Prevention of Progression of Lipedema With Liposuction Using Tumescent Local Anesthesia: Results of an International Consensus Conference.

BACKGROUND: Lipedema is a chronic, progressive disorder of subcutaneous adipose tissue that usually affects the lower extremities of women. Also known as "two-body syndrome," the fat accumulations in lipedema are unsightly and painful. The disorder is well-known in Europe but is largely unrecognized and underdiagnosed in the United States. OBJECTIVE: To hold the First International Consensus Conference on Lipedema with the purpose of reviewing current European guidelines and the literature regarding the long-term benefits that have been reported to occur after lymph-sparing liposuction for lipedema using tumescent local anesthesia. METHODS: International experts on liposuction for lipedema were convened as part of the First International Congress on Lipedema in Vienna, Austria, June 9 to 10, 2017. RESULTS: Multiple studies from Germany have reported long-term benefits for as long as 8 years after liposuction for lipedema using tumescent local anesthesia. CONCLUSION: Lymph-sparing liposuction using tumescent local anesthesia is currently the only effective treatment for lipedema.

On-Surface Assembly of Hydrogen- and Halogen-Bonded Supramolecular Graphyne-Like Networks.

Demonstrated here is a supramolecular approach to fabricate highly ordered monolayered hydrogen- and halogen-bonded graphyne-like two-dimensional (2D) materials from triethynyltriazine derivatives on Au(111) and Ag(111). The 2D networks are stabilized by N⋅⋅⋅H-C(sp) bonds and N⋅⋅⋅Br-C(sp) bonds to the triazine core. The structural properties and the binding energies of the supramolecular graphynes have been investigated by scanning tunneling microscopy in combination with density-functional theory calculations. It is revealed that the N⋅⋅⋅Br-C(sp) bonds lead to significantly stronger bonded networks compared to the hydrogen-bonded networks. A systematic analysis of the binding energies of triethynyltriazine and triethynylbenzene derivatives further demonstrates that the X3 -synthon, which is commonly observed for bromobenzene derivatives, is weaker than the X6 -synthon for our bromotriethynyl derivatives.

On-Surface Synthesis of Porous Carbon Nanoribbons on Silver: Reaction Kinetics and the Influence of the Surface Structure.

We report on the influence of the surface structure and the reaction kinetics in the bottom-up fabrication of porous nanoribbons on silver surfaces using low-temperature scanning tunneling microscopy. The porous carbon nanoribbons are fabricated by the polymerization of 1,3,5-tris(3-bromophenyl)benzene directly on the Ag surface using an Ullmann-type reaction in combination with dehydrogenative coupling reactions. We demonstrate the successful on-surface synthesis of porous nanoribbons on Ag(111) and Ag(100) even though the self-assemblies of the intermediate organometallic structures and covalently-linked polymer chains are different on both surfaces. Furthermore, we present the formation of isolated porous nanoribbons by kinetic control. Our results give valuable insights into the role of substrate-induced templating effects and the reaction kinetics in the on-surface synthesis of conformationally flexible molecules.

On-Surface Synthesis of Porous Carbon Nanoribbons from Polymer Chains.

We demonstrate the on-surface synthesis of porous carbon nanoribbons on Ag(111) via a preprogrammed isomerization of conformationally flexible polymer chains followed by dehydrogenation reactions using thermal annealing. The carbon chains are fabricated by polymerization of prochiral 1,3,5-tris(3-bromophenyl)benzene (mTBPB) directly on the surface using an Ullmann-type reaction. At room temperature, mTBPB partially self-assembles in halogen-bonded 2D networks, which transform into organometallic chains and rings after debromination. The chain and ring formation is facilitated by conformational switching from a C3h to Cs symmetry of mTBPB via rotation of m-phenylene units. The high conformational selectivity toward Cs-conformers is templated by the twofold coordination to Ag adatoms. After thermally induced covalent-linking through aryl-aryl coupling, well-ordered nanoporous chains are created. Finally, the rotation of single phenylene units in combination with dehydrogenation cross-linking reactions within the polymer chains leads to the unexpected formation of porous carbon nanoribbons. We unveil the reaction mechanism in a low-temperature scanning tunneling microscopy study and demonstrate that the rotation of m-phenylene units is a powerful design tool to promote structural control in the synthesis of cyclic covalent organic nanostructures on metal surfaces.

