bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain and reward circuits antagonistically modulate alcohol expectancy to regulate drinking
Authors: Le Thang M. , Zhornitsky Simon , Zhang Sheng , Li Chiang-Shan R. 
Published: July 2020

AbstractExpectancy of physical and social pleasure (PSP) promotes excessive drinking despite the potential aversive effects of misuse, suggesting an imbalance in the response to reward and pain in alcohol seeking. Here, we investigated the competing roles of the reward and pain circuits in PSP expectancy and problem drinking in humans. Using fMRI data during resting (n = 180) and during alcohol cue exposure (n = 71), we examined the antagonistic effects of the reward-related medial orbitofrontal cortex (mOFC) and pain-related periaqueductal gray (PAG) connectivities on PSP expectancy and drinking severity. The two regions’ connectivity maps and strengths were characterized to assess their shared substrates and net relationship with PSP expectancy. We evaluated mediation and path models to further delineate how mOFC and PAG connectivities interacted through the shared substrates to differentially impact expectancy and alcohol use. During resting, whole-brain regressions showed mOFC connectivity in positive and PAG connectivity in negative association with PSP scores, with convergence in the precentral gyrus (PrCG). Notably, greater PAG-PrCG relative to mOFC-PrCG connectivity strength predicted lower PSP expectancy. During the alcohol cue exposure task, the net strength of the PAG vs. mOFC cue-elicited connectivity with the occipital cortex again negatively predicted PSP expectancy. Finally, mediation and path models revealed that the PAG and mOFC connectivities indirectly and antagonistically modulated problem drinking via their opposing influences on expectancy and craving. Thus, the pain and reward circuits exhibit functional antagonism such that the mOFC connectivity increases expectancy of drinking pleasure whereas the PAG serves to counter that effect.
Dopamine manipulations modulate paranoid social inferences in healthy people
Authors: Barnby J. M. , Bell V. , Deeley Q. , Mehta M. A. 
Published: July 2020

AbstractAltered dopamine transmission is thought to influence the formation of persecutory delusions. However, despite extensive evidence from clinical studies there is little experimental evidence on how modulating the dopamine system changes social attributions related to paranoia, and the salience of beliefs more generally. Twenty seven healthy male participants received 150mg L-DOPA, 3 mg haloperidol, or placebo in a double-blind, randomised, placebo-controlled study, over three within-subject sessions. Participants completed a multi-round Dictator Game modified to measure social attributions, and a measure of belief salience spanning themes of politics, religion, science, morality, and the paranormal. We preregistered predictions that altering dopamine function would affect (i) attributions of harmful intent and (ii) salience of paranormal beliefs. As predicted, haloperidol reduced attributions of harmful intent across all conditions compared to placebo. L-DOPA reduced attributions of harmful intent in fair conditions compared to placebo. Unexpectedly, haloperidol increased attributions of self-interest about opponents’ decisions. There was no change in belief salience within any theme. These results could not be explained by scepticism or subjective mood. Our findings demonstrate the selective involvement of dopamine in social inferences related to paranoia in healthy individuals.
Vitamin D supplementation: a potential therapeutic agent for metastatic colorectal cancer
Authors: Yuan Chen , Ng Kimmie 
Published: July 2020

SummaryPreclinical and epidemiological evidence suggests that vitamin D may have anti-cancer activities in patients with colorectal cancer. A recently completed, randomised Phase 2 trial of vitamin D3 supplementation in patients with metastatic colorectal cancer has shown promising results, and a Phase 3 trial is currently underway.
Polygenic risk score opportunities for early detection and prevention strategies in endometrial cancer
Authors: O’Mara Tracy A. , Crosbie Emma J. 
Published: July 2020

SummaryRecent large-scale genetic studies, particularly genome-wide association studies (GWAS), have emphasised the importance of common genetic variation in endometrial cancer susceptibility. Although each of these variants only confer modest effects on endometrial cancer risk, together they are likely to explain a substantial amount of the familial relative risk of the disease. Therefore, methods to combine genetic risk variants, such as polygenic risk scores (PRS) have gained traction as an attractive method for individualised risk prediction and management. Here, we discuss the benefits of a PRS for endometrial cancer and considerations required for clinical implementation.
Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation
Authors: Wagner Steffen , Prigge Elena-Sophie , Wuerdemann Nora , Reder Henrike , Bushnak Ayman , Sharma Shachi Jenny , Obermueller Theresa , von Knebel Doeberitz Magnus , Dreyer Thomas , Gattenlöhner Stefan , Wolf Gregor , Pons-Kühnemann Jörn , Wittekindt Claus , Klussmann Jens Peter 
Published: July 2020

