bluuebunny/crossref_metadata_2025_split huggingface dataset:
The therapeutic value of SC66 in human renal cell carcinoma cells
Authors: Xu Ming , Wang Yin , Zhou Li-Na , Xu Li-jun , Jin Zhi-chang , Yang Dong-rong , Chen Min-bin , Zhu Jin 
Published: May 2020

AbstractThe PI3K-AKT-mTOR cascade is required for renal cell carcinoma (RCC) progression. SC66 is novel AKT inhibitor. We found that SC66 inhibited viability, proliferation, migration and invasion of RCC cell lines (786-O and A498) and patient-derived primary RCC cells. Although SC66blocked AKT-mTORC1/2 activation in RCC cells, it remained cytotoxic in AKT-inhibited/-silenced RCC cells. In RCC cells, SC66 cytotoxicity appears to occur via reactive oxygen species (ROS) production, sphingosine kinase 1inhibition, ceramide accumulation and JNK activation, independent of AKT inhibition. The ROS scavenger N-acetylcysteine, the JNK inhibitor (JNKi) and the anti-ceramide sphingolipid sphingosine-1-phosphate all attenuated SC66-induced cytotoxicity in 786-O cells. In vivo, oral administration of SC66 potently inhibited subcutaneous 786-O xenograft growth in SCID mice. AKT-mTOR inhibition, SphK1 inhibition, ceramide accumulation and JNK activation were detected in SC66-treated 786-O xenograft tumors, indicating that SC66 inhibits RCC cell progression through AKT-dependent and AKT-independent mechanisms.
Haplotype-specific PCR for NAT2 diplotyping
Authors: Wichukchinda Nuanjun , Pakdee Jirapa , Kunhapan Punna , Imunchot Wimala , Toyo-oka Licht , Tokunaga Katsushi , Mahasirimongkol Surakameth 
Published: May 2020

AbstractN-acetyltransferase 2 (NAT2) is an enzyme that acetylates many kinds of drugs, including the antituberculosis drug isoniazid. The NAT2 gene is highly diverse across populations. An individual can be classified as having a slow acetylator (SA), an intermediate acetylator (IA), or a rapid acetylator (RA) phenotype based on its two haplotypes (diplotype) of NAT2. SA individuals are at a higher risk for isoniazid-induced hepatitis, while the RA phenotype contributes to failure in tuberculosis treatment. Being able to predict individual NAT2 phenotypes is important for dose adjustment of isoniazid. NAT2 haplotypes are commonly determined via an indirect method of statistical haplotype inference from SNP genotyping. Here, we report a direct NAT2 haplotyping method using haplotype-specific PCR (HS-PCR) for the 6 most commonly found NAT2 haplotypes: NAT2*4, NAT2*5B, NAT2*6A, NAT2*7B, NAT2*12A, and NAT2*13A. Validation of this HS-PCR method via comparison with a sequencing method in 650 Thai DNA samples (107 RA, 279 IA, and 264 SA samples) showed a concordance rate for diplotype calls of 99.23% (645/650 samples). The discordant results in 5 samples were due to 3 rare NAT2 haplotypes: NAT*5C (n = 3), NAT2*7C (n = 1), and NAT2*11A (n = 1). This novel HS-PCR method allows direct NAT2 diplotyping, enabling the implementation of NAT2 acetylator phenotypes in clinical pharmacogenetic testing.
Deep learning enables accurate clustering with batch effect removal in single-cell RNA-seq analysis
Authors: Li Xiangjie , Wang Kui , Lyu Yafei , Pan Huize , Zhang Jingxiao , Stambolian Dwight , Susztak Katalin , Reilly Muredach P. , Hu Gang , Li Mingyao 
Published: May 2020

