bluuebunny/crossref_metadata_2025_split huggingface dataset:
VEGF-A, VEGFR1 and VEGFR2 single nucleotide polymorphisms and outcomes from the AGITG MAX trial of capecitabine, bevacizumab and mitomycin C in metastatic colorectal cancer
Authors: Chionh Fiona , Gebski Val , Al-Obaidi Sheren J. , Mooi Jennifer K. , Bruhn Maressa A. , Lee Chee K. , Chüeh Anderly C. , Williams David S. , Weickhardt Andrew J. , Wilson Kate , Scott Andrew M. , Simes John , Hardingham Jennifer E. , Price Timothy J. , Mariadason John M. , Tebbutt Niall C. 
Published: January 2022

AbstractThe phase III MAX clinical trial randomised patients with metastatic colorectal cancer (mCRC) to receive first-line capecitabine chemotherapy alone or in combination with the anti-VEGF-A antibody bevacizumab (± mitomycin C). We utilised this cohort to examine whether single nucleotide polymorphisms (SNPs) in VEGF-A, VEGFR1, and VEGFR2 are predictive of efficacy outcomes with bevacizumab or the development of hypertension. Genomic DNA extracted from archival FFPE tissue for 325 patients (69% of the MAX trial population) was used to genotype 16 candidate SNPs in VEGF-A, VEGFR1, and VEGFR2, which were analysed for associations with efficacy outcomes and hypertension. The VEGF-A rs25648 ‘CC’ genotype was prognostic for improved PFS (HR 0.65, 95% CI 0.49 to 0.85; P = 0.002) and OS (HR 0.70, 95% CI 0.52 to 0.94; P = 0.019). The VEGF-A rs699947 ‘AA’ genotype was prognostic for shorter PFS (HR 1.32, 95% CI 1.002 to 1.74; P = 0.048). None of the analysed SNPs were predictive of bevacizumab efficacy outcomes. VEGFR2 rs11133360 ‘TT’ was associated with a lower risk of grade ≥ 3 hypertension (P = 0.028). SNPs in VEGF-A, VEGFR1 and VEGFR2 did not predict bevacizumab benefit. However, VEGF-A rs25648 and rs699947 were identified as novel prognostic biomarkers and VEGFR2 rs11133360 was associated with less grade ≥ 3 hypertension.
Quantum optical immunoassay: upconversion nanoparticle-based neutralizing assay for COVID-19
Authors: Rajil Navid , Esmaeili Shahriar , Neuman Benjamin W. , Nessler Reed , Wu Hung-Jen , Yi Zhenhuan , Brick Robert W. , Sokolov Alexei V. , Hemmer Philip R. , Scully Marlan O. 
Published: January 2022

AbstractIn a viral pandemic, a few important tests are required for successful containment of the virus and reduction in severity of the infection. Among those tests, a test for the neutralizing ability of an antibody is crucial for assessment of population immunity gained through vaccination, and to test therapeutic value of antibodies made to counter the infections. Here, we report a sensitive technique to detect the relative neutralizing strength of various antibodies against the SARS-CoV-2 virus. We used bright, photostable, background-free, fluorescent upconversion nanoparticles conjugated with SARS-CoV-2 receptor binding domain as a phantom virion. A glass bottom plate coated with angiotensin-converting enzyme 2 (ACE-2) protein imitates the target cells. When no neutralizing IgG antibody was present in the sample, the particles would bind to the ACE-2 with high affinity. In contrast, a neutralizing antibody can prevent particle attachment to the ACE-2-coated substrate. A prototype system consisting of a custom-made confocal microscope was used to quantify particle attachment to the substrate. The sensitivity of this assay can reach 4.0 ng/ml and the dynamic range is from 1.0 ng/ml to 3.2 $$\upmu$$
μ
g/ml. This is to be compared to 19 ng/ml sensitivity of commercially available kits.
An age-structured model of hepatitis B viral infection highlights the potential of different therapeutic strategies
Authors: Fatehi Farzad , Bingham Richard J. , Stockley Peter G. , Twarock Reidun 
Published: January 2022

