bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational interactions define novel cancer subgroups
Authors: Kuipers Jack , Thurnherr Thomas , Moffa Giusi , Suter Polina , Behr Jonas , Goosen Ryan , Christofori Gerhard , Beerenwinkel Niko 
Published: October 2018

AbstractLarge-scale genomic data highlight the complexity and diversity of the molecular changes that drive cancer progression. Statistical analysis of cancer data from different tissues can guide drug repositioning as well as the design of targeted treatments. Here, we develop an improved Bayesian network model for tumour mutational profiles and apply it to 8198 patient samples across 22 cancer types from TCGA. For each cancer type, we identify the interactions between mutated genes, capturing signatures beyond mere mutational frequencies. When comparing mutation networks, we find genes which interact both within and across cancer types. To detach cancer classification from the tissue type we perform de novo clustering of the pancancer mutational profiles based on the Bayesian network models. We find 22 novel clusters which significantly improve survival prediction beyond clinical information. The models highlight key gene interactions for each cluster potentially allowing genomic stratification for clinical trials and identifying drug targets.
Engaging cervical spinal circuitry with non-invasive spinal stimulation and buspirone to restore hand function in chronic motor complete patients
Authors: Freyvert Yevgeniy , Yong Nicholas Au , Morikawa Erika , Zdunowski Sharon , Sarino Melanie E. , Gerasimenko Yury , Edgerton V. Reggie , Lu Daniel C. 
Published: October 2018

AbstractThe combined effects of cervical electrical stimulation alone or in combination with the monoaminergic agonist buspirone on upper limb motor function were determined in six subjects with motor complete (AIS B) injury at C5 or above and more than one year from time of injury. Voluntary upper limb function was evaluated through measures of controlled hand contraction, handgrip force production, dexterity measures, and validated clinical assessment batteries. Repeated measure analysis of variance was used to evaluate functional metrics, EMG amplitude, and changes in mean grip strength. In aggregate, mean hand strength increased by greater than 300% with transcutaneous electrical stimulation and buspirone while a corresponding clinically significant improvement was observed in upper extremity motor scores and the action research arm test. Some functional improvements persisted for an extended period after the study interventions were discontinued. We demonstrate that, with these novel interventions, cervical spinal circuitry can be neuromodulated to improve volitional control of hand function in tetraplegic subjects. The potential impact of these findings on individuals with upper limb paralysis could be dramatic functionally, psychologically, and economically.
Host lipid sensing promotes invasion of cells with pathogenic Salmonella
Authors: Shivcharan Sonia , Yadav Jitender , Qadri Ayub 
Published: October 2018

AbstractPathogenicSalmonellaspecies initiate infection by invading non-phagocytic intestinal epithelial cells (IEC). This invasion is brought about by a number ofSalmonellainvasion promoting molecules (Sips) encoded by theSalmonellaPathogenicity Island - 1 (SPI-1). Intracellular delivery of some of these molecules also brings about caspase-1 – mediated pyroptotic cell death that contributes to pathogen clearance. These molecules are secreted and delivered inside cells upon contact ofSalmonellawith one or more host signals whose identity has not been established. We show that lysophosphatidylcholine (LPC) released following activation of caspase-1 inSalmonella– infected cells and abundant in plasma amplifies production of Sips from this pathogen and promotes its cellular invasion. LPC brings about adenylate cyclase and cAMP receptor protein (CRP) - dependentde novosynthesis of SipC that is accompanied by its translocation to bacterial cell surface and release into the outside milieu. Treatment ofSalmonellawith LPC produces sustained induction of SPI - 1 transcriptional regulator, hilA. Our findings reveal a novel host lipid sensing - driven regulatory mechanism forSalmonellainvasion.
In-depth study on resonant tunneling for subwavelength imaging
Authors: Anzan-Uz-Zaman Md. , Song Kyungjun , Lee EunJoong , Hur Shin 
Published: October 2018

