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This article, titled "OC21.05: Assessing racial disparities in sonographic detection of endometrial cancer," compares the effectiveness of different methods (transvaginal sonogram, sonohysterogram, and endometrial aspiration) in detecting endometrial cancer or hyperplasia (ECH) between black and non-black women. The study included 1,840 women over the age of 50 who underwent endometrial evaluation. The results showed that there were no significant racial disparities in the detection rates of ECH between black and non-black women. However, the completion rate of transvaginal sonograms was lower in black women compared to non-black women, with fibroids negatively impacting the likelihood of completion. [Extracted from the article]

To evaluate the performance of transvaginal sonogram (TVS), sonohysterogram (SIS) and endometrial aspiration (EA) in detecting type 2 (T2) endometrial cancers (EC), compared to type 1 (T1) EC. Conclusions TVS, SIS and EA had excellent T2EC detection rates which were similar or better than for T1EC. Methods failure rates: T1EC - TVS 6.6%, SIS 1.6%, EA 1.6%; T2EC - TVS 17.9%, SIS 0.0%, EA 7.1%. [Extracted from the article]

SEAS performance was calculated for both current ECH and for all ECH cases (including ECH that developed > 1 year after SEAS). Conclusions TVS, SIS and SEAS had excellent sensitivity and NPP for current ECH, but SA performed best overall. Evaluate Simultaneous Endometrial Aspiration and Sonohysterography (SEAS) as a method of detecting Endometrial Cancer and Hyperplasia (ECH) in Postmenopausal Bleeding (PMB). [Extracted from the article]

Objective: To assess the performance of simultaneous endometrial aspiration and sonohysterography to screen for endometrial cancer or hyperplasia in women aged 50 years or older., Methods: We conducted a prospective study from February 2014 to October 2020 at the ultrasound unit of a large urban academic medical center. The study included 1,635 women aged 50 years or older referred for endometrial evaluation, with follow-up through January 2021. Participants underwent saline infusion sonohysterography combined with ultrasound-guided endometrial aspiration. The primary outcome measured was a diagnosis of endometrial cancer or hyperplasia within 1 year from screening. The diagnostic accuracy of the combined evaluation method, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed., Results: Of 1,170 women who completed the study protocol, 82 (7.0%) had endometrial cancer and 42 (3.6%) had endometrial hyperplasia. Of all patients who developed cancer during the follow-up period, 85.5% were diagnosed within 1 year after evaluation. The application of simultaneous endometrial aspiration and sonohysterography together demonstrated a sensitivity of 99.1%, specificity of 24.9%, PPV of 11.8%, and NPV of 99.6%. Using a theoretical sequential approach, assuming an endometrial aspiration is performed only in patients determined to be high risk by sonohysterography, demonstrated a sensitivity of 93.4%, specificity of 99.9%, PPV of 99.0%, and NPV of 99.3%., Conclusion: Simultaneous endometrial aspiration and sonohysterography is an effective one-stop outpatient screening tool for detecting endometrial cancer and hyperplasia in women aged 50 years or older. With the integration of two screening modalities into a single procedure, simultaneous endometrial aspiration and sonohysterography may overcome the limitations inherent in each of the currently recommended methods individually, potentially improving patient prognosis and streamlining the diagnostic process., Competing Interests: Financial Disclosure Haotian Wu disclosed receiving payments from Montefiore. The other authors did not report any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Matrix metalloproteinases (MMPs) are a family of endopeptidases that degrade extracellular matrix (ECM) proteins, functioning in various physiological processes such as tissue remodeling, embryogenesis, and morphogenesis. Dysregulation of these enzymes is linked to multiple diseases. Specific inhibition of particular MMPs is crucial for anti-MMP drug development as some MMPs have shown anti-disease properties. In this study, we aimed to design a highly specific inhibitor of MMP-9, that plays a crucial role in cell invasion and metastasis, using tissue inhibitor of metalloproteinases 2 (TIMP2), an endogenous broad-family MMP inhibitor, as a prototype. In our earlier work, we were able to narrow down the specificity of the N-terminal domain of TIMP2 (N-TIMP2) toward MMP-9, yet at the expense of lowering its affinity to MMP-9. In this study, a library of N-TIMP2 mutants based on previous design with randomized additional positions was sorted for binding to MMP-9 using yeast surface display. Two selected N-TIMP2 mutants were expressed, purified and their inhibitory activity against a panel of MMPs was measured. The best engineered N-TIMP2 mutant (REY) exhibited a 2-fold higher affinity to MMP-9 compared to that of the WT N-TIMP2, and 6- to 1.1x10 4 -fold increase in binding specificity toward MMP-9 compared to five alternative MMPs. Moreover, REY demonstrated a significant increase in inhibition of cell invasion and proliferation compared to the WT N-TIMP2 in MDA-MB-231 breast cancer cells. Therefore, our engineered N-TIMP2 mutant emerges as a promising candidate for future therapeutic development, offering precise targeting of MMP-9 in MMP-9-driven diseases., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest with the contents of this article, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Morphological variations in the left atrial appendage (LAA) are associated with different levels of ischemic stroke risk for patients with atrial fibrillation (AF). Studying LAA morphology can elucidate mechanisms behind this association and lead to the development of advanced stroke risk stratification tools. However, current categorical descriptions of LAA morphologies are qualitative and inconsistent across studies, which impedes advancements in our understanding of stroke pathogenesis in AF. To mitigate these issues, we introduce a quantitative pipeline that combines elastic shape analysis with unsupervised learning for the categorization of LAA morphology in AF patients. As part of our pipeline, we compute pairwise elastic distances between LAA meshes from a cohort of 20 AF patients, and leverage these distances to cluster our shape data. We demonstrate that our method clusters LAA morphologies based on distinctive shape features, overcoming the innate inconsistencies of current LAA categorization systems, and paving the way for improved stroke risk metrics using objective LAA shape groups.

