The Superficial Peroneal Nerve Is at Risk during the "All Inside" Arthroscopic Broström Procedure: A Cadaveric Study.

Background: The arthroscopic Broström procedure is a promising treatment for chronic ankle instability. However, little is known regarding the location of the intermediate superficial peroneal nerve at the level of the inferior extensor retinaculum; knowledge about this location is important for procedural safety. The purpose of this cadaveric study was to clarify the anatomical relationship between the intermediate superficial peroneal nerve and the sural nerve at the level of the inferior extensor retinaculum. Methods: Eleven dissections of cadaveric lower extremities were performed. The origin of the experimental three-dimensional axis was defined as the location of the anterolateral portal during ankle arthroscopy. The distances from the standard anterolateral portal to the inferior extensor retinaculum, sural nerve, and intermediate superficial peroneal nerve were measured using an electronic digital caliper. The location of inferior extensor retinaculum, the tract of sural nerve, and intermediate superficial peroneal nerve were checked using average and standard deviations. For the statistical analyses, data are presented as average ± standard deviation, and then they are reported as means and standard deviations. Fisher's exact test was used to identify statistically significant differences. Results: At the level of the inferior extensor retinaculum, the mean distances from the anterolateral portal to the proximal and distal intermediate superficial peroneal nerve were 15.9 ± 4.1 (range, 11.3-23.0) mm and 30.1 ± 5.5 (range, 20.8-37.9) mm, respectively. The mean distances from the anterolateral portal to the proximal and distal sural nerve were 47.6 ± 5.7 (range, 37.4-57.2) mm and 47.2 ± 4.1 (range, 41.0-51.8) mm), respectively. Conclusions: During the arthroscopic Broström procedure, the intermediate superficial peroneal nerve may be damaged by the anterolateral portal; the proximal and distal parts of the intermediate superficial peroneal nerve were located within 15.9 and 30.1 mm, respectively, at the level of the inferior extensor retinaculum in cadavers. These areas should be considered danger zones during the arthroscopic Broström procedure.

Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers.

Lineage tracing in mice indicates that LGR5 is an adult stem cell marker in multiple organs, such as the intestine, stomach, hair follicles, ovary, and mammary glands. Despite many studies exploring the presence of LGR5 cells in human tissues, little is known about its expression profile in either human mammary tissue or pathological lesions. In this study we aim to investigate LGR5 expression in normal, benign, and malignant lesions of the human breast using RNA in situ hybridization. LGR5 expression has not been observed in normal lactiferous ducts and terminal duct lobular units, whereas LGR5-positive cells have been specifically observed in the basal myoepithelium of ducts in the regenerative tissues, ductal carcinoma in situ, and in ducts surrounded by invasive cancer cells. These findings suggest LGR5 marks facultative stem cells that are involved in post injury regeneration instead of homeostatic stem cells. LGR5 positivity was found in 3% (9 of 278 cases) of invasive breast cancers (BC), and it showed positive associations with higher histologic grades (P = 0.001) and T stages (P < 0.001), while having negative correlations with estrogen receptor (P < 0.001) and progesterone receptor (P < 0.001) expression. Remarkably, all LGR5-positive BC, except one, belong to triple-negative BC (TNBC), representing 24% (9 of 38 cases) of all of them. LGR5 histoscores have no correlations with EGFR, CK5/6, Ki-67, or P53 expression. Additionally, no ß-catenin nuclear localization was observed in LGR5-positive BC, indicating that canonical Wnt pathway activation is less likely involved in LGR5 expression in BC. Our results demonstrate that LGR5 expression is induced in regenerative conditions in the myoepithelium of human mammary ducts and that its expression is only observed in TNBC subtype among all invasive BC. Further studies regarding the functional and prognostic impact of LGR5 in TNBC are warranted.

Room temperature electrically pumped topological insulator lasers.

Topological insulator lasers (TILs) are a recently introduced family of lasing arrays in which phase locking is achieved through synthetic gauge fields. These single frequency light source arrays operate in the spatially extended edge modes of topologically non-trivial optical lattices. Because of the inherent robustness of topological modes against perturbations and defects, such topological insulator lasers tend to demonstrate higher slope efficiencies as compared to their topologically trivial counterparts. So far, magnetic and non-magnetic optically pumped topological laser arrays as well as electrically pumped TILs that are operating at cryogenic temperatures have been demonstrated. Here we present the first room temperature and electrically pumped topological insulator laser. This laser array, using a structure that mimics the quantum spin Hall effect for photons, generates light at telecom wavelengths and exhibits single frequency emission. Our work is expected to lead to further developments in laser science and technology, while opening up new possibilities in topological photonics.

