bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDAC1 and HDAC2 independently regulate common and specific intrinsic responses in murine enteroids
Authors: Gonneaud Alexis , Turgeon Naomie , Jones Christine , Couture Cassandra , Lévesque Dominique , Boisvert François-Michel , Boudreau François , Asselin Claude 
Published: March 2019

AbstractBoth HDAC1 and HDAC2 are class I deacetylases acting as erasers of lysine-acetyl marks on histones and non-histone proteins. Several histone deacetylase inhibitors, either endogenous to the cell, such as the ketogenic β-hydroxybutyrate metabolite, or exogenous, such as butyrate, a microbial-derived metabolite, regulate HDAC activity. Different combinations of intestinal epithelial cell (IEC)-specific Hdac1 and/or Hdac2 deletion differentially alter mucosal homeostasis in mice. Thus, HDAC1 and HDAC2 could act as sensors and transmitters of environmental signals to the mucosa. In this study, enteroid culture models deleted for Hdac1 or Hdac2 were established to determine IEC-specific function as assessed by global transcriptomic and proteomic approaches. Results show that Hdac1 or Hdac2 deficiency altered differentiation of Paneth and goblet secretory cells, which sustain physical and chemical protection barriers, and increased intermediate secretory cell precursor numbers. Furthermore, IEC Hdac1- and Hdac2-dependent common and specific biological processes were identified, including oxidation-reduction, inflammatory responses, and lipid-related metabolic processes, as well as canonical pathways and upstream regulators related to environment-dependent signaling through steroid receptor pathways, among others. These findings uncover unrecognized regulatory similarities and differences between Hdac1 and Hdac2 in IEC, and demonstrate how HDAC1 and HDAC2 may complement each other to regulate the intrinsic IEC phenotype.
Glandular differentiation in pT1 urothelial carcinoma of bladder predicts poor prognosis
Authors: Zhao Guobin , Wang Chao , Tang Yuhong , Liu Xin , Liu Zihao , Li Gang , Mei Yanhui 
Published: March 2019

AbstractTo evaluate the effect of glandular differentiation (GD) on tumor recurrence and progression of pT1 bladder urothelial carcinoma (UC). We performed a retrospective analysis of 82 bladder urothelial carcinoma with glandular differentiation (UCGD) patients which was pathologically diagnosed as pT1, 166 patients of pT1 UC of bladder without histologic variants served as controls. Patients of UCGD were more likely to have higher recurrence (P = 0.002) rate and higher progression rate (P < 0.001). Moreover, UCGD and a poor 5 -year overall survival (OS) (P = 0.02) while there was no difference in cancer-specific survival (CSS) (P = 0.062) between two groups. According to univariate analysis, largest tumor size (HR 1.502, CI 1.158–1.861, P = 0.029), UCGD (HR 1.787, CI 1.298–2.552, P = 0.001), lymphovascular invasion (LVI) (HR 1.226, CI 1.013–1.945, P = 0.039). UCGD (HR 1.367, CI 1.115–1.853, P = 0.038) and LVI (HR 1.416, CI 1.120–2.254, P = 0.013) were prognostic factors associated with disease recurrence and progression, respectively. Additionally, Additionally, UCGD significantly influence disease recurrence (HR 1.871, CI 1.338–2.589, P < 0.001) and progression (HR 1.462, CI 1.138–2.393, p = 0.007). Similarly, LVI significantly influence disease recurrence (HR 1.356, CI 1.053–2.174, P = 0.042) and progression (HR 1.348, CI 1.052–1.944, p = 0.022) in multivariate analysis. UCGD is significantly associated with higher recurrence and progression rate in patients with newly diagnosed pT1. Recurrent cases should be performed radical cystectomy (RC) earlier.
Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis
Authors: Brčić Luka , Barić Ana , Gračan Sanda , Torlak Vesela , Brekalo Marko , Škrabić Veselin , Zemunik Tatijana , Barbalić Maja , Punda Ante , Boraska Perica Vesna 
Published: March 2019

