bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spinal and paraspinal inflammatory reactions after epidural steroid injection in a patient taking disease-modifying antirheumatic drugs
Authors: Patel Prachi M , Lam Isaac , Liu Benjamin P , Benzon Honorio T 
Published: December 2020

BackgroundDisease-modifying anti-rheumatic drugs (DMARDs) are used in the management of rheumatoid arthritis (RA) and are classified as conventional DMARDs and biologic agents. A concern with DMARDs is the increased risk of infection after surgery. A practice advisory from the American Society of Anesthesiologists recommend alternatives to neuraxial injections in patients who are immunocompromized. We describe a patient who was on several DMARDs and developed inflammatory reactions in her bilateral paraspinal muscles and lumbar spine after an epidural steroid injection (ESI).Case presentationThe patient was a 79-year-old woman; she was taking methotrexate, adalimumab and prednisone for her RA. She had a left L5-S1 paramedian ESI for her L5 radiculitis. After relief of her back and radicular pain for 5 weeks, she had an acute exacerbation of her back pain. MRI showed bilateral paraspinal fluid accumulations and enhancement in her ligamentum flavum. Cultures of the aspirated fluid and biopsy specimens were negative for fungal, aerobic and anaerobic organisms. A repeat MRI 2 months later showed diminution of the fluid collection but with a new fluid accumulation near the left L4-5 facet and left L4 pedicle. Repeat cultures and gram stain of the specimens taken from the pedicle and the paraspinal muscles were negative. The patient was followed by her rheumatologist and in the pain clinic until resolution of her symptoms.ConclusionsSeveral society guidelines recommend the continuation of methotrexate but stoppage of the biologic DMARDS before surgery. The occurrence of an intense inflammatory reaction after an ESI in our patient calls for additional research on the subject and shared decision-making between the pain physician, patient and rheumatologist especially in patients on several DMARDs.
Searches for new phenomena in final states involving leptons and jets using the ATLAS detector
Authors: Novak Tadej 
Published: December 2020

Final states containing both leptons and jets can be used to probe for physics beyond the Standard Model. Searches for new physics models with these signatures, such as heavy neutrinos or leptoquarks, for example, are performed using the ATLAS experiment at the LHC. The results of the most recent searches on 13 TeV [Formula: see text] data will be presented.
New results from the DANSS experiment
Authors: Skrobova Nataliya 
Published: December 2020

We present new results of the DANSS experiment on the searches for sterile neutrinos. They are based on more than 2 million of inverse beta decay events collected at 10.7 m, 11.7 m and 12.7 m from the reactor core of the 3.1 GW Kalinin Nuclear Power Plant in Russia. This data sample is 2.4 times larger than the data sample in the previous DANSS publication. The search for the sterile neutrinos is performed using the ratio of [Formula: see text] spectra at two distances. This method is very robust against systematic uncertainties in the [Formula: see text] spectrum and the detector efficiency. We do not see any statistically significant sign for the [Formula: see text] oscillations. This allows us to exclude further a large and interesting part of the sterile neutrino parameter space. A Gaussian CL[Formula: see text] method was used to obtain exclusion areas. This method is more conservative than a Raster Scan method.
Status and results from the CUORE experiment
Authors: Campani A. , Adams D. Q. , Alduino C. , Alfonso K. , Avignone F. T. , Azzolini O. , Bari G. , Bellini F. , Benato G. , Biassoni M. , Branca A. , Brofferio C. , Bucci C. , Caminata A. , Canonica L. , Cao X. G. , Capelli S. , Cappelli L. , Cardani L. , Carniti P. , Casali N. , Chiesa D. , Chott N. , Clemenza M. , Copello S. , Cosmelli C. , Cremonesi O. , Creswick R. J. , D’Addabbo A. , D’Aguanno D. , Dafinei I. , Davis C. J. , Dell’Oro S. , Di Domizio S. , Dompè V. , Fang D. Q. , Fantini G. , Faverzani M. , Ferri E. , Ferroni F. , Fiorini E. , Franceschi M. A. , Freedman S. J. , Fujikawa B. K. , Giachero A. , Gironi L. , Giuliani A. , Gorla P. , Gotti C. , Gutierrez T. D. , Han K. , Heeger K. M. , Huang R. G. , Huang H. Z. , Johnston J. , Keppel G. , Kolomensky Yu. G. , Ligi C. , Ma Y. G. , Ma L. , Marini L. , Maruyama R. H. , Mei Y. , Moggi N. , Morganti S. , Napolitano T. , Nastasi M. , Nikkel J. , Nones C. , Norman E. B. , Novati V. , Nucciotti A. , Nutini I. , O’Donnell T. , Ouellet J. L. , Pagliarone C. E. , Pagnanini L. , Pallavicini M. , Pattavina L. , Pavan M. , Pessina G. , Pettinacci V. , Pira C. , Pirro S. , Pozzi S. , Previtali E. , Puiu A. , Rosenfeld C. , Rusconi C. , Sakai M. , Sangiorgio S. , Schmidt B. , Scielzo N. D. , Sharma V. , Singh V. , Sisti M. , Speller D. , Surukuchi P. T. , Taffarello L. , Terranova F. , Tomei C. , Vignati M. , Wagaarachchi S. L. , Wang B. S. , Welliver B. , Wilson J. , Wilson K. , Winslow L. A. , Zanotti L. , Zimmermann S. , Zucchelli S. 
Published: December 2020

