bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional evaluation of 16 SCHAD missense variants: Only amino acid substitutions causing congenital hyperinsulinism of infancy lead to loss‐of‐function phenotypes in vitro
Authors: Velasco Kelly , St‐Louis Johanna L. , Hovland Henrikke N. , Thompson Nels , Ottesen Åsta , Choi Man Hung , Pedersen Line , Njølstad Pål R. , Arnesen Thomas , Fjeld Karianne , Aukrust Ingvild , Myklebust Line M. , Molven Anders 
Published: September 2020

AbstractShort‐chain 3‐hydroxyacyl‐CoA dehydrogenase (SCHAD), encoded by the HADH gene, is a ubiquitously expressed mitochondrial enzyme involved in fatty acid oxidation. This protein also plays a role in insulin secretion as recessive HADH mutations cause congenital hyperinsulinism of infancy (CHI) via loss of an inhibitory interaction with glutamate dehydrogenase (GDH). Here, we present a functional evaluation of 16 SCHAD missense variants identified either in CHI patients or by high‐throughput sequencing projects in various populations. To avoid interactions with endogenously produced SCHAD protein, we assessed protein stability, subcellular localization, and GDH interaction in a SCHAD knockout HEK293 cell line constructed by CRISPR‐Cas9 methodology. We also established methods for efficient SCHAD expression and purification in E. coli, and tested enzymatic activity of the variants. Our analyses showed that rare variants of unknown significance identified in populations generally had similar properties as normal SCHAD. However, the CHI‐associated variants p.Gly34Arg, p.Ile184Phe, p.Pro258Leu, and p.Gly303Ser were unstable with low protein levels detectable when expressed in HEK293 cells. Moreover, CHI variants p.Lys136Glu, p.His170Arg, and p.Met188Val presented normal protein levels but displayed clearly impaired enzymatic activity in vitro, and their interaction with GDH appeared reduced. Our results suggest that pathogenic missense variants of SCHAD either make the protein target of a post‐translational quality control system or can impair the function of SCHAD without influencing its steady‐state protein level. We did not find any evidence that rare SCHAD missense variants observed only in the general population and not in CHI patients are functionally affected.
Neutrophil recruitment by chemokines Cxcl1/KC and Cxcl2/MIP2: Role of Cxcr2 activation and glycosaminoglycan interactions
Authors: Sawant Kirti V , Sepuru Krishna Mohan , Lowry Emily , Penaranda Brigith , Frevert Charles W , Garofalo Roberto P , Rajarathnam Krishna 
Published: September 2020

Abstract
Chemokines play a crucial role in combating microbial infection by recruiting blood neutrophils to infected tissue. In mice, the chemokines Cxcl1/KC and Cxcl2/MIP2 fulfill this role. Cxcl1 and Cxcl2 exist as monomers and dimers, and exert their function by activating the Cxcr2 receptor and binding glycosaminoglycans (GAGs). Here, we characterized Cxcr2 G protein and β-arrestin activities, and GAG heparan sulfate (HS) interactions of Cxcl1 and Cxcl2 and of the trapped dimeric variants. To understand how Cxcr2 and GAG interactions impact in vivo function, we characterized their neutrophil recruitment activity to the peritoneum, Cxcr2 and CD11b levels on peritoneal and blood neutrophils, and transport profiles out of the peritoneum. Cxcl2 variants compared with Cxcl1 variants were more potent for Cxcr2 activity. Native Cxcl1 compared with native Cxcl2 and dimers compared with native proteins bound HS with higher affinity. Interestingly, recruitment activity between native Cxcl1 and Cxcl2, between dimers, and between the native protein and the dimer could be similar or very different depending on the dose or the time point. These data indicate that peritoneal neutrophil recruitment cannot be solely attributed to Cxcr2 or GAG interactions, and that the relationship between recruited neutrophils, Cxcr2 activation, GAG interactions, and chemokine levels is complex and highly context dependent. We propose that the ability of Cxcl1 and Cxcl2 to reversibly exist as monomers and dimers and differences in their Cxcr2 activity and GAG interactions coordinate neutrophil recruitment and activation, which play a critical role for successful resolution of inflammation.
Frontline Science: Breast milk confers passive cellular immunity via CD8-dependent mechanisms
Authors: Myles Ian A , Datta Sandip K 
Published: September 2020

