bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower Risk of Multisystem Inflammatory Syndrome in Children (MIS-C) with the Delta and Omicron variants of SARS-CoV-2
Authors: Cohen Jonathan M , Carter Michael J , Cheung C Ronny , Ladhani Shamez ,   Evelina PIMS-TS Study Group
Published: March 2022

AbstractLittle is known about the MIS-C risk with different SARS-CoV-2 variants. In Southeast England, MIS-C rates per confirmed SARS-CoV-2 infections in 0-16 years-olds were 56% lower (rate ratio, 0.34; 95%CI, 0.23-0.50) during pre-vaccine Delta, 66% lower (0.44; 0.28-0.69) during post-vaccine Delta and 95% lower (0.05; 0.02-0.10) during the Omicron period.
Palo: Spatially-aware color palette optimization for single-cell and spatial data
Authors: Hou Wenpin , Ji Zhicheng 
Published: March 2022

AbstractSummaryIn the exploratory data analysis of single-cell or spatial genomic data, single cells or spatial spots are often visualized using a two-dimensional plot where cell clusters or spot clusters are marked with different colors. With tens of clusters, current visualization methods often assigns visually similar colors to spatially neighboring clusters, making it hard to identify the distinction between clusters. To address this issue, we developed Palo that optimizes the color palette assignment for single-cell and spatial data in a spatially-aware manner. Palo identifies pairs of clusters that are spatially neighboring to each other and assigns visually distinct colors to those neighboring pairs. We demonstrate that Palo leads to improved visualization in real single-cell and spatial genomic datasets.AvailabilityPalo R package is freely available at https://github.com/Winnie09/Palo.Contactzhicheng.ji@duke.edu
Effect of GDF15 on acetaminophen (APAP)-induced liver injury in mice
Authors: Jiang Peng , Liu Zhenghong , Fang Tingyu , Zhang Zhidan , Wang Dongdong , Xu Suowen , Weng Jianping 
Published: March 2022

AbstractAcetaminophen (APAP)-induced liver injury (AILI) has been recognized as a pivotal contributor to drug-induced liver failure in western countries, but its molecular mechanism remains poorly understood. After data mining using the Gene Expression Omnibus (GEO) database, we found that the gene expression of growth differentiation factor 15 (GDF15) increased significantly after APAP-induced hepatotoxicity in mouse liver. However, the precise role of GDF15 in AILI has yet to be clarified. To deal with this question, we first examined the temporal gene expression pattern of GDF15 after APAP treatment. Next, overexpression of hepatic GDF15 using adeno-associated virus serotype 8 (AAV8) was employed to investigate the role of GDF15 in AILI. In addition, therapeutic administration of recombinant human GDF15 (rhGDF15) was conducted to probe its curative effect after APAP overdose. We observed that protein expression of GDF15 was significantly increased after APAP overdose. However, there were no significant differences in AILI-related outcomes after overexpression or supplementation of GDF15. The contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), morphological feature of liver, the level of reduced form of glutathione (GSH), the activation of c-Jun-N-terminal kinase (JNK), the expression of genes relevant to oxidative stress and cell proliferation were not remarkably changed between AAV8-GFP and AAV8-Gdf15 groups. Although the liver injury was not improved by rhGDF15 administration, the gene expression levels of glutamate-cysteine ligase modifier subunit (Gclm) and glutamate-cysteine ligase catalytic subunit (Gclc) which function downstream of Nrf2 signaling pathway were significantly increased. Altogether, despite a noticeable elevated expression after APAP overdose, GDF15 overexpression or supplementation exerted no significant ameliorative effect on AILI. Further mechanism and consequence of Gclm and Gclc elevation by GDF15 remains to be elucidated.
Ultrastructure of COPII vesicle formation characterised by correlative light and electron microscopy
Authors: Melero Alejandro , Boulanger Jerome , Kukulski Wanda , Miller Elizabeth A. 
Published: March 2022

