A pilot feasibility study to assess vascularity and perfusion of parathyroid glands using a portable hand-held imager.

OBJECTIVES: Intraoperative localization and preservation of parathyroid glands (PGs) are challenging during thyroid surgery. A new noninvasive technique of combined near-infrared PG autofluorescence detection and dye-free imaging angiography that allows intraoperative feedback has recently been introduced. The objective of this study was to evaluate this technique in real-time. MATERIALS AND METHODS: A pilot feasibility study of a portable imaging device in four patients who underwent either thyroid lobectomy or total thyroidectomy is presented. PG autofluorescence and vascularity/tissue perfusion were monitored using a real-time screen display during the surgical procedure. RESULTS: Three lobectomies and one total thyroidectomy were performed. Among the nine PGs identified by the operating surgeon, eight PGs were confirmed using the autofluorescence device. Each PG was successfully determined to be either well-perfused or devascularized, and devascularized PGs were autotransplanted. CONCLUSIONS: The preliminary results suggest that the combination of PG autofluorescence detection and dye-free angiography can potentially be used to assess PG function. With further validation studies, the effectiveness of this technique in clinical practice can be further delineated.

Halide-Free and Bifunctional One-Component Catalysts for the Coupling of Carbon Dioxide and Epoxides.

In this paper, we first report a new class of halide-free and bifunctional one-component catalysts for the coupling of CO2 with epoxides. The catalysts do not need halide-based additives or tethered salts attached to the ligand when used for this coupling reaction. As the halide-free and bifunctional one-component catalysts, we chose nonionic and monomeric tetracarbonylchromium(0), tetracarbonylmolybdenum(0), and tetracarbonyltungsten(0) complexes chelated by modified ethylenediamines, namely N, N-dimethylethylenediamine, N, N'-dimethylethylenediamine, N, N, N'-trimethylethylenediamine, and N, N, N', N'-tetramethylethylenediamine. A simple mixture of M(CO)6 (M = Cr, Mo, and W) with the modified ethylenediamines shows only one-third of the activity achieved with the tetracarbonyl metal complexes precoordinated to the corresponding modified ethylenediamines. Increasing the number of methyl substituents on the nitrogen atoms of the ethylenediamine derivatives as well as the chromium metal center in the metal carbonyl complex significantly enhanced the catalytic activity. Thus, among the 12 catalysts tested, tetracarbonyl(tetramethylethylenediamine)chromium(0) exhibited the best catalytic activity under the same reaction conditions. Various terminal and internal epoxides were easily converted into the corresponding cyclic carbonates using this chromium system. Calculations based on density functional theory were also carried out to elucidate the mechanism of the coupling reaction.

Scorpionate Catalysts for Coupling CO2 and Epoxides to Cyclic Carbonates: A Rational Design Approach for Organocatalysts.

Novel scorpionate-type organocatalysts capable of effectively coupling carbon dioxide and epoxides under mild conditions to afford cyclic propylene carbonates were developed. On the basis of a combined experimental and computational study, a precise mechanistic proposal was developed and rational optimization strategies were identified. The epoxide ring-opening, which requires an iodide as a nucleophile, was enhanced by utilizing an immonium functionality that can form an ion pair with iodide, making the ring-opening process intramolecular. The CO2 activation and cyclic carbonate formation were catalyzed by the concerted action of two hydrogen bonds originating from two phenolic groups placed at the claw positions of the scorpionate scaffold. Electronic tuning of the hydrogen bond donors allowed to identify a new catalyst that can deliver >90% yield for a variety of epoxide substrates within 7 h at room temperature under a CO2 pressure of only 10 bar, and is highly recyclable.

Highly emissive 4-carbazole-appended salen-indium complex: the effect of strong donor-acceptor interaction.

