bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen receptor signalling in macrophages promotes TREM-1-mediated prostate cancer cell line migration and invasion
Authors: Cioni Bianca , Zaalberg Anniek , van Beijnum Judy R. , Melis Monique H. M. , van Burgsteden Johan , Muraro Mauro J. , Hooijberg Erik , Peters Dennis , Hofland Ingrid , Lubeck Yoni , de Jong Jeroen , Sanders Joyce , Vivié Judith , van der Poel Henk G. , de Boer Jan Paul , Griffioen Arjan W. , Zwart Wilbert , Bergman Andries M. 
Published: September 2020

AbstractThe androgen receptor (AR) is the master regulator of prostate cancer (PCa) development, and inhibition of AR signalling is the most effective PCa treatment. AR is expressed in PCa cells and also in the PCa-associated stroma, including infiltrating macrophages. Macrophages have a decisive function in PCa initiation and progression, but the role of AR in macrophages remains largely unexplored. Here, we show that AR signalling in the macrophage-like THP-1 cell line supports PCa cell line migration and invasion in culture via increased Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) signalling and expression of its downstream cytokines. Moreover, AR signalling in THP-1 and monocyte-derived macrophages upregulates IL-10 and markers of tissue residency. In conclusion, our data suggest that AR signalling in macrophages may support PCa invasiveness, and blocking this process may constitute one mechanism of anti-androgen therapy.
Global patterns of the leaf economics spectrum in wetlands
Authors: Pan Yingji , Cieraad Ellen , Armstrong Jean , Armstrong William , Clarkson Beverley R. , Colmer Timothy D. , Pedersen Ole , Visser Eric J. W. , Voesenek Laurentius A. C. J. , van Bodegom Peter M. 
Published: September 2020

AbstractThe leaf economics spectrum (LES) describes consistent correlations among a variety of leaf traits that reflect a gradient from conservative to acquisitive plant strategies. So far, whether the LES holds in wetland plants at a global scale has been unclear. Using data on 365 wetland species from 151 studies, we find that wetland plants in general show a shift within trait space along the same common slope as observed in non-wetland plants, with lower leaf mass per area, higher leaf nitrogen and phosphorus, faster photosynthetic rates, and shorter leaf life span compared to non-wetland plants. We conclude that wetland plants tend to cluster at the acquisitive end of the LES. The presented global quantifications of the LES in wetland plants enhance our understanding of wetland plant strategies in terms of resources acquisition and allocation, and provide a stepping-stone to developing trait-based approaches for wetland ecology.
Humanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain
Authors: Chi Xiaojing , Liu Xiuying , Wang Conghui , Zhang Xinhui , Li Xiang , Hou Jianhua , Ren Lili , Jin Qi , Wang Jianwei , Yang Wei 
Published: September 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and leads to an unprecedented medical burden and lives lost. Neutralizing antibodies provide efficient blockade for viral infection and are a promising category of biological therapies. Here, using SARS-CoV-2 spike receptor-binding domain (RBD) as a bait, we generate a panel of humanized single domain antibodies (sdAbs) from a synthetic library. These sdAbs reveal binding kinetics with the equilibrium dissociation constant (KD) of 0.99–35.5 nM. The monomeric sdAbs show half maximal neutralization concentration (EC50) of 0.0009–0.07 µg/mL and 0.13–0.51 µg/mL against SARS-CoV-2 pseudotypes, and authentic SARS-CoV-2, respectively. Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2. Fusion of the human IgG1 Fc to sdAbs improve their neutralization activity by up to ten times. These results support neutralizing sdAbs as a potential alternative for antiviral therapies.
Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension
Authors: Cruz Rivera Samantha , Liu Xiaoxuan , Chan An-Wen , Denniston Alastair K. , Calvert Melanie J. ,   The SPIRIT-AI and CONSORT-AI Working Group,   SPIRIT-AI and CONSORT-AI Steering Group, Darzi Ara , Holmes Christopher , Yau Christopher , Moher David , Ashrafian Hutan , Deeks Jonathan J. , Ferrante di Ruffano Lavinia , Faes Livia , Keane Pearse A. , Vollmer Sebastian J. ,   SPIRIT-AI and CONSORT-AI Consensus Group, Lee Aaron Y. , Jonas Adrian , Esteva Andre , Beam Andrew L. , Panico Maria Beatrice , Lee Cecilia S. , Haug Charlotte , Kelly Christophe J. , Yau Christopher , Mulrow Cynthia , Espinoza Cyrus , Fletcher John , Moher David , Paltoo Dina , Manna Elaine , Price Gary , Collins Gary S. , Harvey Hugh , Matcham James , Monteiro Joao , ElZarrad M. Khair , Ferrante di Ruffano Lavinia , Oakden-Rayner Luke , McCradden Melissa , Keane Pearse A. , Savage Richard , Golub Robert , Sarkar Rupa , Rowley Samuel 
Published: September 2020

