bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants
Authors: Inagaki-Kawata Yukiko , Yoshida Kenichi , Kawaguchi-Sakita Nobuko , Kawashima Masahiro , Nishimura Tomomi , Senda Noriko , Shiozawa Yusuke , Takeuchi Yasuhide , Inoue Yoshikage , Sato-Otsubo Aiko , Fujii Yoichi , Nannya Yasuhito , Suzuki Eiji , Takada Masahiro , Tanaka Hiroko , Shiraishi Yuichi , Chiba Kenichi , Kataoka Yuki , Torii Masae , Yoshibayashi Hiroshi , Yamagami Kazuhiko , Okamura Ryuji , Moriguchi Yoshio , Kato Hironori , Tsuyuki Shigeru , Yamauchi Akira , Suwa Hirofumi , Inamoto Takashi , Miyano Satoru , Ogawa Seishi , Toi Masakazu 
Published: October 2020

AbstractThe genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.
Hepatocytes trap and silence coxsackieviruses, protecting against systemic disease in mice
Authors: Kimura Taishi , Flynn Claudia T. , Whitton J. Lindsay 
Published: October 2020

AbstractPrevious research suggests that hepatocytes catabolize chemical toxins but do not remove microbial agents, which are filtered out by other liver cells (Kupffer cells and endothelial cells). Here we show that, contrary to current understanding, hepatocytes trap and rapidly silence type B coxsackieviruses (CVBs). In genetically wildtype mice, this activity causes hepatocyte damage, which is alleviated in mice carrying a hepatocyte-specific deletion of the coxsackievirus-adenovirus receptor. However, in these mutant mice, there is a dramatic early rise in blood-borne virus, followed by accelerated systemic disease and increased mortality. Thus, wild type hepatocytes act similarly to a sponge for CVBs, protecting against systemic illness at the expense of their own survival. We speculate that hepatocytes may play a similar role in other viral infections as well, thereby explaining why hepatocytes have evolved their remarkable regenerative capacity. Our data also suggest that, in addition to their many other functions, hepatocytes might be considered an integral part of the innate immune system.
Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases
Authors: Atsumi Shinichiro , Katoh Hiroto , Komura Daisuke , Hashimoto Itaru , Furuya Genta , Koda Hirotomo , Konishi Hiroki , Suzuki Ryohei , Yamamoto Asami , Yuba Satsuki , Abe Hiroyuki , Rino Yasushi , Oshima Takashi , Ushiku Tetsuo , Fukayama Masashi , Seto Yasuyuki , Ishikawa Shumpei 
Published: October 2020

AbstractDespite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. Here we show that B-cell repertoire sequencing of 102 clinical gastric cancers and molecular biological analyses unexpectedly reveal that the major humoral cancer antigens are not case-specific neo-antigens but are rather commonly identified as ribonucleoproteins (RNPs) in the focal adhesion complex. These common antigens are shared as autoantigens with multiple autoimmune diseases, suggesting a direct molecular link between cancer- and auto-immunity on the focal adhesion RNP complex. This complex is partially exposed to the outside of cancer cell surfaces, which directly evokes humoral immunity and enables functional bindings of antibodies to cancer cell surfaces in physiological conditions. These findings shed light on humoral cancer immunity in that it commonly targets cellular components fundamental for cytoskeletal integrity and cell movement, pointing to a novel modality of immunotherapy using humoral immunological reactions to cancers.
The genetic legacy of legendary and historical Siberian chieftains
Authors: Zvénigorosky Vincent , Duchesne Sylvie , Romanova Liubomira , Gérard Patrice , Petit Christiane , Petit Michel , Alexeev Anatoly , Melnichuk Olga , Gonzalez Angéla , Fausser Jean-Luc , Solovyev Aisen , Romanov Georgii , Barashkov Nikolay , Fedorova Sardana , Ludes Bertrand , Crubézy Eric , Keyser Christine 
Published: October 2020

