bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wastewater monitoring outperforms case numbers as a tool to track COVID-19 incidence dynamics when test positivity rates are high
Authors: Fernandez-Cassi Xavier , Scheidegger Andreas , Bänziger Carola , Cariti Federica , Corzon Alex Tuñas , Ganesanandamoorthy Pravin , Lemaitre Joseph C. , Ort Christoph , Julian Timothy R. , Kohn Tamar 
Published: March 2021

AbstractWastewater-based epidemiology (WBE) has been shown to coincide with, or anticipate, confirmed COVID-19 case numbers. During periods with high test positivity rates, however, case numbers may be underreported, whereas wastewater does not suffer from this limitation. Here we investigated how the dynamics of new COVID-19 infections estimated based on wastewater monitoring or confirmed cases compare to true COVID-19 incidence dynamics. We focused on the first pandemic wave in Switzerland (February to April, 2020), when test positivity ranged up to 26%. SARS-CoV-2 RNA loads were determined 2-4 times per week in three Swiss wastewater treatment plants (Lugano, Lausanne and Zurich). Wastewater and case data were combined with a shedding load distribution and an infection-to-case confirmation delay distribution, respectively, to estimate incidence dynamics. Finally, the estimates were compared to reference incidence dynamics determined by a validated compartmental model. Incidence dynamics estimated based on wastewater data were found to better track the timing and shape of the reference infection peak compared to estimates based on confirmed cases. In contrast, case confirmations provided a better estimate of the subsequent decline in infections. Under a regime of high-test positivity rates, WBE thus provides critical information that is complementary to clinical data to monitor the pandemic trajectory.
Neural dynamics of parametrically modulated human mechanical pain determined using whole-brain quantitative perfusion imaging
Authors: Segerdahl A.R. , Kong Y. , Ho I. , Tracey I 
Published: March 2021

AbstractArterial spin labelling (ASL) FMRI is a powerful tool to noninvasively image tonic and ongoing pain states in both healthy participants and patients. We used ASL to image the neural correlates of extended, parametrically modulated mechanical pain in healthy human participants. The aims of this study were to: i) assess if force-calibrated pin-prick probes could safely and robustly evoke tonic mechanical pain; ii) determine the neural correlates of the parametric changes in both the “force” of the stimulus and the “intensity” of the perception that this elicits using ASL; and iii) provide an initial assessment of the capacity for ALFF to differentiate painful versus non-painful tonic stimuli based on changes in the dynamics of the evoked signal. Our data confirm that it is possible to employ a stimulus force-locked design to induce robust, well maintained ongoing mechanical pain and to observe significant changes in rCBF relative to underlying component processes such as monitoring graded changes in the force applied to the skin (dACC, aMCC, pMCC, PCC, SI, SII, putamen, thalamus and the insula (anterior and posterior subsections); ipsilateral amygdala and hypothalamus; and the contralateral DLPFC) and tracking changes in the perceived intensity of the experience (: bilateral dACC, aMCC, pMCC, PCC, thalamus, SII and the cerebellum; and contralateral SI, insula (including the dpIns). Further exploration of the data using analyses targeting the spectral frequency aspects of the rCBF signal observed reveals that a collection of regions (e.g. the contralateral VLPFC, inferior frontal gyrus, insula (anterior, mid and posterior subsections), SII, putamen, OFC, amygdala, and the hippocampus) exhibit unique perfusion dynamics during extended painful stimulation compared to non-painful ‘touch’. Results from this study provide further validation for the application of ASL to image experimental pain in healthy human subjects while interrogation of the data offers unique insight into the dynamic signal changes underlying the perception of a tonic mechanical pain experience.
Abated immune responses against recombinant hepatitis-b vaccine by chitin in mice
Authors: Joshua Parker Elijah , Ayogu Nnaemeka Emmanuel , Ezeorba Timothy Prince Chidike , Odimegwu Damian Chukwu , Asomadu Rita Onyekachukwu , Ukachukwu Uzochukwu Gospel 
Published: March 2021