AbstractThyroid antibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) are key markers of Hashimoto’s thyroiditis (HT), the most common autoimmune thyroid disorder. Genetic determinants of thyroid antibodies are still poorly known, especially as they were not studied in patients with thyroid diseases. We performed the first genome-wide association analysis of thyroid antibodies in 430 HT patients that may be considered as population extremes for thyroid antibodies distribution. We detected two suggestively associated genetic variants with TgAb, rs6972286 close to ANKRD7 and LSM8 (P = 2.34 × 10−7) and rs756763 inside CA10 (P = 6.05 × 10−7), and one with TPOAb, rs12507813 positioned between TRIM61 and TRIM60 (P = 4.95 × 10−7). Bivariate analysis resulted with three suggestively associated genetic variants that predispose to both antibodies: rs13190616 inside RP11-138J23.1 (P = 2.01 × 10−6), rs561030786 close to DUBR (P = 7.33 × 10−6) and rs12713034 inside FSHR (P = 7.66 × 10−6). All identified genomic regions have a substantial literature record of involvement with female-related traits, immune-mediated diseases and personality traits that are all characterized by increased thyroid antibody levels. Our findings demonstrate the existence of genetic overlap between thyroid autoimmunity in HT and different non-thyroid diseases characterized by the presence of thyroid antibodies. We also suggest that genetic variants that regulate antibody levels may differ between HT patients and individuals with normal thyroid function.
Protein kinase CK2-dependent aerobic glycolysis-induced lactate dehydrogenase A enhances the migration and invasion of cancer cells
Authors: Im Dae-Kyun , Cheong Heesun , Lee Jong Suk , Oh Min-Kyu , Yang Kyung Mi 
Published: March 2019

AbstractWe investigated the intracellular metabolic fluxes of protein kinase CK2-activating (Cα OE) cells and role of lactate dehydrogenase A (LDHA) as a contributor of tumorigenesis after reprogrammed glucose metabolism. Facilitated aerobic glycolysis was confirmed via isotope tracer analysis, in which 13C6-Glc or 13C5-Gln was added to the media, following which metabolites converted from Cα OE cells were identified. We found a greater decrease in cell survival, colony-forming ability, migration, and Cα OE cell invasion under glucose (Glc)-depletion conditions than under glutamine (Gln)-depletion conditions. Cancer cell migration and invasion increased due to LDHA elevation of the altered metabolic axis driven by activated CK2. FX11 treatment and LDHA knockdown suppressed migration and invasion through ROS generation, but this was partially reversed by the antioxidant N-acetylcysteine (NAC). Moreover, LDHA inhibition decreased tumor growth in a mouse xenograft model transplanted with Cα OE cells. Finally, we concluded that LDHA is an excellent metabolic target for tumor therapy, based on CK2α derived aerobic glycolysis.
Fermi level tuning of Ag-doped Bi2Se3 topological insulator
Authors: Uesugi Eri , Uchiyama Takaki , Goto Hidenori , Ota Hiromi , Ueno Teppei , Fujiwara Hirokazu , Terashima Kensei , Yokoya Takayoshi , Matsui Fumihiko , Akimitsu Jun , Kobayashi Kaya , Kubozono Yoshihiro 
Published: March 2019

AbstractThe temperature dependence of the resistivity (ρ) of Ag-doped Bi2Se3 (AgxBi2−xSe3) shows insulating behavior above 35 K, but below 35 K, ρ suddenly decreases with decreasing temperature, in contrast to the metallic behavior for non-doped Bi2Se3 at 1.5–300 K. This significant change in transport properties from metallic behavior clearly shows that the Ag doping of Bi2Se3 can effectively tune the Fermi level downward. The Hall effect measurement shows that carrier is still electron in AgxBi2−xSe3 and the electron density changes with temperature to reasonably explain the transport properties. Furthermore, the positive gating of AgxBi2−xSe3 provides metallic behavior that is similar to that of non-doped Bi2Se3, indicating a successful upward tuning of the Fermi level.
Diagnostic and prognostic implications of parafibromin immunohistochemistry in parathyroid carcinomaT
Authors: Pyo Jung-Soo , Cho Won Jin 
Published: March 2019