Abstract
Most modern research into the immune effects of breast milk has focused on the impacts of immunoglobulin or oligosaccharide content. However, immediately prior to parturition, the cell populations of breast milk become selectively enriched for CD8+ T cells of an effector memory subtype. Despite this observation that the cellular content of breast milk contains a distinct leukocyte population when compared to peripheral blood, the physiologic role of these CD8+ effector memory cells is unknown. Research encompassing animal models and humans has demonstrated that leukocytes are capable of transferring antigen-specific immunity even when lysed, dialyzed to enrich for fractions less than 10 kDa, and orally administered. Our previous work built upon these reports to elucidate several aspects of this dialyzable leukocyte extract (DLE) activity: only DLE from T effector memory CD8+ cells was capable of transferring antigen-specific immunity; the DLE activity was TCRβ dependent; dendritic cells (DCs) were the cellular target of DLE; and DLE enhanced immune activity in epithelial challenge models via induction of IL-6 from DCs. Herein, we reveal that breast milk dialysate activates similar cytokine and genetic pathways as DLE taken from peripheral blood and murine spleens through TCRβ- and CD8-dependent mechanisms. These findings suggest that the CD8+ memory T cells enriched in breast milk, even after potential lysis in the infant gut, may represent a mechanism for passive transfer of cellular immunity from mother to child.
Spatio‐temporal relationships between rainfall and convective clouds during Indian monsoon through a discrete lens
Authors: Sharma Arjun , Mitra Adway , Vasan Vishal , Govindarajan Rama 
Published: September 2020

AbstractThe Indian monsoon, a multi‐variable process causing heavy rains during June–September every year, is very heterogeneous in space and time. We study the relationship between rainfall and outgoing longwave radiation (OLR) – a proxy for convective cloud cover – for monsoon between 2004 and 2010. To identify, classify and visualize spatial patterns of rainfall and OLR we use a discrete and spatio‐temporally coherent representation of the data, created using a statistical model based on Markov Random Field. Our approach clusters the days with similar spatial distributions of rainfall and OLR into a small number of spatial patterns. We find that eight daily spatial patterns each in rainfall and OLR, and seven joint patterns of rainfall and OLR, describe over 90% of all days. Through these patterns, we find that OLR generally has a strong negative correlation with precipitation, but with significant spatial variations. In particular, peninsular India (except for the west coast) is under significant convective cloud cover over a majority of days but remains rainless. We also find that much of the monsoon rainfall co‐occurs with low OLR, but some amount of rainfall in Eastern and North‐western India in June occurs on OLR days, presumably from shallow clouds. To study day‐to‐day variations of both quantities, we identify spatial patterns in the temporal gradients computed from the observations. We find that changes in convective cloud activity across India most commonly occur due to the establishment of a north–south OLR gradient which persists for 1–2 days and shifts the convective cloud cover from light to deep or vice versa. Such changes are also accompanied by changes in the spatial distribution of precipitation. The present work thus provides a highly reduced description of the complex spatial patterns and their day‐to‐day variations, and could form a useful tool for future simplified descriptions of this process.
Different changes in dry and humid heat waves over China
Authors: Xu Feng , Chan Ting On , Luo Ming 
Published: September 2020

AbstractHeat waves (HWs) are expected to increase in many parts of the world under climate warming. However, most existing studies examined the changes in HWs that are derived from air temperature only, possible different changes in humid HWs that consider the combined effects of relative humidity (RH) are much less understood. This study investigates the spatial and temporal changes in two different HW types, namely, dry and humid HWs, in China from 1961 to 2014. Analysis results show that, on average, humid HWs in China occur 20% more frequently than dry HWs. Dry HWs are more commonly located in northern China, while humid events mainly appear in monsoonal southern and eastern regions. It is also found that all measures of both dry and humid HWs across China have been increasing during the past decades, and humid HWs exhibit a more prominent intensifying trend than dry ones. In particular, the national mean frequency, participating days, magnitude, and duration of dry (humid) HWs increased by 0.061 (0.069) events decade−1, 0.32 (0.39) days decade−1, 0.53 (0.62) °C decade−1, and 0.19 (0.21) days decade−1, respectively. These trends vary in different parts of China. The largest increment of dry HW frequency appears in the arid region of northwest China, while the fastest increase of the humid HW frequency is observed in southeastern China. Given the additional stress induced by high humidity to extreme high temperature, we suggest that future climate change mitigation and adaption should consider the change and impacts of humid heat events.
Tornadic environments in the Iberian Peninsula and the Balearic Islands based on ERA5 reanalysis
Authors: Rodríguez Oriol , Bech Joan 
Published: September 2020