Matrix metalloproteinases (MMPs) are significant drivers of many diseases, including cancer, and are established targets for drug development. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous MMP inhibitors and are being pursued for the development of anti-MMP therapeutics. TIMPs possess many attractive properties for drug candidates, such as complete MMP inhibition, low toxicity, low immunogenicity, and high tissue permeability. However, a major challenge with TIMPs is their rapid clearance from the bloodstream due to their small size. This study explores a method for extending the plasma half-life of the N-terminal domain of TIMP2 (N-TIMP2) by appending it with a long, intrinsically unfolded tail containing Pro, Ala, and Thr (PATylation). We designed and produced two PATylated N-TIMP2 constructs with tail lengths of 100 and 200 amino acids (N-TIMP2-PAT 100 and N-TIMP2-PAT 200 ). Both constructs demonstrated higher apparent molecular weights and retained high inhibitory activity against MMP-9. N-TIMP2-PAT 200 significantly increased plasma half-life in mice compared to the non-PATylated variant, enhancing its therapeutic potential. PATylation offers distinct advantages for half-life extension, such as fully genetic encoding, monodispersion, and biodegradability. It can be easily applied to N-TIMP2 variants engineered for high affinity and selectivity toward individual MMPs, creating promising candidates for drug development against MMP-related diseases., Competing Interests: The authors declare no conflicts of interest.