Abstract
The aim of the present study was to elucidate the diagnostic and prognostic implications of parafibromin immunohistochemistry (IHC) in parathyroid carcinoma (PC). We performed a meta-analysis to examine the rate of loss of parafibromin expression from 18 eligible studies. In addition, a diagnostic test accuracy review was conducted to investigate the diagnostic role of parafibromin in PC. The rates of loss of parafibromin expression were 0.522 (95% CI: 0.444–0.599), 0.291 (95% CI: 0.207–0.391), 0.027 (95% CI: 0.011–0.064), and 0.032 (95% CI: 0.008–0.119) in PC, atypical parathyroid adenoma (APA), parathyroid adenoma (PA), and parathyroid hyperplasia, respectively. In the diagnostic test accuracy review for diagnosis of PC, the pooled sensitivity and specificity of parafibromin IHC was 0.53 (95% CI: 0.46–0.59) and 0.96 (95% CI: 0.95–0.97), respectively. The diagnostic odds ratio and the area under curve on summary receiver operating characteristic curve was 25.31 (95% CI: 8.91–71.87) and 0.7954, respectively. In addition, the meta-analysis demonstrated that loss of parafibromin expression was significantly correlated with worse disease-free survival (hazard ratio: 2.832; 95% CI: 1.081–7.421). Loss of parafibromin IHC expression was significantly higher in PC than in APA, PA, and parathyroid hyperplasia. Parafibromin IHC could be useful for diagnosis and prediction of prognosis of PC in daily practice.
Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling
Authors: Chen Hong-Min , Dai Jia-Jia , Zhu Rui , Peng Fang-Fang , Wu Su-Zhen , Yu Hong , Krepinsky Joan C. , Zhang Bai-Fang 
Published: March 2019

Abstract
Parathyroid hormone-related protein (PTHrP) is known to be up-regulated in both glomeruli and tubules in patients with diabetic kidney disease (DKD), but its role remains unclear. Previous studies show that PTHrP-induced hypertrophic response in mesangial cells (MCs) and epithelial-mesenchymal transition (EMT) in tubuloepithelial cells can be mediated by TGF-β1. In the present study, although long-term PHTrP (1–34) treatment increased the mRNA and protein level of TGF-β1 in primary rat MCs, fibronectin up-regulation occurred earlier, suggesting that fibronectin induction is independent of TGF-β1/Smad signaling. We thus evaluated the involvement of epidermal growth factor receptor (EGFR) signaling and found that nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species mediates PTHrP (1–34)-induced Src kinase activation. Src phosphorylates EGFR at tyrosine 845 and then transactive EGFR. Subsequent PI3K activation mediates Akt and ERK1/2 activation. Akt and ERK1/2 discretely lead to excessive protein synthesis of fibronectin. Our study thus demonstrates the new role of PTHrP in fibronectin up-regulation for the first time in glomerular MCs. These data also provided new insights to guide development of therapy for glomerular sclerosis.
Multi-line Herschel/HIFI observations of water reveal infall motions and chemical segregation around high-mass protostars
Authors: van der Tak F. F. S. , Shipman R. F. , Jacq T. , Herpin F. , Braine J. , Wyrowski F. 
Published: March 2019