The Cryogenic Underground Observatory for Rare Events (CUORE) is a tonne-scale cryogenic experiment located at the Laboratori Nazionali del Gran Sasso that exploits bolometric technique to search for neutrinoless double beta decay [Formula: see text] of [Formula: see text]Te. The detector consists of a segmented array of 988 natural [Formula: see text] cubic crystals arranged in a cylindrical compact structure of 19 towers. The detector construction was completed in August 2016 and data taking started in Spring 2017. In this work, we present a brief description of the bolometric technique for rare events search and the CUORE detector, then we concentrate on the data analysis results. In this respect, we focus on the procedure for data processing and on the first [Formula: see text] results we obtained from a total [Formula: see text] exposure of [Formula: see text]. Next, we illustrate the main background sources and the CUORE background model, from which we obtain the most precise measurement of [Formula: see text]Te [Formula: see text] half-life to date. Finally, we discuss the improvements achieved with 2018 and 2019 detector optimization campaigns and the current perspectives of our experiment.
DAMA/LIBRA–phase2 results and implications on several dark matter scenarios
Authors: Bernabei R. , Belli P. , Caracciolo V. , Cerulli R. , Merlo V. , Cappella F. , d’Angelo A. , Incicchitti A. , Di Marco A. , Dai C. J. , He H. L. , Ma X. H. , Sheng X. D. , Montecchia F. , Ye Z. P. 
Published: December 2020

The first DAMA/LIBRA–phase2 model-independent results (exposure: [Formula: see text], and software energy threshold at 1 keV). They further confirm — with high confidence level — the evidence already observed by DAMA/NaI and DAMA/LIBRA–phase1 on the basis of the exploited model-independent dark matter (DM) annual modulation signature. The total exposure of the three experiments above the 2 keV software energy threshold is [Formula: see text]. Here, several DM candidate particles and related scenarios are analyzed including the latest results. Thanks to the increased exposure and to the lower software energy threshold, corollary model-dependent analyses permit to significantly restrict the allowed regions for the parameters spaces of various dark matter candidates and astrophysical, particle and nuclear physics scenarios.
Development and status of active volcano monitoring in China
Authors: Pan Bo , Liu Guoming , Cheng Tao , Zhang Jingwei , Sun Zigang , Ma Baojun , Wu Haijun , Liang Guojing , Guo Mingrui , Kong Qingjun , Wei Feixiang , Zhao Ciping , Zhao Qiang 
Published: December 2020

Abstract
Following decades of geological surveys and studies, 14 active volcanic fields have been identified in China. Evidence for Holocene volcanism in several of these areas highlights the need to understand and monitor volcanic hazards in those regions. Six volcano observatories have thus been established in the past 40 years. This work reviews China's national capability and history of volcano monitoring, with emphasis on the Changbaishan–Tianchi Volcano Observatory and the Tengchong Volcano Observatory. The Changbaishan–Tianchi Volcano Observatory (CTVO) was constructed in 1996 and began monitoring in 1999, with limited recorded observations dating back to 1973. Currently, CTVO is the largest and most advanced observatories in China. The monitoring network of the CTVO incorporates 11 seismic and 15 GPS stations, two levelling routes and three gas geochemistry sampling points. The Changbaishan–Tianchi Volcano experienced unrest during 2002–05, evidenced in elevated levels of seismicity and ground deformation, as well as shifts in gas geochemistry. After 2006, the volcano returned to quiescence, with activities at background levels as recorded in 1973–2001. The monitoring network of Tengchong Volcano Observatory incorporates eight seismic stations, 20 GPS points, 95 levelling points and three gas geochemistry sampling points. The observations made since 1965 indicate significant seismicity, with more than 3000 events recorded in 2011, mostly related to regional tectonics. Tengchong is known for its widespread hot springs, with temperatures up to 105°C recorded at Dagunguo spring. The four other observatories are Longgang Volcano Observatory, Jingbohu Volcano Observatory, Wudalianchi Volcano Observatory and Qiongbei Volcano Observatory. They are equipped with seismic, geodetic and geochemical monitoring equipment. These areas saw only low levels of activity over the past several decades, but related fault systems are relatively active. In a relatively short time, China has gained considerable experience in observatory design and volcano monitoring and has trained up a sizeable task force, laying the foundation for sustained volcano monitoring at the national level. Future efforts must focus on maintaining and expanding observational capacity, as well as gaining better dynamic understanding to inform volcano hazard assessment.
Identifying references to volcanic eruptions in Chinese historical records
Authors: Chen Zhengquan , Chen Zheng 
Published: December 2020