AbstractSingle-cell RNA sequencing (scRNA-seq) can characterize cell types and states through unsupervised clustering, but the ever increasing number of cells and batch effect impose computational challenges. We present DESC, an unsupervised deep embedding algorithm that clusters scRNA-seq data by iteratively optimizing a clustering objective function. Through iterative self-learning, DESC gradually removes batch effects, as long as technical differences across batches are smaller than true biological variations. As a soft clustering algorithm, cluster assignment probabilities from DESC are biologically interpretable and can reveal both discrete and pseudotemporal structure of cells. Comprehensive evaluations show that DESC offers a proper balance of clustering accuracy and stability, has a small footprint on memory, does not explicitly require batch information for batch effect removal, and can utilize GPU when available. As the scale of single-cell studies continues to grow, we believe DESC will offer a valuable tool for biomedical researchers to disentangle complex cellular heterogeneity.
Randomized resonant metamaterials for single-sensor identification of elastic vibrations
Authors: Jiang Tianxi , Li Chong , He Qingbo , Peng Zhi-Ke 
Published: May 2020

AbstractVibrations carry a wealth of useful physical information in various fields. Identifying the multi-source vibration information generally requires a large number of sensors and complex hardware. Compressive sensing has been shown to be able to bypass the traditional sensing requirements by encoding spatial physical fields, but how to encode vibration information remains unexplored. Here we propose a randomized resonant metamaterial with randomly coupled local resonators for single-sensor compressed identification of elastic vibrations. The disordered effective masses of local resonators lead to highly uncorrelated vibration transmissions, and the spatial vibration information can thus be physically encoded. We demonstrate that the spatial vibration information can be reconstructed via a compressive sensing framework, and this metamaterial can be reconfigured while maintaining desirable performance. This randomized resonant metamaterial presents a new perspective for single-sensor vibration sensing via vibration transmission encoding, and potentially offers an approach to simpler sensing devices for many other physical information.
Nucleation and growth of orbital ordering
Authors: Katsufuji Takuro , Kajita Tomomasa , Yano Suguru , Katayama Yumiko , Ueno Kazunori 
Published: May 2020

AbstractThe dynamics of the first-order phase transitions involving a large displacement of atoms, for example, a liquid-solid transition, is generally dominated by the nucleation of the ordered phase and the growth of the nuclei, where the interfacial energy between the two phases plays an important role. On the other hand, electronic phase transitions seldom exhibit such a nucleation-growth behavior, probably because two-phase coexistence is not dominated by only the interfacial energy in such phase transitions. In the present paper, we report that the dynamics of a phase transition associated with an ordering of d orbitals in a vanadate exhibits a clear nucleation-growth behavior and that the interfacial energy between the orbital-ordered and -disordered phases dominated by the orbital-spin coupling can be experimentally obtained.
Multiplex precise base editing in cynomolgus monkeys
Authors: Zhang Wenhui , Aida Tomomi , del Rosario Ricardo C. H. , Wilde Jonathan J. , Ding Chenhui , Zhang Xiaohui , Baloch Zulqurain , Huang Yan , Tang Yu , Li Duanduan , Lu Hongyu , Zhou Yang , Jiang Minqing , Xu Dongdong , Fang Zhihao , Zheng Zhanhong , Huang Qunshan , Feng Guoping , Yang Shihua 
Published: May 2020

AbstractCommon polygenic diseases result from compounded risk contributed by multiple genetic variants, meaning that simultaneous correction or introduction of single nucleotide variants is required for disease modeling and gene therapy. Here, we show precise, efficient, and simultaneous multiplex base editing of up to three target sites across 11 genes/loci in cynomolgus monkey embryos using CRISPR-based cytidine- and adenine-base editors. Unbiased whole genome sequencing demonstrates high specificity of base editing in monkey embryos. Our data demonstrate feasibility of multiplex base editing for polygenic disease modeling in primate zygotes.
Towards stem cell therapies for skeletal muscle repair
Authors: Judson Robert N. , Rossi Fabio M. V. 
Published: May 2020