AbstractTraffic of proteins out of the endoplasmic reticulum (ER) is driven by the COPII coat, a layered protein scaffold that mediates the capture of cargo proteins and the remodelling of the ER membrane into spherical vesicular carriers. Although the components of this machinery have been genetically defined, and the mechanisms of coat assembly extensively explored in vitro, understanding the physical mechanisms of membrane remodelling in cells remains a challenge. Here we use correlative light and electron microscopy (CLEM) to visualize the nanoscale ultrastructure of membrane remodelling at ER exit sites (ERES) in yeast cells. Using various COPII mutants, we have determined the broad contribution that each layer of the coat makes in membrane remodelling. Our data suggest that inner coat components define the radius of curvature whereas outer coat components facilitate membrane fission. The organization of the coat in conjunction with membrane biophysical properties determine the ultrastructure of vesicles and thus the efficiency of protein transport.
Neonatal AKI profile using KDIGO guidelines: A cohort study in tertiary care hospital ICU of Lahore, Pakistan
Authors: Gul Rafia , Anwar Zahid , Sheikh Mehmood , Salamat Ayesha , Iqbal Samer , Saleem Furqan 
Published: March 2022

AbstractBackgroundAKI is witnessed in sick neonates and is associated with poor outcomes. Our cohort represents the profile of neonates who were diagnosed with AKI using KDIGO guidelines during intensive care unit stay.MethodologyA cohort study was conducted in the NICU of FMH from June 2019 to May 2021. Data were collected on standardized proforma. Serum creatinine was measured within 24 hours after enrollment in the study by cytometric analysis using the C311 Rosch machine and subsequently after 24 to 48 hours. Data analysis was done using SPSS v 20.0. All continuous variables were not normally distributed and were expressed as the median and interquartile range (IQR). Categorical variables were analyzed by proportional differences with either the Pearson chi-square test or Fisher’s exact tests. A multinomial logistic regression model was used to explore the independent risk factors of AKI. Time to the event (death) and survival curves for the cohort were plotted by using Cox proportional hazard model.ResultsAKI occurred in 473 (37.6%) of neonates and 15.7%, 16.3% and 5.6% had stage 1, 2 and 3 respectively. The outborn birth (p 0.000, AOR 3.987, 95%CI 2.564 – 6.200), birth asphyxia (p 0.000, AOR 3.567, 95%CI 2.093 – 6.080), inotropic agent (p 0.000, AOR 2.060, 95%CI 1.436 – 2.957), antenatal steroids (p 0.002, AOR 1.721, 95%CI 1.213 – 2.443), central lines (p 0.005, AOR 1.630, 95%CI 1.155 – 2.298), IVH/ICH/DIC (p 0.009, AOR1.580, 95%CI 1.119 – 2.231) and NEC (p 0.054, AOR 1.747, 95%CI 0.990 – 3.083) were independently associated with AKI. Protective factors of neonatal AKI were normal sodium levels, maternal diabetes mellitus as well Hb>10.5 mg/dl. Duration of stay (7 vs 9 days) and mortality rates (3.9% vs16.5%) were significantly higher in neonates with AKI (p <0.001).ConclusionAbout one-third of critically sick neonates had AKI. Significant risk factors for AKI were outborn birth (298%), birth asphyxia (256%), inotropic agents (106%) %, NEC 74.7%, antenatal steroids 72%, central lines 63% and IVH/ICH/DIC 58%. AKI prolongs the duration of stay and reduces the survival of sick neonates.
Reduced Norepinephrine Transporter Binding in Parkinson’s disease with dopa Responsive Freezing Gait
Authors: McKay J. Lucas , Nye Jonathan , Goldstein Felicia C. , Sommerfeld Barbara , Smith Yoland , Weinshenker David , Factor Stewart A. 
Published: March 2022

