bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer-associated fibroblast-induced lncRNA UPK1A-AS1 confers platinum resistance in pancreatic cancer via efficient double-strand break repair
Authors: Zhang Xiang , Zheng Shangyou , Hu Chonghui , Li Guolin , Lin Hongcao , Xia Renpeng , Ye Yuancheng , He Rihua , Li Zhihua , Lin Qing , Chen Rufu , Zhou Quanbo 
Published: March 2022

AbstractThe tumor stroma of pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant and heterogeneous population of cancer-associated fibroblasts (CAFs), which are critically involved in chemoresistance. However, the underlying mechanism of CAFs in chemoresistance is unclear. Here, we show that CAFR, a CAF subset derived from platinum-resistant PDAC patients, assumes an iCAF phenotype and produces more IL8 than CAFS isolated from platinum-sensitive PDAC patients. CAFR-derived IL8 promotes oxaliplatin chemoresistance in PDAC. Based on long noncoding RNA (lncRNA) profiling in tumor cells incubated with CAF-CM, we found that UPK1A-AS1, whose expression is directly induced by IL8/NF-kappa B signaling, functions as a chemoresistance-promoting lncRNA and is critical for active IL8-induced oxaliplatin resistance. Impressively, blocking the activation of UPK1A-AS1 expression increases the oxaliplatin sensitivity of tumor cells in vivo. Mechanistically, UPK1A-AS1 strengthens the interaction between Ku70 and Ku80 to facilitate nonhomologous end joining (NHEJ), thereby enhancing DNA double-strand break (DSB) repair. Clinically, UPK1A-AS1 expression is positively correlated with IL8 expression, a poor chemotherapeutic response and a shorter progression-free survival (PFS) time in advanced PDAC patients. Collectively, our study reveals a lncRNA-mediated mechanism of CAF-derived paracrine IL8-dependent oxaliplatin resistance and highlights UPK1A-AS1 as a potential therapeutic target.
Hepcidin in hepatocellular carcinoma
Authors: Joachim Jonathan H. , Mehta Kosha J. 
Published: March 2022

AbstractHepatocellular carcinoma (HCC) is one of the most common reasons for cancer-related deaths. Excess iron increases HCC risk. Inevitably, hepcidin, the iron hormone that maintains systemic iron homoeostasis is involved in HCC pathology. Distinct from other cancers that show high hepcidin expression, HCC patients can show low hepcidin levels. Thus, it is of immense clinical benefit to address the regulation and action of hepcidin in HCC as this may help in identifying molecular targets for diagnosis, prognosis, and therapeutics. Accordingly, this review explores hepcidin in HCC. It presents the levels of tissue and serum hepcidin and explains the mechanisms that contribute to hepcidin reduction in HCC. These include downregulation ofHAMP, TfR2, HJV, ALK2 and circular RNAcirc_0004913, upregulation of matriptase-2 and GDF15, inactivation ofRUNX3and mutation inTP53. The enigmas around mir-122 and the functionalities of two major hepcidin inducers BMP6 and IL6 in relation to hepcidin in HCC are discussed. Effects of hepcidin downregulation are explained, specifically, increased cancer proliferation via activation of CDK1/STAT3 pathway and increased HCC risk due to reduction in a hepcidin-mediated protective effect against hepatic stellate cell activation. Hepcidin–ferroportin axis in HCC is addressed. Finally, the role of hepcidin in the diagnosis, prognosis and therapeutics of HCC is highlighted.
WWP1 upregulation predicts poor prognosis and promotes tumor progression by regulating ubiquitination of NDFIP1 in intrahepatic cholangiocarcinoma
Authors: Li Yongjian , Cheng Qian , Gao Jie , Chen Zhuomiaoyu , Guo Jingheng , Li Zuyin , Tian Lingyu , Zhang Chao , Li Yuzi , Zheng Jiaxi , Li Zhao , Zhu Jiye 
Published: March 2022