AbstractSkeletal muscle is an ideal target for cell therapy. The use of its potent stem cell population in the form of autologous intramuscular transplantation represents a tantalizing strategy to slow the progression of congenital muscle diseases (such as Duchenne Muscular Dystrophy) or regenerate injured tissue following trauma. The syncytial nature of skeletal muscle uniquely permits the engraftment of stem/progenitor cells to contribute to new myonuclei and restore the expression of genes mutated in myopathies. Historically however, the implementation of this approach has been significantly limited by the inability to expand undifferentiated muscle stem cells (MuSCs) in culture whilst maintaining transplantation potential. This is crucial, as MuSC expansion and/or genetic manipulation is likely necessary for therapeutic applications. In this article, we review recent studies that have provided a number of important breakthroughs to tackle this problem. Progress towards this goal has been achieved by exploiting biochemical, biophysical and developmental paradigms to construct innovative in vitro strategies that are guiding stem cell therapies for muscle repair towards the clinic.
Immune modulation of hair follicle regeneration
Authors: Rahmani Waleed , Sinha Sarthak , Biernaskie Jeff 
Published: May 2020

AbstractThe mammalian hair follicle undergoes repeated bouts of regeneration orchestrated by a variety of hair follicle stem cells. The last decade has witnessed the emergence of the immune niche as a key regulator of stem cell behavior and hair follicle regeneration. Hair follicles chemotactically attract macrophages and T cells so that they are in range to regulate epithelial stem cell quiescence, proliferation and differentiation during physiologic and injured states. Disruption of this dynamic relationship leads to clinically significant forms of hair loss including scarring and non-scarring alopecias. In this review, we summarize key concepts behind immune-mediated hair regeneration, highlight gaps in the literature and discuss the therapeutic potential of exploiting this relationship for treating various immune-mediated alopecias.
Preferential out-of-plane conduction and quasi-one-dimensional electronic states in layered 1T-TaS2
Authors: Martino E. , Pisoni A. , Ćirić L. , Arakcheeva A. , Berger H. , Akrap A. , Putzke C. , Moll P. J. W. , Batistić I. , Tutiš E. , Forró L. , Semeniuk K. 
Published: May 2020

AbstractLayered transition metal dichalcogenides (TMDs) are commonly classified as quasi-two-dimensional materials, meaning that their electronic structure closely resembles that of an individual layer, which results in resistivity anisotropies reaching thousands. Here, we show that this rule does not hold for 1T-TaS2—a compound with the richest phase diagram among TMDs. Although the onset of charge density wave order makes the in-plane conduction non-metallic, we reveal that the out-of-plane charge transport is metallic and the resistivity anisotropy is close to one. We support our findings with ab initio calculations predicting a pronounced quasi-one-dimensional character of the electronic structure. Consequently, we interpret the highly debated metal-insulator transition in 1T-TaS2 as a quasi-one-dimensional instability, contrary to the long-standing Mott localisation picture. In a broader context, these findings are relevant for the newly born field of van der Waals heterostructures, where tuning interlayer interactions (e.g., by twist, strain, intercalation, etc.) leads to new emergent phenomena.
Serum levels of superoxide dismutases in patients with benign paroxysmal positional vertigo
Authors: Li Jing , Wu Rui , Xia Bin , Wang Xinhua , Xue Mengzhou 
Published: May 2020

AbstractObjective: To investigate the possible role of superoxide dismutases (SODs) in the development of benign paroxysmal positional vertigo (BPPV) and recurrence events in a 1-year follow-up study.Methods: This was a prospective one-center study. A total of 204 patients with BPPV and 120 age-and sex matched healthy subjects were included. The levels of SOD between patients and control cases were compared. The levels of SOD between posterior semicircular canal (PSC) and horizontal semicircular canal (HSC) were also compared. In the 1-year follow-up, recurrence events were confirmed. The influence of SOD levels on BPPV and recurrent BPPV were performed by binary logistic regression analysis.Results: The serum levels of SOD in patients with BPPV were lower than in those control cases (P&lt;0.001). Levels of SOD did not differ in patients with PSC and HSC (P=0.42). As a categorical variable, for per interquartile range (IQR) increment of serum level of SOD, the unadjusted and adjusted risks of BPPV would be decreased by 72% (with the odds ratio [OR] of 0.28 [95% confidence interval (CI): 0.21–0.37], P&lt;0.001) and 43% (0.57 [0.42–0.69], P&lt;0.001), respectively. Recurrent attacks of BPPV were reported in 50 patients (24.5%). Patients with recurrent BPPV had lower levels of SOD than in patients without (P&lt;0.001). For per IQR increment of serum level of SOD, the unadjusted and adjusted risks of BPPV would be decreased by 51% (with the OR of 0.49 [95% CI: 0.36–0.68], P&lt;0.001) and 24% (0.76 [0.60–0.83], P&lt;0.001), respectively.Conclusion: Reduced serum levels of SOD were associated with higher risk of BPPV and BPPV recurrence events.
Extracellular matrix-related genes play an important role in the progression of NMIBC to MIBC: a bioinformatics analysis study
Authors: Zhang Heng , Shan Gang , Song Jukun , Tian Ye , An Ling-Yue , Ban Yong , Luo Guang-Heng 
Published: May 2020