AbstractSeventeen years of archaeological and anthropological expeditions in North-Eastern Siberia (in the Sakha Republic, Yakutia) have permitted the genetic analysis of 150 ancient (15th-19th century) and 510 modern individuals. Almost all males were successfully analysed (Y-STR) and this allowed us to identify paternal lineages and their geographical expansion through time. This genetic data was confronted with mythological, historical and material evidence to establish the sequence of events that built the modern Yakut genetic diversity. We show that the ancient Yakuts recovered from this large collection of graves are not representative of an ancient population. Uncommonly, we were also able to demonstrate that the funerary preference observed here involved three specific male lineages, especially in the 18th century. Moreover, this dominance was likely caused by the Russian conquest of Siberia which allowed some male clans to rise to new levels of power. Finally, we give indications that some mythical and historical figures might have been the actors of those genetic changes. These results help us reconsider the genetic dynamics of colonization in some regions, question the distinction between fact and myth in national histories and provide a rare insight into a funerary ensemble by revealing the biased process of its composition.
Benthic ecosystem cascade effects in Antarctica using Bayesian network inference
Authors: Mitchell Emily G. , Whittle Rowan J. , Griffiths Huw J. 
Published: October 2020

AbstractAntarctic sea-floor communities are unique, and more closely resemble those of the Palaeozoic than equivalent contemporary habitats. However, comparatively little is known about the processes that structure these communities or how they might respond to anthropogenic change. In order to investigate likely consequences of a decline or removal of key taxa on community dynamics we use Bayesian network inference to reconstruct ecological networks and infer changes of taxon removal. Here we show that sponges have the greatest influence on the dynamics of the Antarctic benthos. When we removed sponges from the network, the abundances of all major taxa reduced by a mean of 42%, significantly more than changes of substrate. To our knowledge, this study is the first to demonstrate the cascade effects of removing key ecosystem structuring organisms from statistical analyses of Antarctica data and demonstrates the importance of considering the community dynamics when planning ecosystem management.
Multi-scale quantification and modeling of aged nanostructured silicon-based composite anodes
Authors: Vorauer Thomas , Kumar Praveen , Berhaut Christopher L. , Chamasemani Fereshteh F. , Jouneau Pierre-Henri , Aradilla David , Tardif Samuel , Pouget Stephanie , Fuchsbichler Bernd , Helfen Lukas , Atalay Selcuk , Widanage Widanalage D. , Koller Stefan , Lyonnard Sandrine , Brunner Roland 
Published: October 2020

AbstractAdvanced anode material designs utilizing dual phase alloy systems like Si/FeSi2 nano-composites show great potential to decrease the capacity degrading and improve the cycling capability for Lithium (Li)-ion batteries. Here, we present a multi-scale characterization approach to understand the (de-)lithiation and irreversible volumetric changes of the amorphous silicon (a-Si)/crystalline iron-silicide (c-FeSi2) nanoscale phase and its evolution due to cycling, as well as their impact on the proximate pore network. Scattering and 2D/3D imaging techniques are applied to probe the anode structural ageing from nm to μm length scales, after up to 300 charge-discharge cycles, and combined with modeling using the collected image data as an input. We obtain a quantified insight into the inhomogeneous lithiation of the active material induced by the morphology changes due to cycling. The electrochemical performance of Li-ion batteries does not only depend on the active material used, but also on the architecture of its proximity.
Aspiration-assisted freeform bioprinting of pre-fabricated tissue spheroids in a yield-stress gel
Authors: Ayan Bugra , Celik Nazmiye , Zhang Zhifeng , Zhou Kui , Kim Myoung Hwan , Banerjee Dishary , Wu Yang , Costanzo Francesco , Ozbolat Ibrahim T. 
Published: October 2020

AbstractBioprinting of cellular aggregates, such as tissue spheroids, to form three-dimensional (3D) complex-shaped arrangements, has posed a major challenge due to lack of robust, reproducible and practical bioprinting techniques. Here, we demonstrate 3D aspiration-assisted freeform bioprinting of tissue spheroids by precisely positioning them in self-healing yield-stress gels, enabling the self-assembly of spheroids for fabrication of tissues. The presented approach enables the traverse of spheroids directly from the cell media to the gel and freeform positioning of the spheroids on demand. We study the underlying physical mechanism of the approach to elucidate the interactions between the aspirated spheroids and the gel’s yield-stress during the transfer of spheroids from cell media to the gel. We further demonstrate the application of the proposed approach in the realization of various freeform shapes and self-assembly of human mesenchymal stem cell spheroids for the construction of cartilage and bone tissues.
Acceleration of ocean warming, salinification, deoxygenation and acidification in the surface subtropical North Atlantic Ocean
Authors: Bates Nicholas Robert , Johnson Rodney J. 
Published: October 2020

