bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulated Redox Regulation Contributes to Nuclear EGFR Localization and Pathogenicity in Lung Cancer
Authors: Little Andrew C. , Hristova Milena , van Lith Loes , Schiffers Caspar , Dustin Christopher M. , Habibovic Aida , Danyal Karamatullah , Heppner David E. , Lin Miao-Chong J. , van der Velden Jos , Janssen-Heininger Yvonne M. , van der Vliet Albert 
Published: March 2019

AbstractLung cancers are frequently characterized by inappropriate activation of epidermal growth factor receptor (EGFR)-dependent signaling and epigenetic silencing of the NADPH oxidase (NOX) enzyme DUOX1, both potentially contributing to worse prognosis. Based on previous findings linking DUOX1 with redox-dependent EGFR activation, the present studies were designed to evaluate whether DUOX1 silencing in lung cancers may be responsible for altered EGFR regulation. In contrast to normal epithelial cells, EGF stimulation of lung cancer cell lines that lack DUOX1 promotes EGF-induced EGFR internalization and nuclear localization, associated with induction of EGFR-regulated genes and related tumorigenic outcomes. Each of these outcomes could be reversed by overexpression of DUOX1 or enhanced by shRNA-dependent DUOX1 silencing. EGF-induced nuclear EGFR localization in DUOX1-deficient lung cancer cells was associated with altered dynamics of cysteine oxidation of EGFR, and an overall reduction of EGFR cysteines. These various outcomes could also be attenuated by silencing of glutathione S-transferase P1 (GSTP1), a mediator of metabolic alterations and drug resistance in various cancers, and a regulator of cysteine oxidation. Collectively, our findings indicate DUOX1 deficiency in lung cancers promotes dysregulated EGFR signaling and enhanced GSTP1-mediated turnover of EGFR cysteine oxidation, which result in enhanced nuclear EGFR localization and tumorigenic properties.
Impact of predictive medicine on therapeutic decision making: a randomized controlled trial in congenital heart disease
Authors: Naci Huseyin , Salcher-Konrad Maximilian , Mcguire Alistair , Berger Felix , Kuehne Titus , Goubergrits Leonid , Muthurangu Vivek , Wilson Ben , Kelm Marcus 
Published: March 2019

AbstractComputational modelling has made significant progress towards clinical application in recent years. In addition to providing detailed diagnostic data, these methods have the potential to simulate patient-specific interventions and to predict their outcome. Our objective was to evaluate to which extent patient-specific modelling influences treatment decisions in coarctation of the aorta (CoA), a common congenital heart disease. We selected three cases with CoA, two of which had borderline indications for intervention according to current clinical guidelines. The third case was not indicated for intervention according to guidelines. For each case, we generated two separate datasets. First dataset included conventional diagnostic parameters (echocardiography and magnetic resonance imaging). In the second, we added modelled parameters (pressure fields). For the two cases with borderline indications for intervention, the second dataset also included pressure fields after virtual stenting simulations. All parameters were computed by modelling methods that were previously validated. In an online-administered, invitation-only survey, we randomized 178 paediatric cardiologists to view either conventional (control) or add-on modelling (experimental) datasets. Primary endpoint was the proportion of participants recommending different therapeutic options: (1) surgery or catheter lab (collectively, “intervention”) or (2) no intervention (follow-up with or without medication). Availability of data from computational predictive modelling influenced therapeutic decision making in two of three cases. There was a statistically significant association between group assignment and the recommendation of an intervention for one borderline case and one non-borderline case: 94.3% vs. 72.2% (RR: 1.31, 95% CI: 1.14–1.50, p = 0.00) and 18.8% vs. 5.1% (RR: 3.09, 95% CI: 1.17–8.18, p = 0.01) of participants in the experimental and control groups respectively recommended an intervention. For the remaining case, there was no difference between the experimental and control group and the majority of participants recommended intervention. In sub-group analyses, findings were not affected by the experience level of participating cardiologists. Despite existing clinical guidelines, the therapy recommendations of the participating physicians were heterogeneous. Validated patient-specific computational modelling has the potential to influence treatment decisions. Future studies in broader areas are needed to evaluate whether differences in decisions result in improved outcomes (Trial Registration: NCT02700737).
Associations between H19 polymorphisms and neuroblastoma risk in Chinese children
Authors: Hu Chao , Yang Tianyou , Pan Jing , Zhang Jiao , Yang Jiliang , He Jing , Zou Yan 
Published: March 2019

