Low-dose tamoxifen use may cause degenerative changes progressing to full-thickness macular holes, mimicking other degenerative causes for macular holes instead of well-known features of tamoxifen retinopathy. The aim of this report is to present a case of bilateral refractory macular holes related to tamoxifen use and full anatomic restoration of the fovea with autologous retinal graft. A 35-year-old female presented with decreased vision in both eyes and was initially diagnosed with a macular hole in the left eye, followed by a subsequent diagnosis in the right eye. Standard internal limiting membrane (ILM) peeling with gas endotamponade for the left eye and inverted ILM flap with gas endotamponade for the right eye both failed to close the macular hole. Therefore, autologous neurosensory retinal grafting was performed for refractory macular holes in both eyes. She was not receiving tamoxifen at the time of presentation; however, she had previously undergone tamoxifen treatment for breast cancer. During the postoperative period, full reconstitution of the ellipsoid zone and the external limiting membrane, as well as foveal pit formation, were achieved with a dramatic increase in visual acuity. Autologous retinal grafting may be an effective and safe surgical approach not only for macular holes secondary to posterior hyaloid-related traction but also for the management of refractory degenerative macular holes secondary to drug side effects. This approach achieved excellent functional outcome and successful anatomical improvement, as demonstrated on longitudinal optical coherence tomography scans.
Metal-centered π-holes are regions of electronic depletion located above pseudoplanar coordination environments that can promote weak axial interactions. However, their characterization remains limited. In this context, this work establishes quantitative descriptors for identifying and comparing π-holes in transition-metal coordination environments. Here, a high-throughput computational analysis of 1296 {TM(cyclen)}2+ (TM = Co(II), Ni(II), Cu(II), and Zn(II) and cyclen = 1,4,7,10-tetraazacyclododecane) complexes is presented, considering four macrocyclic conformations and all combinations of methyl/ethyl nitrogen substitutions in cyclen. Electrostatic potentials were evaluated on electron density isosurfaces and analyzed using an algorithm that identifies π-hole candidates. Local maxima along the axis perpendicular to the nitrogen coordination plane are also validated by comparison with surrounding sectors. Validated π-holes, typically located 1.8-2.4 Å above the metal center, were detected in 84.6% of the complexes. Analysis of them shows that the maximum electrostatic potential alone does not reliably describe axial electron depletion in charged complexes. Instead, relative electrostatic descriptors provide consistent measurements of π-hole depth and anisotropy. Across the series examined, the π-hole intensity follows the order Zn(II) > Co(II) > Cu(II) > Ni(II), in good agreement with experimental findings. Conformational distortions and nitrogen substitution further modulate the magnitude and spatial distribution of the electrostatic potential.
It is common knowledge that black holes necessarily contain a region where general relativity breaks down, due to the inevitable formation of either a curvature singularity or a Cauchy horizon. In this Letter we challenge this view by analyzing a charged spherically symmetric black hole formed through gravitational collapse and evaporating via Hawking radiation. We show that the electromagnetic repulsion and the violation of energy conditions due to the presence of Hawking radiation can be sufficient to avoid the formation of both a singularity and a Cauchy horizon. We argue that a similar mechanism may apply to astrophysical black holes in which the role of the electric charge is replaced by the angular momentum.
To characterize the surgical management and outcomes of large high myopic macular holes (HMMHs). Global multicenter retrospective case series of HMMHs with minimum linear diameter (MLD) ≥ 400 μm undergoing surgery between 2013-2023 with follow up ≥ 3 months. The main outcome measure was the HMMH closure rate at postoperative month 3. 499 cases of 463 patients from 37 surgeons were included, with mean ± SD age 58.3 ± 12.2 years, 77.0% female, 77.4% primary, 22.6% refractory, and mean ± SD follow-up 18.8 ± 20.2 months. The mean ± SD (range) MLD was 649 ± 280 (400, 2759) µm. Surgery techniques included 127 internal limiting membrane (ILM) peels, 285 ILM flaps, 19 amniotic membrane transplantations (AMT), 36 autologous retinal transplantations (ART), and 32 others. The postoperative month 3 closure rate for all cases was 72.4%. Closure rates significantly decreased with greater CLOSE Study Group size classification for HMMHs treated with ILM peeling or ILM flap (P = 0.006) but not for HMMHs treated with AMT or ART (P > 0.05). Visual acuity (VA) significantly increased from baseline to each follow-up time point among all eyes, with final mean ± SD change in VA of -0.29 (0.55) logMAR (+14.5 ETDRS letters), which did not significantly differ by surgery type. HMMH closure rates are lower than those reported for macular holes in non-highly myopic eyes, but most eyes can still achieve anatomic closure and meaningful VA gains when treated with the appropriate technique.