Nonlinear Circular Dichroism in Mie-Resonant Nanoparticle Dimers.

We studied the nonlinear response of a dimer composed of two identical Mie-resonant dielectric nanoparticles illuminated normally by a circularly polarized light. We developed a general theory describing hybridization of multipolar modes of the coupled nanoparticles and reveal nonvanishing nonlinear circular dichroism (CD) in the second-harmonic generation (SHG) signal enhanced by the multipolar resonances in the dimer, provided its axis is oriented under an angle to the crystalline lattice of the dielectric material. We supported our multipolar hybridization theory by experimental results obtained for the AlGaAs dimers placed on an engineered substrate.

Recent advances in nanocavities and their applications.

High quality factor and small mode volume in nanocavities enable the demonstration of efficient nanophotonic devices with low power consumption, strong nonlinearity, and high modulation speed, due to the strong light-matter interaction. In this review, we focus on recent state-of-the-art nanocavities and their applications. We introduce single nanocavities including semiconductor nanowires, plasmonic cavities, and nanostructures based on quasi-bound states in the continuum (quasi-BIC), for laser, photovoltaic, and nonlinear applications. In addition, nanocavity arrays with unique feedback mechanisms, including BIC cavities, parity-time symmetry coupled cavities, and photonic topological cavities, are introduced for laser applications. These various cavity designs and underlying physics in single and array nanocavities are useful for the practical implementation of promising nanophotonic devices.

Inexpensive water soluble methyl methacrylate-functionalized hydroxyphthalimide: variations of the mycophenolic acid core for selective live cell imaging of free cysteine.

Evident from numerous studies, cysteine plays a crucial role in cellular function. Reactions with analyte also enables for molecular recognition to adhere to molecular therapeutic potential; integration between synthetic probes therefore allows for a potentially deep therapy-related interogation of biological systems (theranostics). The development of molecular cysteine probes with extremely accurate detection is still a key challenge for the field. The development of water-soluble organic molecular fluorescent probes able to efficiently distinguish common biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) by chemical recognition means i.e. by (binding, cleavage) in biological systems is a greatly sought research challenge due to the similarity of the small sulfhydryl-containing species. Herein, we have developed a water-soluble and highly cell viable fluorescent organic molecule (log P = 0.82) for the selective detection of cysteine. The probe (Myco-Cys) shows a "turn-on" response with the cleavage ester linkage of the methacrylate as cysteine is encountered in solution. The probe shows strong fluorescence enhancement (16.5-fold) when treated with Cys (1 equiv., 10 µM) compared to closely related species such as amino acids, including HCy/GSH, and the limit of detection was determined as 45.0 nM. DFT calculations helped confirm the photomechanism of Myco-Cys. Furthermore, the sensing ability of the probe was demonstrated by living cell assays through the use of confocal fluorescence microscopy. Myco-Cys could selectively detect cysteine among biothiols. Myco-Cys was able to monitor the cysteine level, apart from the oxidative stress present in the form of H2O2 in A549 cells.

From Fano to Quasi-BIC Resonances in Individual Dielectric Nanoantennas.

Sharp optical resonances in high-index dielectric nanostructures have recently attracted significant attention for their promising applications in nanophotonics. Fano resonances, as well as resonances associated with bound states in the continuum (BIC), have independently shown a great potential for applications in nanoscale lasers, sensors, and nonlinear optical devices. Here, we demonstrate experimentally a close connection between Fano and quasi-BIC resonances excited in individual dielectric nanoantennas. We analyze systematically the resonant response of AlGaAs nanoantennas pumped with a structured light in the near-infrared range. We trace a variation of the scattering spectrum that fully agrees with an analytical expression governed by a Fano parameter and observe directly a transition to a quasi-BIC resonance. Our results suggest a unified approach toward the analysis of sharp resonances in subwavelength nanostructures originating from strong coupling of optical modes that can provide high energy localization for enhanced light-matter interactions.

Polarization Control of Deterministic Single-Photon Emitters in Monolayer WSe2.

Single-photon emitters, the basic building blocks of quantum communication and information, have been developed using atomically thin transition metal dichalcogenides (TMDCs). Although the bandgap of TMDCs was spatially engineered in artificially created defects for single-photon emitters, it remains a challenge to precisely align the emitter's dipole moment to optical cavities for the Purcell enhancement. Here, we demonstrate position- and polarization-controlled single-photon emitters in monolayer WSe2. A tensile strain of ∼0.2% was applied to monolayer WSe2 by placing it onto a dielectric rod structure with a nanosized gap. Excitons were localized in the nanogap sites, resulting in the generation of linearly polarized single-photon emission with a g(2) of ∼0.1 at 4 K. Additionally, we measured the abrupt change in polarization of single photons with respect to the nanogap size. Our robust spatial and polarization control of emission provides an efficient way to demonstrate deterministic and scalable single-photon sources by integrating with nanocavities.