AbstractWe report new frequency bands for subwavelength imaging by using the resonant tunneling method which have not been explored previously. As per the existing theory of resonant tunneling, imaging frequency is limited for a certain number of crystals. However, after conducting an analytical analysis over a wide range of frequencies, we observed that higher frequencies do exist for subwavelength imaging. We verified this observation both numerically and experimentally. We extended our study to observe the effect of lattice periodicity on image resolution. By reducing periodicity during experiment, we achieved a resolution of λ/9.5 at the conventional region and λ/2.45 at the higher band region.
Tregitope-linked Refined Allergen Vaccines for Immunotherapy in Cockroach Allergy
Authors: Prangtaworn Pannathee , Chaisri Urai , Seesuay Watee , Mahasongkram Kodchakorn , Onlamoon Nattawat , Reamtong Onrapak , Tungtrongchitr Anchalee , Indrawattana Nitaya , Chaicumpa Wanpen , Sookrung Nitat 
Published: October 2018

AbstractAllergen-specific immunotherapy (AIT) facilitates long-term resolution of allergic morbidity resulting in reduced drug use and increased refractoriness to new sensitization. AIT effectiveness has been demonstrated in seasonal and perennial allergies, and insect stings. However, data and studies in AIT relative to cockroach (CR) allergy are relatively scarce. In this study, mice allergic to American CR (Periplaneta americana) were treated with a liposome (L)-entrapped vaccine made of mouse Tregitope289-Per a 9 of the CR, Tregitope167-Per a 9, or Per a 9 alone – or placebo. Allergic mice that received an individual vaccine intranasally had reduced Th2 response, reduced lung inflammation, and reduced respiratory tissue remodeling. However, only L-Tregitope289-Per a 9 and L-Tregitope167-Per a 9 induced expression of immunosuppressive cytokine genes (IL-10,TGF-β, andIL-35for L-Tregitope289-Per a 9, andIL-10andTGF-βfor L-Tregitope167-Per a 9) and increment of idoleamine-2,3-dioxygenase 1 (IDO1), indicating that these vaccines caused allergic disease suppression and reversal of respiratory tissue remodeling via generation of regulatory lymphocytes. Liposome entrapped-recombinant Per a 9 (L-Per a 9) did not cause upregulation of immunosuppressive cytokine genes and IDO1 increment; rather, L-Per a 9 induced high expression ofIFN-γin lungs of treated mice, which resulted in mitigation of allergic manifestations. This study provides compelling evidence that both liposome-entrapped vaccines made of single refined major allergen alone and single refined major allergen linked with Tregitopes are effective for reducing allergen-mediated respiratory tissue inflammation and remodeling, but through different mechanisms.
Synergistic and independent action of endogenous microRNAs 122a and 199a for post-transcriptional liver detargeting of gene vectors
Authors: Dhungel Bijay , Ramlogan-Steel Charmaine A. , Steel Jason C. 
Published: October 2018

AbstractIn hepatocellular carcinoma (HCC), which usually develops in a cirrhotic liver, treatments preserving normal liver function and viability are vitally important. Here, we utilise the differential expression of miRNAs 122a and 199a between normal hepatocytes and HCC to generate vectors harbouring their binding sites for hepatocyte detargeting. Using a reporter gene, we observed a synergistic detargeting of cells expressing both miRNAs as well as cells expressing either of the miRNAs; while expression was retained in HCC cells negative for both miRNA122a and miRNA199a. Mimics and inhibitors for individual miRNAs were used to confirm these results. Furthermore, suicide gene therapy with cytosine deaminase (CD)/5-fluorocytosine system resulted in limited killing of cells expressing either of the two miRNAs. Finally, we report feasibility of using adeno associated virus (AAV) based vectors for delivery of this dual regulated gene delivery system. These results present a novel dual targeted system whereby miRNA122a and miRNA199a act either synergistically or independently in regulating transgene expression with vectors harbouring binding sites of both miRNAs and have implications in detargeting vectors from multiple cell types in the liver.
Carnivory in the larvae of Drosophila melanogaster and other Drosophila species
Authors: Yang Daxiang 
Published: October 2018