This method is for producing a pure bispecific antibody starting from modifying the amino acid sequences of the two monoclonal antibodies to be combined. A mild reduction condition for "splitting the monoclonal antibodies in half" cleaves only the interchain disulfide bonds between two heavy chains, and maintains the cognate light chain-to-heavy chain association or the intact antigen-binding domain (i.e., Fab). The sequence modifications involve the "knobs-into-holes" mutations in the Fc fragment's CH3 dimerization interface for enabling the two different heavy chains to dimerize or the two different Fab's to recombine (i.e., Fab-arm exchange) in the formation of bispecific antibody. In addition to high yield, the pure bispecific antibody can be produced through a fast two-step affinity chromatographic method.
To compare 1-year best-corrected visual acuity (BCVA) after pars plana vitrectomy (PPV) for lamellar macular hole (LMH) between combined phacovitrectomy and sequential strategies, and to explore factors associated with postoperative visual outcome. Multicenter observational study of adults with optical coherence tomography (OCT)-confirmed LMH undergoing PPV. Surgical sequence was classified as combined surgery or sequential surgery (PPV→phacoemulsification, PPV in pseudophakic eyes, or PPV without subsequent cataract extraction). LMHs were classified as tractional, mixed, or degenerative based on OCT criteria. BCVA (logMAR) was recorded preoperatively and at 1 year. Ceiling effect was defined as achieving 1-year BCVA ≤0.22 logMAR. Independent predictors of 1-year BCVA were assessed using a linear mixed-effects model with a random intercept for patient. A total of 175 eyes from 167 patients were included; 1-year BCVA was available for 126 eyes (72.0%), whereas 49 eyes (28.0%) had missing 1-year BCVA. Among eyes with recorded 1-year BCVA, no statistically significant differences were detected between combined and sequential surgery (0.2 [0.1-0.3] vs 0.2 [0.1-0.3]; p = 0.939) or among LMH subtypes. Overall, BCVA improved from 0.4 (IQR 0.3-0.5) to 0.2 (0.1-0.3) at 1 year. In ceiling-effect analysis, baseline BCVA (p = 0.013) and the presence of isolated epiretinal membrane (p = 0.032) were associated with achieving BCVA ≤0.22 logMAR. In the mixed-effects model, baseline BCVA was the only independent predictor of 1-year BCVA (β = 0.60; 95% CI 0.32-0.89; p < 0.001). PPV for LMH was associated with visual improvement at 1 year, and the study did not detect statistically significant differences in final BCVA between combined and sequential strategies or among LMH subtypes. Baseline BCVA was the main determinant of 1-year outcomes, supporting individualized selection of surgical sequence based on lens status and shared patient-surgeon preferences. Lamellar macular hole is a condition that affects the center of the retina. It can make vision blurred, distorted, or less clear for everyday tasks such as reading. Many people who need surgery for lamellar macular hole also have cataract. Surgeons can treat both problems during the same operation, or they can do cataract surgery later. In daily practice, patients and surgeons often need to decide which approach to choose. In this study, we looked at people treated in four Spanish hospitals. We compared vision at 1 year after vitrectomy in those who had combined surgery and those who had sequential surgery. We also studied which factors were linked to better vision after surgery. Overall, vision improved at 1 year after surgery. We did not detect clear differences in vision at 1 year between combined and sequential surgery. People who had better vision before surgery were more likely to have better vision after surgery. Patients with an isolated epiretinal membrane on OCT were also more likely to achieve better visual outcomes. These findings suggest that both surgical approaches can be reasonable. The best choice may depend on the person’s lens status, symptoms, and discussion with the surgeon.
