bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cisplatin-induced ototoxicity in organotypic cochlear cultures occurs independent of gap junctional intercellular communication
Authors: Abitbol Julia , Beach Rianne , Barr Kevin , Esseltine Jessica , Allman Brian , Laird Dale 
Published: May 2020

AbstractCisplatin is a very effective chemotherapeutic, but severe and permanent hearing loss remains a prevalent side effect. The processes underpinning cisplatin-induced ototoxicity are not well understood. Gap junction channels composed of connexin (Cx) subunits allow for the passage of small molecules and ions between contacting neighboring cells. These specialized channels have been postulated to enhance cisplatin-induced cell death by spreading “death signals” throughout the supporting cells of the organ of Corti. This study sought to investigate the role of Cx43 in cisplatin-induced ototoxicity using organotypic cochlear cultures from control and two Cx43-mutant mouse strains harboring either a moderate (Cx43I130T/+) or severe (Cx43G60S/+) reduction of Cx43 function. Cochlear cultures from Cx43-mutant mice with a severe reduction in Cx43-based gap junctional intercellular communication (GJIC) had an enhanced number of hair cells that were positive for cleaved caspase 3, a marker of active apoptosis, after cisplatin treatment. In cisplatin-treated organotypic cochlear cultures, there was a decrease in the co-localization of Cx26 and Cx30 compared with untreated cultures, suggesting that cisplatin causes reorganization of connexin composition in supporting cells. Both Cx26 and Cx30 protein expression as well as GJIC were decreased in organotypic cochlear cultures treated with the gap-junction blocker carbenoxolone. When cisplatin and carbenoxolone were co-administered, there were no differences in hair cell loss compared with cisplatin treatment alone. Using cisplatin-treated control and Cx43-ablated organ of Corti derived HEI-OC1 mouse cells, we found that greatly reducing GJIC led to preferential induction of an ER stress pathway. Taken together, this study strongly suggests that inhibition of GJIC in organ of Corti cells does not lead to differential susceptibility to cisplatin-induced ototoxicity. Although cisplatin causes the same degree of cell death in gap junction competent and incompetent cochlear cells, the engagement of the mitochondrial dysregulation and ER stress differs.
Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity
Authors: Kim Sangman M. , DeFazio Jennifer R. , Hyoju Sanjiv K. , Sangani Kishan , Keskey Robert , Krezalek Monika A. , Khodarev Nikolai N. , Sangwan Naseer , Christley Scott , Harris Katharine G. , Malik Ankit , Zaborin Alexander , Bouziat Romain , Ranoa Diana R. , Wiegerinck Mara , Ernest Jordan D. , Shakhsheer Baddr A. , Fleming Irma D. , Weichselbaum Ralph R. , Antonopoulos Dionysios A. , Gilbert Jack A. , Barreiro Luis B. , Zaborina Olga , Jabri Bana , Alverdy John C. 
Published: May 2020

AbstractDeath due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.
Prominent radiative contributions from multiply-excited states in laser-produced tin plasma for nanolithography
Authors: Torretti F. , Sheil J. , Schupp R. , Basko M. M. , Bayraktar M. , Meijer R. A. , Witte S. , Ubachs W. , Hoekstra R. , Versolato O. O. , Neukirch A. J. , Colgan J. 
Published: May 2020

AbstractExtreme ultraviolet (EUV) lithography is currently entering high-volume manufacturing to enable the continued miniaturization of semiconductor devices. The required EUV light, at 13.5 nm wavelength, is produced in a hot and dense laser-driven tin plasma. The atomic origins of this light are demonstrably poorly understood. Here we calculate detailed tin opacity spectra using the Los Alamos atomic physics suite ATOMIC and validate these calculations with experimental comparisons. Our key finding is that EUV light largely originates from transitions between multiply-excited states, and not from the singly-excited states decaying to the ground state as is the current paradigm. Moreover, we find that transitions between these multiply-excited states also contribute in the same narrow window around 13.5 nm as those originating from singly-excited states, and this striking property holds over a wide range of charge states. We thus reveal the doubly magic behavior of tin and the origins of the EUV light.
Size and surface charge characterization of nanoparticles with a salt gradient
Authors: Rasmussen Martin K. , Pedersen Jonas N. , Marie Rodolphe 
Published: May 2020