Abstract

In this study, we collect and translate observations and witness accounts suggestive of volcanic eruptions in ancient and modern China. The documents from the literature covered confirmed volcanic eruptions and suspected volcanic events. Recorded events concerning Tianchi (
c.
946 AD), Wudalianchi (1720, 1721) and Ashikule (1951) volcanoes relate to confirmed volcanic eruptions. Detailed records of Tianchi eruptions in historical documents span from 946 to 1903 AD. The real-time observations of the 1720–21 eruptions recorded by the government are presented. They describe a violent explosion and the development of lava flows at Laoheishan volcano. Evidence for events suggestive of volcanic activity are also presented for Dayingshan (1609, Tengchong), Man'anling (1883, Haikou), Chahayan (Heilongjiang), the South China Sea, Kui-shan Tao (late 1770s, Taiwan) and Penjia Islet (19 May 1916 and 29 June 1927, Taiwan). However, some supposed historical volcanic activities including Helanshan (Ningxia), Datong volcano, Rendagou (Sichuan) and Shizishan (Hunan) remain highly suspect according to their unclear positions and rough geological settings. These events may arise from the spontaneous combustion of coal. Records in Tianshan and Beiting Beishan (Xinjiang) may represent mud volcanoes. One case of an ancient Chinese Fengshui master interpreting geological processes from mythology is helpful when inspecting volcanology-related myths.
Non-pollen palynomorphs in freshwater sediments and their palaeolimnological potential and selected applications
Authors: McCarthy Francine M. G. , Pilkington Paul M. , Volik Olena , Heyde Autumn , Cocker Scott L. 
Published: December 2020

Abstract

The earliest eukaryotes recorded in continental environments are non-pollen palynomorphs (NPP) in Mesoproterozoic strata, and NPP provide our best insights into lacustrine ecosystems through the Paleogene. They have been underexploited in studies of younger lake sediments, either ignored or only qualitatively observed, because many NPP are destroyed by standard processing techniques for pollen and embryophyte spores. The palaeoenvironmental potential of palynomorphs, with representatives from all eukaryotic kingdoms as well as cyanobacteria and from all trophic levels in various lacustrine environments, has been recognized by a few Quaternary palynologists in the past few decades. NPP have proven particularly valuable in archaeological and environmental monitoring studies of human impact on freshwater ecosystems, with spores of some fungi and eggs/egg cases of some flatworms and roundworms associated with faeces of humans and livestock, and the acid-resistant remains of various life stages of cyanobacteria, algae and their aquatic consumers responding to increased turbidity and nutrient influx associated with permanent human settlements, particularly those associated with agricultural activity. Descriptions of NPP commonly encountered in Quaternary lake sediments and case studies illustrating applications to various research questions should encourage more palynologists that ‘“Quaternary non-pollen palynomorphs” deserve our attention!’, to quote Prof. Bas van Geel (2006,
Review of Paleobotany and Palynology
,
141
, vii–viii,
https://doi.org/10.1016/j.revpalbo.2006.04.001
), undisputed Father of NPP research.
Beneficial Effects of Rosmarinic Acid on IPEC-J2 Cells Exposed to the Combination of Deoxynivalenol and T-2 Toxin
Authors: Pomothy Judit Mercédesz , Barna Réka Fanni , Pászti Erzsébet Anna , Babiczky Ákos , Szóládi Áron , Jerzsele Ákos , Gere Erzsébet Pásztiné 
Published: December 2020