AbstractDrosophila melanogaster is widely used as a model organism for biological investigations, and food is a major aspect of its ecology and evolutionary biology. Previous studies have shown that this insect can use fruits, yeasts and insect carcasses as its food sources. In this study, we demonstrate that this species is an omnivore, that its larvae can exploit not only fruits and yeast but also foods of animal origin (FAOs), and that larvae consume adult carcasses regularly. FAO-fed larvae develop into adulthood within a normal developmental time frame without the help of microbes. Yeast foods are better for Drosophila development than are foods of plant origin (FPOs) or FAO because in yeast foods, more eggs complete their life cycle, and the body size of emerged flies is much greater. Flies can use a mixture of yeast-FAO, which significantly boosts female fertility. Larvae digest FAOs externally. Larval D. virilis, D. hydei, and D. simulans are also omnivorous and demonstrate the same feeding habits as larval D. melanogaster. These findings prompt us to reconsider previous conclusions about the original adaptations of D. melanogaster and other Drosophila species and have direct implications for diet-related studies using Drosophila as a model organism.
Coating two-dimensional MoS2 with polymer creates a corrosive non-uniform interface
Authors: Thi Quoc Huy , Kim Hyun , Zhao Jiong , Ly Thuc Hue 
Published: October 2018

AbstractTwo-dimensional (2D) materials and soft materials are both susceptible to mechanical instabilities, such as buckling, wrinkling, folding and creasing, especially when located on surfaces. Here, we report that weak van der Waals interactions cause the interface between 2D molybdenum disulphide (MoS2) and a soft poly(methyl methacrylate) coating to demonstrate mechanical instability and delamination. The resulting non-uniform and buckled interface greatly hampers the ability of the coating to protect the MoS2 substrate. Also, the corrosion rate of 2D MoS2 and quench rate of intrinsic luminescence in 2D MoS2 were significantly accelerated by the soft coating. Owing to the formation of corrosive cavities at the interface, the geometry and size of the flakes became the dominating factor, and a critical size of 2D flakes for such interfacial instability was determined based on elasticity theory. Such hazardous corrosion in a 2D material caused by a soft coating raises concern for their use in electronic packaging, and for the processing of van der Waals-layered materials for future applications.
Nicht elektive thoraxchirurgische Operationen bei Patienten mit respiratorischer Insuffizienz und Einsatz einer venovenösen extrakorporalen Membranoxygenierung
Authors: Sommerauer Laura , Philipp Alois , Lubnow Matthias , Müller Thomas , Lunz Dirk , Hofmann Hans-Stefan , Ried Michael 
Published: October 2018