AbstractWW domain-containing E3 ubiquitin protein ligase1 (WWP1) is reported to be upregulated in many types of human cancers; however, its expression and function in intrahepatic cholangiocarcinoma (ICC) remain unknown. Here, in this study we investigated the expression pattern, clinical prognosis, tumor biological functions, and molecular mechanisms of WWP1 in ICC. The expression of WWP1 in patient tissues was detected by western blotting, immunohistochemistry (IHC), and immunofluorescence. CCK-8, colony formation, EdU, transwell, and xenograft models were used to explore the role of WWP1 in the proliferation and metastasis of ICC. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, and immunofluorescence were performed to detect the potential mechanisms. Our study revealed that WWP1 was highly expressed in ICC, and high levels of WWP1 were associated with poor prognosis. Functionally, WWP1 overexpression enhanced the proliferation and metastasis of ICC cells and vice versa. Mechanistically, MYC could be enriched in the promoter region of WWP1 to facilitate its expression. Then, WWP1 targets Nedd4 family interacting protein1 (NDFIP1) and reduces NDFIP1 protein levels via ubiquitination. Downregulation of NDFIP1 in ICC cells rescued the effects of silenced WWP1 expression. WWP1 expression was also negatively correlated with the protein level of NDFIP1 in patient tissues. In conclusion, WWP1 upregulated by MYC promotes the progression of ICC via ubiquitination of NDFIP1, which reveals that WWP1 might be a potential therapeutic target for ICC.
A large-scale microelectromechanical-systems-based silicon photonics LiDAR
Authors: Zhang Xiaosheng , Kwon Kyungmok , Henriksson Johannes , Luo Jianheng , Wu Ming C. 
Published: March 2022

AbstractThree-dimensional (3D) imaging sensors allow machines to perceive, map and interact with the surrounding world1. The size of light detection and ranging (LiDAR) devices is often limited by mechanical scanners. Focal plane array-based 3D sensors are promising candidates for solid-state LiDARs because they allow electronic scanning without mechanical moving parts. However, their resolutions have been limited to 512 pixels or smaller2. In this paper, we report on a 16,384-pixel LiDAR with a wide field of view (FoV, 70° × 70°), a fine addressing resolution (0.6° × 0.6°), a narrow beam divergence (0.050° × 0.049°) and a random-access beam addressing with sub-MHz operation speed. The 128 × 128-element focal plane switch array (FPSA) of grating antennas and microelectromechanical systems (MEMS)-actuated optical switches are monolithically integrated on a 10 × 11-mm2 silicon photonic chip, where a 128 × 96 subarray is wire bonded and tested in experiments. 3D imaging with a distance resolution of 1.7 cm is achieved with frequency-modulated continuous-wave (FMCW) ranging in monostatic configuration. The FPSA can be mass-produced in complementary metal–oxide–semiconductor (CMOS) foundries, which will allow ubiquitous 3D sensors for use in autonomous cars, drones, robots and smartphones.
Birds can transition between stable and unstable states via wing morphing
Authors: Harvey C. , Baliga V. B. , Wong J. C. M. , Altshuler D. L. , Inman D. J. 
Published: March 2022

AbstractBirds morph their wing shape to accomplish extraordinary manoeuvres1–4, which are governed by avian-specific equations of motion. Solving these equations requires information about a bird’s aerodynamic and inertial characteristics5. Avian flight research to date has focused on resolving aerodynamic features, whereas inertial properties including centre of gravity and moment of inertia are seldom addressed. Here we use an analytical method to determine the inertial characteristics of 22 species across the full range of elbow and wrist flexion and extension. We find that wing morphing allows birds to substantially change their roll and yaw inertia but has a minimal effect on the position of the centre of gravity. With the addition of inertial characteristics, we derived a novel metric of pitch agility and estimated the static pitch stability, revealing that the agility and static margin ranges are reduced as body mass increases. These results provide quantitative evidence that evolution selects for both stable and unstable flight, in contrast to the prevailing narrative that birds are evolving away from stability6. This comprehensive analysis of avian inertial characteristics provides the key features required to establish a theoretical model of avian manoeuvrability.
Longitudinal evidence on the development of socioeconomic inequalities in mental health due to the COVID-19 pandemic in Norway
Authors: Reme Bjørn-Atle , Wörn Jonathan , Skirbekk Vegard 
Published: March 2022