AbstractExosomes are nanometer-sized lipid vesicles present in liquid biopsies and used as biomarkers for several diseases including cancer, Alzheimer’s, and central nervous system diseases. Purification and subsequent size and surface characterization are essential to exosome-based diagnostics. Sample purification is, however, time consuming and potentially damaging, and no current method gives the size and zeta potential from a single measurement. Here, we concentrate exosomes from a dilute solution and measure their size and zeta potential in a one-step measurement with a salt gradient in a capillary channel. The salt gradient causes oppositely directed particle and fluid transport that trap particles. Within minutes, the particle concentration increases more than two orders of magnitude. A fit to the spatial distribution of a single or an ensemble of exosomes returns both their size and surface charge. Our method is applicable for other types of nanoparticles. The capillary is fabricated in a low-cost polymer device.
Computational stabilization of T cell receptors allows pairing with antibodies to form bispecifics
Authors: Froning Karen , Maguire Jack , Sereno Arlene , Huang Flora , Chang Shawn , Weichert Kenneth , Frommelt Anton J. , Dong Jessica , Wu Xiufeng , Austin Heather , Conner Elaine M. , Fitchett Jonathan R. , Heng Aik Roy , Balasubramaniam Deepa , Hilgers Mark T. , Kuhlman Brian , Demarest Stephen J. 
Published: May 2020

AbstractRecombinant T cell receptors (TCRs) can be used to redirect naïve T cells to eliminate virally infected or cancerous cells; however, they are plagued by low stability and uneven expression. Here, we use molecular modeling to identify mutations in the TCR constant domains (Cα/Cβ) that increase the unfolding temperature of Cα/Cβ by 20 °C, improve the expression of four separate α/β TCRs by 3- to 10-fold, and improve the assembly and stability of TCRs with poor intrinsic stability. The stabilizing mutations rescue the expression of TCRs destabilized through variable domain mutation. The improved stability and folding of the TCRs reduces glycosylation, perhaps through conformational stabilization that restricts access to N-linked glycosylation enzymes. The Cα/Cβ mutations enables antibody-like expression and assembly of well-behaved bispecific molecules that combine an anti-CD3 antibody with the stabilized TCR. These TCR/CD3 bispecifics can redirect T cells to kill tumor cells with target HLA/peptide on their surfaces in vitro.
Loss of wild-type p53 promotes mutant p53-driven metastasis through acquisition of survival and tumor-initiating properties
Authors: Nakayama Mizuho , Hong Chang Pyo , Oshima Hiroko , Sakai Eri , Kim Seong-Jin , Oshima Masanobu 
Published: May 2020

AbstractMissense-type mutant p53 plays a tumor-promoting role through gain-of-function (GOF) mechanism. In addition, the loss of wild-type TP53 through loss of heterozygosity (LOH) is widely found in cancer cells. However, malignant progression induced by cooperation of TP53 GOF mutation and LOH remains poorly understood. Here, we show that mouse intestinal tumors carrying Trp53 GOF mutation with LOH (AKTPM/LOH) are enriched in metastatic lesions when heterozygous Trp53 mutant cells (AKTP+/M) are transplanted. We show that Trp53 LOH is required for dormant cell survival and clonal expansion of cancer cells. Moreover, AKTPM/LOH cells show an increased in vivo tumor-initiating ability compared with AKTPNull and AKTP+/M cells. RNAseq analyses reveal that inflammatory and growth factor/MAPK pathways are specifically activated in AKTPM/LOH cells, while the stem cell signature is upregulated in both AKTPM/LOH and AKTPNull cells. These results indicate that TP53/Trp53 LOH promotes TP53/Trp53 GOF mutation-driven metastasis through the activation of distinct pathway combination.
Persistent cannabis use as an independent risk factor for violent behaviors in patients with schizophrenia
Authors: Beaudoin Mélissa , Potvin Stéphane , Giguère Charles-Edouard , Discepola Sophie-Lena , Dumais Alexandre 
Published: May 2020