Hawking's signature prediction may prevent vexing singularities from forming.
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The entropy of a Schwarzschild black hole is commonly derived using thermodynamic relations whose physical interpretation is not always transparent, in particular with respect to the localization of temperature and entropy. In this paper, we present a derivation of the Bekenstein-Hawking entropy based exclusively on the principles of phenomenological thermodynamics, formulated entirely in regions where spacetime is effectively flat. The analysis considers a reversible evaporation process in which the black hole is surrounded by a tunable thermal radiation bath whose temperature is kept arbitrarily close to the Hawking temperature. In this limit, entropy production can be made negligible. By integrating the entropy flux through a distant reference surface over the evaporation process, the standard entropy formula is obtained without invoking assumptions about the localization of the black hole entropy or about microscopic degrees of freedom. The derivation is mathematically simple but conceptually instructive. The approach is intended to be accessible to readers familiar with classical thermodynamics and general relativity at an advanced undergraduate or graduate level.
The mining industry is in need of automation due to increasing requirements like higher global demands for resources and deposits, which are deeper and more complex. Progressing underground mines lead to longer travel times to the mining face and thus a loss in productive working time, which has to be compensated by automation. Ultimately, stricter health and safety regulations and a decreasing number of skilled operators accelerate the need for automation further. Within the the drill-and-blast cycle in underground mining, the drilling of blast holes is a central step. While semi-automated and supporting systems exist that allow the automated execution of single process steps under supervision, to date, no system is available for the unsupervised blast hole drilling of a mine face. A precondition for unsupervised operation is a perception system, which allows independent decision-making of the machine. To address this gap, this work presents a novel vision system capable of segmenting a mine face into drillable and non-drillable areas, which can serve as the basis for the autonomous adaption of a drilling pattern. An area of the mine face is considered drillable if no leftover blast holes from the previous blast cycle are present and the surface angle is below a certain threshold. The system presented is based on a stereo camera setup mounted on a drill jumbo. The resulting 2D and 3D data are processed by software that employs AI-based computer vision techniques, as well as traditional algorithms. The system was validated, and the performance was verified in the K+S Zielitz mine. Experts assisted in the determination of operational parameters and empirically validated the system's performance. Additionally, the blast hole detection algorithm underwent a data-based analytical verification.
To evaluate vitrectomy with membrane peeling across the spectrum of myopic traction maculopathy (MTM) and identify prognostic factors for anatomical and functional success. Patients with MTM who underwent vitrectomy and membrane peeling between 2018 and 2023 were included. Percentage reduction in mean foveal thickness (MFT) was used as a marker of anatomical outcome, and visual acuity was the primary outcome. The secondary outcomes were factors associated with anatomical success and visual acuity (VA) improvement. Ninety-four eyes from 84 patients were included. For myopic foveoschisis-only (37 eyes), the anatomical success rate was 95% with a mean of an 8-letter gain. For isolated macular detachment (without macular holes) (15 eyes), 93% achieved retinal reattachment with a mean of a 3.5-line gain. Isolated macular holes (22 eyes) achieved macular hole closure in 73% of cases with a mean of a 7-letter gain. Macular hole retinal detachment (20 eyes) achieved retinal reattachment in 80% of cases and simultaneous macular hole closure in 20%, with a mean of 3-letter gain. Higher preoperative MFT (p < 0.001) and more advanced perpendicular staging (p < 0.001) were associated with greater % MFT reduction. Better preoperative VA (p < 0.001), less advanced tangential staging (p = 0.016), and preoperative phakic status (p = 0.004) were predictive of better postoperative VA. For myopic foveschisis-only, the use of long-acting gas was associated with a postoperative VA that was 3 lines worse (p = 0.04). Vitrectomy with membrane peeling is effective in the management of MTM, especially for myopic foveoschisis-only and isolated macular detachment. Less advanced tangential stages and better preoperative VA are predictive of better postoperative VA.