AbstractHepatitis B virus (HBV) is a global health threat, and its elimination by 2030 has been prioritised by the World Health Organisation. Here we present an age-structured model for the immune response to an HBV infection, which takes into account contributions from both cell-mediated and humoral immunity. The model has been validated using published patient data recorded during acute infection. It has been adapted to the scenarios of chronic infection, clearance of infection, and flare-ups via variation of the immune response parameters. The impacts of immune response exhaustion and non-infectious subviral particles on the immune response dynamics are analysed. A comparison of different treatment options in the context of this model reveals that drugs targeting aspects of the viral life cycle are more effective than exhaustion therapy, a form of therapy mitigating immune response exhaustion. Our results suggest that antiviral treatment is best started when viral load is declining rather than in a flare-up. The model suggests that a fast antibody production rate always leads to viral clearance, highlighting the promise of antibody therapies currently in clinical trials.
Live imaging of micro and macro wettability variations of carbonate oil reservoirs for enhanced oil recovery and CO2 trapping/storage
Authors: Ivanova A. , Orekhov A. , Markovic S. , Iglauer S. , Grishin P. , Cheremisin A. 
Published: January 2022

AbstractCarbonate hydrocarbon reservoirs are considered as potential candidates for chemically enhanced oil recovery and for CO2 geological storage. However, investigation of one main controlling parameter—wettability—is usually performed by conventional integral methods at the core-scale. Moreover, literature reports show that wettability distribution may vary at the micro-scale due to the chemical heterogeneity of the reservoir and residing fluids. These differences may profoundly affect the derivation of other reservoir parameters such as relative permeability and capillary pressure, thus rendering subsequent simulations inaccurate. Here we developed an innovative approach by comparing the wettability distribution on carbonates at micro and macro-scale by combining live-imaging of controlled condensation experiments and X-ray mapping with sessile drop technique. The wettability was quantified by measuring the differences in contact angles before and after aging in palmitic, stearic and naphthenic acids. Furthermore, the influence of organic acids on wettability was examined at micro-scale, which revealed wetting heterogeneity of the surface (i.e., mixed wettability), while corresponding macro-scale measurements indicated hydrophobic wetting properties. The thickness of the adsorbed acid layer was determined, and it was correlated with the wetting properties. These findings bring into question the applicability of macro-scale data in reservoir modeling for enhanced oil recovery and geological storage of greenhouse gases.
Matrix metalloproteinases (MMP) 3 and 9 as biomarkers of severity in COVID-19 patients
Authors: Gelzo Monica , Cacciapuoti Sara , Pinchera Biagio , De Rosa Annunziata , Cernera Gustavo , Scialò Filippo , Comegna Marika , Mormile Mauro , Fabbrocini Gabriella , Parrella Roberto , Corso Gaetano , Gentile Ivan , Castaldo Giuseppe 
Published: January 2022

AbstractThe molecular basis of the wide clinical heterogeneity of Coronavirus disease 2019 (COVID-19) is still unknown. Matrix metalloproteinases (MMPs) may have a role in the lung damage and regeneration that occur in severe patients. We studied serum MMP3 and MMP9 as potential biomarkers of COVID-19 severity, in 108 hospitalized patients with different World Health Organization (WHO) severity stage and in 48 controls. At hospital admission, serum MMP3 was increased in COVID-19 patients with a significant trend along the progression of the WHO stage, while serum levels of MMP9 were significantly increased in COVID-19 patients with no correlation with disease severity. At 1 week from hospitalization, MMP3 was reduced, suggesting an early pathogenic role of the protein in lung inflammation, while MMP9 levels were further increased, indicating a late role of the protein in the inflammatory process, specifically during the repairing phase. Furthermore, serum MMP9 was positively correlated with serum interleukin-6, myeloperoxidase, and circulating neutrophils and monocytes number. In conclusion, serum MMP3 may help to early predict the severity of COVID-19 and both proteins, MMP3 and MMP9, may contribute to define severe COVID-19 patients that may benefit from a targeted therapy on MMPs.
The potential for effective reasoning guides children’s preference for small group discussion over crowdsourcing
Authors: Richardson Emory , Keil Frank C. 
Published: January 2022

AbstractCommunication between social learners can make a group collectively “wiser” than any individual, but conformist tendencies can also distort collective judgment. We asked whether intuitions about when communication is likely to improve or distort collective judgment could allow social learners to take advantage of the benefits of communication while minimizing the risks. In three experiments (n = 360), 7- to 10-year old children and adults decided whether to refer a question to a small group for discussion or “crowdsource” independent judgments from individual advisors. For problems affording the kind of ‘demonstrative’ reasoning that allows a group member to reliably correct errors made by even a majority, all ages preferred to consult the discussion group, even compared to a crowd ten times as large—consistent with past research suggesting that discussion groups regularly outperform even their best members for reasoning problems. In contrast, we observed a consistent developmental shift towards crowdsourcing independent judgments when reasoning by itself was insufficient to conclusively answer a question. Results suggest sophisticated intuitions about the nature of social influence and collective intelligence may guide our social learning strategies from early in development.
Single pullout experiment and reinforcement properties of basalt fiber in vegetation concrete
Authors: Zhang Baohua , Liu Daxiang , Su Huaizhi 
Published: January 2022