Zusammenfassung
Hintergrund Patienten mit schwerer respiratorischer Insuffizienz und venovenöser extrakorporaler Membranoxygenierung (vv-ECMO) benötigen häufig eine diagnostische oder therapeutische thoraxchirurgische Intervention.
Material und Methode Retrospektive Analyse von prospektiv erhobenen Daten (Regensburger ECMO-Register) aller Patienten im Zeitraum von Dezember 2010 bis Dezember 2016, die aufgrund eines akuten Lungenversagens (ALV) mit einer vv-ECMO behandelt wurden und bei denen eine diagnostische oder therapeutische thoraxchirurgische Operation (TCH-OP) durchgeführt wurde. Endpunkte waren die Indikation zur TCH-OP sowie die postoperative Morbidität und Letalität.
Ergebnis Es wurden 418 Patienten (m = 285, 68%; mittleres Alter 50,0 ± 16,5 Jahre) mit einer vv-ECMO behandelt. Die häufigsten Indikationen zur vv-ECMO waren ein ALV bei Pneumonie (59,8%), postoperativ (18,7%), posttraumatisch (9,8%), nach Chemotherapie (2,8%) oder sonstigen Gründen (8,9%). Insgesamt wurden 102 (24,4%) Patienten unter vv-ECMO operiert, davon 29 Patienten (28,4%) thoraxchirurgisch. Die häufigste primäre Indikation für eine TCH-OP war therapeutisch bei Hämatothorax (n = 13; 44,8%), gefolgt von karnifizierender Pneumonie/Lungenabszess (n = 5; 17,2%), Pleuraempyem (n = 3; 10,3%) und sonstigen Ursachen (n = 3; 10,3%). Bei interstitieller Lungenerkrankung unklarer Genese (n = 5; 17,2%) erfolgte eine diagnostische Lungenbiopsie. Bei den Ersteingriffen wurde bei 27 Patienten eine Thorakotomie (93,1%), seltener eine VATS (n = 2; 6,9%) durchgeführt. Mindestens eine Rethorakotomie erfolgte in 15 Patienten (51,7%) und 9 Patienten (31,0%) wurden mehr als 2 × operiert. Die Letalität im Krankenhaus der Patienten mit TCH-OP (44,8%) war höher als die der Patienten ohne TCH-OP (35,7%; p = 0,326).
Schlussfolgerung Die Indikationen für eine thoraxchirurgische Operation bei Patienten mit vv-ECMO sollten streng gestellt werden, da häufig postoperative Komplikationen mit einer hohen Reoperationsrate (58,6%) auftreten. Daher sollte eine ECMO-Therapie nur in spezialisierten Zentren mit thoraxchirurgischer Expertise erfolgen.
Wall Shear Stress in the Feeding Native Conduit Arteries of Superficial Arteriovenous Malformations of the Lower Face is a Reliable Marker of Disease Progression
Authors: El sanharawi Imane , Barral Matthias , Lenck Stéphanie , Dillinger Jean Guillaume , Salvan Didier , Mangin Gabrielle , Cogo Adrien , Bailliart Olivier , Levy Bernard I. , Kubis Nathalie , Bisdorff-Bresson Annouk , Bonnin Philippe 
Published: October 2018

Abstract
Purpose To assess the prognostic value of the wall shear stress (WSS) measured in the feeding native arteries upstream from facial superficial arteriovenous malformations (sAVMs). Reliable prognostic criteria are needed to distinguish progressive from stable sAVMs and thus support the indication for an aggressive or a conservative management to avoid severe facial disfigurement.
Materials and Methods We prospectively included 25 patients with untreated facial sAVMs, 15 patients with surgically resected sAVMs and 15 controls. All had undergone Doppler ultrasound examination (DUS) with measurements of inner diameters, blood flow velocities, computation of blood flow and WSS of the feeding arteries. Based on the absence or presence of progression in clinical and imaging examinations 6 months after, we discriminated untreated patients as stable or progressive.
Results WSS in the ipsilateral external carotid artery was higher in progressive compared to stable sAVMs (15.8 ± 3.3dynes/cm² vs. 9.6 ± 2.0dynes/cm², mean±SD, p < 0.0001) with a cut-off of 11.5dynes/cm² (sensitivity: 92 %, specificity: 92 %, AUC: 0.955, [95 %CI: 0.789–0.998], p = 0.0001). WSS in the ipsilateral facial artery was also higher in progressive compared to stable sAVMs (50.7 ± 14.5dynes/cm² vs. 25.2 ± 7.1dynes/cm², p < 0.0001) with a cut-off of 34.0dynes/cm² (sensitivity: 100 %, specificity: 92 %, AUC: 0.974, [95 %CI: 0.819–1.000], p = 0.0001). The hemodynamic data of operated patients were not different from those of the control group.
Conclusion WSS measured in the feeding arteries of an sAVM may be a simple reliable criterion to distinguish stable from progressive sAVMs. This value should be considered to guide the therapeutic strategy as well as the long-term follow-up of patients with facial sAVMs.
Systematische Übersichtsarbeit: moderne Behandlungsverfahren beim postoperativen Chylothorax
Authors: Stange Sebastian , Sziklavari Zsolt 
Published: October 2018