Triethynylmethanol Derivatives: Stable Acetylenic Building Blocks for Surface Chemistry.

The synthesis of non-conjugated, carbon-rich building blocks is described, based on a basic scaffold of triethynylmethanol (TEtM). The substitution of the ethynyl groups can be easily varied (including R3 Si, H, Br), and this allows structural tuning for stabilization, synthetic derivatization, and adsorption on Ag(111) or Au(111). X-ray crystallography helps to explain the surprising stability of the selected derivatives in the solid state, and an unusual form of hydrogen bonding is identified from these analyses. Preliminary efforts to achieve surface-based reactions on Ag(111) and Au(111) are outlined experimentally and computationally.

Growth and Structure of the First Layers of Ice on Ru(0001) and Pt(111).

Scanning tunneling microscopy was used to probe the structure and growth of the first few layers of water on Ru(0001) and Pt(111) at the molecular level. The surface-bound first layer is composed of a mixture of water molecules forming hexagonal structures, both in registry and out-of-registry with the substrate atoms. The hexagons are connected by pentagonal and heptagonal units. At temperatures below 140 K, this layer structure gives rise to the growth of metastable amorphous structures in the second and higher layers. We found that in the transition from amorphous to crystalline ice the structure of the original bottom layer changes to one in perfect local registry with the hexagonal surfaces of Ru(0001) and Pt(111). We further discovered structural defects in the form of extended one-dimensional lines of five- and eight-membered rings that are domain boundaries and stacking faults in the growing ice layers, which lead to the formation of metastable cubic ice.

How Does Water Wet a Surface?

The adsorption and reactions of water on surfaces has attracted great interest, as water is involved in many physical and chemical processes at interfaces. On metal surfaces, the adsorption energy of water is comparable to the hydrogen bond strength in water. Therefore, the delicate balance between the water-water and the water-metal interaction strength determines the stability of water structures. In such systems, kinetic effects play an important role and many metastable states can form with long lifetimes, such that the most stable state may not reached. This has led to difficulties in the theoretical prediction of water structures as well as to some controversial results. The direct imaging using scanning tunneling microscopy (STM) in ultrahigh vacuum at low temperatures offers a reliable means of understanding the local structure and reaction of water molecules, in particular when interpreted in conjunction with density functional theory calculations. In this Account, a selection of recent STM results on the water adsorption and dissociation on close-packed metal surfaces is reviewed, with a particular focus on Ru(0001). The Ru(0001) surface is one where water adsorbs intact in a metastable state at low temperatures and where partially dissociated layers are formed at temperatures above ∼150 K. First, we will describe the structure of intact water clusters starting with the monomer up to the monolayer. We show that icelike wetting layers do not occur on close-packed metal surfaces but instead hydrogen bonded layers in the form of a mixture of pentagonal, hexagonal, and heptagonal molecular rings are observed. Second, we will discuss the dissociation mechanism of water on Ru(0001). We demonstrate that water adsorption changes from dissociative to molecular as a function of the oxygen preadsorbed on Ru. Finally, we briefly review recent STM experiments on bulk ice (Ih and Ic) and water adsorption on insulating thin films. We conclude with an outlook illustrating the manipulation capabilities of STM in respect to probe the proton and hydrogen dynamics in water clusters.

Unveiling the mechanism of water partial dissociation on Ru(0001).