Abstract
Bladder cancer is the 11th most common cancer in the world. Bladder cancer can be roughly divided into muscle invasive bladder cancer (MIBC) and non-muscle invasive bladder cancer (NMIBC). The aim of the present study was to identify the key genes and pathways associated with the progression of NMIBC to MIBC and to further analyze its molecular mechanism and prognostic significance. We analyzed microarray data of NMIBC and MIBC gene expression datasets (GSE31684) listed in the Gene Expression Omnibus (GEO) database. After the dataset was analyzed using R software, differentially expressed genes (DEGs) of NMIBC and MIBC were identified. These DEGs were analyzed using Gene Ontology (GO) enrichment, KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein–protein interaction (PPI) analysis. The effect of these hub genes on the survival of bladder cancer patients was analyzed in The Cancer Genome Atlas (TCGA) database. A total of 389 DEGs were obtained, of which 270 were up-regulated and 119 down-regulated. GO and KEGG pathway enrichment analysis revealed that DEGs were mainly involved in the pathway of protein digestion and absorption, extracellular matrix (ECM) receiver interaction, phantom, toll-like receptor (TLR) signaling pathway, focal adhesion, NF-κB signaling pathway, PI3K/Akt signaling pathway, and other signaling pathways. Top five hub genes COL1A2, COL3A1, COL5A1, POSTN, and COL12A1 may be involved in the development of MIBC. These results may provide us with a further understanding of the occurrence and development of MIBC, as well as new targets for the diagnosis and treatment of MIBC in the future.
Elektrokonvulsionstherapie – bei Kindern und Jugendlichen mit Schizophrenie wirksam und gut verträglich
Authors: Weirich Steffen , Reinhardt Martin , Buchmann Johannes , Dück Alexander , Höppner Jacqueline , Hofmockel Rainer , Grözinger Michael , Häßler Frank 
Published: May 2020

ZusammenfassungWir berichten über vier Patienten im Alter von 12 bis 17 Jahren mit schizophrenen Psychosen, zwei davon mit katatoner Symptomatik, die erfolgreich und sicher mit Elektrokonvulsionstherapie (EKT) behandelt wurden. Unter einer kombinierten Therapie aus EKT und entweder Ziprasidon oder Clozapin verbesserte sich der Zustand aller Patienten erheblich. Schweregrad und Verlauf der akuten Schizophrenie wurden mit der Brief Psychiatric Rating Scale (BPRS) evaluiert. Schweregrad und Verlauf der Katatonie wurden mit der Bush-Francis Catatonia Rating Scale (BFCRS) gemessen. Die Fälle bestätigen frühere Berichte zur Wirksamkeit, zur Sicherheit und Verträglichkeit von EKT bei der Behandlung von Kindern und Jugendlichen mit Schizophrenie.
Spinal Injury Without Neurological Symptoms in Severely Injured Patients: Impact on the Length of Stay?
Authors: Fochtmann Ulrike , Jungbluth Pascal , Zimmermann Werner , Lefering Rolf , Lendemans Sven , Hussmann Bjoern 
Published: May 2020

