Search

Purpose: We assessed the association of cardiac radiation dose with cardiac events and survival post-chemoradiation therapy (CRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) after adoption of modern radiation therapy (RT) techniques, stricter cardiac dose constraints, and immune checkpoint inhibitor (ICI) consolidation., Methods and Materials: This single-institution, multi-site retrospective study included 335 patients with LA-NSCLC treated with definitive, concurrent CRT between October 2017 and December 2021. All patients were evaluated for ICI consolidation. Planning dose constraints included heart mean dose < 20 Gy (<10 Gy if feasible) and heart volume receiving ≥ 50 Gy (V50Gy) < 25 %. Twenty-one dosimetric parameters for three different cardiac structures (heart, left anterior descending coronary artery [LAD], and left ventricle) were extracted. Primary endpoint was any major adverse cardiac event (MACE) post-CRT, defined as acute coronary syndrome, heart failure, coronary revascularization, or cardiac-related death. Secondary endpoints were: grade ≥ 3 cardiac events (per CTCAE v5.0), overall survival (OS), lung cancer-specific mortality (LCSM), and other-cause mortality (OCM)., Results: Median age was 68 years, 139 (41 %) had baseline coronary heart disease, and 225 (67 %) received ICI consolidation. Proton therapy was used in 117 (35 %) and intensity-modulated RT in 199 (59 %). Median LAD V15Gy was 1.4 % (IQR 0-22) and median heart mean dose was 8.7 Gy (IQR 4.6-14.4). Median follow-up was 3.3 years. Two-year cumulative incidence of MACE was 9.5 % for all patients and 14.3 % for those with baseline coronary heart disease. Two-year cumulative incidence of grade ≥ 3 cardiac events was 20.4 %. No cardiac dosimetric parameter was associated with an increased risk of MACE or grade ≥ 3 cardiac events. On multivariable analysis, cardiac dose (LAD V15Gy and heart mean dose) was associated with worse OS, driven by an association with LCSM but not OCM., Conclusions: With modern RT techniques, stricter cardiac dose constraints, and ICI consolidation, cardiac dose was associated with LCSM but not OCM or cardiac events in patients with LA-NSCLC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polymer binders and carbon conductivity enhancers are inevitably required to make improvements in structural durability and electrochemical performance of lithium-ion battery (LIB) electrodes, although these additive constituents incur weight and volume penalties on the overall battery capacity. Here, additive-free electrode architectures were successfully fabricated over 20 × 20 cm 2 electrode areas using a layer-by-layer spray coating approach, with the ultimate goal to boost gravimetric/volumetric electrode capacity and to reduce the total cost of LIB cells. Initially, the binder fraction of spray-coated Li 4 Ti 5 O 12 (LTO) electrodes was reduced progressively, from 40 to 0 wt%. The electrochemical behavior of electrodes was then re-optimized as a proportion of conductivity enhancers within the binder-free electrode decreased to zero. Further, the otherwise identical spray coating process was applied to manufacture LiFePO 4 (LFP) positive electrodes, leading to all-additive-free full-cell LIB configurations with attractive energy density of ∼310 Wh/kg and power performance of ∼1500 W/kg., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Consensus group methods such as the Nominal Group Technique (NGT) and Delphi method are commonly used in research to elicit and synthesize expert opinions when evidence is lacking. Traditionally, the NGT involves a face-to-face interaction. However, due to the COVID-19 pandemic, many in-person meetings have moved to online settings. It is unclear to what extent the NGT has been undertaken in virtual settings. The overarching aim of this scoping review is to explore the use of the virtual NGT in research. Our specific objectives are to answer the following questions: To what extent has the NGT been used virtually? What modifications were made to accommodate this online format? What advantages and disadvantages were noted by authors in comparison with the face-to-face mode of the technique?, Materials and Methods: This scoping review will follow the steps outlined by Arksey and O'Malley and the PRISMA-ScR guidelines. Several pilot searches were completed to refine inclusion and exclusion criteria. Media Synchronicity Theory will provide a conceptual framework to inform the research, including data extraction and summarizing results. As an additional extension to the literature review, online interviews with corresponding authors will be conducted to gather further information., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Humphrey-Murto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Purpose: Prior studies have examined associations of cardiovascular substructure dose with overall survival (OS) or cardiac events after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC). Herein, we investigate an alternative endpoint, death without cancer progression (DWP), which is potentially more specific than OS and more sensitive than cardiac events for understanding CRT toxicity., Materials and Methods: We retrospectively reviewed records of 187 patients with locally advanced or oligometastatic NSCLC treated with definitive CRT from 2008 to 2016 at a single institution. Dosimetric parameters to the heart, lung, and ten cardiovascular substructures were extracted. Charlson Comorbidity Index (CCI), excluding NSCLC diagnosis, was used to stratify patients into CCI low (0-2; n = 66), CCI intermediate (3-4; n = 78), and CCI high (≥5; n = 43) groups. Primary endpoint was DWP, modeled with competing risk regression. Secondary endpoints included OS. An external cohort consisted of 140 patients from another institution., Results: Median follow-up was 7.3 years for survivors. Death occurred in 143 patients (76.5 %), including death after progression in 118 (63.1 %) and DWP in 25 (13.4 %). On multivariable analysis, increasing CCI stratum and mean heart dose were associated with DWP. For mean heart dose ≥ 10 Gy vs < 10 Gy, DWP was higher (5-year rate, 16.9 % vs 6.7 %, p = 0.04) and OS worse (median, 22.9 vs 34.1 months, p < 0.001). Ventricle (left, right, and bilateral) and pericardial but not atrial substructure dose were associated with DWP, whereas all three were inversely associated with OS. Cutpoint analysis identified right ventricle mean dose ≥ 5.5 Gy as a predictor of DWP. In the external cohort, we confirmed an association of ventricle, but not atrial, dose with DWP., Conclusion: Cardiovascular substructure dose showed distinct associations with DWP. Future cardiotoxicity studies in NSCLC could consider DWP as an endpoint., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The broad implementation of thermoelectricity requires high-performance and low-cost materials. One possibility is employing surfactant-free solution synthesis to produce nanopowders. We propose the strategy of functionalizing "naked" particles' surface by inorganic molecules to control the nanostructure and, consequently, thermoelectric performance. In particular, we use bismuth thiolates to functionalize surfactant-free SnTe particles' surfaces. Upon thermal processing, bismuth thiolates decomposition renders SnTe-Bi 2 S 3 nanocomposites with synergistic functions: 1) carrier concentration optimization by Bi doping; 2) Seebeck coefficient enhancement and bipolar effect suppression by energy filtering; and 3) lattice thermal conductivity reduction by small grain domains, grain boundaries and nanostructuration. Overall, the SnTe-Bi 2 S 3 nanocomposites exhibit peak z T up to 1.3 at 873 K and an average z T of ≈0.6 at 300-873 K, which is among the highest reported for solution-processed SnTe., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The broad implementation of thermoelectricity requires high-performance and low-cost materials. One possibility is employing surfactant-free solution synthesis to produce nanopowders. We propose the strategy of functionalizing "naked" particles' surface by inorganic molecules to control the nanostructure and, consequently, thermoelectric performance. In particular, we use bismuth thiolates to functionalize surfactant-free SnTe particles' surfaces. Upon thermal processing, bismuth thiolates decomposition renders SnTe-Bi 2 S 3 nanocomposites with synergistic functions: 1) carrier concentration optimization by Bi doping; 2) Seebeck coefficient enhancement and bipolar effect suppression by energy filtering; and 3) lattice thermal conductivity reduction by small grain domains, grain boundaries and nanostructuration. Overall, the SnTe-Bi 2 S 3 nanocomposites exhibit peak z   T up to 1.3 at 873 K and an average z   T of ≈0.6 at 300-873 K, which is among the highest reported for solution-processed SnTe., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.)