The impact of Al content in the AlGaN hole current confinement layer (HCCL) on the optoelectronic properties of the GaN-based blue vertical-cavity surface-emitting lasers (VCSELs) is systematically studied through numerical simulation. As the Al content in HCCL increases from 0 to 0.25, the barrier height in the valence band for holes shows a significant increase in both vertical and lateral directions, which enhances hole confinement capability and suppresses hole leak outside the aperture. These contribute to the improvement of light output power (LOP) and wall-plug efficiency (WPE), as well as the reduction in threshold current. However, the hole leakage current remains almost unchanged with further increasing Al content to 0.3 in the HCCL. An in-depth analysis of the leakage path in VCSEL confirms that the leakage current is predominantly composed of holes that bypass the HCCL, as the current flowing across the HCCL is suppressed to nearly zero. As a result, further increasing the Al content to 0.3 yields only marginal improvements in LOP and WPE, and a reduction in threshold current. To achieve an optimal trade-off between the optical and electrical performances of the VCSEL, the optimum value of Al content in HCCL is around 0.25. This work has clarified the hole leakage paths and the effectiveness of tuning Al content in AlGaN HCCL for regulating hole transport, which provides theoretical guidance for the design and optimization of high-performance GaN-based VCSELs.
Golf is an increasingly popular sport and presents fierce competition at the professional level. The Professional Golfers' Association (PGA) Tour is the most prestigious professional men's tour in golf, whereas the Ladies Professional Golf Association (LPGA) Tour is the equivalent for women. Among professionals, although women golfers play shorter courses than men, the rules and regulations for men and women are similar. In turn, differing requirements due to anthropometric and physiological sex-based differences may affect variables such as choice of club and playing strategy. Therefore, in our study, we aimed to identify differences in golf performance between men and women and to discuss whether the differences correspond with known physiological and anthropometric sex-based differences. We conducted a natural experiment, using publicly available data, comparing world class men and women golfers' performances on their respective tours. Performance and course data were collected on all 50 PGA and 32 LPGA Tournaments in the 2021-2022 season and differences between the tours were identified. The lengths of the courses and holes on the LPGA Tour were approximately 90% of those on the PGA Tour. Overall, women had better driving accuracy than men but scored fewer eagles and rounds in the 60s. Anthropometric and physiological differences likely contribute to women's adapted movement strategies during the swing and cause them to choose playing strategies that men do not, primarily in driving and approach shots. Altogether, our results suggest that women's golf courses are likely not sufficiently scaled according to anthropometry or physiology. Thus, golf remains more demanding for women, which may, at least partly, explain their differences in performance compared with men.
Increasing bromine content is a common strategy for widening the bandgap of perovskite materials. However, this often accelerates crystallization, thereby degrading film quality and energy-level alignment. To address this, we introduce the multifunctional molecule 2-amino-4-cyanobenzoic acid (2A4CBA) into a 1.68 eV perovskite precursor to simultaneously modulate crystallization and energy-level. The 2A4CBA interacts with perovskite precursors via coordination and hydrogen bonding through its amino, cyano, and carboxyl groups. These interactions significantly delay crystallization, broaden the processing window, and promote complete reaction between lead halide and salt, thereby reduced residual unreacted lead iodide and ultimately yielded high-quality perovskite films with larger grains and lower defect state density. Moreover, 2A4CBA differentially modulates the work functions of top surface and buried interface, establishing a graded energy-level alignment that facilitates separate extraction of electrons and holes. As a result, the single-junction inverted wide-bandgap (WBG) perovskite solar cell (PSC) achieved a power conversion efficiency (PCE) of 23.44% along with markedly improved storage and operational stability. Furthermore, a 1 cm2 perovskite/silicon tandem solar cell (TSC) integrating this optimized WBG perovskite reached a PCE of 33.20% (certified 32.88%) and exhibited excellent operational stability.