Abstract
Background
A remarkably better prognosis is associated with oropharyngeal squamous cell carcinomas (OPSCC) driven by human papillomaviruses (HPV) compared with HPV-negative OPSCC. Consequently, de-escalation of standard treatment has been suggested. Due to modest specificity rates, debates are ongoing, whether p16INK4a, a surrogate marker for HPV-driven OPSCC, is sufficient to correctly identify those tumours and avoid substantial HPV misattribution and thus undertreatment of patients by de-escalation. Robust data estimating the proportion of potentially undertreated patients are missing.

Methods
We assessed a large-scale cohort of consecutively included OPSCC diagnosed between 2000 and 2017 for HPV–DNA, HPV genotypes, p16INK4a expression and multiple tumour- and patient-related risk factors, and investigated their impact on patients’ survival in comprehensive uni- and multivariate analyses.

Results
Aetiological relevance of HPV (p16INK4a- and high-risk HPV–DNA-positivity) was detected in 27.1% (n = 192) of OPSCC, with HPV16 being the most abundant HPV type (94.6%). In 5.5% patients (n = 39), p16INK4a overexpression but no HPV–DNA was detected. Principal component and survival analyses revealed that 60.6% of these p16INK4a-positive OPSCC lacking HPV–DNA did not resemble HPV16-driven but HPV-negative OPSCC regarding risk-factor profile and overall survival. Notably, this group represented 10.6% of all p16INK4a-overexpressing OPSCC.

Conclusions
p16INK4a as a single marker appears insufficient to indicate OPSCC patients suitable for treatment de-escalation.
Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling
Authors: Dolgormaa Gantumur , Harimoto Norifumi , Ishii Norihiro , Yamanaka Takahiro , Hagiwara Kei , Tsukagoshi Mariko , Igarashi Takamichi , Watanabe Akira , Kubo Norio , Araki Kenichiro , Handa Tadashi , Yokobori Takehiko , Oyama Tetsunari , Kuwano Hiroyuki , Shirabe Ken 
Published: July 2020

Abstract
Background
Wisteria floribunda agglutinin (WFA)+ Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness. We aimed to clarify the significance of M2BPGi in HCC.

Methods
The protein expression of M2BPGi and galectin-3, a ligand of M2BP, and the mRNA expression of M2BP were evaluated in surgically resected human HCC samples. M2BPGi-regulating signals in HCC cells were investigated using transcriptome analysis. The effects of M2BPGi on HCC properties and galectin-3/mTOR signaling were evaluated.

Results
M2BPGi and galectin-3 proteins co-localised in HCC cells, while M2BP mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC.

Conclusions
M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway.
Systematic analysis reveals a functional role for STAMBPL1 in the epithelial–mesenchymal transition process across multiple carcinomas
Authors: Ambroise Gorbatchev , Yu Ting-ting , Zhang Boxi , Kacal Merve , Hao Yuqing , Queiroz Andre L. , Ouchida Amanda T. , Lindskog Cecilia , Norberg Erik , Vakifahmetoglu-Norberg Helin 
Published: July 2020