Abated immune responses against recombinant hepatitis-b protein vaccine by chitin in miceMajority of recombinant protein vaccines employ alum-based adjuvants to boost their immunogenicity in subjects. However, the safe-profiled alum-based adjuvants demonstrate relative ineffectiveness with these recombinant vaccines. This work investigated the adjuvant potential of chitin with recombinant Hepatitis-B protein vaccine (HBsAg) and its possible toxicological effects. Six to eight weeks old female albino mice, which were randomly and equally distributed into five groups were used for this study. Blood collection was done before each vaccination schedule and the samples were used for analysis. Results revealed that IgG and IgG1titres of mice administered 2 doses of HBsAg-Chitin formulation was significantly (p < 0.05) lower than those administered 3 doses of HBsAg and was not significantly (p > 0.05) higher than those administered 2 doses of HBsAg. However, a progressive increase in the anti-HBsAg titres in mice that received the HBsAg-Chitin formulation was observed as days came by. Activities of alanine and aspartate aminotransferases of all experimental groups, including their liver weights, inferred that the HBsAg-Chitin formulation exert no toxic effect on the liver. The findings of this research revealed that chitin demonstrated a relatively unimpressive adjuvant activity with the recombinant hepatitis-B protein vaccine.GRAPHICAL ABSTRACT
Brain virtual histology with X-ray phase-contrast tomography Part II: 3D morphologies of amyloid-β plaques in Alzheimer’s disease models
Authors: Chourrout Matthieu , Roux Margaux , Boisvert Carlie , Gislard Coralie , Legland David , Arganda-Carreras Ignacio , Olivier Cécile , Peyrin Françoise , Boutin Hervé , Rama Nicolas , Baron Thierry , Meyronet David , Brun Emmanuel , Rositi Hugo , Wiart Marlène , Chauveau Fabien 
Published: March 2021

AbstractWhile numerous transgenic mouse strains have been produced to model the formation of amyloid-β (Aβ) plaques in the brain, efficient methods for whole-brain 3D analysis of Aβ deposits are lacking. Moreover, standard immunohistochemistry performed on brain slices precludes any shape analysis of Aβ plaques. The present study shows how in-line (propagation-based) X-ray phase-contrast tomography (XPCT) combined with ethanol-induced brain sample dehydration enables hippocampus-wide detection and morphometric analysis of Aβ plaques. Performed in three distinct Alzheimer mouse strains, the proposed workflow identified differences in signal intensity and 3D shape parameters: 3xTg displayed a different type of Aβ plaques, with a larger volume and area, greater elongation, flatness and mean breadth, and more intense average signal than J20 and APP/PS1. As a label-free non-destructive technique, XPCT can be combined with standard immunohistochemistry. XPCT virtual histology could thus become instrumental in quantifying the 3D spreading and the morphological impact of seeding when studying prion-like properties of Aβ aggregates in animal models of Alzheimer’s disease. This is Part II of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part I shows how in-line XPCT enables 3D myelin mapping in the whole rodent brain and in human autopsy brain tissue.HighlightsX-ray phase-contrast tomography (XPCT) enables whole brain detection of Aβ plaquesMorphometric parameters of Aβ plaques may be readily retrieved from XPCT dataNew shape parameters were successfully extracted from three Alzheimer’s disease modelsA Fiji-based “biologist-friendly” analysis workflow is proposed and sharedXPCT is a powerful virtual histology tool that requires minimal sample preparationGraphical abstract
Brain image-derived phenotypes yield insights into causal risk of psychiatric disorders using a Mendelian randomization study
Authors: Guo Jing , Yu Ke , Guo Yan , Yao Shi , Wu Hao , Zhang Kun , Rong Yu , Guo Ming-Rui , Dong Shan-Shan , Yang Tie-Lin 
Published: March 2021