Background: Spinal stenosis is characterized by narrowing of the spinal canal, with mechanical compression of spinal nerve roots. The latter may cause low back pain and/or leg pain, as well as neurogenic claudication. Epidural steroid injection is commonly used to treat patients with lumbar spinal stenosis (LSS), but percutaneous epidural adhesiolysis has been utilized when symptoms prove refractory. Our goal was to assess the relationship between improvement shown on epidurogram and subjective patient response to adhesiolysis., Methods: For this prospective study, 78 patients with degenerative LSS were enrolled. Each subject underwent magnetic resonance imaging of the lumbar spine, with all therapeutic procedures conducted in the operating room. Two weeks later, a second epidurography was performed. Second epidurography was conducted to assess any change in epidural filling defects. Outcome measures were obtained using the visual analogue scale (VAS) score at two weeks, one month, and three months post-treatment., Results: All of the 78 study participants (mean age = 60.9 years, range = 34-85 years) displayed epidural filling defects at baseline. After percutaneous adhesiolysis, epidurographic filling defects were absent in 73% of patients. In the presence or absence of filling defects, mean VAS scores were 5.2 and 4.5, respectively, at two weeks' follow-up. No significant correlation between postprocedural VAS score and status of filling defects (yes or no) was evident during the three-month follow-up period., Conclusion: In patients with LSS, epidurographic findings following percutaneous epidural adhesiolysis failed to correlate with level of pain reduction achieved., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Modern medicine is founded on the discovery of penicillin and subsequent small molecules that inhibit bacterial peptidoglycan (PG) and cell wall synthesis. However, the discovery of new chemically and mechanistically distinct classes of PG inhibitors has become exceedingly rare, prompting speculation that intracellular enzymes involved in PG precursor synthesis are not 'druggable' targets. Here, we describe a β-lactam potentiation screen to identify small molecules that augment the activity of β-lactams against methicillin-resistant Staphylococcus aureus (MRSA) and mechanistically characterize a compound resulting from this screen, which we have named murgocil. We provide extensive genetic, biochemical, and structural modeling data demonstrating both in vitro and in whole cells that murgocil specifically inhibits the intracellular membrane-associated glycosyltransferase, MurG, which synthesizes the lipid II PG substrate that penicillin binding proteins (PBPs) polymerize and cross-link into the cell wall. Further, we demonstrate that the chemical synergy and cidality achieved between murgocil and the β-lactam imipenem is mediated through MurG dependent localization of PBP2 to the division septum. Collectively, these data validate our approach to rationally identify new target-specific bioactive β-lactam potentiation agents and demonstrate that murgocil now serves as a highly selective and potent chemical probe to assist our understanding of PG biosynthesis and cell wall biogenesis across Staphylococcal species.

Activity-guided fractionation of a MeOH extract of the roots of Saussurea lappa C.B.Clarke (Compositae), using an in vitro protein tyrosine phosphatase 1B (PTP1B) inhibition assay, led to the isolation of four active constituents: betulinic acid (1), betulinic acid methyl ester (2), mokko lactone (3) and dehydrocostuslactone (4), along with nine inactive compounds. Our findings indicate that betulinic acid (1) and its methyl ester 2, as well as the two guaiane sesquiterpenoids 3 and 4 are potential lead moieties for the development of new PTP1B inhibitors.

Background and Objectives: Six laboratories consisting of three manufacturers and three national control laboratories participated in a collaborative study to evaluate the suitability of a candidate material to serve as the first Korean National Standard for Antithrombin (AT) concentrate., Materials and Methods: The potency of this candidate preparation was determined using the heparin cofactor chromogenic method. The method is described in the Minimum Requirements for Biological Products in Korea and in the European Pharmacopoeia. The candidate was calibrated against the second International Standard for AT concentrate, coded as 96/520., Results: The participants contributed data from a total of 90 independent assays and the results were accepted as statistically valid when the outcome of the analysis exhibited linear dose-response relationships and intersected at a common point at zero dose in the slope-ratio model. The combined potency estimates were obtained by taking the geometric means of results from all assays at each laboratory, and overall potency estimates were calculated as unweighted geometric means of results from all laboratories. The results were expressed in the form of histograms with 95% confidence intervals., Conclusions: According to the results of the collaborative study, the candidate preparation showed excellent intra- and inter-laboratory correlations and is judged to be suitable to serve as the Korean National Standard for AT concentrate with the following potency: 51.9 IU/vial (95% confidence intervals=48.24 approximately 55.98 IU/vial).