AbstractFreezing of gait (FOG) is a major cause of falling and leads to loss of independence in Parkinson’s disease (PD). The pathophysiology of FOG is poorly understood – although there is a hypothesized link with NE systems. PD-FOG can present in levodopa-responsive and unresponsive forms.We examined NE transporter (NET) binding via brain positron emission tomography (PET) to evaluate changes in NET density associated with FOG using the high affinity selective NET antagonist radioligand [11C]MeNER (2S,3S)(2-[α-(2-methoxyphenoxy)benzyl]morpholine) in N=52 parkinsonian patients. We used a rigorous levodopa challenge paradigm to characterize patients as non-freezing PD (NO-FOG, N=16), levodopa responsive freezing (OFF-FOG, N=10), levodopa-unresponsive freezing (ONOFF-FOG, N=21), and primary progressive freezing of gait (PP-FOG, N=5).Linear mixed models identified significant reductions in whole brain NET binding in the OFF-FOG group compared to the NO-FOG group (−16.8%, P=0.021). Additional contrasts tested post-hoc identified trends toward increased NET expression in ONOFF-FOG vs. OFF-FOG (≈10%; P=0.123). Linear mixed models with interaction terms identified significantly reduced NET binding in right thalamus in the OFF-FOG group (P=0.038). A linear regression analysis identified an association between reduced NET binding and more severe NFOG-Q score only in the OFF-FOG group (P=0.022).This is the first study to examine brain noradrenergic innervation using NET-PET in PD patients with and without FOG. Based on the normal regional distribution of noradrenergic innervation and pathological studies in the thalamus of PD patients, the implications of our findings suggest that noradrenergic limbic pathways may play a key role in OFF-FOG in PD. This finding could have implications for clinical subtyping of FOG as well as development of therapies.
Neutrophil Peptidylarginine Deiminase 4 is Essential for Detrimental Age-related Cardiac Remodeling & Dysfunction in Mice
Authors: Van Bruggen Stijn , Kraisin Sirima , Van Wauwe Jore , Carai Paolo , Frederix Liesbeth , Witsch Thilo , Martinod Kimberly 
Published: March 2022

AbstractAimsWe aimed to study the long-term effect of neutrophils on cardiac health during the process of natural aging. We hypothesized that neutrophil PAD4, via its role in neutrophil extracellular trap (NET) formation, is involved in myocardial remodeling and cardiac fibrosis development, resulting in turn in impaired cardiac function.Methods and resultsWe generated mice with deletion ofPadi4, a NET-essential gene, under the neutrophil-specific promoter S100A8 (PAD4fl/flMRP8Cre+). These mice and their littermate controls were aged for two years (coinciding with approximately 70 years of age in humans; the age at which HF is the number one cause of hospitalization), after which cardiac function and remodeling were evaluated. We performed a comprehensive echocardiography analysis including both structural and functional parameter measurements. Deletion of PAD4 in neutrophils resulted in a protection against both systolic, and diastolic dysfunction. Interestingly, these mice showed protection against age induced fibrosis, detected as through the absence of cardiac collagen deposition. To explore this further, cardiac gene expression and plasma cytokine levels were evaluated. Here we saw a clear impact of PAD4-deficiency on cardiac neutrophil recruitment, with both cardiac genes as well as plasma cytokines involved in neutrophil recruitment being downregulated in aged PAD4fl/flMRP8Cre+animals in comparison to littermate PAD4fl/flcontrols, including decreased plasma levels of C-X-C ligand 1 (CXCL1).ConclusionOur data confirms neutrophil PAD4 involvement in heart failure progression by promoting cardiac remodeling, leading to cardiac dysfunction with old age. We saw that the deletion of PAD4 specifically in neutrophils had an influence on the CXCL1-CXCR2 axis, which is known to be involved in HF development.Translational perspectiveIn the developed world, an estimated 2% of the population lives with heart failure (HF). HF can be viewed as an upcoming pandemic, which is only expected to increase due to the aging of the global population. Therefore, research in HF development and progression are needed to establish new avenues for treatment and improved therapies. In our study, we were able to show the contribution of neutrophil PAD4 to HF pathogenesis, providing new supporting evidence for the involvement of NETs in detrimental cardiac remodeling.
Structural insights into p300 regulation and acetylation-dependent genome organisation
Authors: Ibrahim Ziad , Wang Tao , Destaing Olivier , Salvi Nicola , Hoghoughi Naghmeh , Chabert Clovis , Rusu Alexandra , Gao Jinjun , Feletto Leonardo , Reynoird Nicolas , Schalch Thomas , Zhao Yingming , Blackledge Martin , Khochbin Saadi , Panne Daniel 
Published: March 2022

SummaryHistone modifications are deposited by chromatin modifying enzymes and read out by proteins that recognize the modified state. BRD4-NUT is an oncogenic fusion protein of the acetyl lysine reader BRD4 that binds to the acetylase p300 and enables formation of long-range intra- and interchromosomal interactions. We here examine how acetylation reading and writing enable formation of such interactions. We show that NUT contains an acidic transcriptional activation domain that binds to the TAZ2 domain of p300. We use NMR to investigate the structure of the complex and found that the TAZ2 domain has an autoinhibitory role for p300. NUT-TAZ2 interaction or mutations found in cancer that interfere with autoinhibition by TAZ2 allosterically activate p300. p300 activation results in a self-organizing, acetylation-dependent feed-forward reaction that enables long-range interactions by bromodomain multivalent acetyl-lysine binding. We discuss the implications for chromatin organisation, gene regulation and dysregulation in disease.
Ontogeny of oscillatory slow-wave and neuronal population activity in human iPSC-3D cortical circuits
Authors: Izsak Julia , Theiss Stephan , Illes Sebastian 
Published: March 2022