Abstract
Background H19 polymorphisms have been reported to correlate with an increased susceptibility to a few types of cancers, although their role in neuroblastoma has not yet been clarified.
Materials and methods We investigated the association between three single polymorphisms (rs2839698 G&gt;A, rs3024270 C&gt;G, and rs217727 G&gt;A) and neuroblastoma susceptibility in Chinese Han populations. Three hundred ninety-three neuroblastoma patients and 812 healthy controls were enrolled from the Henan and Guangdong provinces. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to determine the strength of the association of interest.
Results Separated and combined analyses revealed no associations of the rs2839698 G&gt;A, rs3024270 C&gt;G or rs217727 G&gt;A polymorphisms and neuroblastoma susceptibility. In the stratification analysis, female children with rs3024270 GG genotypes had an increased neuroblastoma risk (adjusted OR = 1.61, 95% CI = 1.04–2.50, P=0.032).
Conclusion The rs3024270 GG genotype might contribute to an increased neuroblastoma susceptibility in female Chinese children.
Potential therapeutic targets for atherosclerosis in sphingolipid metabolism
Authors: Yu Zemou , Peng Qing , Huang Yining 
Published: March 2019

Abstract
Sphingolipids, such as sphingomyelins, ceramides, glycosphingolipids, and sphingosine-1-phosphates (S1P) are a large group of structurally and functionally diverse molecules. Some specific species are found associated with atherogenesis and provide novel therapeutic targets. Herein, we briefly review how sphingolipids are implicated in the progression of atherosclerosis and related diseases, and then we discuss the potential therapy options by targetting several key enzymes in sphingolipid metabolism.
Immunological abnormalities in patients with primary biliary cholangitis
Authors: Ma Wen-Tao , Chen De-Kun 
Published: March 2019

Abstract
Primary biliary cholangitis (PBC), an autoimmune liver disease occurring predominantly in women, is characterized by high titers of serum anti-mitochondrial antibodies (AMAs) and progressive intrahepatic cholestasis. The immune system plays a critical role in PBC pathogenesis and a variety of immune cell subsets have been shown to infiltrate the portal tract areas of patients with PBC. Amongst the participating immune cells, CD4 T cells are important cytokine-producing cells that foster an inflammatory microenvironment. Specifically, these cells orchestrate activation of other immune cells, including autoreactive effector CD8 T cells that cause biliary epithelial cell (BEC) injury and B cells that produce large quantities of AMAs. Meanwhile, other immune cells, including dendritic cells (DCs), natural killer (NK) cells, NKT cells, monocytes, and macrophages are also important in PBC pathogenesis. Activation of these cells initiates and perpetuates bile duct damage in PBC patients, leading to intrahepatic cholestasis, hepatic damage, liver fibrosis, and eventually cirrhosis or even liver failure. Taken together, the body of accumulated clinical and experimental evidence has enhanced our understanding of the immunopathogenesis of PBC and suggests that immunotherapy may be a promising treatment option. Herein, we summarize current knowledge regarding immunological abnormalities of PBC patients, with emphasis on underlying pathogenic mechanisms. The differential immune response which occurs over decades of disease activity suggests that different therapies may be needed at different stages of disease.
Spectral width reduction of a laser source by external phase noise compensation
Authors: Thuy H.T. , Won Y.Y. , Seo D.S. 
Published: March 2019

A method to reduce the spectral linewidth of a laser source by direct phase noise compensation is proposed and demonstrated experimentally. To extract the phase noise information, the laser output is phase modulated and the in‐ and quadrature‐phases are detected by homodyne mixing. Phase noise compensation is achieved by simply applying an error signal to an external phase modulator, where the error signal is generated to keep the same power level for the detected in‐ and quadrature‐signals. The spectral linewidth of the laser is reduced significantly from 450 to 60 kHz.
Die Biologie der orthodontischen Zahnbewegung – Status quo der Forschung
Authors: Husari Ayman , Jung Britta 
Published: March 2019

