Clinical features and outcomes of advanced HER2+ esophageal/GEJ cancer with brain metastasis.

BACKGROUND: Brain metastasis (BRM) is uncommon in gastroesophageal cancer. As such, clinicopathologic and molecular determinants of BRM and impact on clinical outcome remain incompletely understood. METHODS: We retrospectively analyzed clinicopathologic data from advanced esophageal/gastroesophageal junction (E/GEJ) patients at Johns Hopkins from 2003 to 2021. We investigated the association between several clinical and molecular features and the occurrence of BRM, with particular focus on human epidermal growth factor receptor 2 (HER2) overexpression. Survival outcomes and time to BRM onset were also evaluated. RESULTS: We included 515 patients with advanced E/GEJ cancer. Tumors were 78.3% esophageal primary, 82.9% adenocarcinoma, 31.0% HER2 positive. Cumulative incidence of BRM in the overall cohort and within HER2+ subgroup was 13.8% and 24.3%, respectively. HER2 overexpression was associated with increased risk of BRM [odds ratio 2.45; 95% confidence interval (CI) 1.10-5.46]. On initial presentation with BRM, 50.7% had a solitary brain lesion and 11.3% were asymptomatic. HER2+ status was associated with longer median time to onset of BRM (14.0 versus 6.3 months, P < 0.01), improved median progression free survival on first-line systemic therapy (hazard ratio 0.35, 95% CI 0.16-0.80), and improved median overall survival (hazard ratio 0.20, 95% CI 0.08-0.54) in patients with BRM. CONCLUSION: HER2 overexpression identifies a gastroesophageal cancer molecular subtype that is significantly associated with increased risk of BRM, though with later onset of BRM and improved survival likely reflecting the impact of central nervous system-penetrant HER2-directed therapy. The prevalence of asymptomatic and solitary brain lesions suggests that brain surveillance for HER2+ patients warrants prospective investigation.

Studies on interstitial carbon doping from a Ti precursor in a hierarchical TiO2 nanostructured photoanode by a single step hydrothermal route.

Carbon doping from a Ti precursor in TiO2 synthesized by a hydrothermal method was studied. The structural, optical and morphological study of the deposited material was carried out using X-ray diffraction, UV-vis spectroscopy and scanning electron microscopy characterization techniques. The elemental composition of the TiO2 deposited with different precursor concentrations was studied using X-ray photoelectron spectroscopy and electron dispersive X-ray spectroscopy. The amount of elemental carbon in the TiO2 matrix is found to be increased as the Ti precursor concentration is increased, which strengthens the proposed idea of carbon doping via a Ti precursor.

Transfer printing of vertical-type microscale light-emitting diode array onto flexible substrate using biomimetic stamp.

We report the transfer printing of GaN-based microscale vertical-type light-emitting diodes (µ-VLEDs) using a functional layer and a biomimetic stamp. An oxide-based functional layer is inserted onto the structure of a µ-VLED and used to separate the chip from the µ-VLED wafer by absorbing the pulse of a UV pulse laser during pick-up of the transfer printing process. Polydimethylsiloxane (PDMS)-based biomimetic stamps have been fabricated to mimic the gecko lizard cilia for improved adhesion and repeatability. The biomimetic stamp has an adhesion force of 25.6 N/cm2, which is 12 times the adhesion of a flat stamp; an adhesion force of 10 N/cm2 or more was maintained after 100,000 repeated adhesion tests. A flexible 10 × 10 prototype array on a polyimide substrate was fabricated, and its bending test results indicated that the strain effect on the forward voltage and the output power was less than 1%. The stable bending test results of the prototype indicate that µ-VLEDs using biomimetic stamps allow the necessary stability for practical transfer printing.

A Feasibility Study of a Tilted Head Position in Helical Tomotherapy for Fractionated Stereotactic Radiotherapy of Intracranial Malignancies.

Herein, we evaluated the feasibility of placing patients in a tilted head position as part of routine clinical practice for fractionated stereotactic radiotherapy (FSRT) of intracranial tumors using helical tomotherapy (HT), by assessing its dosimetric benefit and setup accuracy. We reviewed treatment plans of four cases that were to receive FSRT for brain lesions in normal and head-tilted positions. These patients underwent two computed tomography (CT) scans: first in the normal supine position and then in the supine position with the head tilted at a 458 angle. Two separate HT plans for each position were generated in these four patients, using the same planning parameters. Plans were compared for target conformity and dose homogeneity. Maximum and average doses to critical organs, including normal brain, brain stem, optic chiasm, optic nerves, and the eyes, were considered. To evaluate setup accuracy, patient movement during treatment was assessed by post-treatment megavoltage CT scans. Both HT plans achieved similar conformal and homogeneous dose coverage to the target. Head-tilted HT delivered lower average and maximum doses to critical organs in the cases where the tumor was located on the same plane with critical organs, particularly when they were not directly attached. Placement in the head-tilted position without a mouthpiece allowed for increased patient movement during treatment, while use of a mouthpiece reduced patient movement to even less than that observed for normal setup in the supine position. This pilot study showed that placement in a tilted head position for FSRT of intracranial tumors using HT may be of clinical use, but depends on the tumor location.

Effects of precursor concentration on the properties of ZnO nanowires grown on (1-102) r-plane sapphire substrates by hydrothermal synthesis.