The clinical usefulness of chemokine C-X-C Motif Ligand 12 as a diagnostic marker for Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer worldwide. It is essential to develop methods for the accurate diagnosis of PTC to avoid unnecessary surgery. The chemokine C-X-C motif ligand 12 (CXCL12) is associated with various cancers. We aimed to investigate the efficacy of CXCL12 in the diagnosis of PTC in fine-needle aspiration (FNA) specimens. METHODS: We prospectively collected samples from 58 patients who were scheduled for surgical treatment of PTC from 2013 to 2015. Tissue samples of 31 people with benign thyroid conditions were used as controls. Immunocytochemical and immunohistochemical staining for CXCL12 was performed on FNAs and corresponding tissue specimens. B-type Raf kinase (BRAF) V600E mutant protein expression and gene mutation were also analyzed to compare the clinical usefulness. RESULTS: : The mean age of the patients was 49.1 ± 1.4 years and 88.1% were women. Positive CXCL12 staining was observed in 6.5% of benign and in 98.3% of PTC samples; positive BRAF V600E mutant protein expression was found in 19.4% of benign and 93.1% of PTC samples. For the diagnosis of PTC for CXCL12 staining of FNA specimens, the calculated values were 93.1% sensitivity, 90.3% specificity, 94.7% positive predictive value, 87.5% negative predictive value, and 89.1% accuracy. CXCL12 had 100% sensitivity and specificity for the 12 cases of atypia of undetermined significance (AUS) diagnosed in FNA specimens. CONCLUSIONS: CXCL12 may be a useful diagnostic tool for PTC, especially when the FNA specimen is classified as AUS.

Surgical treatment of rhinophyma using an ordinary bur.

Rhinophyma is a painless benign tumor of the skin of the nose. It is the most severe form of rosacea. Rhinophyma is particularly rare among Asians. It can be treated with surgical resection using various methods, including scalpel excision, dermabrasion, cryosurgery, argon laser, carbon dioxide laser, and electrocautery. However, the gold standard treatment of rhinophyma remains unknown. In the present case, we debulked a giant rhinophyma with a scalpel and contoured it using a bur. Along with a relevant literature review, we present a case of rhinophyma in an Asian patient who was treated at no additional cost using a bur widely used in general plastic surgery.

Integration of Single-Photon Emitters in 2D Materials with Plasmonic Waveguides at Room Temperature.

Efficient integration of a single-photon emitter with an optical waveguide is essential for quantum integrated circuits. In this study, we integrated a single-photon emitter in a hexagonal boron nitride (h-BN) flake with a Ag plasmonic waveguide and measured its optical properties at room temperature. First, we performed numerical simulations to calculate the efficiency of light coupling from the emitter to the Ag plasmonic waveguide, depending on the position and polarization of the emitter. In the experiment, we placed a Ag nanowire, which acted as the plasmonic waveguide, near the defect of the h-BN, which acted as the single-photon emitter. The position and direction of the nanowire were precisely controlled using a stamping method. Our time-resolved photoluminescence measurement showed that the single-photon emission from the h-BN flake was enhanced to almost twice the intensity as a result of the coupling with the Ag nanowire. We expect these results to pave the way for the practical implementation of on-chip nanoscale quantum plasmonic integrated circuits.

Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance.

Secreted Protein Acidic and Rich in Cysteine (SPARC)-related modular calcium-binding protein-2 (SMOC2), a secreted matricellular protein, is reported to be involved in various processes related to cancer progression such as regulating the cell cycle, angiogenesis, and invasion. However, its expression and prognostic significance in papillary thyroid carcinomas (PTCs) remains unknown. Using immunohistochemistry, we evaluated the expression profile of SMOC2 and its prognostic value in a large cohort of PTCs. Real time-PCR analysis with fresh-frozen tissues showed that SMOC2 mRNA expression in PTCs was substantially lower than the expression in matched non-cancerous thyroid tissues, consistent with the results from thyroid cancer cell lines. Immunohistochemical analysis demonstrated that SMOC2 was normally present in thyroid follicular epithelial cells and the expression level was maintained in nodular hyperplasia. However, SMOC2 expression was significantly lower in lymphocytic thyroiditis and follicular tumors including follicular adenomas and carcinomas. In particular, 38% of PTCs exhibited a complete loss of SMOC2 expression, which was associated with the presence of BRAF (V600E) mutation. Moreover, SMOC2 further declined during lymph node metastasis in PTCs. DNA methylation chip analysis revealed one hypermethylated CpG site in the promoter region of SMOC2 gene, suggesting an epigenetic regulation of SMOC2 in PTCs. Remarkably SMOC2 positivity was associated with improved recurrence-free survival along with female sex, tumor size, and the N stage. However, SMOC2 was not identified as an independent prognostic marker in multivariate analyses. Taken together, SMOC2 expression is significantly down-regulated in PTCs and SMOC2 positivity is closely associated with better clinical outcomes, suggesting that SMOC2 can be a prognostic marker in PTC patients.