The clinical features of neuropsychiatric systemic lupus erythematosus (NPSLE) are heterogeneous. Furthermore, therapeutic decision-making for NPSLE depends on the recognition of clinical syndromes that have not been sufficiently studied. This report describes the case of a 36-year-old woman with NPSLE who exhibited severe cognitive dysfunction and affective psychosis with persistent nihilistic delusions such as those described in the Cotard delusion. The patient insisted for several months that she was already dead. CSF analysis showed elevated levels of anti-ribosomal P antibodies and a positive determination of oligoclonal bands. Additionally, 18F -FDG PET/CT imaging revealed severe bilateral frontal hypermetabolism suggestive of brain inflammation and occipital hypometabolism. Results from the Systematic Lupus Erythematosus Disease Activity Index 2000 and the Systemic Lupus Erythematosus Disease Activity Score were consistent with an active state of the immunological disease. We then determined by an algorithm that this neuropsychiatric event could be attributed to the activity of the underlying immunological disease. Despite immunosuppressive and symptomatic treatment, only a partial improvement in cognition was achieved. The psychopathological features of the Cotard delusion remained unchanged 4 months after onset. However, we observed rapid remission of affective psychosis and significant improvement in cognition following electroconvulsive therapy. Subsequent follow-up examinations showed a sustained remission. This case describes a protracted form of the Cotard delusion, the diagnostic challenges that arise in the context of SLE, and treatment dilemmas that necessitate collaboration between neurology, psychiatry, and rheumatology., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Realizing a sensitive photon-number-dependent phase shift on a light beam is required both in classical and quantum photonics. It may lead to new applications for classical and quantum photonics machine learning or pave the way for realizing photon-photon gate operations. Nonlinear phase-shifts require efficient light-matter interaction, and recently quantum dots coupled to nanophotonic devices have enabled near-deterministic single-photon coupling. We experimentally realize an optical phase shift of 0.19π ± 0.03 radians ( ≈ 34 degrees) using a weak coherent state interacting with a single quantum dot in a planar nanophotonic waveguide. The phase shift is probed by interferometric measurements of the light scattered from the quantum dot in the waveguide. The process is nonlinear in power, the saturation at the single-photon level and compatible with scalable photonic integrated circuitry. The work may open new prospects for realizing high-efficiency optical switching or be applied for proof-of-concept quantum machine learning or quantum simulation demonstrations., (© 2024. The Author(s).)

Matrix metallopeptidase 7 (MMP7) plays a crucial role in cancer metastasis and progression, making it an attractive target for therapeutic development. However, the development of selective MMP7 inhibitors is challenging due to the conservation of active sites across various matrix metalloproteinases (MMPs). Here, we have developed mirror-image random nonstandard peptides integrated discovery (MI-RaPID) technology to discover innate protease-resistant macrocyclic peptides that specifically bind to and inhibit human MMP7. One identified macrocyclic peptide against D-MMP7, termed D20, was synthesized in its mirror-image form, D'20, consisting of 12 D-amino acids, one cyclic b-amino acid, and a thioether bond. Notably, it potently inhibited MMP7 with an IC50 value of 90 nM, and showed excellent selectivity over other MMPs with similar substrate specificity. Moreover, D'20 inhibited the migration of pancreatic cell line CFPAC-1, but had no effect on the cell proliferation and viability. D'20 exhibited excellent stability in human serum, as well as in simulated gastric and intestinal fluids. This study highlights that MI-RaPID technology can serve as a powerful tool to develop in vivo stable macrocyclic peptides for therapeutic applications., (© 2024 Wiley‐VCH GmbH.)

Quantum photonic integrated circuits, composed of linear-optical elements, offer an efficient way for encoding and processing quantum information on-chip. At their core, these circuits rely on reconfigurable phase shifters, typically constructed from classical components such as thermo- or electro-optical materials, while quantum solid-state emitters such as quantum dots are limited to acting as single-photon sources. Here, we demonstrate the potential of quantum dots as reconfigurable phase shifters. We use numerical models based on established literature parameters to show that circuits utilizing these emitters enable high-fidelity operation and are scalable. Despite the inherent imperfections associated with quantum dots, such as imperfect coupling, dephasing, or spectral diffusion, we show that circuits based on these emitters may be optimized such that these do not significantly impact the unitary infidelity. Specifically, they do not increase the infidelity by more than 0.001 in circuits with up to 10 modes, compared to those affected only by standard nanophotonic losses and routing errors. For example, we achieve fidelities of 0.9998 in quantum-dot-based circuits enacting controlled-phase and - not gates without any redundancies. These findings demonstrate the feasibility of quantum emitter-driven quantum information processing and pave the way for cryogenically-compatible, fast, and low-loss reconfigurable quantum photonic circuits., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Efficient light-matter interaction at the single-photon level is of fundamental importance in emerging photonic quantum technology. A fundamental challenge is addressing multiple quantum emitters at once, as intrinsic inhomogeneities of solid-state platforms require individual tuning of each emitter. We present the realization of two semiconductor quantum dot emitters that are efficiently coupled to a photonic-crystal waveguide and individually controllable by applying a local electric Stark field. We present resonant transmission and fluorescence spectra in order to probe the coupling of the two emitters to the waveguide. We exploit the single-photon stream from one quantum dot to perform spectroscopy on the second quantum dot positioned 16  μm away in the waveguide. Furthermore, power-dependent resonant transmission measurements reveal signatures of coherent coupling between the emitters. Our work provides a scalable route to realizing multiemitter collective coupling, which has inherently been missing for solid-state deterministic photon emitters.

