM) fundamentally expand light-structuring capabilities. However, current rigid-body generation paradigms constrain transverse OAM to a single scalar property, leaving rich internal wavepacket dynamics inaccessible. This rigidity contrasts with ubiquitous natural vortices where symmetry breaking is the norm. Here, we break rotational symmetry via the nonlinear mapping of the azimuthal phase gradient, realizing programmable spatiotemporal flux breathing. We theoretically and experimentally demonstrate that local phase gradient variations induce instantaneous group velocity anisotropy. This compels local OAM density to spontaneously reorganize into stable, multilobed lattice structures while strictly preserving global topological charge. Furthermore, we harness these structures' modulation frequency for free-space information transfer, achieving high-fidelity encoding and decoding of spatiotemporal topological states. This work transitions STOVs from passive scalar objects to structured functional carriers, opening avenues for high-dimensional optical communications, ultrafast spatiotemporal manipulation, strong-field physics, and high-dimensional quantum entanglement.
Circular dichroism originates from symmetry breaking in a material structure and leads to differential absorption of left-handed and right-handed circularly polarized light. However, circular dichroism in most materials is inherently weak and spectrally narrow, especially in the mid-to-far infrared. Here we uncover giant infrared circular dichroism in the magnetic-field-forced Weyl semimetal Mn(Bi,Sb)2Te4 driven by extreme particle-hole symmetry breaking. Helicity-resolved magneto-infrared spectroscopy reveals circular dichroism exceeding 3,000 mdeg (~130 mdeg nm-1) with an above-degree response extending over the 6-13 μm spectral range. The optical resonances are enhanced by a strong band nesting effect intrinsic to the Landau levels of type-II Weyl dispersion. A symmetry-based k·p model reproduces these magneto-infrared responses and demonstrates that magnetization-induced asymmetric spin-orbit coupling generates particle-hole symmetry breaking, which suppresses spin-up, parity-even wavefunction components in the valence Landau band and thereby produces pronounced optical helicity-selectivity. Our findings establish particle-hole symmetry breaking as an effective route towards helicity-resolved optical control in quantum materials.
The long-term presence of humans in space depends on reducing reliance on Earth's resupply of materials and resources. In situ resource utilization (ISRU) represents a sustainable approach to support human activities in space by converting local materials into consumables, propellants, and structural feedstocks. In parallel, bioregenerative life support systems (BLSS) primarily sustain internal loop closure (LC) by regenerating air, H2O, nutrients, and food from habitat-contained streams. Traditional ISRU concepts have primarily focused on abiotic technologies that process rocks, regolith, and atmospheric components to extract O2, H2O, and metals, although biotic approaches are also under investigation. Biological and bio-hybrid approaches, guided by microorganisms and other living systems, could complement these technologies by supporting both external resource conversion and internal LC in future space exploration. In this review, we adopt a resource-centric framework to compare abiotic, biotic, and coupled resources acquisition pathways across the main functional domains relevant to both ISRU and BLSS, treated as operationally distinct but architecturally coupled subsystems within a broader resource-management framework. We discuss the main functional domains required for human settlement, spanning external resource conversion (O2, CO2, H2, CH4, H2O, materials, manufacturing, energy) and internal regenerative functions (food production, air and H2O revitalization, and waste recycling). For each domain, we describe representative abiotic (e.g., MOXIE, ROXY, molten-regolith electrolysis, fission surface power, and advanced solar arrays) and biotic systems, for both ISRU-relevant bioprocesses (e.g., biomining, biopolymer production) and BLSS components (e.g., plant-growth and microbial recycling loops). The most realistic path toward sustainable human settlements beyond Earth orbit lies in coupled ISRU-BLSS architectures in which external resource acquisition and internal regenerative loops are coordinated across shared material and energy flows.