AbstractAlthough recent studies have shown a moderately strong association between cannabis use and violence among people with severe mental disorders, the direction of this association has not been investigated prospectively in a population with schizophrenia. Therefore, this study aims to determine, using cross-lag models, whether a temporal relationship between cumulative cannabis use and violence exists in a population with schizophrenia. The authors reported findings covering an 18-month period from a randomized, double-blind clinical trial of antipsychotic medications for schizophrenia treatment. Among the 1460 patients enrolled in the trial, 965 were followed longitudinally. Although persistent cannabis use predicted subsequent violence, violence did not predict cannabis use. The relationship was therefore unidirectional and persisted when controlling for stimulants and alcohol use. Finally, a significant body of evidence suggests a link between persistent cannabis use and violence among people with mental illnesses. Studies to further investigate the mechanisms underlying this association should be conducted.
T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers
Authors: Arunachalam Prabhu S. , Charles Tysheena P. , Joag Vineet , Bollimpelli Venkata S. , Scott Madeleine K. D. , Wimmers Florian , Burton Samantha L. , Labranche Celia C. , Petitdemange Caroline , Gangadhara Sailaja , Styles Tiffany M. , Quarnstrom Clare F. , Walter Korey A. , Ketas Thomas J. , Legere Traci , Jagadeesh Reddy Pradeep Babu , Kasturi Sudhir Pai , Tsai Anthony , Yeung Bertrand Z. , Gupta Shakti , Tomai Mark , Vasilakos John , Shaw George M. , Kang Chil-Yong , Moore John P. , Subramaniam Shankar , Khatri Purvesh , Montefiori David , Kozlowski Pamela A. , Derdeyn Cynthia A. , Hunter Eric , Masopust David , Amara Rama R. , Pulendran Bali 
Published: May 2020

AbstractRecent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to elicit nAbs and cellular immunity, including CD8+ tissue-resident memory T cells. After ten vaginal challenges with autologous virus, protection was observed in both vaccine groups at 53.3% and 66.7%, respectively. A nAb titer >300 was generally associated with protection but in the heterologous viral vector + nAb group, titers <300 were sufficient. In this group, protection was durable as the animals resisted six more challenges 5 months later. Antigen stimulation of T cells in ex vivo vaginal tissue cultures triggered antiviral responses in myeloid and CD4+ T cells. We propose that cellular immune responses reduce the threshold of nAbs required to confer superior and durable protection.
Translating evidence into practice: eligibility criteria fail to eliminate clinically significant differences between real-world and study populations
Authors: Averitt Amelia J. , Weng Chunhua , Ryan Patrick , Perotte Adler 
Published: May 2020

AbstractRandomized controlled trials (RCTs) are regarded as the most reputable source of evidence. In some studies, factors beyond the intervention itself may contribute to the measured effect, an occurrence known as heterogeneity of treatment effect (HTE). If the RCT population differs from the real-world population on factors that induce HTE, the trials effect will not replicate. The RCTs eligibility criteria should identify the sub-population in which its evidence will replicate. However, the extent to which the eligibility criteria identify the appropriate population is unknown, which raises concerns for generalizability. We compared reported data from RCTs with real-world data from the electronic health records of a large, academic medical center that was curated according to RCT eligibility criteria. Our results show fundamental differences between the RCT population and our observational cohorts, which suggests that eligibility criteria may be insufficient for identifying the applicable real-world population in which RCT evidence will replicate.
Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids
Authors: Kumar Gupta Ashwani , Sarkar Prasenjit , Wertheim Jason A. , Pan Xinchao , Carroll Thomas J. , Oxburgh Leif 
Published: May 2020

AbstractA fundamental challenge in emulating kidney tissue formation through directed differentiation of human pluripotent stem cells is that kidney development is iterative, and to reproduce the asynchronous mix of differentiation states found in the fetal kidney we combined cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and heterochronic organoids were well vascularized when engrafted under the kidney capsule. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed, but despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study. We propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop similar stromal overgrowth when engrafted under the kidney capsule.
Structure of a cyanobacterial photosystem I surrounded by octadecameric IsiA antenna proteins
Authors: Akita Fusamichi , Nagao Ryo , Kato Koji , Nakajima Yoshiki , Yokono Makio , Ueno Yoshifumi , Suzuki Takehiro , Dohmae Naoshi , Shen Jian-Ren , Akimoto Seiji , Miyazaki Naoyuki 
Published: May 2020