Herein, we report our findings on 4-carbazole (CBZ)-appended salen-based indium complexes, CBZIn1 and CBZIn2, which feature diimine bridges exhibiting different electron-accepting properties. Notably, CBZIn2 exhibited a significantly higher photoluminescence quantum efficiency (PLQY, ΦPL) in toluene than CBZIn1, with a value over 15 times greater (ΦPL = 57.7% for CBZIn2; ΦPL = 3.7% for CBZIn1). In particular, in the rigid state of THF at 77 K, CBZIn2 exhibited a near-unity PLQY of 98.2%. Even in the PMMA film, CBZIn2 maintained a high level of PLQY (ΦPL = 70.2%). These results can be attributed to the highly efficient radiative decay process based on intramolecular charge-transfer (ICT) transition between the moderately twisted CBZ, characterized by its conformational rigidity and the 1,2-dicyanoethylene-bridged salen, which exhibits a strong electron-accepting ability. Furthermore, these findings are supported by theoretical calculations.

Handheld Autofluorescence Imaging System for Intraoperative Parathyroid Detection.

Introduction: Hypoparathyroidism and hypocalcemia are common complications after thyroid surgery. Parathyroids may be incidentally damaged or removed because they are difficult to distinguish from surrounding tissue. Intraoperative optical technologies such as near infrared autofluorescence (NIRAF) are becoming increasingly popular to help identify parathyroids during thyroid surgery. The objective of this video is to introduce a developing NIRAF device called hANDY-i and compare the device with existing Food and Drug Administration approved technology. Materials and Methods: hANDY-i is developed by Optosurgical, LLC. The device consists of a coaxial 785 nm laser excitation module and coregistred red-green-blue and near-infrared cameras. Operation of the device and output from preliminary intraoperative use are shown. Results: hANDY-i performs well, producing intuitive side-by-side NIRAF and RGB images of the operating field. The device demonstrates high contrast between suspected parathyroid glands and surrounding tissue. Operating theater, overhead lamps, and surgical headlights can all be used with the device. The device is also shown to be effective in both in vivo and ex vivo applications. Conclusions: The prototype described advance NIRAF technology by reducing light sensitivity and improving output representation. In doing so, hANDY-i makes NIRAF more accessible and less obstructive to the surgical workflow. Sources of Funding: This study was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number R43EB030874. Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Yoseph Kim is an employee of Optosurgical LLC. Jaepyeong Cha has ownership stake in Optosurgical LLC. For all other authors, no competing financial interests exist.Runtime of video: 7 mins 14 secs.

Parathyroid gland detection using an intraoperative autofluorescence handheld imager - early feasibility study.

Introduction: Parathyroid glands may be compromised during thyroid surgery which can lead to hypoparathyroidism and hypocalcemia. Identifying the parathyroid glands relies on the surgeon's experience and the only way to confirm their presence was through tissue biopsy. Near infrared autofluorescence technology offers an opportunity for real-time, non-invasive identification of the parathyroid glands. Methods: We used a new research prototype (hANDY-I) developed by Optosurgical, LLC. It offers coaxial excitation light and a dual-Red Green Blue/Near Infrared sensor that guides anatomical landmarks and can aid in identification of parathyroid glands by showing a combined autofluorescence and colored image simultaneously. Results: We tested the imager during 23 thyroid surgery cases, where initial clinical feasibility data showed that out of 75 parathyroid glands inspected, 71 showed strong autofluorescence signal and were correctly identified (95% accuracy) by the imager. Conclusions: The hANDY-I prototype demonstrated promising results in this feasibility study by aiding in real-time visualization of the parathyroid glands. However, further testing by conducting randomized clinical trials with a bigger sample size is required to study the effect on levels of hypoparathyroidism and hypocalcemia.

TOETVA parathyroid autofluorescence detection: hANDY-i endoscopy attachment.