Mycotoxin contamination in feedstuffs is a worldwide problem that causes serious health issues both in humans and animals, and it contributes to serious economic losses. Deoxynivalenol (DON) and T-2 toxin (T-2) are major trichothecene mycotoxins and are known to challenge mainly intestinal barrier functions. Polyphenolic rosmarinic acid (RA) appeared to have antioxidant and anti-inflammatory properties in vitro. The aim of this study was to investigate protective effects of RA against DON and T-2 or combined mycotoxin-induced intestinal damage in nontumorigenic porcine cell line, IPEC-J2. It was ascertained that simultaneous treatment of DON and T-2 (DT2:

1

μ
mol
/
L

DON
+
5

nmol
/
L

T
−
2

) for 48 h and 72 h reduced transepithelial electrical resistance of cell monolayer, which was restored by 50 μmol/L RA application. It was also found that DT2 for 48 h and 72 h could induce oxidative stress and elevate interleukin-6 (IL-6) and interleukin-8 (IL-8) levels significantly, which were alleviated by the administration of RA. DT2 administration contributed to the redistribution of claudin-1; however, occludin membranous localization was not altered by combined mycotoxin treatment. In conclusion, beneficial effect of RA was exerted on DT2-deteriorated cell monolayer integrity and on the perturbated redox status of IPEC-J2 cells.
Pharmacologic Activation of LXR Alters the Expression Profile of Tumor-Associated Macrophages and the Abundance of Regulatory T Cells in the Tumor Microenvironment
Authors: Carbó José M. , León Theresa E. , Font-Díaz Joan , De la Rosa Juan Vladimir , Castrillo Antonio , Picard Felix R. , Staudenraus Daniel , Huber Magdalena , Cedó Lídia , Escolà-Gil Joan Carles , Campos Lucía , Bakiri Latifa , Wagner Erwin F. , Caelles Carme , Stratmann Thomas , Van Ginderachter Jo A. , Valledor Annabel F. 
Published: December 2020

AbstractLiver X receptors (LXR) are transcription factors from the nuclear receptor family that are activated by oxysterols and synthetic high-affinity agonists. In this study, we assessed the antitumor effects of synthetic LXR agonist TO901317 in a murine model of syngeneic Lewis Lung carcinoma. Treatment with TO901317 inhibited tumor growth in wild-type, but not in LXR-deficient mice, indicating that the antitumor effects of the agonist depends on functional LXR activity in host cells. Pharmacologic activation of the LXR pathway reduced the intratumoral abundance of regulatory T cells (Treg) and the expression of the Treg-attracting chemokine Ccl17 by MHCIIhigh tumor-associated macrophages (TAM). Moreover, gene expression profiling indicated a broad negative impact of the LXR agonist on other mechanisms used by TAM for the maintenance of an immunosuppressive environment. In studies exploring the macrophage response to GM-CSF or IL4, activated LXR repressed IRF4 expression, resulting in subsequent downregulation of IRF4-dependent genes including Ccl17. Taken together, this work reveals the combined actions of the LXR pathway in the control of TAM responses that contribute to the antitumoral effects of pharmacologic LXR activation. Moreover, these data provide new insights for the development of novel therapeutic options for the treatment of cancer.Significance:This study reveals unrecognized roles of LXR in the transcriptional control of the tumor microenvironment and suggests use of a synthetic LXR agonist as a novel therapeutic strategy to stimulate antitumor activity.
The Glutaminase Inhibitor CB-839 (Telaglenastat) Enhances the Antimelanoma Activity of T-Cell–Mediated Immunotherapies
Authors: Varghese Sruthy , Pramanik Snigdha , Williams Leila J. , Hodges Hannah R. , Hudgens Courtney W. , Fischer Grant M. , Luo Catherine K. , Knighton Barbara , Tan Lin , Lorenzi Philip L. , Mackinnon Andrew L. , McQuade Jennifer L. , Hailemichael Yared , Roszik Jason , Peng Weiyi , Vashisht Gopal Y.N. 
Published: December 2020