AbstractBackgroundDeubiquitinating enzymes (DUBs) are linked to cancer progression and dissemination, yet less is known about their regulation and impact on epithelial–mesenchymal transition (EMT).MethodsAn integrative translational approach combining systematic computational analyses of The Cancer Genome Atlas cancer cohorts with CRISPR genetics, biochemistry and immunohistochemistry methodologies to identify and assess the role of human DUBs in EMT.ResultsWe identify a previously undiscovered biological function of STAM-binding protein like 1 (STAMBPL1) deubiquitinase in the EMT process in lung and breast carcinomas. We show that STAMBPL1 expression can be regulated by mutant p53 and that its catalytic activity is required to affect the transcription factor SNAI1. Accordingly, genetic depletion and CRISPR-mediated gene knockout of STAMBPL1 leads to marked recovery of epithelial markers, SNAI1 destabilisation and impaired migratory capacity of cancer cells. Reversely, STAMBPL1 expression reprogrammes cells towards a mesenchymal phenotype. A significant STAMBPL1-SNAI1 co-signature was observed across multiple tumour types. Importantly, STAMBPL1 is highly expressed in metastatic tissues compared to matched primary tumour of the same lung cancer patient and its expression predicts poor prognosis.ConclusionsOur study provides a novel concept of oncogenic regulation of a DUB and presents a new role and predictive value of STAMBPL1 in the EMT process across multiple carcinomas.
Delayed emergence of a global temperature response after emission mitigation
Authors: Samset B. H. , Fuglestvedt J. S. , Lund M. T. 
Published: July 2020

AbstractA major step towards achieving the goals of the Paris agreement would be a measurable change in the evolution of global warming in response to mitigation of anthropogenic emissions. The inertia and internal variability of the climate system, however, will delay the emergence of a discernible response even to strong, sustained mitigation. Here, we investigate when we could expect a significant change in the evolution of global mean surface temperature after strong mitigation of individual climate forcers. Anthropogenic CO2 has the highest potential for a rapidly measurable influence, combined with long term benefits, but the required mitigation is very strong. Black Carbon (BC) mitigation could be rapidly discernible, but has a low net gain in the longer term. Methane mitigation combines rapid effects on surface temperature with long term effects. For other gases or aerosols, even fully removing anthropogenic emissions is unlikely to have a discernible impact before mid-century.
Two-dimensional halide perovskite as β-ray scintillator for nuclear radiation monitoring
Authors: Yu Dejian , Wang Peng , Cao Fei , Gu Yu , Liu Jiaxin , Han Zeyao , Huang Bo , Zou Yousheng , Xu Xiaobao , Zeng Haibo 
Published: July 2020

AbstractEnsuring nuclear safety has become of great significance as nuclear power is playing an increasingly important role in supplying worldwide electricity. β-ray monitoring is a crucial method, but commercial organic scintillators for β-ray detection suffer from high temperature failure and irradiation damage. Here, we report a type of β-ray scintillator with good thermotolerance and irradiation hardness based on a two-dimensional halide perovskite. Comprehensive composition engineering and doping are carried out with the rationale elaborated. Consequently, effective β-ray scintillation is obtained, the scintillator shows satisfactory thermal quenching and high decomposition temperature, no functionality decay or hysteresis is observed after an accumulated radiation dose of 10 kGy (dose rate 0.67 kGy h−1). Besides, the two-dimensional halide perovskite β-ray scintillator also overcomes the notorious intrinsic water instability, and benefits from low-cost aqueous synthesis along with superior waterproofness, thus paving the way towards practical application.
Limited and localized magmatism in the Central Atlantic Magmatic Province
Authors: Marzen R. E. , Shillington D. J. , Lizarralde D. , Knapp J. H. , Heffner D. M. , Davis J. K. , Harder S. H. 
Published: July 2020

AbstractThe Central Atlantic Magmatic Province (CAMP) is the most aerially extensive magmatic event in Earth’s history, but many questions remain about its origin, volume, and distribution. Despite many observations of CAMP magmatism near Earth’s surface, few constraints exist on CAMP intrusions at depth. Here we present detailed constraints on crustal and upper mantle structure from wide-angle seismic data across the Triassic South Georgia Rift that formed shortly before CAMP. Lower crustal magmatism is concentrated where synrift sedimentary fill is thickest and the crust is thinnest, suggesting that lithospheric thinning influenced the locus and volume of magmatism. The limited distribution of lower crustal intrusions implies modest total CAMP volumes of 85,000 to 169,000 km3beneath the South Georgia Rift, consistent with moderately elevated mantle potential temperatures (<1500 °C). These results suggest that CAMP magmatism in the South Georgia Rift is caused by syn-rift decompression melting of a warm, enriched mantle.
Jawsamycin exhibits in vivo antifungal properties by inhibiting Spt14/Gpi3-mediated biosynthesis of glycosylphosphatidylinositol
Authors: Fu Yue , Estoppey David , Roggo Silvio , Pistorius Dominik , Fuchs Florian , Studer Christian , Ibrahim Ashraf S. , Aust Thomas , Grandjean Frederic , Mihalic Manuel , Memmert Klaus , Prindle Vivian , Richard Etienne , Riedl Ralph , Schuierer Sven , Weber Eric , Hunziker Jürg , Petersen Frank , Tao Jianshi , Hoepfner Dominic 
Published: July 2020