Zusammenfassung
Hintergrund Der Chylothorax ist i. d. R. eine multifaktorielle Komplikation nach Operationen oder Unfällen, seltener die Folge von Tumoren. Da prospektive, randomisierte Studien fehlen, beruht die evidenzbasierte Behandlung auf persönlichen Erfahrungen, im Idealfall erfolgt sie in Kenntnis retrospektiver Analysen.
Material und Methoden Ziel dieser Übersichtsarbeit ist es, einen umfassenden Überblick über die aktuell zur Verfügung stehenden modernen Behandlungsverfahren beim postoperativen Chylothorax zu geben sowie ihre Vor- und Nachteile aufzuzeigen. Hierzu erfolgte eine Literaturrecherche in der Datenbank „PubMed“ unter Beschränkung auf Publikationen der letzten 10 Jahre. Für die Recherche wurde das Schlüsselwort „Chylothorax“ eingesetzt. Der Schwerpunkt lag auf den Publikationen, die eine vergleichende Bewertung der Behandlungsmöglichkeiten beinhalten. Bei der kritischen Analyse der Therapieansätze und Empfehlungen wurden Reviews der letzten 5 Jahre bevorzugt, des Weiteren stützten sich die Autoren auf eine kumulative langjährige klinische Erfahrung.
Ergebnisse Der Erfolg einer konservativen Behandlung zeigt in Abhängigkeit von der Ätiologie eine große Streuungsbreite (3 – 90%). Die Erfolgsrate der nicht invasiven oder semiinvasiven Verfahren liegt zwischen 50 und 100%, ebenfalls in Abhängigkeit von der Ätiologie. Bei einer erfolglosen konservativen Behandlung operabler Patienten besteht die chirurgische Standardtherapie in der meist thorakoskopisch durchgeführten Ligatur des Ductus thoracicus. Alternativ kann eine Pleurodese oder die Platzierung einer permanenten Thoraxdrainage oder eines pleuroperitonealen Shunts durchgeführt werden. Die Erfolgsrate dieser Eingriffe liegt zwischen 64 und 100%. Die Morbiditäts- und Mortalitätsrate kann hierbei Werte bis zu 25% erreichen.
Schlussfolgerung Die Behandlung eines Chylothorax sollte konservativ begonnen werden. Anschließend kann stufenweise eine aggressivere Therapie empfohlen werden, wobei der Zustand des Patienten und das Drainagevolumen den Entscheidungsprozess steuern. Interventionelle radiologische Verfahren sind sicher in der Anwendung bei gleichzeitig hoher Erfolgsquote und haben somit einen berechtigten Platz neben der konservativen Behandlung bzw. den operativen Verfahren. Sie stehen allerdings aktuell nur in einigen größeren Zentren zur Verfügung.
Pene No Conspicuo (Oculto)
Authors: Fernández Nicolás , Puerto Niño Angie , Iregui Parra Juan , Pérez Niño Jaime 
Published: October 2018

ResumenEl término pene no conspicuo (oculto), agrupa las patologías en las que el pene adopta un tamaño aparentemente más pequeño, ya sea porque se oculta bajo el tejido cicatricial en caso del pene atrapado, cuando presenta un pliegue de piel que reduce el ángulo penoescrotal tratándose del pene en vela, o en los casos en los que el pene es cubierto por prepucio redundante produciendo un pene enterrado. Se realiza una revisión de la definición y terminología utilizada a través de la historia, clasificación actual, etiología, diagnóstico y técnica quirúrgica empleada para la corrección del pene no conspicuo (oculto).
Futility and Patients Who Insist on Medically Ineffective Therapy
Authors: Cifrese Laura , Rincon Fred 
Published: October 2018