AbstractIron-stress induced protein A (IsiA) is a chlorophyll-binding membrane-spanning protein in photosynthetic prokaryote cyanobacteria, and is associated with photosystem I (PSI) trimer cores, but its structural and functional significance in light harvesting remains unclear. Here we report a 2.7-Å resolution cryo-electron microscopic structure of a supercomplex between PSI core trimer and IsiA from a thermophilic cyanobacteriumThermosynechococcus vulcanus. The structure showed that 18 IsiA subunits form a closed ring surrounding a PSI trimer core. Detailed arrangement of pigments within the supercomplex, as well as molecular interactions between PSI and IsiA and among IsiAs, were resolved. Time-resolved fluorescence spectra of the PSI–IsiA supercomplex showed clear excitation-energy transfer from IsiA to PSI, strongly indicating that IsiA functions as an energy donor, but not an energy quencher, in the supercomplex. These structural and spectroscopic findings provide important insights into the excitation-energy-transfer and subunit assembly mechanisms in the PSI–IsiA supercomplex.
The role of bot squads in the political propaganda on Twitter
Authors: Caldarelli Guido , De Nicola Rocco , Del Vigna Fabio , Petrocchi Marinella , Saracco Fabio 
Published: May 2020

AbstractNowadays, Social Media are a privileged channel for news spreading, information exchange, and fact checking. Unexpectedly for many users, automated accounts, known as social bots, contribute more and more to this process of information diffusion. Using Twitter as a benchmark, we consider the traffic exchanged, over one month of observation, on the migration flux from Northern Africa to Italy. We measure the significant traffic of tweets only, by implementing an entropy-based null model that discounts the activity of users and the virality of tweets. Results show that social bots play a central role in the exchange of significant content. Indeed, not only the strongest hubs have a number of bots among their followers higher than expected, but furthermore a group of them, that can be assigned to the same political tendency, share a common set of bots as followers. The retweeting activity of such automated accounts amplifies the hubs’ messages.
Atomic-scale control of tunneling in donor-based devices
Authors: Wang Xiqiao , Wyrick Jonathan , Kashid Ranjit V. , Namboodiri Pradeep , Schmucker Scott W. , Murphy Andrew , Stewart M. D. , Silver Richard M. 
Published: May 2020

AbstractAtomically precise donor-based quantum devices are a promising candidate for solid-state quantum computing and analog quantum simulations. However, critical challenges in atomically precise fabrication have meant systematic, atomic scale control of the tunneling rates and tunnel coupling has not been demonstrated. Here using a room temperature grown locking layer and precise control over the entire fabrication process, we reduce unintentional dopant movement while achieving high quality epitaxy in scanning tunnelling microscope (STM)-patterned devices. Using the Si(100)2 × 1 surface reconstruction as an atomically-precise ruler to characterize the tunnel gap in precision-patterned single electron transistors, we demonstrate the exponential scaling of the tunneling resistance on the tunnel gap as it is varied from 7 dimer rows to 16 dimer rows. We demonstrate the capability to reproducibly pattern devices with atomic precision and a donor-based fabrication process where atomic scale changes in the patterned tunnel gap result in the expected changes in the tunneling rates.
Akute Luftnot auf See durch Fehleinschätzung von Vorerkrankungen
Authors: Heblich F. , Kübler C. , Jaschke F. , Mitterhauser M. , Koehler A. , Petutschnigg B. , Kroll M. 
Published: May 2020

ZusammenfassungEin Gast eines Kreuzfahrtschiffs muss wegen akuter Atemnot aufgrund eines wahrscheinlich malignen und nach Entlastungspunktion rezidivierenden Pleuraergusses während der Reise ausgeschifft werden. Patienten wird – wie auch hier – häufig von ihren Haus- oder Fachärzten zur Teilnahme an einer geplanten Kreuzfahrt geraten, obwohl Komplikationen bestehender Grunderkrankungen im Bordhospital nicht immer umfassend behandelt werden können. Die diagnostischen und therapeutischen Möglichkeiten im Bordhospital sind gegenüber Kliniken an Land in vielen Bereichen deutlich eingeschränkt und eine Ausschiffung nicht überall erstrebenswert.
Motor Recovery of the Suprascapular Nerve after Arthroscopic Decompression in the Scapular Notch – a Systematic Review
Authors: von Knoch Marius , Frosch Stephan , Baums Mike H. , Lehmann Wolfgang 
Published: May 2020