AbstractA dataset of 907 tornado and waterspout events recorded from 1980 to 2018 was built to study convective environments in the Iberian Peninsula and Balearic Islands (western Mediterranean). The events were grouped into different categories, distinguishing waterspouts and tornadoes that were stratified by intensity according to the Fujita (F) scale and the Enhanced Fujita (EF) scale. The analysis separated the north‐east (NE) and south‐west (SW) subareas in the region of study, which present different seasonal cycles. For each event, atmospheric profiles from the ERA5 reanalysis data were used to determine convective available potential energy (CAPE), storm‐relative helicity (SRH), vertical wind‐shear (WS), the Universal Tornadic Index (UTI), and the product of wind‐shear and the square root of two times CAPE (WMAXSHEAR). Results showed that the NE events are mostly associated with higher CAPE and lower helicity and wind‐shear than the SW events. Thus, a significant number of SW tornadoes are associated with high‐shear, low‐CAPE environments. Moreover, the low‐shear, high‐LCL tornado environment, which is common inland during warm‐season, is more usual in the NE subarea. Composite parameters such as the UTI and WMAXSHEAR06 are good discriminators between significant and weak tornado events, although WMAXSHEAR06 presents some limitations for the SW events due to low CAPE and weak differences in the WS (0–6 km) between the (E)F1 and (E)F2+ events. This weakness was resolved by using the 0–3 km WS instead of the 0–6 km WS when calculating the WMAXSHEAR. A new threshold for WMAXSHEAR03 is proposed (500 m2⋅s−2) to distinguish between significant and non‐significant tornado environments. Finally, the Szilagyi Waterspout Nomogram, originally developed for the Great Lakes of North America, was successfully tested in the forecasting of waterspout formation for the first time in the western Mediterranean area, although the technique should be adapted to correctly detect cool‐season mid‐latitude waterspouts.
Antimicrobial stewardship in intensive care: identifying areas for improvement
Authors: Maher Dorsa , Larcombe Rebecca , Potts Simon D. , Wiersema Ubbo F. 
Published: September 2020

AbstractBackgroundAntimicrobial stewardship (AMS) programs are increasingly implemented in intensive care units (ICU) to combat the emerging threat of antimicrobial‐resistance. To optimise AMS programs, interventions need to be tailored to target problem areas.AimTo provide an overview of the current antimicrobial prescribing patterns in a 32‐bed ICU and thereby identify areas requiring improvement.MethodA 10‐week prospective observational audit was conducted in the ICU of a public tertiary hospital. Patients on antimicrobial treatment or surgical prophylaxis antibiotics were audited. The primary outcomes were: duration of surgical antibiotic prophylaxis; duration of therapy for pneumonia, urosepsis and peritonitis; de‐escalation within 24‐h of microbiological results returning for empirical therapy; appropriate prescribing in penicillin allergy. Adherence to guidelines was also assessed.ResultsA total of 277 cases were included. The mean duration of surgical antibiotic prophylaxis and adherence to maximum guideline duration were: cardiothoracic 21.6 h (83.9% adherence), vascular 14.9 h (81.8%), neurosurgery 20.4 h (40.0%) and general surgery 11.1 h (79.6%). The mean duration of therapy was 8.8 ± 4.7 days (62.5% adherence) for community‐acquired pneumonia, 8.5 ± 4.6 days (28.6%) for hospital‐acquired pneumonia and 11.9 ± 4.6 days (46.2%) for ventilator‐associated pneumonia. Urosepsis and peritonitis were underpowered and complex. De‐escalation occurred 63.2% of the time, with 75% occurring within 24‐h of microbiological result availability. Antibiotic selection in 68.0% of patients with a documented penicillin allergy was appropriate.ConclusionThis study successfully identified baseline prescribing patterns and areas requiring improvement. With this information, tailored stewardship programs can be developed to improve antimicrobial utilisation in the critical care setting.
In situ Raman quantitative detection of methane concentrations in deep‐sea high‐temperature hydrothermal vent fluids
Authors: Li Lianfu , Zhang Xin , Luan Zhendong , Du Zengfeng , Xi Shichuan , Wang Bing , Cao Lei , Lian Chao , Yan Jun 
Published: September 2020

