bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global evaluation of the use of glycaemic impact measurements to food or nutrient intake
Authors: Trumbo Paula R 
Published: February 2021

AbstractObjective:Measures of glycaemic impact (e.g. postprandial glucose (PPG), oral glucose tolerance test (OGTT) and glycaemic index (GI)) are used by government health and regulatory agencies and public health associations around the world. The objective of this global review was to identify similarities and differences in the use of glycaemic impact measures for potential considerations for harmonisation.Design:A literature and internet search was conducted to identify country government agencies and health associations that provide guidance or recommendations for PPG, OGTT, GI and glycaemic load.Results:Based on this global review, the use of GI for food labelling (e.g. low GI) is limited and its use is voluntary. The application of OGTT as a diagnostic measurement of diabetes and gestational diabetes is widely used and in a consistent manner among the different regions of the world. Time-specific (e.g. 2 h) PPG is commonly used as a target not to exceed in individuals with diabetes and gestational diabetes. PPG is used by regulatory agencies for the substantiation of food labelling. There are differences, however, among regulatory agencies in the specific measure of PPG (i.e. PPG AUC v. peak PPG). Maximum targets for 2-h PPG for individuals with diabetes and gestational diabetes, ranging between 6 and 10 mmol/l, across countries suggest a potential consideration to harmonise PPG targets.Conclusions:There is general consistency in the use and/or target levels of glycaemic impact measures; however, there is a potential need to investigate harmonisation strategies on certain aspects of glycaemic impact measures.
Ionospheric D Region Disturbances due to FAC and LEP Associated With Three Severe Geomagnetic Storms as Observed by VLF Signals
Authors: Kerrache F. , Nait Amor S. , Kumar S. 
Published: February 2021

AbstractThe effects of one super and two intense storms on three European very low frequency (VLF) transmitter signals received at Algiers (Algeria) station, are presented. Two VLF transmitters (DHO and GQD) are located almost at the same mid‐latitude and third transmitter (NRK) at a high latitude, allowing us to study the latitudinal dependence of the storm effect on the VLF propagation. Two kind of ionospheric disturbances were considered: Direct effect of the field aligned currents (FACs) and the second concerning with the lightning‐induced electron precipitation (LEP) events. The FACs effect was clearly evident on the recorded signal amplitude during the daytime and nighttime. Our analysis of the short‐duration VLF perturbations due to LEP events showed that the ducted and non‐ducted LEPs are the majority of VLF perturbations and a small fraction of LEP events was associated with magnetospherically reflected waves on the high latitude transmitter path (NRK–Algiers). The coincident observation of LEP on the mid‐latitude transmitters (DHO and GQD) signals implies that the disturbance was large as much as the distance between the two transmitters (728 km). The modeling using Long‐Wave Propagation Capability (LWPC) code of LEP associated VLF perturbations considering Gaussian distribution of electron density enhancements, showed a decrease in the D‐region reference height from its usual value 87 km to 83.3 km for ducted LEP and 80.3 km for non‐ducted LEP event and that the non‐ducted event exhibited a wider disturbed region.
Comparing Non‐Tidal Ocean Loading Around the Southern North Sea With Subdaily GPS/GLONASS Data
Authors: Geng Jianghui , Xin Shaoming , Williams Simon D. P. , Jiang Weiping 
Published: February 2021

AbstractObserving subdaily surface deformations is important to the interpretation of rapidly developing transient events. However, it is not known whether Global Navigation Satellite System (GNSS) is able to identify millimeter‐level transient displacements over various subdaily timescales. We studied non‐tidal ocean loading (NTOL) using 18 GNSS stations along the southern North Sea for November–December 2013 and compared 3‐h GPS/GLONASS displacements with NTOL predictions. It was found that they overall agreed well with a mean correlation coefficient of 0.6 and their vertical differences had an RMS of 5.7 mm, but a 10‐mm subsidence prediction for December 5th could only be marginally detected. Hence, the spatial coherence among the loading signatures at the 18 stations was harnessed to improve subdaily GNSS, and then the predicted displacements of 5–10‐mm over the subdaily timescales could be discriminated successfully. We envision that adding Galileo/BeiDou signals to GPS/GLONASS can further improve the resolution of subdaily GNSS, which can also enhance the spatial coherence of transient signals captured by regional GNSS stations.
Decadal Changes in Soil and Atmosphere Temperature Differences Linked With Environment Shifts Over Northern Eurasia
Authors: Chen Liangzhi , Aalto Juha , Luoto Miska 
Published: February 2021