AbstractBiosynthesis of glycosylphosphatidylinositol (GPI) is required for anchoring proteins to the plasma membrane, and is essential for the integrity of the fungal cell wall. Here, we use a reporter gene-based screen in Saccharomyces cerevisiae for the discovery of antifungal inhibitors of GPI-anchoring of proteins, and identify the oligocyclopropyl-containing natural product jawsamycin (FR-900848) as a potent hit. The compound targets the catalytic subunit Spt14 (also referred to as Gpi3) of the fungal UDP-glycosyltransferase, the first step in GPI biosynthesis, with good selectivity over the human functional homolog PIG-A. Jawsamycin displays antifungal activity in vitro against several pathogenic fungi including Mucorales, and in vivo in a mouse model of invasive pulmonary mucormycosis due to Rhyzopus delemar infection. Our results provide a starting point for the development of Spt14 inhibitors for treatment of invasive fungal infections.
The proofreading activity of Pfprex from Plasmodium falciparum can prevent mutagenesis of the apicoplast genome by oxidized nucleotides
Authors: Sharma Minakshi , Narayanan Naveen , Nair Deepak T. 
Published: July 2020

AbstractThe DNA polymerase module of the Pfprex enzyme (PfpPol) is responsible for duplication of the genome of the apicoplast organelle in the malaria parasite. We show that PfpPol can misincorporate oxidized nucleotides such as 8oxodGTP opposite dA. This event gives rise to transversion mutations that are known to lead to adverse physiological outcomes. The apicoplast genome is particularly vulnerable to the harmful effects of 8oxodGTP due to very high AT content (~ 87%). We show that the proofreading activity of PfpPol has the unique ability to remove the oxidized nucleotide from the primer terminus. Due to this property, the proofreading domain of PfpPol is able to prevent mutagenesis of the AT-rich apicoplast genome and neutralize the deleterious genotoxic effects of ROS generated in the apicoplast due to normal metabolic processes. The proofreading activity of the Pfprex enzyme may, therefore, represent an attractive target for therapeutic intervention. Also, a survey of DNA repair pathways shows that the observed property of Pfprex constitutes a novel form of dynamic error correction wherein the repair of promutagenic damaged nucleotides is concomitant with DNA replication.
Temporal dynamics of amygdala response to emotion- and action-relevance
Authors: Guex Raphael , Méndez-Bértolo Constantino , Moratti Stephan , Strange Bryan A. , Spinelli Laurent , Murray Ryan J. , Sander David , Seeck Margitta , Vuilleumier Patrik , Domínguez-Borràs Judith 
Published: July 2020

AbstractIt has been proposed that the human amygdala may not only encode the emotional value of sensory events, but more generally mediate the appraisal of their relevance for the individual’s goals, including relevance for action or task-based needs. However, emotional and non-emotional/action-relevance might drive amygdala activity through distinct neural signals, and the relative timing of both kinds of responses remains undetermined. Here, we recorded intracranial event-related potentials from nine amygdalae of patients undergoing epilepsy surgery, while they performed variants of a Go/NoGo task with faces and abstract shapes, where emotion- and action-relevance were orthogonally manipulated. Our results revealed early amygdala responses to emotion facial expressions starting ~ 130 ms after stimulus-onset. Importantly, the amygdala responded to action-relevance not only with face stimuli but also with abstract shapes (squares), and these relevance effects consistently occurred in later time-windows (starting ~ 220 ms) for both faces and squares. A similar dissociation was observed in gamma activity. Furthermore, whereas emotional responses habituated over time, the action-relevance effect increased during the course of the experiment, suggesting progressive learning based on the task needs. Our results support the hypothesis that the human amygdala mediates a broader relevance appraisal function, with the processing of emotion-relevance preceding temporally that of action-relevance.
Effect of nano-hydroxyapatite and ozone on approximal initial caries: a randomized clinical trial
Authors: Grocholewicz Katarzyna , Matkowska-Cichocka Grażyna , Makowiecki Piotr , Droździk Agnieszka , Ey-Chmielewska Halina , Dziewulska Anna , Tomasik Małgorzata , Trybek Grzegorz , Janiszewska-Olszowska Joanna 
Published: July 2020