Context. The physical conditions during high-mass star formation are poorly understood. Outflow and infall motions have been detected around massive protostellar objects, but their dependence on mass, luminosity, and age is unclear. In addition, physical conditions and molecular abundances are often estimated using simple assumptions such as spherical shape and chemical homogeneity, which may limit the accuracy of the results.
Aims. We aim to characterize the dust and gas distribution and kinematics of the envelopes of high-mass protostars. In particular, we search for infall motions, abundance variations, and deviations from spherical symmetry, using Herschel data from the WISH program.
Methods. We used HIFI maps of the 987 GHz H2O 202–111 emission to measure the sizes and shapes of 19 high-mass protostellar envelopes. To identify infall, we used HIFI spectra of the optically thin C18O 9–8 and H218O 111–000 lines. The high-J C18O line traces the warm central material and redshifted H218O 111–000 absorption indicates material falling onto the warm core. We probe small-scale chemical differentiation by comparing H2O 752 and 987 GHz spectra with those of H218O.
Results. Our measured radii of the central part of the H2O 202–111 emission are 30–40% larger than the predictions from spherical envelope models, and axis ratios are <2, which we consider good agreement. For 11 of the 19 sources, we find a significant redshift of the H218O 111–000 line relative to C18O 9–8. The inferred infall velocities are 0.6–3.2 km s−1, and estimated mass inflow rates range from 7 × 10−5 to 2 × 10−2 M⊙ yr−1. The highest mass inflow rates seem to occur toward the sources with the highest masses, and possibly the youngest ages. The other sources show either expanding motions or H218O lines in emission. The H218O 111–000 line profiles are remarkably similar to the differences between the H2O 202–111 and 211–202 profiles, suggesting that the H218O line and the H2O 202–111 absorption originate just inside the radius where water evaporates from grains, typically 1000–5000 au from the center. In some sources, the H218O line is detectable in the outflow, where no C18O emission is seen.
Conclusions. Together, the H218O absorption and C18O emission profiles show that the water abundance around high-mass protostars has at least three levels: low in the cool outer envelope, high within the 100 K radius, and very high in the outflowing gas. Thus, despite the small regions, the combination of lines presented in this work reveals systematic inflows and chemical information about the outflows.
Infektiologie – Pionier der Digitalen Medizin
Authors: Vehreschild Jörg , Claßen Annika , Jakob Carolin 
Published: March 2019

Was ist neu?
Von der personalisierten zur digitalen Medizin Über Impfungen und gezielte Erregerdiagnostik und -therapie ist die Infektionsmedizin Vorreiterin der personalisierten Medizin. Datenprozesse im Rahmen neuer Infektionsepidemien sind Musterbeispiele der Möglichkeiten der digitalen Medizin.
Klinische Entscheidungshilfen Die oft gut definierten Krankheitsbilder der Infektiologie und das hohe Niveau der verfügbaren Leitlinien sind ideale Voraussetzungen für computerunterstützte Behandlungsentscheidungen.
Datengetriebene Infektionsforschung Durch die Verbindung von Daten aus elektronischen Patientenakten mit den umfassenden Datensätzen neuer Technologien aus der sogenannten „Omics“-Forschung können neue Zusammenhänge erkannt und Prognosen verbessert werden.
Elektronische Gesundheitsakte Die elektronische Gesundheitsakte eröffnet großes Potenzial im Sinne einer zielgerichteten Behandlung, insbesondere bei infektiologischen Notfällen.
Telemedizin In Deutschland fehlen Infektiologen, ein Strukturwandel kann nur schrittweise vollzogen werden. Telemedizinische Konsultationen können helfen, infektiologische Expertise in unzureichend versorgte Regionen zu bringen.
Mobile Health Die fast vollständige Verbreitung mobiler Digitalgeräte schafft neue Möglichkeiten für die Gestaltung der Arzt-Patient-Kommunikation sowie der heimatnahen Nachsorge.
Mobile Versorgung chronischer Infektionen Beim Langzeitmanagement chronischer Erkrankungen sowie bei der Versorgung in Regionen mit schwacher Infrastruktur entstehen Möglichkeiten einer verbesserten medizinischen Behandlung.
Balance der Interessen Die Digitale Medizin birgt Risiken durch die Schaffung großer Datensätze mit potenziell stigmatisierenden Patienteninformationen. Softwaresysteme, die Entscheidungen von klinischer Relevanz beeinflussen, bedürfen sorgfältiger Prüfung und Transparenz.
Digitalisierung in der Intensivmedizin
Authors: Baumgärtel Matthias , Riessen Reimer , John Stefan 
Published: March 2019