AbstractThe SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials–Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials–Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human–AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.
Dynamic behavior of reversible oxygen migration in irradiated-annealed high temperature superconducting wires
Authors: Zhang Yi , Rupich M. W. , Solovyov Vyacheslav , Li Qiang , Goyal Amit 
Published: September 2020

AbstractWe use atomically resolved scanning transmission electron microscopy and electron energy loss spectroscopy to determine the atomic-scale structural, chemical and electronic properties of artificial engineered defects in irradiated-annealed high temperature superconducting wires based on epitaxial Y(Dy)BCO film. We directly probe the oxygen vacancy defects in both plane and chain sites after irradiation with 18-meV Au ions. The plane site vacancies are reoccupied during post-annealing treatment. Our results demonstrate the dynamic reversible behavior of oxygen point defects, which explains the depression and recovery of self-field critical current and critical temperature in irradiation-annealing process. These findings reveal the strong effect of oxygen vacancies in different sites on the superconductivity properties of irradiated Y(Dy)BCO film, and provide important insights into defects engineering of 2G HTS coil wires.
Discovery of a selective, state-independent inhibitor of NaV1.7 by modification of guanidinium toxins
Authors: Pajouhesh H. , Beckley J. T. , Delwig A. , Hajare H. S. , Luu G. , Monteleone D. , Zhou X. , Ligutti J. , Amagasu S. , Moyer B. D. , Yeomans D. C. , Du Bois J. , Mulcahy J. V. 
Published: September 2020

AbstractThe voltage-gated sodium channel isoform NaV1.7 is highly expressed in dorsal root ganglion neurons and is obligatory for nociceptive signal transmission. Genetic gain-of-function and loss-of-function NaV1.7 mutations have been identified in select individuals, and are associated with episodic extreme pain disorders and insensitivity to pain, respectively. These findings implicate NaV1.7 as a key pharmacotherapeutic target for the treatment of pain. While several small molecules targeting NaV1.7 have been advanced to clinical development, no NaV1.7-selective compound has shown convincing efficacy in clinical pain applications. Here we describe the discovery and characterization of ST-2262, a NaV1.7 inhibitor that blocks the extracellular vestibule of the channel with an IC50 of 72 nM and greater than 200-fold selectivity over off-target sodium channel isoforms, NaV1.1–1.6 and NaV1.8. In contrast to other NaV1.7 inhibitors that preferentially inhibit the inactivated state of the channel, ST-2262 is equipotent in a protocol that favors the resting state of the channel, a protocol that favors the inactivated state, and a high frequency protocol. In a non-human primate study, animals treated with ST-2262 exhibited reduced sensitivity to noxious heat. These findings establish the extracellular vestibule of the sodium channel as a viable receptor site for the design of selective ligands targeting NaV1.7.
Novel role of lncRNA CHRF in cisplatin resistance of ovarian cancer is mediated by miR-10b induced EMT and STAT3 signaling
Authors: Tan Wen-Xi , Sun Ge , Shangguan Meng-Yuan , Gui Zhi , Bao Yang , Li Yu-Feng , Jia Zan-Hui 
Published: September 2020