AbstractThe economic and health consequences of the COVID-19 pandemic are unequally distributed. A growing literature finds evidence that those with low socioeconomic status have carried a greater burden in terms of both unemployment and infection risk. Against this background, it is natural to also expect increasing socioeconomic inequalities in mental health. We report from a population-based longitudinal study, assessing the mental health of more than 100,000 Norwegian adults during a period of more than 20 years, and into the COVID-19 pandemic. We find substantial, and equally high, increases in depressive symptoms across socioeconomic status. In addition, we show that the increase was particularly strong among women and those with lower levels of depressive symptoms prior to COVID-19.
24-month decline of non-invasive liver fibrosis markers in HCV-mono and HCV/HIV coinfection after direct-acting antiviral therapy
Authors: Pérez-Is Laura , Collazos Julio , de la Fuente Belén , Morano Luis , Rivas-Carmenado Maria , Rodriguez Manuel , Romero-Favela Adolfo , Fonseca–González Galilea de Jesús , Melón Santiago , Valle-Garay Eulalia , Asensi Víctor 
Published: March 2022

AbstractLong term liver fibrosis (LF) changes and their best -monitoring non-invasive markers (NILFM) after effective anti-HCV DAA therapy are little- known. Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs) are pivotal in liver inflammation repair. Their plasma levels might assess long-term LF changes after therapy. Overall 374 HCV-infected adult patients, 214 HCV-HIV coinfected, were followed-up for 24 months after starting DAA. LF was assessed by transient elastometry (TE), biochemical indexes (APRI, Forns, FIB-4) and, in 61 individuals, by MMPs and TIMP-1 plasma levels. Several MMPs and TIMP-1 SNPs were genotyped in 319 patients. TE was better than biochemical indexes for early and long-term LF monitoring. MMPs-2,-8,-9 and-TIMP-1 levels and TE displayed parallel declining curves although only TIMP-1 correlated with TE (P = 0.006) and biochemical indexes (P < 0.02). HCV monoinfected had significantly higher baseline NILFM and TIMP-1 plasma values, but lower MMPs levels than coinfected patients. No differences in NILFM course were observed between mono-and coinfected or between different DAA regimens. Only the MMP-2 (-1306 C/T) variant TT genotype associated with higher values of NILFM NILFM decline extends 24 months after therapy. TE and TIMP1 are reliable LF-monitoring tools. NILFM courses were similar in mono-and coinfected patients, DAA regimens type did not influence NILFM course.
Synoviocytes from pigmented villonodular synovitis are less sensitive to cadmium-induced cell death than synoviocytes from rheumatoid arthritis
Authors: Farese Héléna , Noack Mélissa , Miossec Pierre 
Published: March 2022

AbstractPigmented villonodular synovitis (PVNS) is a rare inflammatory articular disease sharing common characteristics with rheumatoid arthritis (RA), notably hyperplasia of the synovium due to a hyperproliferation of synoviocytes, and with cancer owing to mutations of the CSF1/M-CCSF gene. Targeting synovium hyperplasia by the local delivery of Cadmium (Cd) has been already tested in vitro and in vivo models of RA and could be applied to PVNS. PVNS and RA synoviocytes were exposed to low doses of Cd. After different culture time points, a qualitative analysis was done by microscopy and quantitative measurements of apoptosis, cell viability and IL-6 production were carried. IL-6 production by PVNS synovial tissue was also quantified after Cd treatment with or without the presence of pro-inflammatory cytokines (IL-17 + TNF). Addition of Cd induced cell death in both PVNS (1 ppm) and RA (0.1 ppm) synoviocytes, which increased with time and Cd concentrations. Cd increased the percentage of apoptotic cells and decreased cell viability and IL-6 production. In all these experiments, PVNS synoviocytes were tenfold less sensitive to Cd than RA synoviocytes. Cd decreased IL-6 production by PVNS synovial tissue and its effect was enhanced with pro-inflammatory cytokines. In summary, PVNS synoviocytes show resistance to Cd-induced cell death and decreased inflammation. Intra-articular use of Cd could represent a potential therapeutic tool in PVNS.
Tissue accumulation of neutrophil extracellular traps mediates muscle hyperalgesia in a mouse model
Authors: Suzuki Kazuaki , Tsuchiya Masahiro , Yoshida Shinichirou , Ogawa Kazumi , Chen Weijian , Kanzaki Makoto , Takahashi Tadahisa , Fujita Ryo , Li Yuqing , Yabe Yutaka , Aizawa Toshimi , Hagiwara Yoshihiro 
Published: March 2022