In this study, we grew ZnO nanowires hydrothermally on (1-102) r-plane sapphire substrates in an aqueous solution which contained zinc nitrate hexahydrate and hexamethylenetetramine (HMT) at 90 °C. First, the AZO seed layer of 80 nm thickness was deposited on the r-plane sapphire substrate by a radio frequency magnetron sputter. After that, we grew the ZnO nanowires on the seed layer by changing the precursor concentration of the aqueous solution from 0.025 M to 0.01 M. When the molar concentration of the precursor was changed, the diameter, length, density and number of ZnO nanowires also changed significantly: diameter, length and density increased with increasing molar concentration but the number of ZnO nanowires decreased. The ZnO nanowires grown at the higher molar concentration tended to grow along with the c-axis direction, as revealed by atomic force microscope and X-ray diffraction peaks. Furthermore, the PL spectra measured at room-temperature revealed a UV emission of 380 nm which can be attributed to the radiative recombination of free and bound excitons (Near Band edge Emission). The NBE emission was also increased with increasing molar concentration.

Vascularized bone marrow-based immunosuppression inhibits rejection of vascularized composite allografts in nonhuman primates.

Vascularized composite allograft (VCA) transplantation (also referred to as composite tissue allotransplantation) has demonstrated clinical success in cases of hand, arm and face transplantation despite prior belief that skin provides an insurmountable barrier to allograft rejection. These overall good outcomes are facilitated by substantial immunosuppressive requirements in otherwise healthy patients, yet still demonstrate frequent rejection episodes. We developed a nonhuman primate model of facial segment allotransplantation to elucidate the unique pathophysiology and immunosuppressive requirements of VCA with addition of concomitant vascularized bone marrow (VBM). Heterotopically transplanted facial segment VCA with VBM treated only with tacrolimus and mycophenolate mofetil (MMF) demonstrated prolonged rejection-free survival, compared to VCA without VBM that demonstrated early rejection episodes and graft loss. While VCA with VBM demonstrated sporadic macrochimerism, acute and chronic rejection and graft loss occurred after discontinuation of immunosuppression. These data support an immunomodulatory role of VBM in VCA that reduces immunosuppressive requirements while providing improved outcomes.

Long term effects of temperature and substrate level on BNR with an external nitrification reactor.

This study was conducted with a BNR (biological nutrient removal) process with an external nitrification and switching arrangement of anoxic and oxic stages. It was observed that the SPRR (specific phosphorus release rate) and SDNR (specific denitrification rate) were greatly affected by the organic loads, and SDNR had a higher temperature effect than other kinetic rates including nitrification. It was further observed that the stoichiometric values like PHA (poly hydroxyalkanoate) stored for P release and PHA consumed for P uptake also varied. Variations of % Px (phosphorus content) and PHA as intracellular matter suggest the PAOs were more active at lower temperatures with this process configuration, where more than 70% of NH4-N and phosphorus were removed at temperatures below 10 degrees.

Heptameric ring structure of the heat-shock protein ClpB, a protein-activated ATPase in Escherichia coli.

The heat-shock protein ClpB is a protein-activated ATPase that is essential for survival of Escherichia coli at high temperatures. ClpB has also recently been suggested to function as a chaperone in reactivation of aggregated proteins. In addition, the clpB gene has been shown to contain two translational initiation sites and therefore encode two polypeptides of different size. To determine the structural organization of ClpB, the ClpB proteins were subjected to chemical cross-linking analysis and electron microscopy. The average images of the ClpB proteins with end-on orientation revealed a seven-membered, ring-shaped structure with a central cavity. Their side-on view showed a two-layered structure with an equal distribution of mass across the equatorial plane of the complex. Since the ClpB subunit has two large regions containing consensus sequences for nucleotide binding, each layer of the ClpB heptamer appears to represent the side projection of one of the major domains arranged on a ring. In the absence of salt and ATP, the ClpB proteins showed a high tendency to form a heptamer. However, they dissociated into various species of oligomers with smaller sizes, depending on salt concentration. Above 0.2 M NaCl, the ClpB proteins behaved most likely as a monomer in the absence of ATP, but assembled into a heptamer in its presence. Furthermore, mutations of the first ATP-binding site, but not the second site, prevented the ATP-dependent oligomerization of the ClpB proteins in the presence of 0.3 M NaCl. These results indicate that ClpB has a heptameric ring-shaped structure with a central cavity and this structural organization requires ATP binding to the first nucleotide-binding site localized to the N-terminal half of the ATPase.

4-Hydroxybenzaldehyde from Gastrodia elata B1. is active in the antioxidation and GABAergic neuromodulation of the rat brain.

Ether fraction of G. elata methanol extract significantly inhibited the recovery time and severity induced by pentylenetetrazole (PTZ) treatment. Pretreatment of ether fraction of G. elata methanol extract successfully prevented diminution of brain GABA level in subconvulsive dose of PTZ-treated rats. 4-Hydroxybenzaldehyde, an analogue of p-hydroxybenzyl alcohol, showed an inhibitory effect on the GABA transaminase, and its inhibitory activity was higher than that of valproic acid, a known anticonvulsant. In the brain of PTZ-treated rats, brain lipid peroxidation was significantly increased, while it recovered to the control level after treatment with 4-hydroxybenzaldehyde. It may be concluded that antioxidation and positive modulation of GABAergic neuromodulation of 4-hydroxybenzaldehyde partially contribute to an antiepileptic and anticonvulsive activity of G. elata B1.

Velocity field of pulsatile flow in a porous tube.

This paper describes velocity fields for fully developed periodic laminar flow in a rigid tube with a porous wall. We obtained an analytical solution of the flow by the linear approximation of the Navier-Stokes equation. Unlike the previous works with a constant seepage rate along the axis, we used a wall velocity which contained hydraulic permeation constant Lp. The axial velocity profile shows a local maximum velocity near the wall at a large Womersley number alpha. This suggests that concentration polarization in porous tubular membrane may be reduced at high frequencies if a membrane device is operated under pulsatile flow conditions. The magnitude of wall permeation velocity decreases linearly along the tube axis because the damping of the pressure difference between the inside and the outside of the tube is very small.