AbstractOvarian Cancer (OC) is a highly lethal gynecological cancer which often progresses through acquired resistance against the administered therapy. Cisplatin is a common therapeutic for the treatment of OC patients and therefore it is critical to understand the mechanisms of resistance against this drug. We studied a paired cell line consisting of parental and cisplatin resistant (CR) derivative ES2 OC cells, and found a number of dysregulated lncRNAs, with CHRF being the most significantly upregulated lncRNA in CR ES2 cells. The findings corroborated in human patient samples and CHRF was significantly elevated in OC patients with resistant disease. CHRF was also found to be elevated in patients with liver metastasis. miR-10b was found to be mechanistically involved in CHRF mediated cisplatin resistance. It induced resistance in not only ES2 but also OVCAR and SKOV3 OC cells. Induction of epithelial-to-mesenchymal-transition (EMT) and activation of STAT3 signaling were determined to be the mechanisms underlying the CHRF-miR-10b axis-mediated cisplatin resistance. Down-regulation of CHRF reversed EMT, STAT3 activation and the resulting cisplatin resistance, which could be attenuated by miR-10b. The results were also validated in an in vivo cisplatin resistance model wherein CR cells were associated with increased tumor burden, CHRF downregulation associated with decreased tumor burden and miR-10b again attenuated the CHRF downregulation effects. Our results support a novel role of lncRNA CHRF in cisplatin resistance of OC and establish CHRF-miR-10b signaling as a putative therapeutic target for sensitizing resistant OC cells.
Effectiveness and moderators of individual cognitive behavioral therapy versus treatment as usual in clinically depressed adolescents: a randomized controlled trial
Authors: Stikkelbroek Yvonne , Vink Gerko , Nauta Maaike H. , Bottelier Marco A. , Vet Leonieke J. J. , Lont Cathelijne M. , van Baar Anneloes L. , Bodden Denise H. M. 
Published: September 2020

AbstractWe examined if manualized cognitive behavioral therapy (CBT) was more effective than Treatment As Usual (TAU) for clinically depressed adolescents within routine care. This multisite Randomized controlled trail included 88 clinically depressed adolescents (aged 12–21 years) randomly assigned to CBT or TAU. Multiple assessments (pre-, post treatment and six-month follow-up) were done using semi-structured interviews, questionnaires and ratings and multiple informants. The primary outcome was depressive or dysthymic disorder based on the KSADS. Completers, CBT (n = 19) and TAU (n = 26), showed a significant reduction of affective diagnoses at post treatment (76% versus 76%) and after six months (90% versus 79%). Intention-to-treat analyses on depressive symptoms showed that 41.6% within CBT and 31.8% within the TAU condition was below clinical cut-off at post treatment and after six-months, respectively 61.4% and 47.7%. No significant differences in self-reported depressive symptoms between CBT and TAU were found. No prediction or moderation effects were found for age, gender, child/parent educational level, suicidal criteria, comorbidity, and severity of depression. We conclude that CBT did not outperform TAU in clinical practice in the Netherlands. Both treatments were found to be suitable to treat clinically referred depressed adolescents. CBT needs further improvement to decrease symptom levels below the clinical cut-off at post treatment.
Representation of edges, head direction, and swimming kinematics in the brain of freely-navigating fish
Authors: Vinepinsky Ehud , Cohen Lear , Perchik Shay , Ben-Shahar Ohad , Donchin Opher , Segev Ronen 
Published: September 2020