We have studied the mechanism of the partial dissociation of water on Ru(0001) by high resolution scanning tunneling microscopy (STM). The thermal evolution of water at submonolayer coverage has been tracked in the 110-145 K temperature range to identify the precursor structures for the partial dissociation. These were found to consist of hexagons arranged in thin stripes aligned along the close packed Ru [21¯1¯0] directions. The partially dissociated phase, on the other hand, contains a mixture of H2O and OH hexagons arranged into wider stripes and rotated by 30° with respect to the intact water stripes. The atomic structure of both types of stripes is determined with the aid of density functional theory and STM simulations, providing insights into the partial dissociation reaction path. The reaction is found to be exothermic by around 0.4 eV and initiating at the edges of the intact water stripes. Hydrogen atoms, from water dissociation or already present at the surface, are found to play an important role in the kinetics of the reactions.

Optically pure, monodisperse cis-oligodiacetylenes: aggregation- induced chirality enhancement.

Conformational changes in the conjugated backbone of poly- and oligodiacetylenes (PDAs and ODAs) play an important role in determining the electronic properties of these compounds. At the same time, conformational changes can also result in a folded structure that shows helical chirality. Using d-camphor as a chiral building block, we have designed a high-yielding, iterative synthesis of monodisperse, optically pure cis-oligodiacetylenes (ODAs). cis-ODAs up to the tridecamer have been formed, which is the longest monodisperse cis-ODA reported to date. UV/Vis spectroscopy suggests a large effective conjugation length in THF, likely the result of a linear, planar conformation in this solvent. High-resolution STM/AFM measurements of the nonamer cast from THF onto HOPG show a linear structure. In iPrOH, circular dichroism (CD) spectra suggest the formation of chiral aggregates for ODAs with at least nine d-camphor units, based on a strong CD response.

Intrinsically Patterned Two-Dimensional Transition Metal Halides.

Patterning and defect engineering are key methods for tuning the properties and enabling distinctive functionalities in two-dimensional (2D) materials. However, generating 2D periodic patterns of point defects in 2D materials, such as vacancy lattices that can serve as antidot lattices, has been elusive until now. Herein, we report on 2D transition metal dihalides epitaxially grown on metal surfaces featuring periodically assembled halogen vacancies that result in alternating coordination of the transition metal atom. Using low-temperature scanning probe microscopy and low-energy electron diffraction, we identified the structural properties of intrinsically patterned FeBr2 and CoBr2 monolayers grown epitaxially on Au(111). Density functional theory reveals that Br vacancies are facilitated by low formation energies, and the formation of a vacancy lattice results in a substantial decrease in the lattice mismatch with the underlying Au(111). We demonstrate that interfacial strain engineering presents a versatile strategy for controlled patterning in two dimensions with atomic precision over several hundred nanometers to solve a long-standing challenge of growing atomically precise antidot lattices. In particular, patterning of 2D materials containing transition metals provides a versatile method to achieve unconventional spin textures with noncollinear spin.

Baseline Radiomic Signature to Estimate Overall Survival in Patients With NSCLC.

INTRODUCTION: We aimed to define a baseline radiomic signature associated with overall survival (OS) using baseline computed tomography (CT) images obtained from patients with NSCLC treated with nivolumab or chemotherapy. METHODS: The radiomic signature was developed in patients with NSCLC treated with nivolumab in CheckMate-017, -026, and -063. Nivolumab-treated patients were pooled and randomized to training, calibration, or validation sets using a 2:1:1 ratio. From baseline CT images, volume of tumor lesions was semiautomatically segmented, and 38 radiomic variables depicting tumor phenotype were extracted. Association between the radiomic signature and OS was assessed in the nivolumab-treated (validation set) and chemotherapy-treated (test set) patients in these studies. RESULTS: A baseline radiomic signature was identified using CT images obtained from 758 patients. The radiomic signature used a combination of imaging variables (spatial correlation, tumor volume in the liver, and tumor volume in the mediastinal lymph nodes) to output a continuous value, ranging from 0 to 1 (from most to least favorable estimated OS). Given a threshold of 0.55, the sensitivity and specificity of the radiomic signature for predicting 3-month OS were 86% and 77.8%, respectively. The signature was identified in the training set of patients treated with nivolumab and was significantly associated (p < 0.0001) with OS in patients treated with nivolumab or chemotherapy. CONCLUSIONS: The radiomic signature provides an early readout of the anticipated OS in patients with NSCLC treated with nivolumab or chemotherapy. This could provide important prognostic information and may support risk stratification in clinical trials.