To compare lateral locked plating (LLP) to a combined treatment approach utilizing a retrograde intramedullary nail (rIMN) alongside a minimally invasive lateral locked periprosthetic plating system (PPS) (Smith & Nephew; Memphis, TN) in the management of Vancouver C periprosthetic femoral fractures. Retrospective chart review. Single, academic, Level-1 Trauma center. All adult patients who underwent fixation of a Vancouver C periprosthetic femur fracture (AO/OTA Type 32C [IVC/D]) with a rIMN and PPS (NP Group) or LLP (LLP group) between 2019 and 2025 with follow-up to union, reoperation, or a minimum of one year were included. Patients in the NP group were recommended to fully bear weight immediately while patients in the LLP group were recommended to remain non-weight bearing for 8 weeks. The primary outcome was fracture union. Secondary outcomes included implant failure, infection, and alignment immediately postoperatively and at final follow-up. Primary and secondary outcome measures were compared between the NP and LLP groups. A total of 52 patients were included. 31 in the NP group (68% female, mean age 79 years (range, 67 - 99)) and 21 in the LLP group (67% female, 69 years (range, 53 - 85)), (p = 0.54 for sex, p = 0.26 for age). In both groups, the lateral plate extended proximal to the hip prosthesis by at least 3 screw holes. There were no differences when comparing body mass index, diabetes, smoking status, mechanism of injury, or fracture classification between groups (p > 0.05). In the NP group the mean immediate aLDFA was 82 degrees range (79-87 degrees) compared to 80 degrees (range 79 - 87 degrees) at final follow-up (p = 0.37; 95% CI -5.08 to 12.9). In the LLP group the mean immediate aLDFA was 80 degrees (range, 63 - 87 degrees), compared to 82 degrees (range 69 - 87 degrees) at final follow-up (p = 0.43; 95% CI, -5.35 to 2.37). There was no difference in alignment both immediately postoperatively and at final follow-up between groups (p = 0.20 and 0.45, respectively). There were 2 reoperations (6%) in the NP group, both a removal of a loose interlocking screw. There were 3 reoperations (14%) in the LLP group, all nonunions without implant failure that were revised to nail-plate constructs and subsequently achieved union. There was no difference in reoperation between groups (p = 0.68). There were 0 nonunions in the NP group compared to 3 (14%) in the LLP group (p = 0.03). There were no cases of implant failure or infection. Retrograde nail/plate combination demonstrated a high union rate when treating Vancouver C periprosthetic femur fractures. When compared to lateral locked plating alone which does not facilitate immediate weight-bearing, this implant combination demonstrated lower rates of nonunion with the benefit of allowing immediate post-operative weight bearing. Level III.
Semiconductor-mediated photoreforming is promising for concurrent H2 and value-added chemical production but suffers from rapid charge recombination and slow reaction kinetics. Herein, we construct an ultrathin porous CdS nanosheet co-modified with atomically dispersed Ru and S vacancies, which synergistically promotes the photocatalytic dehydrogenation of ethanol to H2 and acetaldehyde, with subsequent acid-catalyzed condensation yielding 1,1-diethoxyethane (DEE) at 100% overall selectivity. We demonstrate that Ru single atoms extract photogenerated electrons, while S vacancies localize holes, markedly enhancing bulk carrier separation and migration. Beyond spatial charge separation, operando studies further reveal that these dual sites cooperatively strengthen the oxidation state of adjacent S atoms, facilitating charge injection into the key C2H5O* intermediate and reducing the dehydrogenation barrier. The optimized catalyst achieves an H2 evolution rate of 157.9 μmol h-1, 81.5 times that of pristine CdS, along with full selectivity for DEE. This system also demonstrates generality in lactic acid photoreforming, yielding a 27.3-fold enhancement in H2 evolution and 93.3% pyruvic acid selectivity. This work provides a fundamental mechanistic insight into steering photoreforming reaction via atomic-site engineering for solar-to-chemical conversion.