AbstractOscillatory slow-wave activity (0.5—100 Hz) emerges during fetal human cortex development reflecting functional consequences of cellular brain ontogeny. Human induced pluripotent stem cell-derived (iPSC) neural in vitro models recapitulate aspects of in vivo cellular brain ontogeny, while neuronal mesoscale functional ontogeny is largely uncharacterized. We utilized a human iPSC-derived 3D cortical aggregate model to assess properties of emerging oscillatory slow-wave activity and its relation to synchronous neuronal population activity in cortical circuits. We reveal that oscillatory slow-wave activity (< 1 Hz), phased locked to synchronous population bursting, emerges within 14 days in vitro followed by consecutive stages of emerging delta (1—4 Hz), theta (4—11 Hz), beta (11—30 Hz), and gamma (30—55 Hz) oscillatory activity, accompanied by stage-specific changes in neuronal population burst pattern characteristics.We provide a classification of neuronal mesoscale functional ontogeny stages of developing human iPSC-cortical circuits, where each stage is defined by specific oscillatory slow-wave activity and characteristic synchronous neuronal bursting patterns.
Domain decomposition and upscaling technique for metascreens
Authors: Leumüller Michael , Hollaus Karl , Schöberl Joachim 
Published: March 2022

Purpose
This paper aims to consider a multiscale electromagnetic wave problem for a housing with a ventilation grill. Using the standard finite element method to discretise the apertures leads to an unduly large number of unknowns. An efficient approach to simulate the multiple scales is introduced. The aim is to significantly reduce the computational costs.

Design/methodology/approach
A domain decomposition technique with upscaling is applied to cope with the different scales. The idea is to split the domain of computation into an exterior domain and multiple non-overlapping sub-domains. Each sub-domain represents a single aperture and uses the same finite element mesh. The identical mesh of the sub-domains is efficiently exploited by the hybrid discontinuous Galerkin method and a Schur complement which facilitates the transition from fine meshes in the sub-domains to a coarse mesh in the exterior domain. A coarse skeleton grid is used on the interface between the exterior domain and the individual sub-domains to avoid large dense blocks in the finite element discretisation matrix.

Findings
Applying a Schur complement to the identical discretisation of the sub-domains leads to a method that scales very well with respect to the number of apertures.

Originality/value
The error compared to the standard finite element method is negligible and the computational costs are significantly reduced.
Pulse flaking: Opportunities and challenges, a review
Authors: Cork Stephen David , Blanchard Chris , Mawson Andrew John , Farahnaky Asgar 
Published: March 2022

AbstractPulses provide economic and health benefits to people in many countries around the world; however, their adoption in western diets, particularly in processed and formulated foods, is limited. One strategy to increase the level of pulses in western diets is to improve pulse accessibility to the ready‐to‐eat (RTE) food market sector. Pulses have compositional and structural differences when compared to cereals and behave differently during processing. While there have been numerous studies on pulses processed using traditional processing methods, there are limited studies describing processing of pulses as a major ingredient in RTE forms such as flakes. To understand the full processing potential of pulses, systematic studies are required using commercial‐scale RTE pilot processing equipment coupled with fundamental property determination techniques to evaluate the effects of processing and pulse material on pulse flake attributes. In‐depth studies of pulse properties and their processability are likely to result in the production of high‐quality pulse‐based foods with superior health benefits. This review explores the current and potential opportunities for processing pulses with a focus on flake products. The roles of pulse type and major structure‐forming components such as fiber, carbohydrates, and proteins on end‐product quality of processed pulses are discussed.
Biomarkers and biosensors for the diagnosis of noncompliant pH, dark cutting beef predisposition, and welfare in cattle
Authors: Nelis Joost L. D. , Bose Utpal , Broadbent James A. , Hughes Joanne , Sikes Anita , Anderson Alisha , Caron Karine , Schmoelzl Sabine , Colgrave Michelle L. 
Published: March 2022