AbstractOcean chemical and physical conditions are changing. Here we show decadal variability and recent acceleration of surface warming, salinification, deoxygenation, carbon dioxide (CO2) and acidification in the subtropical North Atlantic Ocean (Bermuda Atlantic Time-series Study site; 1980s to present). Surface temperatures and salinity exhibited interdecadal variability, increased by ~0.85 °C (with recent warming of 1.2 °C) and 0.12, respectively, while dissolved oxygen levels decreased by ~8% (~2% per decade). Concurrently, seawater DIC, fCO2 (fugacity of CO2) and anthropogenic CO2 increased by ~8%, 22%, and 72% respectively. The winter versus summer fCO2 difference increased by 4 to 8 µatm decade−1 due to seasonally divergent thermal and alkalinity changes. Ocean pH declined by 0.07 (~17% increase in acidity) and other acidification indicators by ~10%. Over the past nearly forty years, the highest increase in ocean CO2 and ocean acidification occurred during decades of weakest atmospheric CO2 growth and vice versa.
Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice
Authors: Hada Yoshiko , Uchida Haruhito A. , Mukai Tomoyuki , Kojima Fumiaki , Yoshida Masashi , Takeuchi Hidemi , Kakio Yuki , Otaka Nozomu , Morita Yoshitaka , Wada Jun 
Published: October 2020

AbstractThe aim of the present study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice. Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks. These mice were stratified into four groups: MR16-1 treatment groups, KO/MR low group (first 2.0 mg, following 0.5 mg/week, n=14) and KO/MR high group (first 4.0 mg, following 2.0 mg/week, n=19) in IL-1RA KO mice, and IgG treatment groups, KO/IgG group (first 2.0 mg, following 1.0 mg/week, n=22) in IL-1RA KO mice, and wild/IgG group (first 2.0 mg, following 1.0 mg/week, n=17) in wild mice. Aortitis, cardiac hypertrophy and arthropathy were histologically analyzed. Sixty-eight percent of the KO/IgG group developed aortitis (53% developed severe aortitis). In contrast, only 21% of the KO/MR high group developed mild aortitis, without severe aortitis (P&lt;0.01, vs KO/IgG group). Infiltration of inflammatory cells, such as neutrophils, T cells, and macrophages, was frequently observed around aortic sinus of the KO/IgG group. Left ventricle and cardiomyocyte hypertrophy were observed in IL-1RA KO mice. Administration of high dosage of MR16-1 significantly suppressed cardiomyocyte hypertrophy. MR16-1 attenuated the incidence and severity of arthritis in IL-1RA KO mice in a dose-dependent manner. In conclusion, blockade of IL-6 signaling may exert a beneficial effect to attenuate severe aortitis, left ventricle hypertrophy, and arthritis.
BRITE photometry and STELLA spectroscopy of bright stars in Auriga: Rotation, pulsation, orbits, and eclipses
Authors: Strassmeier K. G. , Granzer T. , Weber M. , Kuschnig R. , Pigulski A. , Popowicz A. , Moffat A. F. J. , Wade G. A. , Zwintz K. , Handler G. 
Published: October 2020