AbstractBrain imaging-derived phenotypes (IDPs) serve as underlying functional intermediates in psychiatric disorders, both of which are highly polygenic and heritable. Observational studies have elucidated the correlation between IDPs and psychiatric disorders, yet no systematic screening of IDPs to confer the causal liability in such disorders. We conducted a bidirectional two-sample Mendelian randomization framework to explore the causality of 1,901 IDPs on 10 psychiatric disorders and established the BrainMR database (http://brainmr.online/idp2psy/Index.php). We identified 17 causalities in forward MR analyses and 14 causalities in reverse MR analyses, which all rigorously examined them through various sensitivity analyses. The top significant relationship in forward was a unit lower volume of right central lateral of the thalamic nuclei, which was causally associated with an increased anorexia nervosa risk with an estimated OR of 0.52 (95% CI 0.41-0.64,P= 3.32 × 10−9). In reverse, the top significant IDP to be affected was the area of superior segment of the circular sulcus of the insula in the right hemisphere, which was increased by the reason of SCZ risk with an estimated association effect size of 0.068 (95% CI 0.046-0.090,P= 1.12 × 10−6). Overall, our study provides unique insights into causal pathways of psychiatric disorders at the imaging levels.
Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress
Authors: Coronel Luis , Riege Konstantin , Schwab Katjana , Förste Silke , Häckes David , Semerau Lena , Bernhart Stephan H. , Siebert Reiner , Hoffmann Steve , Fischer Martin 
Published: March 2021

AbstractDespite its prominence, the mechanisms through which the tumor suppressor p53 regulates most genes remain unclear. Recently, the regulatory factor X 7 (RFX7) emerged as a suppressor of lymphoid neoplasms, but its regulation and target genes mediating tumor suppression remain unknown. Here, we identify a novel p53-RFX7 signaling axis. Integrative analysis of the RFX7 DNA binding landscape and the RFX7-regulated transcriptome in three distinct cell systems reveals that RFX7 directly controls multiple established tumor suppressors, including PDCD4, PIK3IP1, MXD4, and PNRC1, across cell types and is the missing link for their activation in response to p53 and stress. RFX7 target gene expression correlates with cell differentiation and better prognosis in numerous cancer types. Interestingly, we find that RFX7 sensitizes cells to Doxorubicin by promoting apoptosis. Together, our work establishes RFX7’s role as a ubiquitous regulator of cell growth and fate determination and a key node in the p53 transcriptional program.
Endocytic recycling is central to circadian collagen fibrillogenesis and disrupted in fibrosis
Authors: Chang Joan , Pickard Adam , Herrera Jeremy A. , O’Keefe Sarah , Garva Richa , Knox John , Jowitt Thomas A. , Hartshorn Matthew , Hoyle Anna , Dingle Lewis , Coy Madeleine , Zeltz Cédric , Wong Jason , Reid Adam , Venkateswaran Rajamiyer V. , Lu Yinhui , Caswell Patrick , High Stephen , Gullberg Donald , Kadler Karl E. 
Published: March 2021

AbstractCollagen-I fibrillogenesis is crucial to health and development, where dysregulation is a hallmark of fibroproliferative diseases. Here, we show that collagen-I fibril assembly required a functional endocytic system that recycles collagen-I to assemble new fibrils. Endogenous collagen production was not required for fibrillogenesis if exogenous collagen was available, but the circadian-regulated vacuolar protein sorting (VPS) 33b and collagen-binding integrin α11 subunit were crucial to fibrillogenesis. Cells lacking VPS33B secrete soluble collagen-I protomers but were deficient in fibril formation, thus secretion and assembly are separately controlled. Overexpression of VPS33B led to loss of fibril rhythmicity and over-abundance of fibrils, which was mediated through integrin α11β1. Endocytic recycling of collagen-I was enhanced in human fibroblasts isolated from idiopathic pulmonary fibrosis, where VPS33B and integrin α11 subunit were overexpressed at the fibrogenic front; this correlation between VPS33B, integrin α11 subunit, and abnormal collagen deposition was also observed in samples from patients with chronic skin wounds. In conclusion, our study showed that circadian-regulated endocytic recycling is central to homeostatic assembly of collagen fibrils and is disrupted in diseases.
Intra- and inter-specific density dependence of body condition, growth, and habitat temperature in chub mackerel (Scomber japonicus)
Authors: Kamimura Yasuhiro , Taga Makoto , Yukami Ryuji , Watanabe Chikako , Furuichi Sho 
Published: March 2021