Light carries both spin (polarization) and orbital angular momentum. Combining these degrees of freedom produces hybrid spin-orbit states that live in a high-dimensional Hilbert space, offering greater information capacity and robustness for optical communication, quantum technologies, and metrology. However, generating arbitrary states in these spaces and characterizing them efficiently has remained difficult. Here we show a compact metasurface that generates arbitrary spin-orbit states in a four-dimensional Hilbert space, visualized on a Poincaré hypersphere, with straightforward scalability to higher dimensions. Using a tetratomic unit cell, the single-layer device precisely controls complex amplitude, phase, and polarization. We further introduce an efficient interferometric scheme that reconstructs the full density matrix of any N-dimensional spin-orbit state using only three interferograms. This approach uncovers an intrinsic spin-orbit parity order that governs the symmetry of projected intensity patterns, independent of the weighting of the eigenmodes, and enables controlled mode transformations through higher-order geometric phases. These advances establish a versatile platform for high-dimensional photonic technologies.
Achieving multistep magnetization switching in two-dimensional (2D) ferrimagnets demonstrates substantial promise for advancing high-density non-Boolean logic and memory devices. However, existing 2D ferrimagnets are still hampered by low Curie temperatures and a lack of tunable multiple magnetic states. Here, we report the successful synthesis of a family of 2D Fe0.875S(1-x)Sex alloy with robust room-temperature ferrimagnetism. The key magnetic and electrical properties can be effectively regulated by tailoring the chalcogen ratio in Fe0.875S(1-x)Sex alloy. Notably, multiple magnetic states and resistance plateaus are observed because of the spin canting behavior, enabling the realization of several distinct spin states by adjusting magnetic fields and temperatures, thereby demonstrating great potential for multistate applications. Density functional theory calculations further reveal that the evolution of magnetic anisotropy originates from variations in the orbital occupation of electronic states near the Fermi level. Our work can expand the library of 2D metallic ferrimagnets and pave the way for designing high-density spintronic devices.
Focusing on craniofacial bones, this study investigates morphological variation related to sexual dimorphism in order to deepen our understanding of human biological diversity and to provide new data from a contemporary reference sample. Accordingly, the research was guided by three objectives (i) identify the facial regions exhibiting the greatest sexual dimorphism using landmark-based geometric morphometric method; (ii) evaluate the reliability of discriminant models based on these dimorphic regions; and (iii) conduct exploratory analyses to assign sex classification probabilities to ancient subjects using the discriminant models derived from a contemporary reference sample. The reference sample comprised 44 skulls from subjects of known sex who died in 2024. The ancient sample included 4 skulls recovered from the Grotte de La Medecine (France), attributed to the chalcolithic period. Fourteen facial landmarks were digitized using 3DSlicer. Generalized Procrustes Analysis was performed to extract shape variables and standardized coordinates for statistical analysis. Thin-Plate Spline transformations quantified and visualized deformation amplitudes between the female and male shapes. Landmarks in the orbital showed the highest deformation amplitudes. Goodall F-test comparing male and female shapes across three facial regions revealed significant sexual dimorphism only in the orbital region and the global facial shape. Discriminant analysis demonstrated that the orbital region provided the highest classification accuracy (88.6%) compared to the global facial region (72.7%). The discriminant models yielded high probabilities of male and female sex classification for the ancient subjects. Using a reproducible method, comparable levels of accuracy to those reported in the scientific literature were achieved despite a relatively modest sample size. These findings further confirm the significant role of the orbital region in human craniofacial sexual dimorphism.
The horizon of a black hole, the 'surface of no return', is characterized by its rotation frequency ΩH and surface gravity κ. A striking signature is that any infalling object appears to orbit at ΩH owing to frame dragging, while its emitted signals decay exponentially at a rate set by κ as a consequence of gravitational redshift. Recent theoretical work1 predicts that gravitational waves from binary black-hole mergers carry direct imprints of the properties of the merger remnant in the form of a 'direct wave'. This gravitational-wave component oscillates near 2ΩH, reflecting the horizon's frame dragging, and decays at an increasing rate characterized by κ, with additional screening from the black hole's spacetime. Here we report observational evidence of a direct wave in GW2501142, with a 90% credible matched-filter signal-to-noise ratio of 15.8 - 0.5 + 0.1 ( 17.1 - 0.4 + 0.1 ) in the LIGO Hanford (Livingston) detector. The measured properties are in full agreement with theoretical predictions for a Kerr black hole. These findings establish an observational channel to directly measure frame-dragging effects in black-hole ergospheres and explore (near-)horizon physics in dynamical, strong-gravity regimes.