Context. Knowing rotational and pulsational periods across the Hertzsprung-Russell diagram is of top priority for understanding stellar activity as a function of time.
Aims. We aim to determine periods for bright stars in the Auriga field that are otherwise not easily accessible for ground-based photometry.
Methods. Continuous photometry with up to three BRITE satellites was obtained for 12 targets and subjected to a period search. Contemporaneous high-resolution optical spectroscopy with STELLA was used to obtain radial velocities through cross correlation with template spectra as well as to determine astrophysical parameters through a comparison with model spectra.
Results. The Capella red light curve was found to be constant over 176 days with a root mean square of 1 mmag, but the blue light curve showed a period of 10.1 ± 0.6 d, which we interpret to be the rotation period of the G0 component. From STELLA we obtained an improved orbital solution based on 9600 spectra from the previous 12.9 yr. We derive masses precise to ≈0.3% but 1% smaller than previously published. The BRITE light curve of the F0 supergiant ε Aur suggests 152 d as its main pulsation period, while the STELLA radial velocities reveal a clear 68 d period. An ingress of an eclipse of the ζ Aur binary system was covered with BRITE and a precise timing for its eclipse onset derived. A possible 70 d period fits the proposed tidal-induced, nonradial pulsations of this ellipsoidal K4 supergiant. η Aur is identified as a slowly pulsating B (SPB) star with a main period of 1.29 d and is among the brightest SPB stars discovered so far. The rotation period of the magnetic Ap star θ Aur is detected from photometry and spectroscopy with a period of 3.6189 d and 3.6177 d, respectively, likely the same within the errors. The radial velocities of this star show a striking non-sinusoidal shape with a large amplitude of 7 km s−1. Photometric rotation periods are also confirmed for the magnetic Ap star IQ Aur of 2.463 d and for the solar-type star κ1 Cet of 9.065 d, and also for the B7 HgMn giant β Tau of 2.74 d. Revised orbital solutions are derived for the eclipsing SB2 binary β Aur, which replaces the initial orbit dating from 1948 for the 27-year eclipsing SB1 ε Aur, and for the RS CVn binary V711 Tau, for which a spot-corrected orbital solution was achieved. The two stars ν Aur and ι Aur are found to be long-term, low-amplitude RV and brightness variables, but provisional orbital elements based on a period of 20 yr and an eccentricity of 0.7 could only be extracted for ν Aur. The variations of ι Aur are due to oscillations with a period of ≈4 yr.
Lipoedema and Pain: What is the role of the psyche? – Results of a pilot study with 150 patients with Lipoedema
Authors: Erbacher Gabriele , Bertsch Tobias 
Published: October 2020

Abstract
Introduction The present exploratory study is the first so far to investigate the psychological stress in the period before the development of pain symptoms typical for lipoedema.
Methods 150 patients diagnosed with lipoedema syndrome were questioned in semi-structured interviews about psychological stress and were diagnosed with psychological disorders according to ICD-10 criteria. The development of the symptoms typical for lipoedema was recorded in a second interview. Both interviews were blended together in collaboration with the patients, this means Lipoedema-associated pain and psychological stress were related to time.
Result Exactly 80 % of the patients diagnosed with lipedema show a high level of psychological distress immediately before the onset of lipedema-associated symptoms! In this study, mental distress was defined as the presence of a manifest mental disorder (ICD 10 F diagnosis) such as Depression, eating disorder or post-traumatic stress disorder and/or serious psychological distress such as burnout syndrome or chronic stress.
Summary These results contradict a widespread statement that all psychological problems of patients with the diagnosis lipoedema syndrome are caused solely by lipoedema, that lipoedema even causes the patient’s mental disorder.Moreover, depression and posttraumatic stress disorders are significantly related to the maximum pain intensity estimated by patients in everyday life. This demonstrates that it is imperative to rethink lipoedema therapy and to implement a psychosocial pillar in an overall therapy concept.
Multiple Sklerose in Deutschland: aktualisierte Auswertungen des MS-Registers der DMSG 2014–2018
Authors: Flachenecker Peter , Eichstädt Kerstin , Berger Klaus , Ellenberger David , Friede Tim , Haas Judith , Kleinschnitz Christoph , Pöhlau Dieter , Rienhoff Otto , Stahmann Alexander , Zettl Uwe K. 
Published: October 2020