ZusammenfassungDie orthodontische Zahnbewegung involviert Zellen des Parodonts und deren Moleküle. Durch die Verbindung von Matrix und Zellen, reagieren die Zellen hierbei mit der Expression bestimmter Moleküle, die dann die Umbauprozesse im Ligament und später im Knochen induzieren, sodass die Zahnbewegung ablaufen kann.
Geschlechterspezifische Inanspruchnahme von Gesundheitsleistungen in einer urbanen Erwachsenenpopulation
Authors: Keil Jan , Brendler Verena , Sachse Catherina , Zülke Andrea , Zeynalova Samira , Engel Christoph , Loeffler Markus , Riedel-Heller Steffi G. , König Hans-Helmut , Stengler Katarina 
Published: March 2019

Zusammenfassung
Ziel der Studie Ziel der Studie ist es, Ergebnisse zur geschlechterspezifischen Inanspruchnahme von Gesundheitsleistungen in einer urbanen Erwachsenenpopulation bereitzustellen.
Methoden Im Zuge der LIFE-ADULT-Studie wurden 2244 Erwachsene (19–79 Jahre) zum Inanspruchnahmeverhalten von Gesundheitsleistungen innerhalb des letzten Jahres befragt. Die Angaben zu Haus- und Facharztkonsultation, hausärztliche Beratung sowie Inanspruchnahme präventiver- bzw. gesundheitsfördernder Maßnahmen wurden ausgewertet.
Ergebnisse Frauen nahmen innerhalb eines Jahres häufiger Haus- oder Fachärzte sowie präventive bzw. gesundheitsfördernde Maßnahmen in Anspruch. Keine Geschlechterunterschiede ergaben sich bezüglich der hausärztlichen Beratungshäufigkeit.
Schlußfolgerung Die vorliegende Studie bestätigt weitestgehend bisherige Befunde zur häufigeren Inanspruchnahme von Gesundheitsleistungen seitens der Frauen. Allerdings zeigt sich auch, dass die geschlechterspezifische Inanspruchnahme vom verwendeten Indikator abhängig ist und daher stets differenziert diskutiert werden sollte.
Die Nadeln im Heuhaufen finden: Qualitätskriterien für den Einsatz von internetbasierten Selbstmanagement-Interventionen in Prävention und Behandlung psychischer Störungen
Authors: Klein Jan Philipp , Knaevelsrud Christine , Bohus Martin , Ebert David Daniel , Gerlinger Gabriel , Günther Kristina , Jacobi Corinna , Löbner Margrit , Riedel-Heller Steffi G. , Sander Julia , Sprick Ulrich , Hauth Iris 
Published: March 2019

ZusammenfassungZahlreiche Selbstmanagement Interventionen haben in randomisierten Studien ihre Wirksamkeit in der Behandlung von einer Reihe von psychischen Störungen gezeigt. Dennoch sind diese Interventionen gegenwärtig noch nicht überall in der klinischen Routine angekommen. Das liegt unter anderem daran, dass neben den evidenzbasierten Interventionen auch Interventionen angeboten werden, die nie wissenschaftlich untersucht worden sind und teilweise noch nicht einmal auf evidenzbasierten Psychotherapiemethoden beruhen. Die vorliegenden Qualitätskriterien der beiden Fachgesellschaften DGPs und DGPPN sollen Betroffenen, Behandlern und Entscheidern im Gesundheitswesen helfen, sichere und wirksame Interventionen zu identifizieren. Im Mittelpunkt der Qualitätskriterien stehen die Sicherheit der Patienten und ihrer Daten; die Sicherstellung der therapeutischen Qualität durch Rückgriff auf evidenzbasierte Psychotherapiemethoden und Begleitung der Entwicklung durch approbierte Psychotherapeuten oder Fachärzte; das Vorliegen eines Wirksamkeitsnachweises aus mindestens einer randomisierten Studie; und die Transparenz bezüglich zentraler Informationen, z. B. der Kosten der Intervention. Wir hoffen, dass diese Kriterien dazu beitragen können, dass Selbstmanagement Interventionen in den Leistungskatalog der Krankenkassen aufgenommen werden.
Cascades Involving anti-Carbopalladation Steps: From Our Initial Hypothesis to Natural Product Synthesis
Authors: Schitter Theresa , Reding Andreas , Werz Daniel B. 
Published: March 2019