AbstractRaman spectroscopy is an ideal approach for measuring methane concentrations in deep‐sea high‐temperature hydrothermal vent fluids due to its advantages of being nondestructive and noninvasive and not requiring sample pretreatment. However, no application of Raman spectroscopy in the measurement of hydrothermal methane has yet been reported because of the lack of Raman quantitative calibration models for CH4suitable for hydrothermal fluid detection and available for deep‐sea in situ Raman experiments. In this study, a new Raman quantitative calibration model suitable for hydrothermal fluid detection was established with the linear equation= (2.61E‐3 ± 8.52E‐6) ×, whereis the peak area ratio of CH4and H2O andis the concentration of dissolved CH4in mmol/kg. In situ Raman spectra of deep‐sea hydrothermal fluids were acquired using an adapted deep‐sea in situ Raman spectrometer, Raman insertion probe (RiP) system, and then the methane concentrations were determined based on the quantitative calibration model for CH4. The concentrations of methane measured by RiP are approximately 1.5–4.0 times higher than those derived from the gas‐tight samples collected simultaneously at the same vents, which indicates that the amount of methane released from the hydrothermal system has probably been underestimated.
Analysis of Raman spectra for the verification of Australian grass‐ and grain‐fed beef using principal component analysis and partial least square models
Authors: Logan Bridgette G. , Hopkins David L. , Schmidtke Leigh M. , Fowler Stephanie M. 
Published: September 2020

AbstractThe diet of cattle has been shown to alter both subcutaneous fat and muscle fatty acid composition, and these differences cause a change in the Raman spectra of the fat due to the different chemical bonds associated with these biochemical changes. Because biochemical changes only lead to subtle changes in the Raman spectra, statistical methods based upon chemometric modelling are necessary to extract indicative information on the type of feed consumed. This investigation undertook a feasibility study using a limited sample set derived from two producers in one location to ascertain the potential for Raman spectroscopy to accurately discriminate grain‐fed cattle from grass‐fed cattle and investigated the usefulness of principal component analysis (PCA) and partial least squares discriminate analysis (PLS‐DA) to best discriminate between feeding groups using the information from the Raman spectra. The first two principal components accounted for 83% of the variation in the spectra and demonstrated discrimination of samples by feed type. PLS‐DA resulted in a model that was able to accurately predict grain‐ and grass‐fed carcases with a misclassification rate of 3.5%. Changes in beef cattle diets lead to subtle changes in subcutaneous fat; using Raman spectroscopy with chemometric modelling, these changes can be identified and used to identify the production system of beef products. This study successfully uses Raman spectroscopy as an automated, nondestructive and rapid technique in the range of 600–2000 cm−1 in combination with pattern recognition of unsupervised (PCA) and supervised (PLS‐DA) techniques to classify the production system of cattle between grain and grass fed.
Comparison of seed fatty and amino acids in edamame dried using two oven‐drying methods and mature soybeans
Authors: Jiang Guo‐Liang , Katuuramu Dennis N 
Published: September 2020