Subwavelength dielectric resonators for nonlinear nanophotonics.

Subwavelength optical resonators made of high-index dielectric materials provide efficient ways to manipulate light at the nanoscale through mode interferences and enhancement of both electric and magnetic fields. Such Mie-resonant dielectric structures have low absorption, and their functionalities are limited predominantly by radiative losses. We implement a new physical mechanism for suppressing radiative losses of individual nanoscale resonators to engineer special modes with high quality factors: optical bound states in the continuum (BICs). We demonstrate that an individual subwavelength dielectric resonator hosting a BIC mode can boost nonlinear effects increasing second-harmonic generation efficiency. Our work suggests a route to use subwavelength high-index dielectric resonators for a strong enhancement of light-matter interactions with applications to nonlinear optics, nanoscale lasers, quantum photonics, and sensors.

Detecting Synchronous Thyroid Adenoma and False-Positive Findings on Technetium-99m MIBI Single Photon-Emission Computed Tomography/Computed Tomography.

Technetium (Tc)-99m-methoxyisobutylisonitrile (MIBI) single photon-emission computed tomography/computed tomography (SPECT/CT) is now being used increasingly for preoperative localization of parathyroid adenomas. Tc-99m-MIBI scintigraphy in a 52-year-old man with a diagnosis of primary hyperparathyroidism revealed two focal areas with retention of radioactivity in the left lobe of the thyroid gland on the delayed phase of MIBI SPECT/CT but no significant focal radioactive uptake on MIBI planar images. The patient subsequently underwent left partial parathyroidectomy. Histological analysis identified one lesion to be thyroid hyperplasia and the other to be parathyroid adenoma. This case demonstrates the value of MIBI SPECT/CT for localization of a parathyroid lesion when compared with planar images and that false-positive findings can lead to misdiagnosis in a patient with coexisting thyroid disease. An appropriate diagnostic work-up that includes Tc-99m MIBI SPECT/CT in addition to ultrasonography is helpful for an accurate diagnosis in patients with concomitant thyroid disease.

Dual-Time-Point FDG Uptake Correlates with Prognostic Factors of Invasive Breast Cancer: Clinical Usefulness of Early Delayed Scanning.

This study investigated correlations between fluorodeoxyglucose (FDG) uptake in tumors as assessed by modified dual-time-point (mDTP) FDG positron emission tomography/computed tomography (PET/CT) in invasive breast cancer (iBC) and several prognostic parameters. Thirty-two women who underwent mastectomies for iBC were retrospectively evaluated. mDTP scanning was performed using standard FDG PET/CT (PET1), followed by early delayed acquisition (PET2) without repositioning and additional CT scanning. Using maximal standardized uptake values on PET1 (SUV1) and PET2 (SUV2) in the primary breast tumor, the percentage changes between SUV1 and SUV2 (retention index, (RI)) were calculated. Prognostic parameters (e.g., tumor size and stage; number of metastatic lymph nodes; histologic grade; expression of estrogen receptor (ER), progesterone, epidermal growth factor receptor (HER-2), and p53; and the Ki-67 labeling index (LI)) were evaluated from the surgical specimens. PET2 scans were conducted 17.7 ± 1.5 min after PET1. RI values gradually increased as the histologic grade increased (p = 0.016), and were significantly higher when ER expression was absent (p = 0.023) and Ki-67 LI was high (p < 0.001). RI values also showed a moderately positive correlation with Ki-67 LI (r = 0.629; p < 0.001). RI correlated with well-known biologic prognostic factors of iBC and mDTP scanning, which could be used as a substitute for conventional DTP PET.

Overriding Phthalate Decomposition When Exploring Mycophenolic Acid Intermediates as Selenium-Based ROS Biological Probes.