Our endeavors in the design, realization and application of a formal anti-carbopalladation of alkynes are summarized. Whereas numerous examples of syn-carbopalladation steps embedded in cascade reactions are known, there have been almost no examples of the corresponding anti-carbopalladation steps. From a personal perspective, this account provides insights on the original considerations and hypotheses, and their validation or invalidation by experimental and computational means. This account also aims at clarifying how different ideas have been developed and how novel reaction sequences paving the way to a plethora of different scaffolds have been designed. The reader will recognize the importance of the interplay between elucidating reaction mechanisms and developing novel methodologies. As a result, useful methods to create homo- and heterotetrasubstituted double bonds have been developed. The broad versatility of these methods has been demonstrated by a novel total synthesis of the indole alkaloid (+)-lysergol.1	Introduction2	Initial Studies3	Various Termination Steps4	Termination with Heteronucleophiles5	Natural Product Synthesis6	anti-Carbopalladations Realized by the Lautens Lab7	Conclusion and Outlook
Novel Coagulation Analyzers in Development: A Glimpse toward the Future of Microfluidics
Authors: Emani Sitaram 
Published: March 2019

AbstractCoagulation diagnostic testing in pediatric patients currently requires large volume blood sampling and is performed on analyzers that are not well-suited for multiplexed assays on a given sample. For patients who require serial testing at regular intervals, repetitive phlebotomy leads to iatrogenic anemia and need for blood transfusions. Over the past decade, novel microfluidic platforms have been developed that allow for complex multiplexed assays to be performed on small sample volumes, near patient, with high fidelity. In the next few years, these devices will be introduced into clinical trials, and offer the promise of reliable, rapid, multiplexed coagulation assays for pediatric patients who require coagulation diagnostic testing.
Antiquity of forelimb ecomorphological diversity in the mammalian stem lineage (Synapsida)
Authors: Lungmus Jacqueline K. , Angielczyk Kenneth D. 
Published: March 2019

Significance
Mammals and their closest fossil relatives use their shoulders and forelimbs for many functions, which is reflected by the great range of mammalian forelimb shapes. We found that forelimb shape diversity in the early mammalian lineage (Synapsida) began to increase about 270 million years ago, with the emergence of a group called Therapsida, and is accompanied by new forelimb functions. The functional diversification of therapsid forelimbs was curtailed by the Permo-Triassic mass extinction, but eventually continued as more mammal-like therapsids evolved new ecologies. Our analyses characterize the deep time origin of a quintessential part of the mammalian body plan: evolutionarily labile forelimbs that can be deployed in a wide range of functional and ecological roles.
Measuring the impact of interaction between children of a matrilineal and a patriarchal culture on gender differences in risk aversion
Authors: Liu Elaine M. , Zuo Sharon Xuejing 
Published: March 2019

Significance
Studies show that women are more risk averse than men. We explore sources and malleability of such differences in a setting where children of two culturally distinct populations, the matrilineal Mosuo and the traditionally patriarchal Han, come together to attend school. Using survey and field experiments, we elicit individual risk attitudes from elementary and middle school students from the two populations. When they first enter school, Mosuo girls take more risks than Mosuo boys, while Han girls are more risk averse than Han boys, reflecting cultural differences. However, after spending time in the majority-Han environment, Mosuo children adopt the risk preferences of the majority. This shows that risk preferences are shaped by culture and malleable in response to new environments.
ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis
Authors: Shanbhag Vinit , Jasmer-McDonald Kimberly , Zhu Sha , Martin Adam L. , Gudekar Nikita , Khan Aslam , Ladomersky Erik , Singh Kamlendra , Weisman Gary A. , Petris Michael J. 
Published: March 2019

Significance
The family of copper-dependent lysyl oxidase (LOX) enzymes contributes to tumor metastasis. In this study, we show that the ATP7A copper transporter is required to deliver copper to LOX family members. Deletion of ATP7A inhibited LOX activity in breast and lung cancer cell lines, resulting in a significant loss of tumor growth and metastatic potential of these cells in mice. Elevated expression of ATP7A was found to be associated with reduced survival of breast cancer patients. Our study suggests that blocking the function of ATP7A could be an approach to inhibiting LOX-dependent malignancies.
Key role of soluble epoxide hydrolase in the neurodevelopmental disorders of offspring after maternal immune activation
Authors: Ma Min , Ren Qian , Yang Jun , Zhang Kai , Xiong Zhongwei , Ishima Tamaki , Pu Yaoyu , Hwang Sung Hee , Toyoshima Manabu , Iwayama Yoshimi , Hisano Yasuko , Yoshikawa Takeo , Hammock Bruce D. , Hashimoto Kenji 
Published: March 2019