Was ist neu?
Stand der Dinge Intensivstationen sind prädestiniert für den Einsatz digitaler Hilfsmittel. Digitale Systeme bieten eine gute Plattform für modernes Qualitätsmanagement und Forschungsprojekte.
Patientendatenmanagementsysteme (PDMS) Die Verwendung von Patientendatenmanagementsystemen ist die Grundvoraussetzung für eine erfolgreiche Digitalisierung in der Intensivmedizin und sollte nachhaltig gefördert werden.
Telemedizin Es gibt vielversprechende neue Konzepte zur Nutzung der Telemedizin in der Intensivmedizin. Telemedizin ermöglicht die Betreuung von Intensivstationen in Krankenhäusern der Grundversorgung durch spezialisierte Zentren.
Digitale Stationsorganisation Die Logistik der Patientenversorgung ist ein häufig unterschätzter Faktor auf Intensivstationen. Digitale Systeme zur Stationsorganisation können hier eine Lücke schließen.
Ausblick Die weitere Digitalisierung kann dabei helfen, die Prozesse auf einer Intensivstation zu optimieren und eine Patientenversorgung auf dem aktuellen wissenschaftlichen Stand zu erleichtern.
Digital Health in der Rheumatologie – Statuserhebung 2018/19
Authors: Richter Jutta , Chehab Gamal , Kiltz Uta , Callhoff Johanna , Voormann Anna , Lorenz Hanns-Martin , Schneider Matthias , Specker Christof 
Published: March 2019

Was ist neu?
Stand der Dinge Innovationen in der Informations- und Kommunikationstechnologie haben in der Rheumatologie eine jahrzehntelange Tradition, die Deutsche Gesellschaft für Rheumatologie hat im Jahr 2018 die Kommission „Digitale Rheumatologie“ gegründet.
Digitale Anwendungen in der deutschen Rheumatologie Mobile Datenerfassung rheumatologischer Patienten ist valide möglich. Sie eröffnet damit neuartige Möglichkeiten bei der Umsetzung moderner Behandlungsstrategien. Zum Screening auf entzündlich-rheumatische Systemerkrankungen stehen Interessierten z. B. mit dem „Rheuma-Check“ und dem „Bechterew-Check“ jederzeit digitale Anwendungen zur Verfügung. Die digitalen Angebote sowie moderne Netzwerkstrukturen erlauben eine Triage der Patienten. Mit dem Rhekiss- und dem RABBIT-SpA-Register stehen erstmals vollständig digitalisierte Register zur Verfügung, die kurzfristig Daten zu Fragestellungen liefern, die in klinischen Studien der pharmazeutischen Industrie nicht abgebildet werden.
Ausblick Durch die Digitalisierung in der Rheumatologie können wichtige Fragen der Versorgungsforschung zukünftig deutlich schneller beantwortet werden.
Digitalisierung in der Gastroenterologie
Authors: Weidemann Robin , Meining Alexander , Lynen Petra , Lammert Frank , Möller Yvonne , Malek Nisar , Hampe Jochen 
Published: March 2019

Was ist neu?
Digitalisierung in der personalisierten Medizin Fortschritte in der genomischen Diagnostik und digitale innovative Technologien lassen die personalisierte Therapie gastrointestinaler entzündlicher und onkologischer Erkrankungen bald möglich erscheinen.
Digitalisierung in der interventionellen Diagnostik und Therapie In der interventionellen Gastroenterologie lassen sich neue IT-gestützte Diagnostik- und Therapieverfahren und Formen der Mensch-Technik-Kollaboration gut testen und im Versorgungalltag validieren.
Digitale Kompetenzen und Kommunikation Um die Arzt-Patienten-Kommunikation auf Augenhöhe zu erhalten, müssen auf beiden Seiten Kompetenzen im Umgang mit digitalen Anwendungen aufgebaut werden. Qualitativ hochwertige digitale Gesundheitsprodukte im unübersichtlichen Markt zu identifizieren bleibt eine Herausforderung.
Wissensmanagement und ärztliche Weiterbildung Die Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselerkrankungen entwickelt digitale Angebote für verschiedene Interessengruppen und engagiert sich bei der Wissensvermittung über soziale Netzwerke. Die ärztliche Weiterbildung im Zeitalter der Digitalisierung ist ebenfalls ein wichtiges Thema.
Implementierungsprobleme und Handlungsoptionen Um die Qualität technologischer Innovationen zu steigern und einen erfolgreichen Transfer in die Versorgung zu ermöglichen ist eine engere Kooperation zwischen Patienten, praktisch tätigen Ärzten und technischen Experten unabdingbar. Entsprechende Strukturen hierfür fehlen weitgehend.
Das Projekt PRIMA – Elektronische Erstellung und Aktualisierung von Medikationsplänen als gemeinsame Aufgabe von Ärzten und Apothekern
Authors: Eickhoff Christiane , Müller Uta , Strunz Ann Kathrin , Seidling Hanna M. , Lampert Anette , Felberg Miriam , Breiholz Sabine , Klintworth Dirk , Schulz Martin 
Published: March 2019