Tailored photonics cavities enhance light-matter interactions, ultimately enabling a fully coherent quantum interface. Here, we report an integrated microdisk cavity containing self-assembled quantum dots to coherently route photons between different access waveguides. We measure a Purcell factor of F exp = 6.9 ± 0.9 for a cavity quality factor of about 10,000, allowing us to observe clear signatures of coherent scattering of photons by the quantum dots. We show how this integrated system can coherently reroute photons between the drop and bus ports and how this routing is controlled by detuning the quantum dot and resonator or through the strength of the excitation beam, where a critical photon number less than one photon per lifetime is required. We discuss the strengths and limitations of this approach, focusing on how the coherent scattering and single-photon nonlinearity can be used to increase the efficiency of quantum devices such as routers or Bell-state analyzers.

Coherent photon-emitter interfaces offer a way to mediate efficient nonlinear photon-photon interactions, much needed for quantum information processing. Here we experimentally study the case of a two-level emitter, a quantum dot, coupled to a single optical mode in a nanophotonic waveguide. We carry out few-photon transport experiments and record the statistics of the light to reconstruct the scattering matrix elements of one- and two-photon components. This provides direct insight to the complex nonlinear photon interaction that contains rich many-body physics.

Primary intraosseous meningiomas (PIMs) are rare tumors that present with a variable radiological appearance and a clinical behavior that is considerably different from that of intracranial meningiomas. Treatment of PIMs consists of complete resection, which may be difficult to achieve due to the lack of clear tumor margins on conventional imaging studies. PET/CT using 68Ga-DOTA-conjugated peptides has been used for the diagnosis and treatment planning of different types of meningiomas due to these tracers' affinity to somatostatin receptors, which are found in most meningiomas. However, this imaging modality's use as an intraoperative adjunct has not been reported for PIMs. In this technical note, the authors describe a [68Ga-DOTA0-Tyr3]octreotide (68Ga-DOTATOC)-PET/CT-guided resection of a PIM. In this case, the area of increased uptake in the 68Ga-DOTATOC-PET/CT study extended well beyond the tumor margins identified on MRI. The patient's pathology report confirmed the presence of tumor cells within peripheral bone, which macroscopically appeared normal. The authors propose 68Ga-DOTATOC-PET/CT as a valuable adjunct in the surgical management of PIMs and offer a reasonable justification for its use based on current evidence. Its use for intraoperative image guidance may aid neurosurgeons in achieving a complete resection, thus minimizing the risk of recurrence of this complex pathological entity.