Hypochlorous (OCl-) acid is the most well-known bacterial oxidant to be produced by neutrophils. Excess amounts of OCl- can cause various disorders in living systems. Herein, we have designed, synthesized, and characterized two novel organoselenium-based target molecules (Probe-1 and Probe-OCl) based on a synthetic intermediate of mycophenolic acid for the aqueous detection of OCl-. Probe 1 has been recently reported (Org. Lett. 2018, 20, 3557-3561); both probes show immediate "turn-on" fluorescence (<1 s) upon the addition of OCl-, display an increase in the fluorescence quantum yield (3.7-fold in Probe-1 and 11.6-fold in Probe-OCl), and are completely soluble in aqueous media without the help of any cosolvent. However, a decrease in the "turn-on" intensity with the oxidized version of Probe-1 in cell assays due to the anhydride/phthalate functionality suggests that probe degradation occurs based on hydrolytic action (a probe degradation half-life of ∼1500 s at 15 µM Probe-1 and 150 µM OCl). Thus, the change of "anhydride" to "methylamide" begets Probe-OCl, which possesses more stability without sacrificing its water solubility properties and responses at short times. Further studies suggest that Probe-OCl is highly stable within physiological pH (pH = 7.4). Surprisingly, in live cell experiments involving U-2 OS cells and HeLa cells, Probe-OCl accumulated and aggregated in lipid droplets and gives a "turn-on" fluorescence response. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays confirmed that Probe-OCl is not toxic. Cuvette aggregation studies were also performed (tetrahydrofuran/H2O) to demonstrate aggregation-induced fluorescence at longer times. Our current hypothesis is that the "turn-on" fluorescence effect is caused by the aggregation-induced emission mechanism available for Probe-OCl. In this case, in tandem, we reanalyzed the Mes-BOD-SePh derivative to compare and contrast cell localization as imaged by confocal microscopy; fluorescence emission occurs in the absence of, or prior to, Se oxidation.

A Hemicyanine-Embedded Diphenylselenide-Containing Probe "HemiSe" in which SePh2 Stays Reduced for Selective Detection of Superoxide in Living Cells.

A simple one-step synthesis of fluorescent probe HemiSe has been developed for the detection of superoxide (O2 .- ). The probe undergoes reaction specifically with O2 .- when in the presence of other competitive ROS/RNS/metal ions. The diphenylselenide was incorporated to completely quench the fluorescence of the hemicyanine unit through the action of a photoinduced electron transfer (PET) photomechanism. However, after the addition of O2 .- , the latent fluorophore regains its fluorescence owing to the reaction at the C=C bond of the hemicyanine with O2 .- through nucleophilic attack; the increase in blue emission is due to a reaction of the double bond within HemiSe followed by an increase in fluorescence quantum yield (Φ) up to 0.45; the limit of detection (LOD) is 11.9 nm. A time-dependent study shows that HemiSe can detect superoxide within 13 min with high sensitivity, high selectivity, over a wide pH range, and through confirmation with a xanthine/xanthine oxidase biochemical assay (λem =439 nm). A study in the RAW 264.7 macrophage living cells also shows that HemiSe is not toxic, cell permeable (experimental log P=2.11); confocal imaging results show that HemiSe can detect O2 .- in endogenous and exogeneous systems.

Photon-triggered nanowire transistors.

Photon-triggered electronic circuits have been a long-standing goal of photonics. Recent demonstrations include either all-optical transistors in which photons control other photons or phototransistors with the gate response tuned or enhanced by photons. However, only a few studies report on devices in which electronic currents are optically switched and amplified without an electrical gate. Here we show photon-triggered nanowire (NW) transistors, photon-triggered NW logic gates and a single NW photodetection system. NWs are synthesized with long crystalline silicon (CSi) segments connected by short porous silicon (PSi) segments. In a fabricated device, the electrical contacts on both ends of the NW are connected to a single PSi segment in the middle. Exposing the PSi segment to light triggers a current in the NW with a high on/off ratio of >8 × 106. A device that contains two PSi segments along the NW can be triggered using two independent optical input signals. Using localized pump lasers, we demonstrate photon-triggered logic gates including AND, OR and NAND gates. A photon-triggered NW transistor of diameter 25 nm with a single 100 nm PSi segment requires less than 300 pW of power. Furthermore, we take advantage of the high photosensitivity and fabricate a submicrometre-resolution photodetection system. Photon-triggered transistors offer a new venue towards multifunctional device applications such as programmable logic elements and ultrasensitive photodetectors.

The role of adjuvant external beam radiation therapy for papillary thyroid carcinoma invading the trachea.

PURPOSE: To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. MATERIALS AND METHODS: Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). RESULTS: The age range was 26-87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. CONCLUSION: Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients.