bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the electrical and optical properties of a gliding arc tornado device
Authors: Barni R. , Alex P. , Salanti A. , Canevali C. , Zoia L. , Orlandi M. , Riccardi C. 
Published: May 2021

AbstractOptical emission spectroscopy was used to characterize the gas phase in a gliding arc tornado reactor used for plasma applications. Results concerning the transition between spark and fully developed arc regimes are presented, by comparing with the electrical characteristics of the discharge. An extended analysis of spectra of air and helium discharges mixed with water and hexamethyldisiloxane vapors was performed, with the identification of active radical species involved in the surface functionalization of polymeric nanoparticles.Graphic abstract
A Series of Frequency Shift Antennas Based on Shape Blending
Authors: Wu Aiting , Sun Yuebin , Zhang Pengquan , Du Tiejun 
Published: May 2021

In this paper, an automatic antenna design method based on the shape blending algorithm is proposed. The algorithm is used to construct the shape of the wide slot of a CPW-fed antenna. Firstly, two basic shapes are chosen as the initial shape and the target shape. The shape blending process is then applied on them to get a series of shapes, which are used as the geometry structure of the wide slot. In this way, a series of CPW-fed wide slot antennas are obtained. And they have similar but gradually changing characteristics. The bandwidth ranges are 8.00–9.24 GHz, 7.95–9.05 GHz, 7.05–8.55 GHz, 6.95–8.13 GHz, and 6.55–7.50 GHz, respectively. The overall size of the antenna is 26 mm

∗

20 mm

∗

0.6 mm. Experimental results show that the resonant frequencies vary (via translation) with the change of slot shape in a specific frequency band. The experiments also validate that the antennas have omnidirectional radiation characteristics. The radiation gains and aperture efficiencies of the antennas are about 3.8–5.5 dBi and 57.7–83.0% at their centre frequencies, respectively. The experiment results show that the proposed antennas could be used in C-band and X-band radar applications.
Long Noncoding RNA CTD-2245E15.3 Promotes Anabolic Enzymes ACC1 and PC to Support Non–Small Cell Lung Cancer Growth
Authors: Wang Chen , Meng Xiangfeng , Zhou Yu , Yu Jing , Li Qing , Liao Zhicong , Gu Yuanyuan , Han Jiayi , Linghu Shuo , Jiao Zichen , Wang Tao , Zhang Chen-Yu , Chen Xi 
Published: May 2021

Abstract

Long noncoding RNAs (lncRNA) have been shown to play critical regulatory roles in the onset and progression of human cancers. However, the functions of a large proportion of lncRNAs are still unexplored. Here we describe a novel lncRNA, CTD-2245E15.3, that promotes lung tumorigenesis by regulating the anabolic enzymes acetyl-CoA carboxylase 1 (ACC1, encoded by the ACACA gene) and pyruvate carboxylase (PC). Differentially expressed lncRNAs between non–small cell lung cancer (NSCLC) and paired adjacent nontumor tissues were identified by a microarray and validated using quantitative real-time polymerase chain reaction. CTD-2245E15.3 was significantly upregulated in NSCLC and was mainly located in the cytoplasm. Knockdown of CTD-2245E15.3 by specific antisense oligonucleotides suppressed cell growth in vitro and in vivo, largely due to cell-cycle arrest and induction of apoptosis. Overexpression of CTD-2245E15.3 in an orthotopic model of lung cancer led to a significant increase in total tumor burden. CTD-2245E15.3 exerted its oncogenic function by binding ACC1 and PC, which are key anabolic factors for biomolecule synthesis in rapidly proliferating tumor cells. Knockdown of CTD-2245E15.3 increased phosphorylation of ACC1 at an inhibitory site for enzymatic activity and promoted PC degradation via ubiquitination. Supplements of palmitate or oxaloacetate, products of ACC1 and PC, alleviated the suppression of cell growth caused by loss of CTD-2245E15.3. These findings reveal the important role of CTD-2245E15.3 as an oncogenic lncRNA in the anabolic process for tumor growth.

Significance:
These findings demonstrate a novel lncRNA CTD-2245E15.3 that binds and positively regulates anabolic enzymes ACC1 and PC to promote tumor growth.
Disabling the Fanconi Anemia Pathway in Stem Cells Leads to Radioresistance and Genomic Instability
Authors: Deng Xinzhu , Tchieu Jason , Higginson Daniel S. , Hsu Kuo-Shun , Feldman Regina , Studer Lorenz , Shaham Shai , Powell Simon N. , Fuks Zvi , Kolesnick Richard 
Published: May 2021

Abstract

Fanconi anemia is an inherited genome instability syndrome characterized by interstrand cross-link hypersensitivity, congenital defects, bone marrow failure, and cancer predisposition. Although DNA repair mediated by Fanconi anemia genes has been extensively studied, how inactivation of these genes leads to specific cellular phenotypic consequences associated with Fanconi anemia is not well understood. Here we report that Fanconi anemia stem cells in the C. elegans germline and in murine embryos display marked nonhomologous end joining (NHEJ)–dependent radiation resistance, leading to survival of progeny cells carrying genetic lesions. In contrast, DNA cross-linking does not induce generational genomic instability in Fanconi anemia stem cells, as widely accepted, but rather drives NHEJ-dependent apoptosis in both species. These findings suggest that Fanconi anemia is a stem cell disease reflecting inappropriate NHEJ, which is mutagenic and carcinogenic as a result of DNA misrepair, while marrow failure represents hematopoietic stem cell apoptosis.

Significance:
This study finds that Fanconi anemia stem cells preferentially activate error-prone NHEJ-dependent DNA repair to survive irradiation, thereby conferring generational genomic instability that is instrumental in carcinogenesis.
Inhibition of Jumonji Histone Demethylases Selectively Suppresses HER2+ Breast Leptomeningeal Carcinomatosis Growth via Inhibition of GMCSF Expression
Authors: Bhan Arunoday , Ansari Khairul I. , Chen Mike Y. , Jandial Rahul 
Published: May 2021

Abstract

HER2+ breast leptomeningeal carcinomatosis (HER2+ LC) occurs when tumor cells spread to cerebrospinal fluid–containing leptomeninges surrounding the brain and spinal cord, a complication with a dire prognosis. HER2+ LC remains incurable, with few treatment options. Currently, much effort is devoted toward development of therapies that target mutations. However, targeting epigenetic or transcriptional states of HER2+ LC tumors might efficiently target HER2+ LC growth via inhibition of oncogenic signaling; this approach remains promising but is less explored. To test this possibility, we established primary HER2+ LC (Lepto) cell lines from nodular HER2+ LC tissues. These lines are phenotypically CD326+CD49f−, confirming that they are derived from HER2+ LC tumors, and express surface CD44+CD24−, a cancer stem cell (CSC) phenotype. Like CSCs, Lepto lines showed greater drug resistance and more aggressive behavior compared with other HER2+ breast cancer lines in vitro and in vivo. Interestingly, the three Lepto lines overexpressed Jumonji domain–containing histone lysine demethylases KDM4A/4C. Treatment with JIB04, a selective inhibitor of Jumonji demethylases, or genetic loss of function of KDM4A/4C induced apoptosis and cell-cycle arrest and reduced Lepto cell viability, tumorsphere formation, regrowth, and invasion in vitro. JIB04 treatment of patient-derived xenograft mouse models in vivo reduced HER2+ LC tumor growth and prolonged animal survival. Mechanistically, KDM4A/4C inhibition downregulated GMCSF expression and prevented GMCSF-dependent Lepto cell proliferation. Collectively, these results establish KDM4A/4C as a viable therapeutic target in HER2+ LC and spotlight the benefits of targeting the tumorigenic transcriptional network.

Significance:
HER2+ LC tumors overexpress KDM4A/4C and are sensitive to the Jumonji demethylase inhibitor JIB04, which reduces the viability of primary HER2+ LC cells and increases survival in mouse models.
Host-Dependent Phenotypic Resistance to EGFR Tyrosine Kinase Inhibitors
Authors: Haga Yuya , Marrocco Ilaria , Noronha Ashish , Uribe Mary Luz , Nataraj Nishanth Belugali , Sekar Arunachalam , Drago-Garcia Diana , Borgoni Simone , Lindzen Moshit , Giri Suvendu , Wiemann Stefan , Tsutsumi Yasuo , Yarden Yosef 
Published: May 2021

Abstract

Lung cancers driven by mutant forms of EGFR invariably develop resistance to kinase inhibitors, often due to secondary mutations. Here we describe an unconventional mechanism of resistance to dacomitinib, a newly approved covalent EGFR kinase inhibitor, and uncover a previously unknown step of resistance acquisition. Dacomitinib-resistant (DR) derivatives of lung cancer cells were established by means of gradually increasing dacomitinib concentrations. These DR cells acquired no secondary mutations in the kinase or other domains of EGFR. Along with resistance to other EGFR inhibitors, DR cells acquired features characteristic to epithelial–mesenchymal transition, including an expanded population of aldehyde dehydrogenase–positive cells and upregulation of AXL, a receptor previously implicated in drug resistance. Unexpectedly, when implanted in animals, DR cells reverted to a dacomitinib-sensitive state. Nevertheless, cell lines derived from regressing tumors displayed renewed resistance when cultured in vitro. Three-dimensional and cocultures along with additional analyses indicated lack of involvement of hypoxia, fibroblasts, and immune cells in phenotype reversal, implying that other host-dependent mechanisms might nullify nonmutational modes of resistance. Thus, similar to the phenotypic resistance of bacteria treated with antibiotics, the reversible resisters described here likely evolve from drug-tolerant persisters and give rise to the irreversible, secondary mutation–driven nonreversible resister state.

Significance:
This study reports that stepwise acquisition of kinase inhibitor resistance in lung cancers driven by mutant EGFR comprises a nonmutational, reversible resister state.
TIMP1 Triggers Neutrophil Extracellular Trap Formation in Pancreatic Cancer
Authors: Schoeps Benjamin , Eckfeld Celina , Prokopchuk Olga , Böttcher Jan , Häußler Daniel , Steiger Katja , Demir Ihsan Ekin , Knolle Percy , Soehnlein Oliver , Jenne Dieter E. , Hermann Chris D. , Krüger Achim 
Published: May 2021

AbstractTumor-derived protein tissue inhibitor of metalloproteinases-1 (TIMP1) correlates with poor prognosis in many cancers, including highly lethal pancreatic ductal adenocarcinoma (PDAC). The noncanonical signaling activity of TIMP1 is emerging as one basis for its contribution to cancer progression. However, TIMP1–triggered progression-related biological processes are largely unknown. Formation of neutrophil extracellular traps (NET) in the tumor microenvironment is known to drive progression of PDAC, but factors or molecular mechanisms initiating NET formation in PDAC remain elusive. In this study, gene-set enrichment analysis of a human PDAC proteome dataset revealed that TIMP1 protein expression most prominently correlates with neutrophil activation in patient-derived tumor tissues. TIMP1 directly triggered formation of NETs in primary human neutrophils, which was dependent on the interaction of TIMP1 with its receptor CD63 and subsequent ERK signaling. In genetically engineered PDAC-bearing mice, TIMP1 significantly contributed to NET formation in tumors, and abrogation of TIMP1 or NETs prolonged survival. In patient-derived PDAC tumors, NETs predominantly colocalized with areas of elevated TIMP1 expression. Furthermore, TIMP1 plasma levels correlated with DNA-bound myeloperoxidase, a NET marker, in the blood of patients with PDAC. A combination of plasma levels of TIMP1 and NETs with the clinically established marker CA19–9 allowed improved identification of prognostically distinct PDAC patient subgroups. These observations may have a broader impact, because elevated systemic levels of TIMP1 are associated with the progression of a wide range of neutrophil-involved inflammatory diseases.Significance:These findings highlight the prognostic relevance of TIMP1 and neutrophil extracellular traps in highly lethal pancreatic cancer, where a noncanonical TIMP1/CD63/ERK signaling axis induces NET formation.
T Cells Expressing Receptor Recombination/Revision Machinery Are Detected in the Tumor Microenvironment and Expanded in Genomically Over-unstable Models
Authors: Morello Gaia , Cancila Valeria , La Rosa Massimo , Germano Giovanni , Lecis Daniele , Amodio Vito , Zanardi Federica , Iannelli Fabio , Greco Daniele , La Paglia Laura , Fiannaca Antonino , Urso Alfonso M. , Graziano Giulia , Ferrari Francesco , Pupa Serenella M. , Sangaletti Sabina , Chiodoni Claudia , Pruneri Giancarlo , Bardelli Alberto , Colombo Mario P. , Tripodo Claudio 
Published: May 2021

AbstractTumors undergo dynamic immunoediting as part of a process that balances immunologic sensing of emerging neoantigens and evasion from immune responses. Tumor-infiltrating lymphocytes (TIL) comprise heterogeneous subsets of peripheral T cells characterized by diverse functional differentiation states and dependence on T-cell receptor (TCR) specificity gained through recombination events during their development. We hypothesized that within the tumor microenvironment (TME), an antigenic milieu and immunologic interface, tumor-infiltrating peripheral T cells could reexpress key elements of the TCR recombination machinery, namely, Rag1 and Rag2 recombinases and Tdt polymerase, as a potential mechanism involved in the revision of TCR specificity. Using two syngeneic invasive breast cancer transplantable models, 4T1 and TS/A, we observed that Rag1, Rag2, and Dntt in situ mRNA expression characterized rare tumor-infiltrating T cells. In situ expression of the transcripts was increased in coisogenic Mlh1-deficient tumors, characterized by genomic overinstability, and was also modulated by PD-1 immune-checkpoint blockade. Through immunolocalization and mRNA hybridization analyses, we detected the presence of rare TDT+RAG1/2+ cells populating primary tumors and draining lymph nodes in human invasive breast cancer. Analysis of harmonized single-cell RNA-sequencing data sets of human cancers identified a very small fraction of tumor-associated T cells, characterized by the expression of recombination/revision machinery transcripts, which on pseudotemporal ordering corresponded to differentiated effector T cells. We offer thought-provoking evidence of a TIL microniche marked by rare transcripts involved in TCR shaping.
Effect of Amiodarone and Hypothermia on Arrhythmia Substrates During Resuscitation
Authors: Piktel Joseph S. , Suen Yi , Kouk Shalen , Maleski Danielle , Pawlowski Gary , Laurita Kenneth R. , Wilson Lance D. 
Published: May 2021

Background
Amiodarone is administered during resuscitation, but its antiarrhythmic effects during targeted temperature management are unknown. The purpose of this study was to determine the effect of both therapeutic hypothermia and amiodarone on arrhythmia substrates during resuscitation from cardiac arrest.

Methods and Results

We utilized 2 complementary models: (1) In vitro no‐flow global ischemia canine left ventricular transmural wedge preparation. Wedges at different temperatures (36°C or 32°C) were given 5 µmol/L amiodarone (36‐Amio or 32‐Amio, each n=8) and subsequently underwent ischemia and reperfusion. Results were compared with previous controls. Optical mapping was used to measure action potential duration, dispersion of repolarization (DOR), and conduction velocity (CV). (2) In vivo pig model of resuscitation. Pigs (control or targeted temperature management, 32–34°C) underwent ischemic cardiac arrest and were administered amiodarone (or not) after 8 minutes of ventricular fibrillation. In vitro: therapeutic hypothermia but not amiodarone prolonged action potential duration. During ischemia, DOR increased in the 32‐Amio group versus 32‐Alone (84±7 ms versus 40±7 ms,
P
<0.05) while CV slowed in the 32‐Amio group. Amiodarone did not affect CV, DOR, or action potential duration during ischemia at 36°C. Conduction block was only observed at 36°C (5/8 36‐Amio versus 6/7 36‐Alone, 0/8 32‐Amio, versus 0/7 32‐Alone). In vivo: QTc decreased upon reperfusion from ischemia that was ameliorated by targeted temperature management. Amiodarone did not worsen DOR or CV. Amiodarone suppressed rearrest caused by ventricular fibrillation (7/8 without amiodarone, 2/7 with amiodarone,
P
=0.041), but not pulseless electrical activity (2/8 without amiodarone, 5/7 with amiodarone,
P
=0.13).

Conclusions
Although amiodarone abolishes a beneficial effect of therapeutic hypothermia on ischemia‐induced DOR and CV, it did not worsen susceptibility to ventricular tachycardia/ventricular fibrillation during resuscitation.
Patterns and predictors of trajectories for subjective quality of life in patients with early psychosis: Three-year follow-up of the randomized controlled trial on extended early intervention
Authors: Kam Candice Tze Kwan , Chang Wing Chung , Kwong Vivian Wing Yan , Lau Emily Sin Ki , Chan Gloria Hoi Kei , Jim Olivia Tsz Ting , Hui Christy Lai Ming , Chan Sherry Kit Wa , Lee Edwin Ho Ming , Chen Eric Yu Hai 
Published: May 2021

Objective: Subjective quality of life is an important outcome of psychotic disorders. However, longitudinal course of subjective quality of life in the early illness stage is under-studied. We aimed to investigate the patterns and baseline predictors of subjective quality of life trajectories over 3 years in early psychosis patients, utilizing growth mixing modeling analysis, in the context of a 3-year follow-up of a randomized controlled trial comparing 1-year extension of early intervention with step-down psychiatric care for first-episode psychosis. Method: One hundred sixty Chinese patients were recruited from specialized early intervention program for first-episode psychosis in Hong Kong after they had completed this 2-year early intervention service, and underwent 1-year randomized controlled trial as well as 2-year post–randomized controlled trial follow-up (i.e. 3-year follow-up). Assessments on premorbid adjustment, onset profile, psychopathology, functioning and treatment characteristics were conducted. Individual class membership of subjective quality of life trajectory derived from growth mixing modeling was based on the 36-Item Short Form Health Survey mental component summary scores measured at four different time-points (baseline, 1, 2 and 3 years) among 142 participants across 3-year follow-up. Results: Three distinct subjective quality of life trajectories were identified including higher-improving (68.3%, n = 97), lower-stable (24.6%, n = 35) and deteriorating (7%, n = 10) trajectories. Age of onset; duration of untreated psychosis; depressive, positive and negative symptoms; and intervention condition were significantly different between good (higher-improving trajectory) and poor (combined lower-stable and deteriorating trajectories) trajectory groups. Multiple regression analysis revealed that younger age of onset, more severe depression and receipt of step-down care independently predicted poor subjective quality of life trajectory. Conclusion: Approximately one-third of patients displayed poor subjective quality of life trajectory in the early phase of psychotic illness. Our results affirm depression as a critical determinant of prospective subjective quality of life and underscores positive effect of extended early intervention on sustained subjective quality of life improvement. Further longitudinal research is warranted to facilitate better characterization of subjective quality of life course patterns and development of targeted intervention to optimize subjective quality of life in patients with early psychosis.
Numerical simulation on year-round performance of water-flow window with different shading control modes
Authors: Li Chunying , Tang Haida , Tan Junyi , Li Cuimin , Yang Yinan , Zeng Fanbo 
Published: May 2021

Water-flow window combines the functions of transparent building envelop, solar collector, as well as sun shading. Coloured particles are added to the flowing water within window cavity in order to provide extra shading, prevent indoor glare and enhance solar collection. The energy consumption of both air-conditioning system and water heating device can be further reduced. The aim of present investigation is to predict and analyze the year-round energy performance of a well-insulated water-flow window with different shading control modes. Accordingly, physical model of water-flow window is built up. FORTRAN program is developed and utilized in the numerical simulation. Results show that water-flow window can achieve exceptional sun blocking and cooling load reduction without occupying extra space. The year-round solar energy collection efficiency is within the range of 17.95∼21.06%. At the same time, indoor heat gain through the window can be reduced by around 50% compared with common double-layer window. The water-flow window under discussion has great application potential in buildings with constant hot water demand and high-density air-conditioning cooling load. In practice, the shading control mode should be carefully decided, and factors including climate region, hot water demand, window size and occupants' preference on indoor light environment should be taken into consideration. Numerical simulation proves to be an efficient method in predicting the energy performance of similar innovative-designed windows and a good assist in decision-making of real projects.
E-diary use in clinical headache practice: A prospective observational study
Authors: van Casteren Daphne S , Verhagen Iris E , de Boer Irene , de Vries Lentsch Simone , Fronczek Rolf , van Zwet Erik W , MaassenVanDenBrink Antoinette , Terwindt Gisela M 
Published: May 2021

Aim To determine whether our E-diary can be used to diagnose migraine and provide more reliable migraine-related frequency numbers compared to patients’ self-reported estimates. Methods We introduced a self-developed E-diary including automated algorithms differentiating headache and migraine days, indicating whether a patient has migraine. Reliability of the E-diary diagnosis in combination with two previously validated E-questionnaires was compared to a physician’s diagnosis as gold standard in headache patients referred to the Leiden Headache Clinic (n = 596). In a subset of patients with migraine (n = 484), self-estimated migraine-related frequencies were compared to diary-based results. Results The first migraine screening approach including an E-headache questionnaire, and the E-diary revealed a sensitivity of 98% and specificity of 17%. In the second approach, an E-migraine questionnaire was added, resulting in a sensitivity of 79% and specificity of 69%. Mean self-estimated monthly migraine days, non-migrainous headache days and days with acute medication use were different from E-diary-based results (absolute mean difference ± standard deviation respectively 4.7 ± 5.0, 6.2 ± 6.6 and 4.3 ± 4.8). Conclusion The E-diary including algorithms differentiating headache and migraine days showed usefulness in diagnosing migraine. The use emphasised the need for E-diaries to obtain reliable information, as patients do not reliably recall numbers of migraine days and acute medication intake. Adding E-diaries will be helpful in future headache telemedicine.