AbstractThe density dependence of growth and body condition have important impacts on fish population dynamics and fisheries management. Although population density is known to affect the temperature of the habitat selected, how this affects the density dependence of growth and body condition remains unclear. Here, we investigated annual changes in body condition, habitat temperature, and cohort-specific growth of chub mackerel (Scomber japonicus) in the western North Pacific and examined quarterly changes in the density dependence of body condition. We hypothesized that chub mackerel body condition is affected both directly (e.g., through competition for food) and indirectly (through changes in habitat temperature) by the abundance of both conspecifics (i.e., chub mackerel) and heterospecifics (the Japanese sardineSardinops melanostictus). Indeed, chub mackerel body condition, habitat temperature, and growth all decreased with increasing conspecific and heterospecific abundance. Mean annual growth rates in chub mackerel were positively corelated with body condition. The best model showed that conspecific and/or heterospecific abundance had strong negative effects on chub mackerel body condition in all seasons, and influenced habitat temperature in some seasons. By contrast, temperature effects on body condition were weak. Therefore, direct effects likely have more impact than indirect effects on density-dependent body condition and growth.
Pyrethroid and metal residues in different coffee bean preparing processes and their human health risk assessments via consumption
Authors: Khunlert Paphatsara , Tanhan Phanwimol , Poapolathep Amnart , Poapolathep Saranya , Imsilp Kanjana 
Published: March 2021

AbstractThe study was conducted on 50 samples of coffee beans from various origins. The samples included green coffee beans, roasted beans, brew coffee drinks and coffee sludge. Three processes were used to prepare these samples: dried, semi-washed, and washed. Three synthetic pyrethroid insecticides and nine heavy metals were subsequently analyzed using modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) and acid digestion methods, respectively. The quantification of pyrethroids was performed by GC-μECD whereas those of metals were determined using flame atomic absorption spectrophotometer. According to the results, concentrations of both pyrethroids and heavy metals were predominantly found in green coffee beans except for Cr. Pyrethroid insecticides were not detectable in brew coffee drink and heavy metal concentrations were below the acceptable daily intake (ADI) level. Risk estimations for daily coffee intake using the health risk indices (HRIs) and target hazard quotients (THQs) of normal and the 97.5 percentile Thai consumers were less than 1. This indicated that the coffee drinks from studied samples could not cause potential health risk.
Cooperation amongc-subunits of FoF1-ATP synthase in rotation-coupled proton translocation
Authors: Mitome Noriyo , Kubo Shintaroh , Ohta Sumie , Takashima Hikaru , Shigefuji Yuto , Niina Toru , Takada Shoji 
Published: March 2021

AbstractIn FoF1-ATP synthase, proton translocation through Fodrives rotation of thec-subunit oligomeric ring relative to thea-subunit. Recent studies suggest that in each step of the rotation, key glutamic acid residues in differentc-subunits contribute to proton release to and proton uptake from thea-subunit. However, no studies have demonstrated cooperativity amongc-subunits toward FoF1-ATP synthase activity. Here, we addressed this usingBacillusPS3 ATP synthase harboringc-ring with various combinations of wild-type andcE56D, enabled by genetically fused single-chainc-ring. ATP synthesis and proton pump activities were decreased by a singlecE56D mutation and further decreased by doublecE56D mutations. Moreover, activity further decreased as the two mutation sites were separated, indicating cooperation amongc-subunits. Similar results were obtained for proton transfer-coupled molecular simulations. Simulations revealed that prolonged proton uptake in mutatedc-subunits is shared between twoc-subunits, explaining the cooperation observed in biochemical assays.
Ovalbumin antigen-specific activation of T cell receptor closely resembles soluble antibody stimulation as revealed by BOOST phosphotyrosine proteomics
Authors: Chua Xien Yu , Salomon Arthur 
Published: March 2021