AbstractLike most animals, the survival of fish depends on navigation in space. This capacity has been documented in behavioral studies that have revealed navigation strategies. However, little is known about how freely swimming fish represent space and locomotion in the brain to enable successful navigation. Using a wireless neural recording system, we measured the activity of single neurons in the goldfish lateral pallium, a brain region known to be involved in spatial memory and navigation, while the fish swam freely in a two-dimensional water tank. We found that cells in the lateral pallium of the goldfish encode the edges of the environment, the fish head direction, the fish swimming speed, and the fish swimming velocity-vector. This study sheds light on how information related to navigation is represented in the brain of fish and addresses the fundamental question of the neural basis of navigation in this group of vertebrates.
A laser emitting contact lens for eye tracking
Authors: Khaldi A. , Daniel E. , Massin L. , Kärnfelt C. , Ferranti F. , Lahuec C. , Seguin F. , Nourrit V. , de Bougrenet de la Tocnaye J.-L. 
Published: September 2020

AbstractIn this paper, we present the first realisation and experimentation of a new eye tracking system using an infrared (iR) laser pointer embedded into a wireless smart contact lens. We denote this contact lens prototype as the cyclops lens, in reference to the famous hero of the X-Men comics. The full eye tracker device combines the smart contact lens and its eyewear, which provides a primary source of energy and the beam detection system. We detail the assembling and encapsulation process of the main functionalities into the contact lens and present how a gaze tracking system is achieved, compared to existing conventional eye-tracking ones. Finally, we discuss future technical improvements.
The olivocochlear reflex strength in awake chinchillas is relevant for behavioural performance during visual selective attention with auditory distractors
Authors: Bowen Macarena , Terreros Gonzalo , Moreno-Gómez Felipe N. , Ipinza Macarena , Vicencio Sergio , Robles Luis , Delano Paul H. 
Published: September 2020

AbstractThe auditory efferent system comprises descending projections from the cerebral cortex to subcortical nuclei, reaching the cochlear receptor through olivocochlear fibres. One of the functions attributed to this corticofugal system is to suppress irrelevant sounds during selective attention to visual stimuli. Medial olivocochlear neurons can also be activated by sounds through a brainstem reflex circuit. Whether the individual variability of this reflex is related to the cognitive capacity to suppress auditory stimuli is still controversial. Here we propose that the individual strength per animal of the olivocochlear reflex is correlated with the ability to suppress auditory distractors during visual attention in awake chinchillas. The olivocochlear reflex was elicited with a contralateral broad-band noise at ~ 60 dB and ipsilateral distortion product otoacoustic emissions were obtained at different frequencies (1–8 kHz). Fourteen chinchillas were evaluated in a behavioural protocol of visual attention with broad-band noise and chinchilla vocalizations as auditory distractors. Results show that the behavioural performance was affected by both distractors and that the magnitudes of the olivocochlear reflex evaluated at multiple frequencies were relevant for behavioural performance during visual discrimination with auditory distractors. These results stress the ecological relevance of the olivocochlear system for suppressing natural distractors.
Membrane disruption, but not metabolic rewiring, is the key mechanism of anticancer-action of FASN-inhibitors: a multi-omics analysis in ovarian cancer
Authors: Grunt Thomas W. , Slany Astrid , Semkova Mariya , Colomer Ramón , López-Rodríguez María Luz , Wuczkowski Michael , Wagner Renate , Gerner Christopher , Stübiger Gerald 
Published: September 2020