AbstractAs medical decisions fall under more scrutiny and society demands increasing transparency of care, it is likely that more opportunities for conflicts will emerge. Similarly, with increasing demand and a static supply, the issue of who receives treatment and for how long naturally will arise. This mismatch leads to discussions of resource utilization and limitation of care in light of patients' values and rights. Clinicians should always be forthcoming with the uncertainty of prognostication while also articulating the severity of a patient's disease in relation to the risk and benefits of an intervention. However, dispute over treatment course and the idea of futile care can arise for in a variety of reasons, both from the clinician and the patient. Without identifying the cause of these conflicts, it is impossible to have effective communication. At times, it is important to utilize various negotiating skills when resolving these disagreements. Regardless of the approach, practitioners need more training in and exposure to these types of conflicts. In this review, we provide a framework for the origins and current state of futility, challenges in the application of the term, and recommendations on how to approach conflict in these situations.
Ethical Issues Pertaining to Conflicts of Interest Between Neurologists and the Pharmaceutical and Medical Device Industries
Authors: Robbins Nathaniel 
Published: October 2018

AbstractA conflict of interest (COI) exists when a physician's professional responsibilities are compromised by personal or financial relationships. COIs between physicians and the pharmaceutical or medical device industry (Industry) are common. Collaborations with Industry have many potential benefits, but also raise potential ethical pitfalls. Industry-related COIs have widespread influence on medical education, research, and clinical practice, and therefore have profound implications for the integrity of the field of medicine. Full disclosure is an important step toward mitigating COI but does not redress subconscious accompanying biases. I review the spectrum of potential COI faced by physicians, with a focus on the ethics surrounding the relationship between neurologists and Industry. Other financial and nonfinancial COIs that influence neurologists and nonindividual entities, such as academic institutions, medical journals, and professional societies, are also discussed. Solutions ranging from disclosure to avoidance and recusal are briefly considered.
Adaptation limits ecological diversification and promotes ecological tinkering during the competition for substitutable resources
Authors: Good Benjamin H. , Martis Stephen , Hallatschek Oskar 
Published: October 2018

Significance
Most mutations are subject to competitive exclusion: Their descendants will either take over the population or go extinct. In special cases, a mutant may evade competitive exclusion by exploiting a different ecological niche. Both types of mutations can be found in large microbial populations, yet little is known about how they interact. By generalizing consumer-resource theory to include heritable beneficial mutations, we show that interactions between diversification and competitive exclusion can produce dramatic departures from existing models of evolution or ecology alone. These results suggest that short-term evolutionary processes could play an important role in shaping the structure of microbial communities.
Disorder induced power-law gaps in an insulator–metal Mott transition
Authors: Wang Zhenyu , Okada Yoshinori , O’Neal Jared , Zhou Wenwen , Walkup Daniel , Dhital Chetan , Hogan Tom , Clancy Patrick , Kim Young-June , Hu Y. F. , Santos Luiz H. , Wilson Stephen D. , Trivedi Nandini , Madhavan Vidya 
Published: October 2018

Significance
Correlated electron systems often show unexpected behavior that defies theoretical explanations. One such mystery is the universal presence of V-shaped gaps with surprisingly linear energy dependence, whose origins are as-yet unknown. Conventional wisdom implicates static order like charge density waves or fluctuations of a nearby order parameter like superconductivity or antiferromagnetism. However, adding dopants to correlated systems inevitably leads to the opposite of order—i.e., electronic disorder—which begs the question: Could disorder create well-defined signatures in electronic properties? By carefully choosing a material with no additional order, we show that order is not the only path to gaps and that disorder may play a surprising role in generating universal signatures in the density of states of disordered correlated systems.