Zusammenfassung
Einleitung Der Gesamtüberblick über die Medikation eines Patienten ist wesentliche Voraussetzung für die Arzneimitteltherapiesicherheit. Ein aktueller und vollständiger Medikationsplan (MP) ist hierfür ein geeignetes Instrument. Ziel war zu untersuchen, inwiefern die elektronische Bearbeitung des bundeseinheitlichen Medikationsplans gemeinsam durch Arzt und Apotheker in ihren Primärsystemen technisch machbar ist, die definierten Prozesse praktikabel sind und akzeptiert werden.
Methoden Ärzte und Apotheker testeten in einem mehrstufigen Verfahren die elektronische Umsetzung. Die Bearbeitung der MP erfolgte anhand definierter Prozesse und Verantwortlichkeiten; Machbarkeit und Akzeptanz wurden in schriftlichen Befragungen und einem Workshop evaluiert.
Ergebnisse Erstmalig in Deutschland wurden die Voraussetzungen zur elektronischen Erstellung, zum Austausch und zur Aktualisierung von MP in einem Arzt- und vier Apothekenverwaltungssystemen geschaffen. Gelöste Probleme waren technische und AMTS-relevante Fehler, abweichende Darstellungen, mangelnde Benutzerfreundlichkeit und begrenzte Speicherkapazität des Barcodes. Elf Arzt-Apotheker-Teams betreuten 196 Patienten. Insgesamt waren 60 % mit den Prozessen und 80 % der Ärzte sowie 63 % der Apotheker mit den Verantwortlichkeiten zufrieden. Ärzte bewerteten die Erfassung der Gesamtmedikation durch Apotheker positiv. Die Kooperation verbesserte den fachlichen Austausch. Dies führt bei 70 % der Ärzte bei der Medikation und bei 88 % der Apotheker zum Gesundheitszustand der Patienten zu einem Wissenszuwachs. Alle Ärzte und Apotheker sahen eine strukturierte Zusammenarbeit als wichtig (25 %) oder sehr wichtig (75 %) für die Qualität der MP an.
Diskussion Der MP wurde erstmalig in Primärsysteme implementiert. Prozesse und Verantwortlichkeiten fanden bei Ärzten und Apothekern Akzeptanz. Dies sind wichtige Voraussetzungen, um den MP flächendeckend und nachhaltig zu implementieren.
Radiologic Update on Arthroplasties in the Wrist and Hand
Authors: Petscavage-Thomas Jonelle , Gustas-French Cristy , Walker Eric 
Published: March 2019

AbstractArthritis involving the hand and wrist can significantly impair functions of daily living. Although arthrodesis provides pain relief, it limits range of motion at the affected joint. Arthroplasty is an alternative surgical treatment for hand and wrist arthritis, providing both pain relief and restoration of a range of motion. Over the past decade, several advances have occurred in hand and wrist arthroplasty designs. This article reviews component design, normal imaging appearance, and common complications of arthroplasty used in the wrist and hand. It also introduces readers to newer arthroplasty designs.
Fractures Around the Shoulder: Radiologic Update on Surgical Fixation Techniques
Authors: Gaetke-Udager Kara , Yablon Corrie 
Published: March 2019

AbstractAlthough radiologists are likely familiar with basic fracture patterns around the shoulder, certain fracture types in this area have particularly relevant and controversial clinical management issues. These include proximal humeral fractures, in which conservative management is favored but some patients receive surgical treatment; glenoid fractures and Hill-Sachs lesions, in which surgery may be performed depending on the amount of bone loss; and distal clavicular fractures, in which certain displaced fractures have high rates of nonunion, but there is no clearly favored surgical technique. Knowledge of the different clinical issues and surgical options can aid the radiologist in identifying key imaging findings and creating a useful report.