AbstractFatty-acid(FA)-synthase(FASN) is a druggable lipogenic oncoprotein whose blockade causes metabolic disruption. Whether drug-induced metabolic perturbation is essential for anticancer drug-action, or is just a secondary—maybe even a defence response—is still unclear. To address this, SKOV3 and OVCAR3 ovarian cancer(OC) cell lines with clear cell and serous histology, two main OC subtypes, were exposed to FASN-inhibitor G28UCM. Growth-inhibition was compared with treatment-induced cell-metabolomes, lipidomes, proteomes and kinomes. SKOV3 and OVCAR3 were equally sensitive to low-dose G28UCM, but SKOV3 was more resistant than OVCAR3 to higher concentrations. Metabolite levels generally decreased upon treatment, but individual acylcarnitines, glycerophospholipids, sphingolipids, amino-acids, biogenic amines, and monosaccharides reacted differently. Drug-induced effects on central-carbon-metabolism and oxidative-phosphorylation (OXPHOS) were essentially different in the two cell lines, since drug-naïve SKOV3 are known to prefer glycolysis, while OVCAR3 favour OXPHOS. Moreover, drug-dependent increase of desaturases and polyunsaturated-fatty-acids (PUFAs) were more pronounced in SKOV3 and appear to correlate with G28UCM-tolerance. In contrast, expression and phosphorylation of proteins that control apoptosis, FA synthesis and membrane-related processes (beta-oxidation, membrane-maintenance, transport, translation, signalling and stress-response) were concordantly affected. Overall, membrane-disruption and second-messenger-silencing were crucial for anticancer drug-action, while metabolic-rewiring was only secondary and may support high-dose-FASN-inhibitor-tolerance. These findings may guide future anti-metabolic cancer intervention.
Functional outcome of traumatic spinopelvic instabilities treated with lumbopelvic fixation
Authors: Yilmaz Emre , Hoffmann Martin F. , von Glinski Alexander , Kruppa Christiane , Hamsen Uwe , Schmidt Cameron K. , Oernek Ahmet , Koenigshausen Matthias , Dudda Marcel , Schildhauer Thomas A. 
Published: September 2020

AbstractThe aim of this study was to assess the functional outcome after lumbopelvic fixation (LPF) using the SMFA (short musculoskeletal functional assessment) score and discuss the results in the context of the existing literature. The last consecutive 50 patients who underwent a LPF from January 1st 2011 to December 31st 2014 were identified and administered the SMFA-questionnaire. Inclusion criteria were: (1) patient underwent LPF at our institution, (2) complete medical records, (3) minimum follow-up of 12 months. Out of the 50 recipients, 22 questionnaires were returned. Five questionnaires were incomplete and therefore seventeen were included for analysis. The mean age was 60.3 years (32–86 years; 9m/8f) and the follow-up averaged 26.9 months (14–48 months). Six patients (35.3%) suffered from a low-energy trauma and 11 patients (64.7%) suffered a high-energy trauma. Patients in the low-energy group were significantly older compared to patients in the high-energy group (72.2 vs. 53.8 years; p = 0.030). Five patients (29.4%) suffered from multiple injuries. Compared to patients with low-energy trauma, patients suffering from high-energy trauma showed significantly lower scores in “daily activities” (89.6 vs. 57.1; p = 0.031), “mobility” (84.7 vs. 45.5; p = 0.015) and “function” (74.9 vs. 43.4; p = 0.020). Our results suggest that patients with older age and those with concomitant injuries show a greater impairment according to the SMFA score. Even though mostly favorable functional outcomes were reported throughout the literature, patients still show some level of impairment and do not reach normative data at final follow-up.
All-optical charging and charge transport in quantum dots
Authors: Hastrup Jacob , Leandro Lorenzo , Akopian Nika 
Published: September 2020

AbstractOptically active quantum dots are one of the promising candidates for fundamental building blocks in quantum technology. Many practical applications would comprise of multiple coupled quantum dots, each of which must be individually chargeable. However, the most advanced demonstrations are limited to devices with only a single dot, and individual charging has neither been demonstrated nor proposed for an array of optically active quantum dots. Here we propose and numerically demonstrate a method for controlled charging of multiple quantum dots and charge transport between the dots. We show that our method can be implemented in realistic structures with fidelities greater than 99.9%. The scheme is based on all-optical resonant manipulation of charges in an array of quantum dots formed by a type-II band alignment, such as crystal-phase quantum dots in nanowires. Our work opens new practical avenues for realizations of advanced quantum photonic devices, for instance, solid-state quantum registers with a photonic interface.