Water splits epitaxial graphene and intercalates.

The adsorption and reactions of small molecules, such as water and oxygen, with graphene films is an area of active research, as graphene may hold the key to unique applications in electronics, batteries, and other technologies. Since the graphene films produced so far are typically polycrystalline, with point and line defects that can strongly affect gas adsorption, there is a need to understand their reactivity with environmentally abundant molecules that can adsorb and alter their properties. Here we report a study of the adsorption and reactions of water, oxygen, hydrogen, and ammonia on epitaxial graphene grown on Ru and Cu substrates using scanning tunneling microscopy (STM). We found that on Ru(0001) graphene line defects are extremely fragile toward chemical attack by water, which splits the graphene film into numerous fragments at temperatures as low as 90 K, followed by water intercalation under the graphene. On Cu(111) water can also split graphene but far less effectively, indicating that the chemical nature of the substrate strongly affects the reactivity of the C-C bonds in epitaxial graphene. Interestingly, no such effects were observed with other molecules, including oxygen, hydrogen, and ammonia also studied here.

Ultra-high vacuum cleaver for the preparation of ionic crystal surfaces.

Cleaving single crystals in situ under ultra-high vacuum conditions provides a reliable and straightforward approach to prepare clean and atomically well-defined surfaces. Here, we present a versatile sample cleaver to efficiently prepare ionic crystal surfaces under ultra-high vacuum conditions, which is suitable for preparation of softer materials, such as alkali halides, and harder materials, such as metal oxides. One of the advantages of the presented cleaver design is that the cleaving blade and anvil to support the crystal are incorporated into the device. Therefore, no particularly strong mechanical manipulator is needed, and it is compatible with existing vacuum chambers equipped with an xyz-manipulator. We demonstrate atomically flat terraces and the atomic structure of NaCl(001), KBr(001), NiO(001), and MgO(001) cleavage planes prepared in situ under ultra-high vacuum conditions and imaged by low-temperature non-contact atomic force microscopy.

Planar π-extended cycloparaphenylenes featuring an all-armchair edge topology.

The [n]cycloparaphenylenes ([n]CPPs)-n para-linked phenylenes that form a closed-loop-have attracted substantial attention due to their unique cyclic structure and highly effective para-conjugation leading to a myriad of fascinating electronic and optoelectronic properties. However, their strained topology prevents the π-extension of CPPs to convert them either into armchair nanobelts or planarized CPP macrocycles. Here we successfully tackle this long-standing challenge and present the bottom-up synthesis and characterization of atomically precise in-plane π-extended [12]CPP on Au(111) by low-temperature scanning probe microscopy and spectroscopy combined with density functional theory. The planar π-extended CPP is a nanographene with an all-armchair edge topology. The exclusive para-conjugation at the periphery yields delocalized electronic states and the planarization maximizes the overlap of p orbitals, which both reduce the bandgap compared to conventional CPPs. Calculations predict ring currents and global aromaticity in the doubly charged system. The intriguing planar ring topology and unique electronic properties make planar π-extended CPPs promising quantum materials.

Differential gene expression patterns of EBV infected EBNA-3A positive and negative human B lymphocytes.