Abstract
Background The suprascapular nerve can be compromised as a result of a compression syndrome in different locations. A (proximal) compression within the scapular notch can lead to dorsal shoulder pain and simultaneous weakness of the infraspinatus and supraspinatus muscles. By transection of the lig. transversum this compression syndrome can be treated. By means of a systematic review, the present work analyzes the motor recovery potential after arthroscopic decompression.
Material and Methods A systematic review of the U. S. National Library of Medicine/National Institutes of Health (PubMed) database and the Cochrane Library was performed using the PRISMA checklist. The search words used were “suprascapular” and “arthroscopic”; “suprascapular” and “arthroscopy”. Based on the evaluated literature, articles in English with at least a partial arthroscopic case series from 4 cases on and a compression syndrome of the suprascapular nerve treated with arthroscopic decompression in the scapular notch were identified. Motor recovery was described by means of EMG, clinical strength and MRI.
Results Primarily 408 hits were generated. Six articles met the inclusion criteria and were further analyzed. The number of arthroscopic cases was between 4 and a maximum of 27. The level of evidence was between III and IV. The majority of the reported clinical results were good. Motor recovery as measured by EMG was observed, recovery of full strength was not achieved in the majority of reported cases (60%), neither was regression of structural (fatty) degeneration of the muscle bellies.
Conclusion Arthroscopic decompression of the suprascapular nerve in the scapular notch provides good clinical results and considerable pain relief. However, in the majority of cases it does not lead to a complete recovery of the strength of the supra- and infraspinatus muscles. Patients should be informed about this. An early decompression after diagnosis in the event of proximal compression within the suprascapular notch combined with beginning EMG or MRI changes appears reasonable. These beginning changes should be further defined. Future studies should develop prognostic criteria for motor recovery. Awareness regarding the diagnosis needs to be improved due to the probably time-dependent irreversibility of resulting muscular weakness.
Multimodiale Therapie von Hirnmetastasen
Authors: Ahmed M. , Meier F. , Beissert S. 
Published: May 2020

ZusammenfassungDas Langzeitüberleben hat sich für Patienten mit metastasiertem Melanom durch die Etablierung der zielgerichteten Therapien sowie Immuntherapien mit 5-Jahres-Überlebensraten von ca. 50 % deutlich verbessert. Hirnmetastasen stellen jedoch weiterhin eine therapeutische Herausforderung dar. In der Vergangenheit lag das mediane Überleben für Patienten mit neu diagnostizierten Hirnmetastasen bei 2 – 6 Monaten 1. Retrospektive Analysen sprechen für einen Überlebensbenefit unter multimodaler Therapie mit einer 5-Jahres-Überlebensrate von über 20 % 1.Wir berichten über einen 50-jährigen Patienten mit multiplen symptomatischen Hirnmetastasen bei Erstdiagnose. Nach Exstirpation einer symptomatischen Metastase wurde bei BRAF-V600E-Mutation eine Systemtherapie mit dem BRAF-Inhibitor Dabrafenib in Kombination mit dem MEK-Inhibitor Trametinib eingeleitet. Hierunter zeigte sich ein rascher deutlicher Regress der zerebralen und extrazerebralen Metastasen. Nach 8 Wochen wurde die Systemtherapie auf eine Immuntherapie mit Nivolumab plus Ipilimumab umgesetzt. Kurz nach Therapieeinleitung trat ein epileptischer Anfall auf und die Hirnmetastasen zeigten sich wieder progredient. Zwei symptomatische Hirnmetastasen wurden reseziert, eine Ganzhirnradiatio mit Hippocampusschonung wurde eingeleitet und die Immuntherapie fortgesetzt. Aktuell erfolgt eine zielgerichtete Therapie mit Encorafenib und Binimetinib. 17 Monate nach Erstdiagnose befindet sich der Patient in gutem Allgemeinzustand ohne neurologische Defizite. Dieser Fallbericht bestätigt den retrospektiv beobachteten Überlebensbenefit für Patienten mit Hirnmetastasen unter multimodaler Therapie.