Background: Treatment options for thyroid pathologies have expanded to include scarless and remote access methods such as the transoral endoscopic thyroidectomy vestibular approach (TOETVA). Currently, no standardized methods exist for locating parathyroid glands (PGs) in patients undergoing TOETVA, which can lead to parathyroid injury and subsequent hypocalcemia. This early feasibility study describes and evaluates the hANDY-i endoscopic attachment for detecting PGs in transoral thyroidectomy. Methods: We used a prototype parathyroid autofluorescence imager (hANDY-i) that was mounted to a 10-mm 0-degree endoscope. The device delivers a split screen view of Red-green-blue (RGB) and near-infrared autofluorescence (NIRAF) which allows for simultaneous anatomical localization and fluorescence visualization of PGs during endoscopic thyroid dissection. Results: One cadaveric case and two patient cases were included in this study. The endoscopic hANDY-i imaging system successfully visualized PGs during all procedures. Conclusion: The ability to leverage parathyroid autofluorescence during TOETVA may lead to improved PG localization and preservation. Further human studies are needed to assess its effect on postoperative hypocalcemia and hypoparathyroidism.

A coaxial excitation, dual-red-green-blue/near-infrared paired imaging system toward computer-aided detection of parathyroid glands in situ and ex vivo.

Early and precise detection of parathyroid glands (PGs) is a challenging problem in thyroidectomy due to their small size and similar appearance to surrounding tissues. Near-infrared autofluorescence (NIRAF) has stimulated interest as a method to localize PGs. However, high incidence of false positives for PGs has been reported with this technique. We introduce a prototype equipped with a coaxial excitation light (785 nm) and a dual-sensor to address the issue of false positives with the NIRAF technique. We test the clinical feasibility of our prototype in situ and ex vivo using sterile drapes on 10 human subjects. Video data (1287 images) of detected PGs were collected to train, validate and compare the performance for PG detection. We achieved a mean average precision of 94.7% and a 19.5-millisecond processing time/detection. This feasibility study supports the effectiveness of the optical design and may open new doors for a deep learning-based PG detection method.

Development of a non-invasive, dual-sensor handheld imager for intraoperative preservation of parathyroid glands.

Intraoperative localization and preservation of parathyroid glands (PTGs) are challenging during thyroid surgery. Using a technique of combined near-infrared PTG autofluorescence detection and dye-free imaging angiography, this study developed a portable device for localization of PTGs and assessment of viability by confirming tissue perfusion. The imager's performance was evaluated through a pilot clinical study (N=10).

Inflammatory conversion of quiescent osteoblasts by metastatic breast cancer cells through pERK1/2 aggravates cancer-induced bone destruction.

Disruption of bone homeostasis caused by metastatic osteolytic breast cancer cells increases inflammatory osteolysis and decreases bone formation, thereby predisposing patients to pathological fracture and cancer growth. Alteration of osteoblast function induces skeletal diseases due to the disruption of bone homeostasis. We observed increased activation of pERK1/2 in osteolytic breast cancer cells and osteoblasts in human pathological specimens with aggressive osteolytic breast cancer metastases. We confirmed that osteolytic breast cancers with high expression of pERK1/2 disrupt bone homeostasis via osteoblastic ERK1/2 activation at the bone-breast cancer interface. The process of inflammatory osteolysis modulates ERK1/2 activation in osteoblasts and breast cancer cells through dominant-negative MEK1 expression and constitutively active MEK1 expression to promote cancer growth within bone. Trametinib, an FDA-approved MEK inhibitor, not only reduced breast cancer-induced bone destruction but also dramatically reduced cancer growth in bone by inhibiting the inflammatory skeletal microenvironment. Taken together, these findings suggest that ERK1/2 activation in both breast cancer cells and osteoblasts is required for osteolytic breast cancer-induced inflammatory osteolysis and that ERK1/2 pathway inhibitors may represent a promising adjuvant therapy for patients with aggressive osteolytic breast cancers by altering the shared cancer and bone microenvironment.

Dual-Functional Electrolyte Additives toward Long-Cycling Lithium-Ion Batteries: Ecofriendly Designed Carbonate Derivatives.