AbstractAccumulation of uric acid (UA) during muscular trauma is a factor involved in the development of muscle hyperalgesia. Neutrophil extracellular traps (NETs), DNA-based reticular structures to capture UA, play a central role in the pain onset of gout attacks; however, the involvement of NETs via the elevation of local UA level in muscle hyperalgesia due to injuries from muscle overuse remains unknown. The triceps surae muscles (TSMs) in the unilateral hindlimb of mice were electrically stimulated to induce excessive muscle contraction. Mechanical withdrawal thresholds, tissue UA levels, neutrophil recruitment, and protein amount of citrullinated histone 3 (citH3), a major marker of NETs, were investigated. Furthermore, whether neutrophil depletion, extracellular DNA cleavage, and administration of the urate-lowering agent febuxostat improved muscle hyperalgesia caused by NET formation was examined. CitH3 expression upon neutrophil recruitment was significantly increased in the stimulated TSMs with increased tissue UA levels, whereas febuxostat administration improved muscle hyperalgesia with decreased citH3 and tissue UA levels, as observed in neutrophil depletion and extracellular DNA digestion. The underlying mechanism of muscle hyperalgesia associated with locally recruited neutrophils forming NETs due to increased tissue UA levels potentially plays a significant role in creating a vicious circle of muscle pain.
TNF-α induces AQP4 overexpression in astrocytes through the NF-κB pathway causing cellular edema and apoptosis
Authors: Lu Hong , Ai Li , Zhang Baoyue 
Published: March 2022

Abstract
Aquaporin 4 (AQP4) is highly expressed on astrocytes and is critical for controlling brain water transport in neurological diseases. Tumor necrosis factor (TNF)-α is a common cytokine found in disease microenvironment. The aim of the present study was to determine whether TNF-α can regulate the expression of AQP4 in astrocytes. Primary astrocyte cultures were treated with different concentrations of TNF-α and the cell viability was assessed through cell counting kit-8 (CCK-8) assay and AQP4 expression was detected by qPCR, Western blots, and immunofluorescence assays. The activation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) pathway was detected by Western blot. Further, dual-luciferase reporting system and chromatin immunoprecipitation (ChIP) were used to detect the transcriptional regulation of AQP4 by p65. These experiments demonstrated that treatment with TNF-α can lead to astrocyte edema and an increase in AQP4 expression. Following TNF-α treatment, the expression levels of P-IKKα/β-IκBα and P-p65 increased significantly over time. The results of the dual-luciferase reporter system and ChIP assays revealed that p65 protein and AQP4 promoter had a robust binding effect after TNF-α treatment, and the NF-κB pathway inhibitor, BAY 11-7082 could inhibit these effects of TNF-α. The expression level of AQP4 was significantly decreased upon p65 interference, while the astrocyte viability was significantly increased compared with that in the TNF-α only group. In conclusion, TNF-α activated NF-κB pathway, which promoted the binding of p65 to the AQP4 gene promoter region, and enhanced AQP4 expression, ultimately reducing astrocyte viability and causing cell edema.
Interrelationships between the extracellular matrix and the immune microenvironment that govern epithelial tumour progression
Authors: Kolesnikoff Natasha , Chen Chun-Hsien , Samuel Michael Susithiran 
Published: March 2022