AbstractBasalt fiber (BF) reinforced vegetation concrete (VC) technique has attracted the attention of researchers. In order to investigate the reinforcement properties of BF reinforced VC, the optimal BF length and content. Through the single BF pullout test and direct shear test, the properties of interfacial strength between BF/VC and the reliability of the formula for calculating the optimal BF reinforcement length are studied. It has been found that the designed equipment is an efficient method to obtain the interfacial peak shear strength and residual shear strength of BF/VC. Moreover, the direct shear test proves the feasibility of the formula, which is used as a basis for mixing BF length in engineering. The anchoring effect between the cement hydration product and the fiber in the VC changes the mechanical action between BF/VC and significantly improves the shear strength of the interface. Higher dry density effectively enhanced the peak tension of a single BF by 149.23%. The optimal BF length and content make the softening degree of vegetation concrete not evident, which improves the durability of VC engineering. The formula of optimum fiber reinforced length and empirical formula can be used as reference for mixing basalt fiber in practical engineering.
Clinical factors and outcomes associated with immune non-response among virally suppressed adults with HIV from Africa and the United States
Authors: Noiman Adi , Esber Allahna , Wang Xun , Bahemana Emmanuel , Adamu Yakubu , Iroezindu Michael , Kiweewa Francis , Maswai Jonah , Owuoth John , Maganga Lucas , Ganesan Anuradha , Maves Ryan C. , Lalani Tahaniyat , Colombo Rhonda E. , Okulicz Jason F. , Polyak Christina , Crowell Trevor A. , Ake Julie A. , Agan Brian K. 
Published: January 2022

AbstractA significant minority of people living with HIV (PLWH) achieve viral suppression (VS) on antiretroviral therapy (ART) but do not regain healthy CD4 counts. Clinical factors affecting this immune non-response (INR) and its effect on incident serious non-AIDS events (SNAEs) have been challenging to understand due to confounders that are difficult to control in many study settings. The U.S. Military HIV Natural History Study (NHS) and African Cohort Study (AFRICOS). PLWH with sustained VS (< 400 copies/ml for at least two years) were evaluated for INR (CD4 < 350 cells/µl at the time of sustained VS). Logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHRs) for factors associated with incident SNAE after sustained VS. INR prevalence was 10.8% and 25.8% in NHS and AFRICOS, respectively. Higher CD4 nadir was associated with decreased odds of INR (aOR = 0.34 [95% CI 0.29, 0.40] and aOR = 0.48 [95% CI 0.40, 0.57] per 100 cells/µl in NHS and AFRICOS, respectively). After adjustment, INR was associated with a 61% increase in relative risk of SNAE [95% CI 1.12, 2.33]. Probability of "SNAE-free" survival at 15 years since sustained VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups. CD4 monitoring before and after VS is achieved can help identify PLWH at risk for INR. INR may be a useful clinical indicator of future risk for SNAEs.
Bioindicators of severe ocean acidification are absent from the end-Permian mass extinction
Authors: Foster William J. , Hirtz J. A. , Farrell C. , Reistroffer M. , Twitchett R. J. , Martindale R. C. 
Published: January 2022

AbstractThe role of ocean acidification in the end-Permian mass extinction is highly controversial with conflicting hypotheses relating to its timing and extent. Observations and experiments on living molluscs demonstrate that those inhabiting acidic settings exhibit characteristic morphological deformities and disordered shell ultrastructures. These deformities should be recognisable in the fossil record, and provide a robust palaeo-proxy for severe ocean acidification. Here, we use fossils of originally aragonitic invertebrates to test whether ocean acidification occurred during the Permian–Triassic transition. Our results show that we can reject a hypothesised worldwide basal Triassic ocean acidification event owing to the absence of deformities and repair marks on bivalves and gastropods from the Triassic Hindeodus parvus Conodont Zone. We could not, however, utilise this proxy to test the role of a hypothesised acidification event just prior to and/or during the mass extinction event. If ocean acidification did develop during the mass extinction event, then it most likely only occurred in the latest Permian, and was not severe enough to impact calcification.
Bayesian modeling of item heterogeneity in dichotomous recognition memory data and prospects for computerized adaptive testing
Authors: Güsten Jeremie , Berron David , Düzel Emrah , Ziegler Gabriel 
Published: January 2022