Long-term stability of the solid electrolyte interphase (SEI) and cathode-electrolyte interface (CEI) layers formed on anodes and cathodes is imperative to mitigate the interfacial degradation of electrodes and enhance the cycle life of lithium-ion batteries (LIBs). However, the SEI on the anode and CEI on the cathode are vulnerable to the reactive species of PF5 and HF produced by the decomposition and hydrolysis of the conventional LiPF6 electrolyte in a battery inevitably containing a trace amount of water. Here, we report a new class of cyclic carbonate-based electrolyte additives to preserve the integrity of SEI and CEI in LIBs. This new class of additives is designed and synthesized by an ecofriendly approach that involves fixing CO2 with functional epoxides bearing various reactive side chains. It was found that the cyclic carbonates of 3-(1-ethoxyethoxy)-1,2-propylene carbonate and 3-trimethoxysilylpropyloxy-1,2-propylene carbonate, possessing high capability for the stabilization of Lewis-acidic PF5, exhibit a capacity retention of 79.0% after 1000 cycles, which is superior to that of the pristine electrolyte of 54.7%. Moreover, TMSPC has HF-scavenging capability, which, along with PF5 stabilization, results in enhanced rate capability of commercial LiNi0.6Mn0.2Co0.2O2 (NCM622)/graphite full cells, posing a significant potential for high-energy-density LIBs with long cycle stability.

Expansion of a core regulon by transposable elements promotes Arabidopsis chemical diversity and pathogen defense.

Plants synthesize numerous ecologically specialized, lineage-specific metabolites through biosynthetic gene duplication and functional specialization. However, it remains unclear how duplicated genes are wired into existing regulatory networks. We show that the duplicated gene CYP82C2 has been recruited into the WRKY33 regulon and indole-3-carbonylnitrile (ICN) biosynthetic pathway through exaptation of a retroduplicated LINE retrotransposon (EPCOT3) into an enhancer. The stepwise development of a chromatin-accessible WRKY33-binding site on EPCOT3 has potentiated the regulatory neofunctionalization of CYP82C2 and the evolution of inducible defense metabolite 4-hydroxy-ICN in Arabidopsis thaliana. Although transposable elements (TEs) have long been recognized to have the potential to rewire regulatory networks, these results establish a more complete understanding of how duplicated genes and TEs contribute in concert to chemical diversity and pathogen defense.

Efficient Aluminum Catalysts for the Chemical Conversion of CO2 into Cyclic Carbonates at Room Temperature and Atmospheric CO2 Pressure.

A series of dimeric aluminum compounds [Al(OCMe2 CH2 N(R)CH2 X)]2 [X=pyridin-2-yl, R=H (PyrH ); X= pyridin-2-yl, R=Me (PyrMe ); X=furan-2-yl, R=H (FurH ); X= furan-2-yl, R=Me (FurMe ); X=thiophen-2-yl, R=H (ThioH ); X= thiophen-2-yl, R=Me (ThioMe )] containing heterocyclic pendant group attached to the nitrogen catalyze the coupling of CO2 with epoxides under ambient conditions. In a comparison of their catalytic activities with those of aluminum complexes without pendant groups at N [X=H, R=H (HH ); X=H, R=Me (HMe )] or with non-heterocyclic pendant groups [X=CH2 CH2 OMe, R=H (OMeH ); X=CH2 CH2 NMe2 , R=H (NMe2H ); X=CH2 CH2 NMe2 , R=Me (NMe2Me )], complexes containing heterocycles, in conjunction with (nBu)4 NBr as a cocatalyst, show higher catalytic activities for the synthesis of cyclic carbonates under the same ambient conditions. The best catalyst system for this reaction is PyrH /(nBu)4 NBr system, which gives a turnover number of 99 and a turnover frequency of 4.1 h-1 , making it 14- and 20-times more effective than HH /(nBu)4 NBr and HMe /(nBu)4 NBr, respectively. Although there are no direct interactions between the aluminum and the heteroatoms in the heterocyclic pendants, electronic effects combined with the increased local concentration of CO2 around the active centers influences the catalytic activity in the coupling of CO2 with epoxides. In addition, PyrH /(nBu)4 NBr shows broad epoxide substrate scope and seven terminal epoxides and two internal epoxides undergo the designed reaction.