AbstractMeat quality can be affected by stress, exhaustion, feed composition, and other physical and environmental conditions. These stressors can alter the pH in postmortem muscle, leading to high pH and low‐quality dark cutting (DC) beef, resulting in considerable economic loss. Moreover, the dark cutting prediction may equally provide a measure for animal welfare since it is directly related to animal stress. There are two needs to advance on‐site detection of dark cutters: (1) a clear indication that biomarker (signature compounds) levels in cattle correlate with stress and DC outcome; and (2) measuring these biomarkers rapidly and accurately on‐farm or the abattoir, depending on the objectives. This critical review assesses which small molecules and proteins have been identified as potential biomarkers of stress and dark cutting in cattle. We discuss the potential of promising small molecule biomarkers, including catecholamine/cortisol metabolites, lactate, succinate, inosine, glucose, and β‐hydroxybutyrate, and we identify a clear research gap for proteomic biomarker discovery in live cattle. We also explore the potential of chemical‐sensing and biosensing technologies, including direct electrochemical detection improved through nanotechnology (e.g., carbon and gold nanostructures), surface‐enhanced Raman spectroscopy in combination with chemometrics, and commercial hand‐held devices for small molecule detection. No current strategy exists to rapidly detect predictive meat quality biomarkers due to the need to further validate biomarkers and the fact that different biosensor types are needed to optimally detect different molecules. Nonetheless, several biomarker/biosensor combinations reported herein show excellent potential to enable the measurement of DC potential in live cattle.
Multilocus DNA metabarcoding diet analyses of small cetaceans: a case study on highly vulnerable humpback dolphins and finless porpoises from the Pearl River Estuary, China
Authors: ZHANG Xiyang , LUO Dingyu , YU Ri‐Qing , WU Yuping 
Published: March 2022

AbstractAccurate diet identification of top predators is crucial to fully understand their ecological roles. Compared to terrestrial animals, gathering dietary information from cetaceans is notoriously difficult. Here, we applied a multilocus metabarcoding approach to investigate the diet of vulnerable Indo‐Pacific humpback dolphins and Indo‐Pacific finless porpoises from the Pearl River Estuary (PRE), China. Our analyses identified 21 prey fish species from the 42 humpback dolphin stomachs, as well as 10 species of fish and 1 species of cephalopod from the 13 finless porpoise stomachs. All of the taxa were assigned to the species level, highlighting that the multimarker approach could facilitate species identification. Most of the prey species were small‐ and medium‐sized fishes that primarily fed on zooplankton. The calculated similarity index revealed a moderated dietary overlap between the 2 cetaceans, presumably due to the feeding of the 2 predators in association with fishing vessels in the PRE. A more diverse diet was observed in humpback dolphins in the closed fishing season compared to the fishing season, implying the influence on the dolphin diet due to the availability of commercial fishery resources. However, according to the results of species rarefaction curves, our findings on the feeding habits of the 2 cetaceans are still limited by insufficient sample size and therefore should be interpreted with caution. This study represents a first attempt to apply the multilocus DNA metabarcoding technique in the diet analysis of small cetaceans, although more efforts are needed to improve this type of analysis.
Ethnobotanical and phytochemical aspects of the edible herb Coriandrum sativum L.
Authors: Sobhani Zahra , Mohtashami Leila , Amiri Mohammad Sadegh , Ramezani Mahin , Emami Seyed Ahmad , Simal‐Gandara Jesus 
Published: March 2022

AbstractCoriandrum sativum (coriander) is an edible herb in the family Apiaceae. The leaves, fruits, and stems of C. sativum have long been used as culinary spice due to their favorable odor. Traditional practitioners used this plant for treating different diseases like blepharitis, scabies, aphthous stomatitis, laryngitis, headache, and palpitation. In modern researches, coriander has demonstrated anxiolytic, anticonvulsant, antimigraine, neuroprotective, analgesic, diuretic, hypoglycemic, hypolipidemic, hypotensive, anticancer, and antioxidant activities. Coriander contains a wide range of bioactive phytochemicals among which phenylpropenes, terpenoids, isocoumarins, phytosterols, and fatty acids are the most important. This review provides information about the botanical and ethnobotanical aspects, chemical profile, therapeutic uses in Islamic traditional medicine (ITM), and recent pharmacological studies of coriander effects. The results have shown that coriander and its monoterpenoid compound, linalool, can be considered as potential drug candidates for treating metabolic syndrome and different inflammatory conditions especially neural and CNS diseases.