Abstract
Background The impact of spinal injuries on clinical outcome in most severely injured patients is currently being controversially discussed. At the same time, most of the studies examine patients with post-traumatic neurological disorders. The aim of this study was therefore to analyse severely injured patients with spinal injuries but without neurological symptoms with regard to their clinical outcome. Here the focus was then on the question, whether spinal injury is an independent risk factor increasing length of stay in the intensive care unit and in the hospital in total.
Material and Methods Data of the TraumaRegister DGU® were retrospectively analysed. Inclusion criteria were: Injury Severity Score ≥ 16, primary admission, age ≥ 16 years, time interval 2009 – 2016, and a full data set on length of stay in the hospital and the intensive care unit, respectively. Following a univariate analysis in the first step, independent risk factors for the length of stay in the intensive care unit and in the hospital in total were investigated using a multivariate regression analysis.
Results 98,240 patients met the inclusion criteria. In this population, patients with Abbreviated Injury Scale (AIS) 2 and 3 spinal injuries were significantly younger (up to 60 years), and injuries were significantly more commonly caused by falls from a great height and traffic accidents (age ≤ 60 years: AISSpine 0: 58.4%, AISSpine 3: 65%; p < 0.001). Multivariate analysis showed that spinal injury without neurological symptoms is an independent risk factor for increased length of stay in the intensive care unit (odds ratio: + 1.1 d) and in the hospital in total (AIS 3 odds ratio: + 3.4 d).
Conclusion It has been shown for the first time that spinal injury without initial neurological symptoms has a negative impact on the length of stay of most severely injured patients in the intensive care unit and in the hospital in total and thus represents an independent risk factor in this group of patients.
Health in All Policies – Entwicklungen, Schwerpunkte und
Umsetzungsstrategien für Deutschland
Authors: Geene Raimund , Kurth Bärbel-Maria , Matusall Svenja 
Published: May 2020

ZusammenfassungHealth in All Policies (HiAP) ist ein Konzept, das Gesundheit intersektoral
betrachtet. Dabei werden zum einen die Auswirkungen von Entscheidungen der
verschiedenen Politikbereiche auf die Gesundheit der Menschen untersucht und zum
anderen Synergien gesucht, um gesundheitliche Chancengleichheit zu verbessern.
HiAP bildet die Grundlage, um gesundheitliche Herausforderungen wie Klimawandel,
menschenwürdige Pflege, Inklusion, soziale Chancengleichheit,
städtische Lebensqualität oder flächendeckende
Versorgung zu bewältigen. Eine Arbeitsgruppe des Zukunftsforums Public
Health hat eine Bestandsaufnahme zu HiAP und dessen Umsetzung erstellt, deren
Kurzform hier wiedergegeben wird. International gibt es Erfahrungen mit einigen
Modellprojekten zu HiAP, in denen durch intersektorale Zusammenarbeit die
Krankheitslast nichtübertragbarer Krankheiten verringert und die
gesundheitliche Chancengleichheit erhöht werden konnte. In Deutschland
haben einige Akteure HiAP als Ziel formuliert und es gibt in einigen Kommunen
themenspezifische Modellprojekte, allerdings sind diese bislang weder fachlich
noch politisch ausreichend gesichert und analysiert. Internationale Erfahrungen
zeigen, dass ein explizites Bekenntnis der politischen Führung eine
wesentliche Voraussetzung für HiAP-Prozesse bildet. Durch
zivilgesellschaftliche Initiativen eröffnen sich immer wieder
themenspezifische Möglichkeitsfenster, die für HiAP genutzt
werden können, wenn Politik und Verwaltung tätig werden und
über das einzelne Thema hinausgehend nachhaltige Strukturen einrichten.
Zentrale Aufgabe solch nachhaltiger Strukturen ist es, die Vielfalt bestehender
Ansätze in Erfahrungs- und Wissensplattformen zu bündeln und mit
Koordination und gemeinsamer Zielorientierung zu stärken. Dazu bedarf es
eines gestärkten Public-Health-Systems. HiAP ist in diesem Sinne
Bestandteil und Motor auf dem Weg zu einer Public-Health-Strategie für
Deutschland, die durch das Zukunftsforum Public Health ausgearbeitet wird, um
durch ein gemeinsames Vorgehen die Gesundheit der Menschen in Deutschland zu
verbessern. HiAP kann hier ein entsprechendes Claim darstellen und die
Instrumente liefern um dieses Ziel in die Praxis umzusetzen.
Erfolgreiche Therapie mit Dupilumab bei Prurigo nodularis – 2 Fallberichte
Authors: Messaoudi S. , Bauer A. , Meinel G. , Al-Gburi S. , Beissert S. , Abraham S. 
Published: May 2020