The genome of Epstein-Barr virus (EBV) encodes 86 proteins, but only a limited set is expressed in EBV-growth transformed B cells, termed lymphoblastoid cell lines (LCLs). These cells proliferate via the concerted action of EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), some of which are rate limiting to establish a stable homeostasis of growth promoting and anti-apoptotic activities. We show here that EBV mutants, which lack the EBNA-3A gene, are impaired but can still initiate cell cycle entry and proliferation of primary human B cells in contrast to an EBNA-2 deficient mutant virus. Surprisingly, and in contrast to previous reports, these viral mutants are attenuated in growth transformation assays but give rise to permanently growing EBNA-3A negative B cell lines which exhibit reduced proliferation rates and elevated levels of apoptosis. Expression profiles of EBNA-3A deficient LCLs are characterized by 129 down-regulated and 167 up-regulated genes, which are significantly enriched for genes involved in apoptotic processes or cell cycle progression like the tumor suppressor gene p16/INK4A, or might contribute to essential steps of the viral life cycle in the infected host. In addition, EBNA-3A cellular target genes remarkably overlap with previously identified targets of EBNA-2. This study comprises the first genome wide expression profiles of EBNA-3A target genes generated within the complex network of viral proteins of the growth transformed B cell and permits a more detailed understanding of EBNA-3A's function and contribution to viral pathogenesis.

Host guest chemistry and supramolecular doping in triphenylamine-based covalent frameworks on Au(111).

The post-synthetic modification of covalent organic frameworks (COFs) via host-guest chemistry is an important method to tailor their electronic properties for applications. Due to the limited structural control in the assembly of two-dimensional surface-supported COFs, supramolecular networks are traditionally used at present for host-guest experiments on surfaces, which lack structural and thermal stability, however. Here, we present a combined scanning tunneling microscopy and density functional theory study to understand the host-guest interaction in triphenylamine-based covalently-linked macrocycles and networks on Au(111). These triphenylamine-based structures feature carbonyl and hydrogen functionalized pores that create preferred adsorption sites for trimesic acid (TMA) and halogen atoms. The binding of the TMA through optimized hydrogen-bond interactions is corroborated by selective adsorption positions within the pores. Band structure calculations reveal that the strong intermolecular charge transfer through the TMA bonding reduces the band gap in the triphenylamine COFs, demonstrating the concept of supramolecular doping by host-guest interactions in surface-supported COFs. Halogen atoms selectively adsorb between two carbonyl groups at Au hollow sites. The mainly dispersive interaction of the halogens with the triphenylamine COF leads to a small downshift of the bands. Most of the halogens change their adsorption position selectively upon annealing near the desorption temperature. In conclusion, we demonstrate evidence for supramolecular doping via post-synthetic modification and to track chemical reactions in confined space.

DNA methylation markers predict outcome in node-positive, estrogen receptor-positive breast cancer with adjuvant anthracycline-based chemotherapy.

PURPOSE: We have shown that DNA methylation of the PITX2 gene predicts risk of distant recurrence in steroid hormone receptor-positive, node-negative breast cancer. Here, we present results from a multicenter study investigating whether PITX2 and other candidate DNA methylation markers predict outcome in node-positive, estrogen receptor-positive, HER-2-negative breast cancer patients who received adjuvant anthracycline-based chemotherapy. EXPERIMENTAL DESIGN: Using a microarray platform, we analyzed DNA methylation in regulatory regions of PITX2 and 60 additional candidate genes in 241 breast cancer specimens. Using Cox regression analysis, we assessed the predictive power of the individual marker/marker panel candidates. Clinical endpoints were time to distant metastasis, disease-free survival, and overall survival. A nested bootstrap/cross-validation strategy was applied to identify and validate marker panels. RESULTS: DNA methylation of PITX2 and 14 other genes was correlated with clinical outcome. In multivariate models, each methylation marker added significant information to established clinical factors. A four-marker panel including PITX2, BMP4, FGF4, and C20orf55 was identified that resulted in improvement of outcome prediction compared with PITX2 alone. CONCLUSIONS: This study provides further evidence for the PITX2 biomarker, which has now been successfully confirmed to predict outcome among different breast cancer patient populations. We further identify new DNA methylation biomarkers, three of which can be combined into a panel with PITX2 to increase the outcome prediction performance in our anthracycline-treated primary breast cancer population. Our results show that a well-defined panel of DNA methylation markers enables outcome prediction in lymph node-positive, HER-2-negative breast cancer patients treated with anthracycline-based chemotherapy.