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Myxoid epithelioid sarcoma is a rare morphologic variant of epithelioid sarcoma characterized by abundant myxoid stroma and frequent loss of SMARCB1/INI1 expression. Orbital involvement is exceptionally uncommon. We report a case of a SMARCB1-deficient malignant orbital neoplasm with features overlapping myxoid epithelioid sarcoma in a 61-year-old man presenting with visual disturbance. Imaging studies revealed a 2.5-cm medial orbital mass without evidence of another primary lesion. The tumor was excised without prior biopsy. Histologically, the lesion was predominantly composed of abundant myxoid stroma containing scattered atypical epithelioid, signet ring-like, and spindle cells, with focal fascicular proliferation infiltrating skeletal muscle. Immunohistochemically, tumor cells were positive for pan-cytokeratin, EMA, vimentin, and CD34, while negative for S100, ΔNp63 (p40), p63, SS18-SSX, and TLE1. Complete loss of SMARCB1/INI1 expression was observed in tumor cells. The overall findings suggested a SMARCB1-deficient malignant neoplasm showing substantial morphologic and immunophenotypic overlap with myxoid epithelioid sarcoma. This case highlights the diagnostic challenges posed by SMARCB1-deficient tumors arising in unusual anatomical sites and expands the clinicopathological spectrum of myxoid epithelioid sarcoma-like neoplasms involving the orbit.
Valence CASSCF (vCAS) calculations for (H2O)2, (HF)2, and HF-H2O dimers fail to capture donor bond lengthening and associated redshift of its stretching frequency due to hydrogen bonding. Analysis of the orbitals in the vCAS calculation reveals that one of the active weakly occupied dimer orbitals correlates electrons in the acceptor lone pairs, not the donor bond, which is left without left-right correlation. This has significant implications for subsequent treatments of dynamical correlation that are based on a vCAS reference wave function.
Carbazole-based aminoboranes are promising luminophores exhibiting both delayed fluorescence and room-temperature phosphorescence. However, the structural and electronic factors governing intersystem crossing (ISC) and reverse ISC (RISC) remain elusive. Using femtosecond transient absorption and stimulated Raman spectroscopy, we reveal that rapid evolution along the B-N stretching/torsional coordinates facilitates the formation of a twisted intramolecular charge-transfer (TICT) state, bringing the singlet and triplet states energetically closer. In a series of N-borylated carbazoles, bromine incorporation enhances ISC via heavy-atom effects, while "magic methyl" groups impact the torsional dynamics, which increase the nonradiative relaxation pathway and ISC rate. Solvent-dependent and computational studies found that both ISC and reverse ISC proceed through higher-lying triplet and hybrid charge-transfer states that enable spin flipping. This interplay between torsional control and spin-orbit coupling finely tunes the balance between delayed fluorescence and phosphorescence.
While most ophthalmologists and medical oncologists are aware of the excessive tearing and canalicular and lacrimal duct blockage associated with docetaxel, there is lack of deeper understanding of the appropriate management of this side effect and what clinical settings justify surgical intervention as opposed to conservative management. In this review, we summarize the findings in the seminal original research studies that document the association between the frequency of administration of docetaxel and treatment duration and the frequency of excessive tearing as a subjective symptom versus canalicular and lacrimal duct blockage as anatomic findings seen during probing and irrigation. Based on the published literature to date, we note that excessive tearing is a common and important side effect of docetaxel and can be seen in breast cancer patients who are receiving docetaxel either weekly or every three weeks in metastatic or adjuvant settings. However, the anatomic findings of canalicular and lacrimal duct stenosis are almost exclusively seen in patients receiving weekly docetaxel or in patients with metastatic breast cancer who are treated with docetaxel for prolonged periods. Lacrimal duct blockage is much less commonly reported in patients with early breast cancer who are receiving docetaxel every three weeks for short durations and, to our knowledge to date, have not been reported in the literature in breast cancer patients receiving docetaxel in the adjuvant setting.