Background: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis causes substantial neurological disability. Autoantibodies causing encephalitis directed against the neuronal cell surface or synapse are of diagnostic importance giving the possibility of successful immunotherapy., Objective: In this study, we aim to provide supporting evidence that brain 18F-FDG-PET may be helpful in identifying likely patterns of regional brain glucose metabolism., Methods: Thirty-three patients (18 men and 15 women; age range of 17-55 y) with positive NMDA receptor antibody encephalitis that underwent an 18F-FDG-PET imaging examination were prospectively selected and compared with a reference group of 14 brain 18F-FDG-PET scans from healthy volunteers using voxel-based statistical analysis. Clusters of hyper- and hypo-metabolism were reported for the whole sample of patients (FWE-corrected P < 0.05), and uncorrected at P < 0.005 for a group of relapsed patients., Results: Mixed metabolic patterns (focal/bilateral hypermetabolism in the temporal lobe, insula, and cerebellum; associated with severe bilateral hypometabolism in the occipital and parietal lobes) were found., Conclusions: Our findings suggest that 18F-FDG-PET should be included as an imaging tool when assessing affected patients in the clinical workup to rule out anti-NMDA encephalitis and help determine the most effective treatment., (Copyright © 2019 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Establishing a highly efficient photon-emitter interface where the intrinsic linewidth broadening is limited solely by spontaneous emission is a key step in quantum optics. It opens a pathway to coherent light-matter interaction for, e.g., the generation of highly indistinguishable photons, few-photon optical nonlinearities, and photon-emitter quantum gates. However, residual broadening mechanisms are ubiquitous and need to be combated. For solid-state emitters charge and nuclear spin noise are of importance, and the influence of photonic nanostructures on the broadening has not been clarified. We present near-lifetime-limited linewidths for quantum dots embedded in nanophotonic waveguides through a resonant transmission experiment. It is found that the scattering of single photons from the quantum dot can be obtained with an extinction of 66 ± 4%, which is limited by the coupling of the quantum dot to the nanostructure rather than the linewidth broadening. This is obtained by embedding the quantum dot in an electrically contacted nanophotonic membrane. A clear pathway to obtaining even larger single-photon extinction is laid out; i.e., the approach enables a fully deterministic and coherent photon-emitter interface in the solid state that is operated at optical frequencies.

The feasibility of many proposals in nanoquantum-optics depends on the efficient coupling of photons to individual quantum emitters, the possibility to control this interaction on demand, and the scalability of the experimental platform. To address these issues, we report on chip-based systems made of one-dimensional subwavelength dielectric waveguides (nanoguides) and polycyclic aromatic hydrocarbon molecules. We discuss the design and fabrication requirements, present data on extinction spectroscopy of single molecules coupled to a nanoguide mode, and show how an external optical beam can switch the propagation of light via a nonlinear optical process. The presented architecture paves the way for the investigation of many-body phenomena and polaritonic states and can be readily extended to more complex geometries for the realization of quantum integrated photonic circuits.

We introduce core-shell plasmonic nanohelices, highly tunable structures that have a different response in the visible for circularly polarized light of opposite handedness. The glass core of the helices is fabricated using electron beam induced deposition and the pure gold shell is subsequently sputter coated. Optical measurements allow us to explore the chiral nature of the nanohelices, where differences in the response to circularly polarized light of opposite handedness result in a dissymmetry factor of 0.86, more than twice of what has been previously reported. Both experiments and subsequent numerical simulations demonstrate the extreme tunability of the core-shell structures, where nanometer changes to the geometry can lead to drastic changes of the optical responses. This tunability, combined with the large differential transmission, make core-shell plasmonic nanohelices a powerful nanophotonic tool for, for example, (bio)sensing applications.

Nanophotonic interfaces between single emitters and light promise to enable new quantum optical technologies. Here, we use a combination of finite element simulations and analytic quantum theory to investigate the interaction of various quantum emitters with slot-waveguide rings. We predict that for rings with radii as small as 1.44 μm, with a Q-factor of 27,900, near-unity emitter-waveguide coupling efficiencies and emission enhancements on the order of 1300 can be achieved. By tuning the ring geometry or introducing losses, we show that realistic emitter-ring systems can be made to be either weakly or strongly coupled, so that we can observe Rabi oscillations in the decay dynamics even for micron-sized rings. Moreover, we demonstrate that slot waveguide rings can be used to directionally couple emission, again with near-unity efficiency. Our results pave the way for integrated solid-state quantum circuits involving various emitters.

We present experimental observations of visible wavelength second- and third-harmonic generation on single plasmonic nanowires of variable widths. We identify that near-infrared surface plasmon polaritons, which are guided along the nanowire, act as the source of the harmonics generation. We discuss the underlying mechanism of this nonlinear process, using a combination of spatially resolved measurements and numerical simulations to show that the visible harmonics are generated via a combination of both local and propagating plasmonic modes. Our results provide the first demonstration of nanoscale nonlinear optics with guided, propagating plasmonic modes on a lithographically defined chip, opening up new routes toward integrated optical circuits for information processing.