AbstractSolid tumours are composed of cancer cells characterised by genetic mutations that underpin the disease, but also contain a suite of genetically normal cells and the extracellular matrix (ECM). These two latter components are constituents of the tumour microenvironment (TME), and are key determinants of tumour biology and thereby the outcomes for patients. The tumour ECM has been the subject of intense research over the past two decades, revealing key biochemical and mechanobiological principles that underpin its role in tumour cell proliferation and survival. However, the ECM also strongly influences the genetically normal immune cells within the microenvironment, regulating not only their proliferation and survival, but also their differentiation and access to tumour cells. Here we review recent advances in our knowledge of how the ECM regulates the tumour immune microenvironment and vice versa, comparing normal skin wound healing to the pathological condition of tumour progression.
Patellafrakturen
Authors: Buschbeck Stefan , Götz Kristina , Barzen Stefan , Hoffmann Reinhard 
Published: March 2022

ZusammenfassungPatellafrakturen sind mit 0,5 – 1,5% aller Frakturen seltene Verletzungen, die jedoch bei inadäquater Ausheilung zu hohen funktionellen Einschränkungen fü̈hren können. Dieser Artikel gibt
eine Übersicht über die Frakturanatomie, die Einteilung und Diagnostik von Patellafrakturen sowie über die aktuellen operativen Versorgungsmöglichkeiten.
Psychische Auffälligkeiten bei Kindern aus Sicht des
psychisch erkrankten Elternteils
Authors: Höller Inken , Forkmann Thomas , Natrop Lisa , Hündlings Andrea , Specka Michael , Scherbaum Norbert 
Published: March 2022

Zusammenfassung
Hintergrund Das Risiko für Kinder psychisch erkrankter
Elternteile, ebenfalls zu erkranken, ist deutlich erhöht. In Deutschland
geht man davon aus, dass das Risiko, psychisch auffällig zu werden,
für ein Kind mit psychisch erkranktem Elternteil um das 2,4-fache
erhöht ist. Ziel dieser Studie war es daher, einen Überblick
über etwaige psychische Auffälligkeiten der Kinder psychisch
erkrankter Elternteile zu erhalten.
Methoden Patient:innen wurden während ihres stationären
Aufenthalts in der Psychiatrie zu ihren Kindern und den psychischen
Auffälligkeiten ihrer Kinder befragt. Daten von N=118 Kindern
(51,7% weiblich) konnten zur Auswertung herangezogen werden.
Ergebnisse Es zeigte sich, dass ca. ¼ der Kinder psychische
Auffälligkeiten vorwiesen. ¼ der Kinder befand sich zudem laut
Aussage des Elternteils in psychiatrisch/psychotherapeutischer
Behandlung. Es zeigten sich keine Unterschiede in den psychischen
Auffälligkeiten der Kinder je nach Diagnose oder
sozioökonomischem Status des Elternteils. Die Ergebnisse zeigen, dass
Kinder von psychisch erkrankten Elternteilen psychische Auffälligkeiten
aufweisen. Genauere Untersuchungen der Versorgungssituation der betroffenen
Kinder sowie die direkte Befragung ebendieser sind notwendig.
Implementierung einer Verhaltensmedizinisch Orientierten
Rehabilitation in der Kardiologie
Authors: Benninghoven Dieter , Menke Elisabeth , China Claudia , Schroeder Friedrich , Bethge Matthias 
Published: March 2022