AbstractMost current models of recognition memory fail to separately model item and person heterogeneity which makes it difficult to assess ability at the latent construct level and prevents the administration of adaptive tests. Here we propose to employ a General Condorcet Model for Recognition (GCMR) in order to estimate ability, response bias and item difficulty in dichotomous recognition memory tasks. Using a Bayesian modeling framework and MCMC inference, we perform 3 separate validation studies comparing GCMR to the Rasch model from IRT and the 2-High-Threshold (2HT) recognition model. First, two simulations demonstrate that recovery of GCMR ability estimates with varying sparsity and test difficulty is more robust and that estimates improve from the two other models under common test scenarios. Then, using a real dataset, face validity is confirmed by replicating previous findings of general and domain-specific age effects (Güsten et al. in Cortex 137:138–148, https://doi.org/10.1016/j.cortex.2020.12.017, 2021). Using cross-validation we show better out-of-sample prediction for the GCMR as compared to Rasch and 2HT model. In addition, we present a hierarchical extension of the model that is able to estimate age- and domain-specific effects directly, without recurring to a two-stage procedure. Finally, an adaptive test using the GCMR is simulated, showing that the test length necessary to obtain reliable ability estimates can be significantly reduced compared to a non-adaptive procedure. The GCMR allows to model trial-by-trial performance and to increase the efficiency and reliability of recognition memory assessments.
Identification of an allatostatin C signaling system in mollusc Aplysia
Authors: Jiang Hui-Min , Yang Zhe , Xue Ying-Yu , Wang Hui-Ying , Guo Shi-Qi , Xu Ju-Ping , Li Ya-Dong , Fu Ping , Ding Xue-Ying , Yu Ke , Liu Wei-Jia , Zhang Guo , Wang Jian , Zhou Hai-Bo , Susswein Abraham J. , Jing Jian 
Published: January 2022

AbstractNeuropeptides, as pervasive intercellular signaling molecules in the CNS, modulate a variety of behavioral systems in both protostomes and deuterostomes. Allatostatins are neuropeptides in arthropods that inhibit the biosynthesis of juvenile hormones. Based on amino acid sequences, they are divided into three different types in arthropods: allatostatin A, allatostatin B, allatostatin C. Allatostatin C (AstC) was first isolated from Manduca sexta, and it has an important conserved feature of a disulfide bridge formed by two cysteine residues. Moreover, AstC appears to be the ortholog of mammalian somatostatin, and it has functions in common with somatostatin, such as modulating feeding behaviors. The AstC signaling system has been widely studied in arthropods, but minimally studied in molluscs. In this study, we seek to identify the AstC signaling system in the marine mollusc Aplysia californica. We cloned the AstC precursor from the cDNA of Aplysia. We predicted a 15-amino acid peptide with a disulfide bridge, i.e., AstC, using NeuroPred. We then cloned two putative allatostatin C-like receptors and through NCBI Conserved Domain Search we found that they belonged to the G protein-coupled receptor (GPCR) family. In addition, using an inositol monophosphate 1 (IP1) accumulation assay, we showed that Aplysia AstC could activate one of the putative receptors, i.e., the AstC-R, at the lowest EC50, and AstC without the disulfide bridge (AstC') activated AstC-R with the highest EC50. Moreover, four molluscan AstCs with variations of sequences from Aplysia AstC but with the disulfide bridge activated AstC-R at intermediate EC50. In summary, our successful identification of the Aplysia AstC precursor and its receptor (AstC-R) represents the first example in molluscs, and provides an important basis for further studies of the AstC signaling system in Aplysia and other molluscs.
Uncovering serum placental-related non-coding RNAs as possible biomarkers of preeclampsia risk, onset and severity revealed MALAT-1, miR-363 and miR-17
Authors: Abdelazim Samy A. , Shaker Olfat G. , Aly Yehya Aly Hussein , Senousy Mahmoud A. 
Published: January 2022