AbstractImmune-checkpoint inhibitors and adoptive tumor-infiltrating lymphocyte (TIL) therapies have profoundly improved the survival of patients with melanoma. However, a majority of patients do not respond to these agents, and many responders experience disease relapse. Although numerous innovative treatments are being explored to offset the limitations of these agents, novel therapeutic combinations with immunotherapies have the potential to improve patient responses. In this study, we evaluated the antimelanoma activity of immunotherapy combinations with Telaglenastat (CB-839), a potent glutaminase inhibitor (GLSi) that has favorable systemic tolerance. In in vitro TIL:tumor coculture studies, CB-839 treatment improved the cytotoxic activity of autologous TILs on patient-derived melanoma cells. CB-839 treatment decreased the conversion of glutamine to alpha-ketoglutarate (αKGA) more potently in tumor cells versus TILs in these cocultures. These results suggest that CB-839 may improve immune function in a tumor microenvironment by differentially altering tumor and immune cell metabolism. In vivo CB-839 treatment activated melanoma antigen–specific T cells and improved their tumor killing activity in an immune-competent mouse model of adoptive T-cell therapy. Additionally, the combination of CB-839 with anti-PD1 or anti-CTLA4 antibodies increased tumor infiltration by effector T cells and improved the antitumor activity of these checkpoint inhibitors in a high mutation burden mouse melanoma model. Responsiveness to these treatments was also accompanied by an increase of interferon gamma (IFNγ)–associated gene expression in the tumors. Together, these results provide a strong rationale for combining CB-839 with immune therapies to improve efficacy of these treatments against melanoma.
Exosome Surface Display of IL12 Results in Tumor-Retained Pharmacology with Superior Potency and Limited Systemic Exposure Compared with Recombinant IL12
Authors: Lewis Nuruddeen D. , Sia Chang Ling , Kirwin Katherine , Haupt Sonya , Mahimkar Gauri , Zi Tong , Xu Ke , Dooley Kevin , Jang Su Chul , Choi Bryan , Boutin Adam , Grube Andrew , McCoy Christine , Sanchez-Salazar Jorge , Doherty Michael , Gaidukov Leonid , Estes Scott , Economides Kyriakos D. , Williams Douglas E. , Sathyanarayanan Sriram 
Published: December 2020

AbstractThe promise of IL12 as a cancer treatment has yet to be fulfilled with multiple tested approaches being limited by unwanted systemic exposure and unpredictable pharmacology. To address these limitations, we generated exoIL12, a novel, engineered exosome therapeutic that displays functional IL12 on the surface of an exosome. IL12 exosomal surface expression was achieved via fusion to the abundant exosomal surface protein PTGFRN resulting in equivalent potency in vitro to recombinant IL12 (rIL12) as demonstrated by IFNγ production. Following intratumoral injection, exoIL12 exhibited prolonged tumor retention and greater antitumor activity than rIL12. Moreover, exoIL12 was significantly more potent than rIL12 in tumor growth inhibition. In the MC38 model, complete responses were observed in 63% of mice treated with exoIL12; in contrast, rIL12 resulted in 0% complete responses at an equivalent IL12 dose. This correlated with dose-dependent increases in tumor antigen–specific CD8+ T cells. Rechallenge studies of exoIL12 complete responder mice showed no tumor regrowth, and depletion of CD8+ T cells completely abrogated antitumor activity of exoIL12. Following intratumoral administration, exoIL12 exhibited 10-fold higher intratumoral exposure than rIL12 and prolonged IFNγ production up to 48 hours. Retained local pharmacology of exoIL12 was further confirmed using subcutaneous injections in nonhuman primates. This work demonstrates that tumor-restricted pharmacology of exoIL12 results in superior in vivo efficacy and immune memory without systemic IL12 exposure and related toxicity. ExoIL12 is a novel cancer therapeutic candidate that overcomes key limitations of rIL12 and thereby creates a therapeutic window for this potent cytokine.
Aberrant Induction of a Mesenchymal/Stem Cell Program Engages Senescence in Normal Mammary Epithelial Cells
Authors: Bryson Benjamin L. , Tamagno Ilaria , Taylor Sarah E. , Parameswaran Neetha , Chernosky Noah M. , Balasubramaniam Nikhila , Jackson Mark W. 
Published: December 2020

Abstract

Although frequently associated with tumor progression, inflammatory cytokines initially restrain transformation by inducing senescence, a key tumor-suppressive barrier. Here, we demonstrate that the inflammatory cytokine, oncostatin M, activates a mesenchymal/stem cell (SC) program that engages cytokine-induced senescence (CIS) in normal human epithelial cells. CIS is driven by Snail induction and requires cooperation between STAT3 and the TGFβ effector, SMAD3. Importantly, as cells escape CIS, they retain the mesenchymal/SC program and are thereby bestowed with a set of cancer SC (CSC) traits. Of therapeutic importance, cells that escape CIS can be induced back into senescence by CDK4/6 inhibition, confirming that the mechanisms allowing cells to escape senescence are targetable and reversible. Moreover, by combining CDK4/6 inhibition with a senolytic therapy, mesenchymal/CSCs can be efficiently killed. Our studies provide insight into how the CIS barriers that prevent tumorigenesis can be exploited as potential therapies for highly aggressive cancers.

Implications:
These studies reveal how a normal cell's arduous escape from senescence can bestow aggressive features early in the transformation process, and how this persistent mesenchymal/SC program can create a novel potential targetability following tumor development.