ZusammenfassungIn der vorliegenden Studie wurde die Implementierung eines verhaltensmedizinisch
orientierten Rehabilitationskonzeptes in einer kardiologischen
Rehabilitationsklinik geprüft. Die dabei eingesetzten
psychotherapeutischen Interventionen orientierten sich an der Akzeptanz- und
Commitment-Therapie. Die Teilnehmer unserer Studie wurden in der neu
implementierten verhaltensmedizinischen Kardiologie (VMK; n=149) oder in
einer regulären kardiologischen Heilbehandlung (KHB; n=100)
behandelt. Wir prüften und verglichen die Erreichung der Zielgruppe
(reach), die Genauigkeit der Umsetzung (fidelity), die Vollständigkeit
der Interventionsdurchführung (dose delivered) sowie die von den
Teilnehmern wahrgenommenen verhaltensmedizinischen Behandlungsinhalte (dose
received). Ergänzend wurden Veränderungen gesundheitsbezogener
Zielkriterien vom Rehabilitationsbeginn bis zur Entlassung in beiden
Behandlungsgruppen erfasst. Die in der VMK behandelten Patienten waren
stärker belastet, und sie bestätigten mehr
verhaltensmedizinische Inhalte, eine höhere Konsistenz der
verhaltensmedizinischen Strategie und einen stärkeren Kompetenzgewinn
als die Patienten der KHB. Die durchgeführten Adhärenzratings
zeigten eine weitgehend konzeptgetreue Umsetzung des Ansatzes. In beiden
Behandlungsgruppen verbesserten sich von der Aufnahme bis zur Entlassung die
Depressivität, die Somatisierung, die Ängstlichkeit, die
Herzangst, die Selbstwirksamkeitserwartung bezogen auf die Umsetzung sportlicher
Aktivität im Alltag sowie die körperliche
Leistungsfähigkeit im Ergometertraining statistisch signifikant.
Darüber hinaus wurden große oder annähernd große
Effekte in der VMK für das Vermeidungsverhalten bei Herzangst
(d=0,78), für Somatisierung (d=0,82),
Depressivität (d=0,76) und Ängstlichkeit
(d=0,72) sowie für die Ergometerleistung (d=0,86)
erzielt. Eine randomisierte kontrollierte Studie zur weiteren
Überprüfung der Wirksamkeit sollte dieser Implementierungsstudie
folgen.
Update Mammakarzinom 2021 Teil 2 – fortgeschrittene Stadien, Langzeitfolgen und Biomarker
Authors: Ditsch Nina , Stickeler Elmar , Behrens Annika , Belleville Erik , Fasching Peter A. , Fehm Tanja N. , Hartkopf Andreas D. , Jackisch Christian , Janni Wolfgang , Kolberg-Liedtke Cornelia , Kolberg Hans-Christian , Lüftner Diana , Lux Michael P. , Müller Volkmar , Schneeweiss Andreas , Schütz Florian , Schulmeyer Carla E. , Tesch Hans , Thomssen Christoph , Uleer Christoph , Untch Michael , Welslau Manfred , Wöckel Achim , Wurmthaler Lena A. , Würstlein Rachel , Thill Marc , Aktas Bahriye 
Published: March 2022

ZusammenfassungIn dieser Übersichtsarbeit werden relevante Aspekte kürzlich veröffentlichter Studien zur Behandlung von Brustkrebspatientinnen in fortgeschrittenen Stadien sowie zu Biomarkern beim Mammakarzinom zusammenfassend dargestellt und diskutiert. In den letzten Jahren wurde eine Vielzahl von Medikamenten für alle molekularen Subtypen bis zu Phase-III-Studien entwickelt. In Bezug auf die Immuncheckpoint-Inhibitoren wurde in letzter Zeit für die metastasierte Situation der optimale Chemotherapie-Kombinationspartner diskutiert. Mit oralen Taxanen könnte sich eine neue Art von oralen Chemotherapien etablieren. Die Datenlage zu Biomarkern für die Anwendung der CDK4/6-Inhibitoren wächst, was auch eine Weiterentwicklung für andere molekulare Subtypen bedeuten könnte. Beim HER2 +, metastasierten Mammakarzinom wurden neue Substanzen entwickelt, die auch nach massiver Vorbehandlung und/oder zerebraler Metastasierung noch gute Remissionen zeigen. Ebenso wächst das Wissen um zielgerichtete Therapien mit Antikörper-Wirkstoff-Konjugaten (ADC) gegen Trop-2, die bei triple-negativen Mammakarzinomen (TNBC) eine therapeutische Bereicherung bedeuten könnten. Des Weiteren steht das Verständnis des Fertilitätserhaltes nach einer Brustkrebserkrankung im klinischen Fokus. Hier schaffen gepoolte Analysen einen neuen Einblick.