Several methods of surgically treating displaced, ulno-humerally stable olecranon fractures (Mayo type 2a and 2b) have been suggested. Cerclage wires have been used for at least a century to achieve fracture fixation but have been replaced by tension band wiring or plate fixation as the commonly recognized "gold standard" treatments. Thin soft tissues and migrating K-wires result in high complication rates following these 2 methods. We suggest double cerclage wiring as an alternative method that allows for the omission of K-wires. The method can be used for the same indications as tension band wiring: Mayo type 2a and 2b fractures. Two cerclages are placed, in figure-of-eight and figure-of-zero configurations, respectively, through separate drill holes distally and through the triceps tendon proximally. In a retrospective study, the reoperation rate and complication rate were twice as high following tension band wiring compared with double cerclage wiring (27% vs. 13% and 45% vs. 18%, respectively). An ongoing RCT will provide more robust evidence, but current studies indicate that double cerclage wiring is a safe and possibly superior alternative to tension band wiring.
To report a case of spontaneous closure of full-thickness macular hole in highly myopic eye. A 68-year-old female with a known history of high myopia presented for routine annual ophthalmologic evaluation. Optical coherence tomography (OCT) was performed revealing an incidental finding of a full-thickness macular hole (FTMH) in the left eye. Given the patient's stable vision and absence of symptoms, a decision was made to observe without surgical intervention. At the 3-month follow-up, repeat OCT demonstrated spontaneous closure of the macular hole with structural and functional improvement of the photoreceptors. Routine imaging in myopic patients can reveal silent but potentially vision-threatening lesions such as macular holes. Although uncommon, spontaneous closure of FTMH in myopic eyes can occur and warrants consideration in patient counselling and management decisions with appropriate caution regarding long-term stability.
Imidazolinone herbicides such as imazethapyr (IMT) pose potential ecological risks due to their high mobility and ecotoxicity. This study synthesized the bismuth-based photocatalyst BiOIO3 via a facile hydrothermal method and systematically characterized its physicochemical properties. BiOIO3 features a 2D lamellar structure, pure phase composition, and a built-in internal polarization electric field that efficiently separates photogenerated electron-hole pairs. Photocatalytic experiments exhibited that BiOIO3 achieved 84.5% elimination of IMT, with a rate constant 66 times higher than that of TiO2 (Rutile). Mechanistic studies revealed that photogenerated electrons (e-), holes (h+), and superoxide radicals (·O2-) are the primary reactive species. HPLC-MS/MS identified key intermediates, and QSAR-based toxicity prediction showed reduced mutagenicity for most intermediates. Importantly, BiOIO3 effectively eliminated five imidazolinone herbicides simultaneously. This work highlights BiOIO3 as a promising photocatalyst for efficient and practical remediation of imidazolinone herbicide-contaminated water.
Robust generation of bispecific antibodies (BsAbs) in single-cell expression systems is essential for basic research and industrial manufacturing. However, the low yield of BsAbs and complicated downstream processing caused by the random assembly of heavy chains (HCs) and light chains (LCs) have limited the use of BsAbs in clinical and preclinical studies. Major technological improvements have been established to address the issues of HC homodimerization and noncognate HC and LC pairing. Nevertheless, current existing methods need to determine common light chains, extensively engineer each Fv portion or perform labor-intensive biochemical processing making downstream processing highly challenging. Here, we describe an engineering technology for preferential cognate HC/LC and HC/HC pairing called four-chain assembly by electrostatic steering technology-immunoglobulin (FAST-IgTM). When co-expressed in single host cells, parental monoclonal antibodies incorporating these interfaces can preferentially assemble into BsAbs. The remaining trace amount of mispairing antibodies can be easily removed via ion exchange chromatography. In this chapter, we provide a detailed protocol for the systematic generation of IgG-like BsAb designs based on the FAST-Ig™ technology in combination with knobs-into-holes technology to obtain highly purified BsAbs. Additionally, we present a detailed protocol for the analysis and characterization of target BsAbs.