AbstractBACKGROUNDEdamame is a vegetable soybean (Glycine max) rich in protein with well‐balanced amino acid profiles, including all the essential amino acids. It is also relatively high in oil consisting of five fatty acids. In this study, fatty and amino acid contents in oven‐dried edamame and mature seeds in 54 genotypes were analyzed to help edamame breeding and relevant research.RESULTSSignificant differences (P < 0.01) between dried edamame and mature soybeans were found for all traits, suggesting that the contents of seed fatty and amino acids varied with drying method and/or growth stage. The genotypic effects were significant for amino acids in all cases and mostly for fatty acids. Fatty acid content was more variable than amino acids in both edamame and mature soybeans. The broad‐sense heritability estimates of traits in mature soybeans (51.89–90.37%) were larger than those in edamame seeds (13.10–81.83%), and the estimates for amino acids were larger than those for fatty acids. Correlations between the two edamame drying methods or between the edamame and mature soybeans were significant for all fatty and amino acids with few exceptions, and the correlation coefficients for amino acids (0.36–0.89) were larger than those for fatty acids (0.29–0.81).CONCLUSIONSSelection for both fatty and amino acids in edamame seems less effective than that in mature soybeans, and the improvement of amino acids would be more achievable than fatty acid improvement. Indirect selection through mature soybeans may benefit the edamame improvement for most of the amino acids. © 2020 Society of Chemical Industry
Influence of oil matrixes on stability, antioxidant activity, bioaccessibility and bioavailability of astaxanthin ester
Authors: Yang Lu , Gu Jiayu , Luan Tianle , Qiao Xing , Cao Yunrui , Xue Changhu , Xu Jie 
Published: September 2020

AbstractBACKGROUNDAstaxanthin ester (Asta‐E) is used as functional nutraceuticals in many food products. Unfortunately, Asta‐E utilization is currently limited owing to its chemical instability and low bioavailability. The purpose of this study is to investigate the promotion effect of oil matrixes on the stability, antioxidant activity, bioaccessibility and bioavailability of Asta‐E.RESULTSThe results showed that the stability of Asta‐E in six oil matrixes was improved. Based on the 2, 2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging activity experiment, the antioxidant activity of Asta‐E was positively correlated with the degree of unsaturation of the oil matrixes, but not with the side chain length. The in vitro gastrointestinal tract (GIT) simulation model and in vivo experiment using mice were also employed to investigate the digestion and absorption characteristics of Asta‐E in various oil matrixes. The results demonstrated that the bioaccessibility and bioavailability of Asta‐E increased with the increase of fatty acid chain length of oil matrixes (triglyceride oleate > triglyceride caprylate > triglyceride butyrate), as well as with the decrease of unsaturation degree (olive oil > corn oil > fish oil).CONCLUSIONMonounsaturated fatty acids (MUFA) and long‐chain triglyceride (LCT) in an oil matrix were the factors that could efficiently improve the bioavailability of Asta‐E. Moreover, the size of the mixed micelles of Asta‐E during digestion was the main factor influencing the bioaccessibility of Asta‐E. This study provides references for the design of suitable oil matrixes for Asta‐E. © 2020 Society of Chemical Industry
Usefulness of Lung Ultrasound Examinations Performed by Primary Care Physicians in Patients With Suspected COVID‐19
Authors: Calvo‐Cebrián Antonio , Alonso‐Roca Rafael , Rodriguez‐Contreras Francisco Javier , Rodríguez‐Pascual Maria de las Nieves , Calderín‐Morales Maria del Pino 
Published: September 2020

ObjectivesIn patients with suspected coronavirus disease 2019 (COVID‐19) consulting primary care (PC) centers, clinical criteria may not be sensitive enough to detect many cases in which complications first occur. We intended to assess whether lung ultrasound (LUS) examinations performed by PC physicians are a useful tool to detect lung injury and may help in decisions about hospital referral.MethodsThis study included 61 patients with moderate symptoms suggesting COVID‐19 who were evaluated with LUS by PC physicians and then referred to a hospital during the current pandemic peak in Madrid. We analyzed association of a simple self‐designed LUS severity scale (grade 0, normal; grade 1, multiple separated B‐lines, pleural irregularity, or both; and grade 2, coalescent B‐lines, consolidations, pleural effusion, or a combination thereof) with the main outcome indicating adequacy of hospital referral, and also with chest x‐ray (CXR) findings.ResultsThe proposed LUS severity scale was significantly associated with the main outcome of appropriate referral (P = 0.001): the higher the scale, the higher the percentage of adequate referrals. The LUS scale was also associated with a CXR severity scale (P = 0.034). The presence of coalescent B‐lines was the only independent LUS finding significantly associated with the appropriate‐referral outcome (P =0 .008) and also with a higher probability of hospital admission (P = 0.02) and with several CXR findings.ConclusionsThis study supports the use of LUS in PC as a tool to assess patients with suspected COVID‐19. Its use can reduce uncertainty during clinical evaluations of moderate patients, facilitate early detection of lung involvement, allow early appropriate referral, and avoid unnecessary referral.