We have introduced well-defined nanopillar arrays of polyethylene glycol (PEG) as a platform for studying the adhesion and growth of cultured cardiomyocytes. The nanopillar arrays were fabricated by using a simple molding technique involving the placement of a patterned polyurethane acrylate mold on top of a drop-dispensed ultraviolet (UV) curable PEG polymer followed by UV exposure and mold removal. The adhesion and growth of cardiomyocytes turned out be guided by an external nanotopography, which has been characterized in terms of cell morphology and cytoskeletal arrangement. In particular, the nanopillars provided guiding posts to both elongating filopodia and expanding lamellipodia. Interestingly, the 3D growth of cardiomyocytes was mediated by the increased hydrophobicity of the nanostructured PEG substrate, indicating that the cell adhesion and growth is very sensitive to the nanotopography. The precise nanostructures of PEG-based polymer with controlled geometrical features presented in this study not only open opportunities for understanding and tailoring cell adhesion and growth, but could serve as a template for better tissue engineering by controlling cellular activities at the molecular level.

The expression and regional distribution of cFos protein, which is an oncogene product and metabolic marker of neural excitation, were investigated in the vestibular nuclear complex following acute hypotension in adult Sprague-Dawley rats. Intravenous administration of nitroprusside elicited a 10-50% reduction in mean blood pressure for 10 min. Unilateral or bilateral chemical labyrinthectomies were performed 14 days before the start of the experiment to eliminate afferent signals from the peripheral vestibular receptors in the inner ear. All of the animals were sacrificed and the tissues were fixed 2 h after the onset of acute hypotension using the cardiac perfusion method for c-Fos immunohistochemical staining. The cFos-like immunoreactive (cFLI) neurons were expressed selectively in the central area of the medial vestibular nucleus following a 10% reduction in blood pressure. Once the blood pressure had fallen by 30%, bilateral expression of cFLI neurons was observed in the superior, medial, and spinal vestibular nuclei, but not in the lateral vestibular nucleus, of control rats with intact labyrinths. The expression of cFLI neurons increased proportionately with reductions in blood pressure. In unilaterally labyrinthectomized rats, acute hypotension induced the expression of cFLI neurons in vestibular nuclei contra lateral to the injured labyrinth, but not in the ipsilateral vestibular nuclei. However, cFLI neurons were not expressed in bilateral vestibular nuclei following acute hypotension in bilateral labyrinthectomized rats. These results suggest that afferent signals from the peripheral vestibular receptors are essential for cFos protein expression in the vestibular nuclei following acute hypotension.

Carcinogenesis is characterized by deregulation of the cell cycle. Although p53 is still the most important cell-cycle regulator in human malignancies, there is an increased body of evidence indicating that the aberrant expression of cyclins and cyclin-dependent kinase (CDK) inhibitors is considered as one of the most important events in malignant transformation of various human cancers. Among these cell-cycle regulators, the role of cyclin E and p27(KIP1) in the tumorigenesis of the uterine cervix has been poorly defined. Using formalin-fixed, paraffin-embedded cervical tissues, we investigated the expression of cyclin E and p27(KIP1) by immunohistochemistry, and human papillomavirus (HPV) types 16 and 18 by nested polymerase chain reaction (PCR) in 22 control cases, 23 cases with cervical intraepithelial neoplasia (CIN), and 45 patients with invasive cervical carcinoma (ICC). The p27 index (P27I) was significantly lower in patients with ICC and CIN compared to those with a normal cervix. Patients with either invasive cancer or CIN were found to have a significantly higher cyclin E index (CEI) than the controls (P<0.05). Our results were consistent with the concept that the deregulated expression of cyclin E and p27(KIP1) may play an important role in the neoplastic transformation of cervical carcinoma.