Metalated Graphyne-Based Networks as Two-Dimensional Materials: Crystallization, Topological Defects, Delocalized Electronic States, and Site-Specific Doping.

Graphyne-based two-dimensional (2D) carbon allotropes feature extraordinary physical properties; however, their synthesis as crystalline single-layered materials has remained challenging. We report on the fabrication of large-area organometallic Ag-bis-acetylide networks and their structural and electronic properties on Ag(111) using low-temperature scanning tunneling microscopy combined with density functional theory (DFT) calculations. The metalated graphyne-based networks are robust at room temperature and assembled in a bottom-up approach via surface-assisted dehalogenative homocoupling of terminal alkynyl bromides. Large-area networks of several hundred nanometers with topological defects at domain boundaries are obtained due to the Ag-acetylide bonds' reversible nature. The thermodynamically controlled growth mechanism is explained through the direct observation of intermediates, which differ on Ag(111) and Au(111). Scanning tunneling spectroscopy resolved unoccupied states delocalized across the network. The energy of these states can be shifted locally by the attachment of a different number of Br atoms within the network. DFT revealed that free-standing metal-bis-acetylide networks are semimetals with a linear band dispersion around several high-symmetry points, which suggest the presence of Weyl points. These results demonstrate that the organometallic Ag-bis-acetylide networks feature the typical 2D material properties, which make them of great interest for fundamental studies and electronic materials in devices.

Metal- and hydrogen-bonding competition during water adsorption on Pd(111) and Ru(0001).

The initial stages of water adsorption on the Pd(111) and Ru(0001) surfaces have been investigated experimentally by scanning tunneling microscopy in the temperature range between 40 and 130 K, and theoretically with density functional theory (DFT) total energy calculations and scanning tunneling microscopy (STM) image simulations. Below 125 K, water dissociation does not occur at any appreciable rate, and only molecular films are formed. Film growth starts by the formation of flat hexamer clusters where the molecules bind to the metal substrate through the O-lone pair while making H-bonds with neighboring molecules. As coverage increases, larger networks of linked hexagons are formed with a honeycomb structure, which requires a fraction of the water molecules to have their molecular plane perpendicular to the metal surface with reduced water-metal interaction. Energy minimization favors the growth of networks with limited width. As additional water molecules adsorb on the surface, they attach to the periphery of existing islands, where they interact only weakly with the metal substrate. These molecules hop along the periphery of the clusters at intermediate temperatures. At higher temperatures, they bind to the metal to continue the honeycomb growth. The water-Ru interaction is significantly stronger than the water-Pd interaction, which is consistent with the greater degree of hydrogen-bonded network formation and reduced water-metal bonding observed on Pd relative to Ru.

Coordination-Controlled C-C Coupling Products via ortho-Site C-H Activation.

The coordination-restricted ortho-site C-H bond activation and dehydrogenative homocoupling of 4,4'-(1,3-phenylene)dipyridine (1,3-BPyB) and 4,4'-(1,4-phenylene)dipyridine (1,4-BPyB) on different metal surfaces were studied by a combination of scanning tunneling microscopy, noncontact atomic force microscopy, and density functional theory calculations. The coupling products on Cu(111) exhibited certain configurations subject to the spatial restriction of robust two-fold Cu-N coordination bonds. Compared to the V-shaped 1,3-BPyB, the straight backbone of 1,4-BPyB helped to further reduce the variety of reactive products. By utilizing the three-fold coordination of Fe atoms with 1,4-BPyB molecules on Au(111), a large-scale network containing single products was constructed. Our results offer a promising protocol for controllable on-surface synthesis with the aid of robust coordination interactions.