Significance
Maternal immune activation (MIA) plays a role in neurodevelopmental disorders such as schizophrenia and autism spectrum disorder (ASD); however, the precise mechanisms of its etiology remain largely unknown. Soluble epoxide hydrolase (sEH) plays a role in the inflammation associated with MIA. Expression of sEH protein in the prefrontal cortex of juvenile offspring after MIA was higher than controls. Expression of sEH mRNA in neurospheres from induced pluripotent stem cells of schizophrenia patients with the 22q11.2 deletion and in the postmortem brains from ASD patients was higher than controls. Treatment with sEH inhibitor could prevent the onset of behavioral abnormalities in offspring after MIA. Our findings indicate that sEH inhibitors are promising prophylactic or therapeutic drugs for neurodevelopmental disorders in offspring after MIA.
Biomaterials-aided mandibular reconstruction using in vivo bioreactors
Authors: Tatara Alexander M. , Koons Gerry L. , Watson Emma , Piepergerdes Trenton C. , Shah Sarita R. , Smith Brandon T. , Shum Jonathan , Melville James C. , Hanna Issa A. , Demian Nagi , Ho Tang , Ratcliffe Anthony , van den Beucken Jeroen J. J. P. , Jansen John A. , Wong Mark E. , Mikos Antonios G. 
Published: March 2019

Significance
People may suffer large losses of mandibular (jaw) bone due to cancer, infection, trauma, congenital disease, or other disorders. The resulting bony defects are both aesthetically disfiguring and functionally disabling. We have designed a strategy to use biomaterials and 3D printing to leverage the body’s own innate healing capacity to generate customized engineered tissues that fit the patient’s defect. Using a large animal (sheep) model, we 3D printed bioreactors, filled them with biomaterial scaffold materials, and implanted them against the ribs to grow customized bony tissues. These tissues were then successfully surgically transplanted to repair a large defect in the sheep mandible. This approach results in tissue flaps with custom geometry and reduced risk of rejection.
Triggering of a Dll4–Notch1 loop impairs wound healing in diabetes
Authors: Zheng Xiaowei , Narayanan Sampath , Sunkari Vivekananda Gupta , Eliasson Sofie , Botusan Ileana Ruxandra , Grünler Jacob , Catrina Anca Irinel , Radtke Freddy , Xu Cheng , Zhao Allan , Ekberg Neda Rajamand , Lendahl Urban , Catrina Sergiu-Bogdan 
Published: March 2019

Significance
Diabetic foot ulcerations (DFUs) represent a major medical and economic problem with still-unclear pathogenic mechanisms. The Notch pathway plays a pivotal role in cell differentiation, proliferation, and angiogenesis, processes that are profoundly disturbed in diabetic wounds. Notch signalling is activated upon interactions between membrane-bound Notch receptors (Notch 1–4) and ligands (Jagged 1–2 and Delta-like 1, 3, 4). Here, we report that a specific positive Delta-like 4–Notch1 feedback loop is activated by high glucose levels and specifically impairs wound healing in diabetes. Local inhibition of Notch signalling in experimental wounds using chemical and genetic approaches markedly improves healing exclusively in diabetic, but not in nondiabetic, animals, making Notch1 signalling an attractive locally therapeutic target for the treatment of DFUs.
Spontaneity and Self-Consciousness in theGroundworkand the B-Critique
Authors: Choi Yoon 
Published: March 2019

AbstractAccording to some influential readings of theGroundwork of the Metaphysics of Morals, the view presented there of the kind of spontaneity we are conscious of through theoretical reason and the significance of such self-consciousness is irremediably at odds with the Critical theory, and thus roundly and rightly rejected in the second edition of theCritique of Pure Reasonand theCritique of Practical Reason. This paper argues, on the contrary, that theGroundworkcan be read as articulating for the first time the account of self-consciousness and spontaneity that Kant goes on to develop in the B-Critique, especially the B-Transcendental Deduction.