AbstractNew predictors that could boost early detection of preeclampsia (PE) and prognosticate its severity are urgently needed. We examined serum miR-17, miR-363, MALAT-1 and HOTAIR as potential biomarkers of PE risk, onset and severity. This prospective study included 160 pregnant females; 82 PE cases and 78 healthy pregnancies. Serum samples were collected between 20 to 40 weeks of gestation. Early-onset PE was defined as developing clinical manifestations at ≤ 34 gestational weeks. Severe PE was defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg and proteinuria (≥ 2 g/24 h or ≥ 2+ dipstick). Selection of PE-related non-coding RNAs and functional target gene analysis were conducted using bioinformatics analysis. Expression profiles were assessed by RT-qPCR. Serum miR-363 and MALAT-1 were downregulated, meanwhile miR-17 was upregulated, and HOTAIR was not significantly altered in PE compared with healthy pregnancies. miR-17 was elevated while miR-363 and MALAT-1 were reduced in severe versus mild PE. miR-363 was lower in early-onset versus late-onset PE. MALAT-1, miR-17 and miR-363 showed diagnostic potential and discriminated severe PE, whereas miR-363 distinguished early-onset PE in the receiver-operating-characteristic analysis. miR-363 and MALAT-1 were significantly associated with early and severe PE, respectively in multivariate logistic analysis. In PE, miR-17 and MALAT-1 were significantly correlated with gestational age (r = − 0.328 and r = 0.322, respectively) and albuminuria (r = 0.312, and r = − 0.35, respectively). We constructed the MALAT-1, miR-363, and miR-17-related protein–protein interaction networks linked to PE. Serum miR-17, miR-363 and MALAT-1 could have utility as new biomarkers of PE diagnosis. miR-363 may be associated with early-onset PE and MALAT-1 downregulation correlates with PE severity.
The newborn brain is sensitive to the communicative function of language
Authors: Forgács Bálint , Tauzin Tibor , Gergely György , Gervain Judit 
Published: January 2022

AbstractRecent studies demonstrated neural systems in bilateral fronto-temporal brain areas in newborns specialized to extract linguistic structure from speech. We hypothesized that these mechanisms show additional sensitivity when identically structured different pseudowords are used communicatively in a turn-taking exchange by two speakers. In an fNIRS experiment newborns heard pseudowords sharing ABB repetition structure in three conditions: two voices turn-takingly exchanged different pseudowords (Communicative); the different pseudowords were produced by a (Single Speaker); two voices turn-takingly repeated identical pseudowords (Echoing). Here we show that left fronto-temporal regions (including Broca’s area) responded more to the Communicative than the other conditions. The results demonstrate that newborns’ left hemisphere brain areas show additional activation when various pseudowords sharing identical structure are exchanged in turn-taking alternation by two speakers. This indicates that language processing brain areas at birth are not only sensitive to the structure but to the functional use of language: communicative information transmission. Newborns appear to be equipped not only with innate systems to identify the structural properties of language but to identify its use, communication itself, that is, information exchange between third party social agents—even outside of the mother–infant dyad.
Zinc oxide and indium-gallium-zinc-oxide bi-layer synaptic device with highly linear long-term potentiation and depression characteristics
Authors: Choi Hyun-Woong , Song Ki-Woo , Kim Seong-Hyun , Nguyen Kim Thanh , Eadi Sunil Babu , Kwon Hyuk-Min , Lee Hi-Deok 
Published: January 2022

AbstractThe electrical properties, resistive switching behavior, and long-term potentiation/depression (LTP/LTD) in a single indium-gallium-zinc-oxide (IGZO) and bi-layer IGZO/ZnO (ZnO: zinc oxide) memristors were investigated for synapse application. The use of the oxide bi-layer memristors, in particular, improved electrical properties such as stability, memristor reliability, and an increase in synaptic weight states. The set voltage of bi-layer IGZO/ZnO memristors was 0.9 V, and the reset voltage was around − 0.7 V, resulting in a low-operating voltage for neuromorphic systems. The oxygen vacancies in the X-ray photoelectron spectroscopy analysis played a role in the modulation of the high-resistance state (HRS) (oxygen-deficient) and the low-resistance state (oxygen-rich) region. The VRESET of the bi-layer IGZO/ZnO memristors was lower than that of a single IGZO, which implied that oxygen-vacancy filaments could be easily ruptured due to the higher oxygen vacancy peak HRS layer. The nonlinearity of the LTP and LTD characteristics in a bi-layer IGZO/ZnO memristor was 6.77% and 11.49%, respectively, compared to those of 20.03% and 51.1% in a single IGZO memristor, respectively. Therefore, the extra ZnO layer in the bi-layer memristor with IGZO was potentially significant and essential to achieve a small set voltage and a reset voltage, and the switching behavior to form the conductive path.