AbstractActivation of T cell receptors (TCR) leads to a network of early signaling predominantly orchestrated by tyrosine phosphorylation in T cells. TCR are commonly activated using soluble anti-TCR antibodies, but this approach is not antigen-specific. Alternatively, activating the TCR using specific antigens of a range of binding affinities in the form of peptide-major histocompatibility complex (pMHC) is presumed to be more physiological. However, due to the lack of wide-scale phosphotyrosine (pTyr) proteomic studies directly comparing anti-TCR antibodies and pMHC, a comprehensive definition of these activated states remains enigmatic. Elucidation of the tyrosine phosphoproteome using quantitative pTyr proteomics enables a better understanding of the unique features of these activating agents and the role of ligand binding affinity on signaling. Here, we apply the recently established Broad-spectrum Optimization Of Selective Triggering (BOOST) to examine perturbations in tyrosine phosphorylation of TCR triggered by anti-TCR antibodies and pMHC. Our data reveals that high-affinity ovalbumin (OVA) pMHC activation of the TCR triggers a largely similar, albeit potentially stronger, pTyr-mediated signaling regulatory axis compared to anti-TCR antibody. Signaling output resulting from OVA pMHC variants correlates well with their weaker affinities, enabling affinity-tunable control of signaling strength. Collectively, we provide a framework for applying BOOST to compare pTyr-mediated signaling pathways of T cells activated in an antigen-independent and antigen-specific manner.Abstract Graphic
Mathematical Models of Retinitis Pigmentosa: The Trophic Factor Hypothesis
Authors: Roberts Paul A. 
Published: March 2021

AbstractRetinitis pigmentosa (RP) is the term used to denote a group of inherited retinal-degenerative conditions that cause progressive sight loss. Individuals with this condition lose their light-sensitive photoreceptor cells, known as rods and cones, over a period of years to decades; degeneration starting in the retinal periphery, and spreading peripherally and centrally over time. RP is a rod-cone dystrophy, meaning that rod health and function are affected earlier and more severely than that of cones. Rods degenerate due to an underlying mutation, whereas the reasons for cone degeneration are unknown. A number of mechanisms have been proposed to explain secondary cone loss and the spatio-temporal patterns of retinal degeneration in RP. One of the most promising is the trophic factor hypothesis, which suggests that rods produce a factor necessary for cone survival, such that, when rods degenerate, cone degeneration follows. In this paper we formulate and analyse mathematical models of RP under the trophic factor hypothesis. These models are constructed as systems of reaction-diffusion partial differential equations in one spatial dimension, and are solved and analysed using a combination of numerical and analytical methods. We predict the conditions under which cones will degenerate following the loss of a patch of rods from the retina, the critical trophic factor treatment rate required to prevent cone degeneration following rod loss and the spatio-temporal patterns of cone loss that would result if the trophic factor mechanism alone were responsible for retinal degeneration.
Mining signaling flow to interpret mechanisms of synergy of drug combinations using deep graph neural networks
Authors: Zhang Heming , Chen Yixin , Payne Philip , Li Fuhai 
Published: March 2021

AbstractComplex signaling pathways/networks are believed to be responsible for drug resistance in cancer therapy. Drug combinations inhibiting multiple signaling targets within cancer-related signaling networks have the potential to reduce drug resistance. Deep learning models have been reported to predict drug combinations. However, these models are hard to be interpreted in terms of mechanism of synergy (MoS), and thus cannot well support the human-AI based clinical decision making. Herein, we proposed a novel computational model,DeepSignalingFlow, which seeks to address the preceding two challenges. Specifically, a graph convolutional network (GCN) was developed based on a core cancer signaling network consisting of 1584 genes, with gene expression and copy number data derived from 46 core cancer signaling pathways. The novel up-stream signaling-flow (from up-stream signaling to drug targets), and the down-stream signaling-flow (from drug targets to down-stream signaling), were designed using trainable weights of network edges. The numerical features (accumulated information due to the signaling-flows of the signaling network) of drug nodes that link to drug targets were then used to predict the synergy scores of such drug combinations. The model was evaluated using the NCI ALMANAC drug combination screening data. The evaluation results showed that the proposedDeepSignalingFlowmodel can not only predict drug combination synergy score, but also interpret potentially interpretable MoS of drug combinations.