AbstractThe aim of the study was to assess the efficacy of three methods of enamel remineralization on initial approximal caries: (1) a nano-hydroxyapatite gel, (2) gaseous ozone therapy, (3) combination of a nano-hydroxyapatite gel and ozone. Patients (n = 92, age 20–30 years) with initial approximal enamel lesions on premolar and molar teeth (n = 546) were randomly allocated to three groups subjected to a 6-months treatment: Group I: domestic nano-hydroxyapatite remineralizing gel, group II: in-office ozone therapy, group III: both domestic remineralizing gel and ozone therapy. Caries lesions were assessed on bitewing radiographs at baseline, after 1 year and after 2 years. At one-year follow-up, the smallest rate of lesions with remineralisation (36.5%) was found in group I, and the highest (69.3%)—in group III. In group III a significant remineralisation was noticed in after 1 year and then a demineralisation after 2 years. Thus nano-hydroxyapatite gel and ozone therapy exert some capacities to remineralize approximal enamel and dentine subsurface lesions of premolar and molar teeth. Moreover, the combination of both methods produces the best effect compared to nano-hydroxyapatite or ozone therapy applied alone. However, the treatment should be continued for a long time in order to achieve nonrestorative recovery of caries.
Social enrichment by separated pair housing of male C57BL/6JRj mice
Authors: Hohlbaum Katharina , Frahm Silke , Rex André , Palme Rupert , Thöne-Reineke Christa , Ullmann Kristina 
Published: July 2020

AbstractLaboratory male mice are often housed individually due to aggressive behavior or experimental requirements, though social isolation can cause welfare issues. As a strategy to refine housing of male mice, we introduce the separated pair housing system. A perforated transparent wall divides the cage into two compartments and allows olfactory, acoustic, and visual communication between the two mice but prevents fighting and injuries. Long-term effects of separated pair housing on well-being and distress of adult male C57BL/6JRj mice were investigated and compared with both single- and group-housed mice. Behavioral analysis after eight weeks in three different housing systems revealed no differences in burrowing performance, social interaction, anxiety, and stress hormone concentrations. However, pair-housed mice built more complex nests compared to single-housed mice and the nest position suggested that pair-housed mice preferred the close proximity to their cage mates. Moreover, pair-housed mice showed less locomotor activity compared to group- and single-housed mice. Body weight was higher in group-housed mice. All in all, no unambiguous long-term beneficial effects of pair housing on the well-being were found. However, the findings emphasized that effects of the housing systems on behavioral, physical, and biochemical parameters must be considered in the design of animal experimental studies.
Fabrication of an efficient vanadium redox flow battery electrode using a free-standing carbon-loaded electrospun nanofibrous composite
Authors: Maleki Mahboubeh , El-Nagar Gumaa A. , Bernsmeier Denis , Schneider Jonathan , Roth Christina 
Published: July 2020

AbstractVanadium redox flow batteries (VRFBs) are considered as promising electrochemical energy storage systems due to their efficiency, flexibility and scalability to meet our needs in renewable energy applications. Unfortunately, the low electrochemical performance of the available carbon-based electrodes hinders their commercial viability. Herein, novel free-standing electrospun nanofibrous carbon-loaded composites with textile-like characteristics have been constructed and employed as efficient electrodes for VRFBs. In this work, polyacrylonitrile-based electrospun nanofibers loaded with different types of carbon black (CB) were electrospun providing a robust free-standing network. Incorporation of CBs (14% and 50% weight ratio) resulted in fibers with rough surface and increased mean diameter. It provided higher BET surface area of 83.8 m2 g−1 for as-spun and 356.7 m2 g−1 for carbonized fibers compared to the commercial carbon felt (0.6 m2 g−1). These loaded CB-fibers also had better thermal stability and showed higher electrochemical activity for VRFBs than a commercial felt electrode.