Zusammenfassung
Einleitung Unter Federführung der Deutschen Multiple Sklerose Gesellschaft (DMSG), Bundesverband e. V. wurde 2001 ein bundesweites MS-Register initiiert, um epidemiologische Daten zur MS, deren Verlaufsformen und der Versorgungssituation in Deutschland zu erheben. Das Ziel der vorliegenden Auswertung war es, die Daten der letzten Auswertung von vor 10 Jahren zu aktualisieren.
Methodik Zum Stichtag 28. Februar 2018 nahmen 168 Zentren verschiedener Versorgungsbereiche (Universitätskliniken, Akutkliniken, Rehabilitationskliniken und neurologische Praxen) teil. Von 2014 bis 2016 wurde der Wechsel der Dokumentationsplattform zu einem internetbasierten elektronischen Datenerfassungssysstem (EDC) vorgenommen, das eine umfassende Datenerhebung und die Integration verschiedener Dokumentationssysteme erlaubt. Eine Reihe von Qualitätssicherungsmaßnahmen sichert eine valide und representative Datenerhebung. Um eine möglichst aktuelle Beschreibung der Versorgungssituation zu gewährleisten, wurde die Querschnittsanalyse auf Patientendaten der aktuellsten Visite aus den letzten 4 Jahren beschränkt.
Ergebnisse Daten von 18.030 MS-Betroffenen konnten ausgewertet werden. Das mittlere (± Standardabweichung) Alter betrug 46,3 ± 12,2 Jahre, 72 % der Patienten waren weiblich, im Mittel waren die Patienten 10,6 ± 8,7 Jahre erkrankt, der mediane EDSS lag bei 3,0. Die Mehrzahl der Patienten litt an einem schubförmigen Verlauf (74,2 %), 16,1 % hatten einen sekundär und 5,5 % einen primär progredienten Verlauf. Eine Immuntherapie wurde bei 75,2 % durchgeführt, am häufigsten mit Interferonen, gefolgt von Fingolimod, Glatirameracetat, Dimethylfumarat, Natalizumab und Teriflunomid. Symptomatische Therapiemaßnahmen erhielten zwischen 28,3 % (kognitive Störungen) und 86,0 % (Spastik) der Patienten, die an diesen Symptomen litten. Voll berufstätig waren nur noch 37,5 % der Betroffenen; 22,5 % waren vorzeitig berentet. Die berufliche Leistungsfähigkeit war negativ mit dem Alter und dem Behinderungsgrad assoziiert.
Diskussion Die vorliegende Auswertung des deutschen MS-Registers gibt einen aktuellen Überblick zur MS und deren Versorgungssituation in Deutschland. Die Ergebnisse sprechen für einen günstigeren Verlauf der MS im Lauf der letzten 10 Jahre. Während die Mehrzahl der Patienten mit immunmodulatorischen Substanzen therapiert wird, sind nach wie vor einige Symptome der MS wie Fatigue und kognitive Störungen unzureichend behandelt. Zwar hat die Beschäftigungsrate im Vergleich zu früheren Auswertungen zugenommen; dennoch erfordert der hohe Anteil der vorzeitig Berenteten effektive Maßnahmen, um die funktionellen Einschränkungen der Betroffenen zu verringern und ihnen die Teilhabe am gesellschaftlichen und beruflichen Leben möglichst lange zu ermöglichen.
Misteltherapie in der Onkologie – Update der aktuellen Forschungsergebnisse
Authors: Schad Friedemann 
Published: October 2020

ZusammenfassungMistelpräparate finden seit über 100 Jahren Anwendung in der Tumortherapie und sind im deutschsprachigen Raum nach wie vor die am häufigsten eingesetzten Arzneimittel in der integrativen Onkologie. Sie werden sowohl adjuvant als auch palliativ, meist in Kombination mit konventionellen Therapieverfahren angewandt und dienen in erster Linie zur Verminderung der durch diese Therapien bedingten Nebenwirkungen, der Verbesserung der Lebensqualität sowie der Reduktion tumorbedingter Symptome. In manchen Fällen kann auch eine direkte Tumorhemmung oder Tumorreduktion beobachtet werden. Einige Studien weisen auch auf eine Verlängerung des Gesamtüberlebens durch die Misteltherapie hin.Zur Misteltherapie liegt eine Vielzahl an präklinischen und klinischen Studien vor. In dieser Übersicht wird die klinische Wirksamkeit anhand der aktuellen Studienlage und systematischen Reviews bzw. Metaanalysen besprochen. Außerdem werden Möglichkeiten einer Kombination mit gängigen Onkologika aufgezeigt.