ZusammenfassungDupilumab ist ein humaner rekombinanter monoklonaler Antikörper, gerichtet gegen die Alpha-Untereinheit des Interleukin-4-Rezeptors und des Interleukin-13-Rezeptors. Seit September 2017 ist Dupilumab zur Behandlung der mittelschweren bis schweren Neurodermitis zugelassen, im Verlauf erfolgten Zulassungen für weitere Indikationen wie das Asthma bronchiale sowie die chronische Rhinosinusitis mit Nasenpolypen.Prurigo nodularis (PN) ist eine chronische Dermatose, charakterisiert durch das Auftreten von stark juckenden Papeln und Nodi, meist am Stamm und an den Extremitäten. Die Patienten klagen über stechend-quälenden Juckreiz. Eine Besserung trotz intensivierter topischer und systemischer antipruriginöser Therapie wird meist nur erschwert erreicht. Dupilumab scheint vielversprechende antipruriginöse Effekte bei Prurigo nodularis zu haben, vergleichende Studien stehen jedoch aus. Wir demonstrieren hier 2 Patienten, die seit mehreren Jahren unter einer therapierefraktären Prurigo nodularis bei atopischer Diathese litten. Beide Patienten zeigten nach Beginn der Therapie mit Dupilumab eine rasche und anhaltende Besserung der pruriginösen Papeln. Relevante Nebenwirkungen traten nicht auf.
Herausforderungen der Prävalenz- und Inzidenzbestimmung in
der frühen Nutzenbewertung am Beispiel Urothelkarzinom
Authors: Wortmann Joelin , Wirth Daniel 
Published: May 2020

ZusammenfassungDurch das Arzneimittelmarktneuordnungsgesetz (AMNOG) 2011 ergeben sich
für die pharmazeutischen Hersteller strukturelle Veränderungen,
begründet durch die frühe Nutzenbewertung bei der
Markteinführung neuer Arzneimittel. Dadurch zeigen sich im Bereich der
Bestimmung der Zielpopulation bei der Prävalenz- und Inzidenzbestimmung
Herausforderungen. Selbst im selben Indikationsgebiet finden sich häufig
unterschiedliche Modelle zur Schätzung der Zielpopulation. Für
das Harnblasenkarzinom (ICD-10 C67), dem vierthäufigsten Tumor bei
Männern, gab es für die Behandlung lokal fortgeschrittener oder
metastasierter Karzinome zuletzt viele Fortschritte im Bereich der
Immuntherapien, die sich zum Vergleich der bestehenden Dossiers anbieten. Das
Ziel dieser Untersuchung war, die Qualität der Prävalenz- und
Inzidenzbestimmung der Dossiers im Indikationsgebiet Urothelkarzinom zu bewerten
und festzustellen, welche Handlungsempfehlungen sich für deren
zukünftige Bestimmung ableiten lassen. Auf der Grundlage des
Methodenpapiers des Instituts für Qualität und
Wirtschaftlichkeit im Gesundheitswesen sowie den Nutzenbewertungen und den
Beschlüssen des G-BA wurde diese Problematik beleuchtet. Der Vergleich
zeigte neben Gemeinsamkeiten bei der Nutzung der epidemiologischen Maße
Unterschiede bei den Berechnungsschritten der Zielpopulation, die zu Variationen
der Prävalenz und Inzidenz in den Dossiers führten. Die
Qualität der Dossiers unterscheidet sich v. a. in der
Nachvollziehbarkeit der Berechnungen und der Datengrundlage. Im Hinblick auf die
externe Validität und Generalisierbarkeit auf das deutsche
Gesundheitswesen besteht noch Verbesserungsbedarf.