AbstractThe difference between soil and air temperatures (ΔT) in a specified time is dependent on meteorological conditions, properties of soil and land covers. Understanding ΔT is critical in assessing land–atmosphere thermal interactions in changing environment. However, systematic knowledge of interannual variations and responses of ΔT to the environmental changes (e.g., snow cover and soil moisture) at decadal scales remain limited. Here, variations of the mean annual air and soil temperatures, and ΔT were investigated at 217 sites in northern Eurasia during 1981–2015. It is found that changes in the mean annual air and soil temperatures were inconsistent as the average increase in soil temperature was generally less than that of air. The relationships between trends in soil and air temperatures were significant in the upper ground (0.2 and 0.8 m) over the seasonal frost region but insignificant in the permafrost regions and deeper ground. During the period, widespread changes in ΔT occurred and closely responded to the environmental changes, but the relationships varied with soil depth. Among the tested factors, trends in snow cover thickness dominantly control trends in ΔT, followed by trends in snow cover duration and solar radiation. Both linear and nonlinear analyses indicate enhanced relationships between trends in snow depth and ΔT as depth increases. This study provides the first view of decadal trends in ΔT and conjunctions with the environmental changes during 1981–2015 over northern Eurasia. The findings are relevant to quantify land–atmosphere thermal interactions given impacts of future environmental changes.
Historical Water Storage Changes Over China's Loess Plateau
Authors: Shao Rui , Zhang Baoqing , He Xiaogang , Su Tongxuan , Li Yao , Long Biao , Wang Xuejin , Yang Wenjing , He Chansheng 
Published: February 2021

AbstractSince 1999, the Loess Plateau, China, has undergone one of the world's largest revegetation programs (Grain for Green Project, GfGP). Revegetation has profound impacts on hydrological cycle and water balance, especially in arid and semi‐arid areas. As an essential component of water balance, the long‐term change in water storage (ΔS) is generally treated as zero. However, it remains unclear how to define the time scale of “long‐term,” especially over regions undergoing dramatic vegetation restoration. In this study, we quantify ΔS over the Loess Plateau from 1982 to 2009 from a water balance perspective, with a particular focus on the impact of vegetation on ΔS at different time scales. Results show that a 44.78% increase in vegetation coverage could lead to a 37.72% decrease in ΔS. Moreover, the better the vegetation growth, the lower the ratio of ΔS to precipitation (ΔS/P) in the Loess Plateau. ΔS/P achieved a local minimum at the 4‐ to 5‐year scale and reached a plateau after 10 years. We further use the Budyko framework to verify the above conclusions. We find that errors of simulated streamflow over 11/16 of catchments become stable after 4–5 years, and all 16 catchments become stable after 10 years. Ignoring ΔS at a 10‐year scale has the least influence on water budget closure. These findings highlight the importance of considering time scales when ignoring ΔS in the water balance analysis, especially when the length of measurement is limited.
Secondary analyses of global datasets: do obesity and physical activity explain variation in diabetes risk across populations?
Authors: Alkaf Budour , Blakemore Alexandra I. , Järvelin Marjo-Riitta , Lessan Nader 
Published: February 2021

AbstractType 2 diabetes rates vary significantly across geographic regions. These differences are sometimes assumed to be entirely driven by differential distribution of environmental triggers, including obesity and insufficient physical activity (IPA). In this review, we discuss data which conflicts with this supposition. We carried out a secondary analysis of publicly available data to unravel the relative contribution of obesity and IPA towards diabetes risk across different populations. We used sex-specific, age-standardized estimates from Non-Communicable Disease Risk Factor Collaboration (NCD-RisC) on diabetes (1980–2014) and obesity (1975–2016) rates, in 200 countries, and from WHO on IPA rates in 168 countries in the year 2016. NCD-RisC and WHO organized countries into nine super-regions. All analyses were region- and sex-specific. Although obesity has been increasing since 1975 in every part of the world, this was not reflected in a proportional increase in diabetes rates in several regions, including Central and Eastern Europe, and High-income western countries region. Similarly, the association of physical inactivity with diabetes is not homogeneous across regions. Countries from different regions across the world could have very similar rates of diabetes, despite falling on opposite ends of IPA rate spectrum. The combined effect of obesity and IPA on diabetes risk was analyzed at the worldwide and country level. The overall findings highlighted the larger impact of obesity on disease risk; low IPA rates do not seem to be protective of diabetes, when obesity rates are high. Despite that, some countries deviate from this overall observation. Sex differences were observed across all our analyses. Overall, data presented in this review indicate that different populations, while experiencing similar environmental shifts, are apparently differentially subject to diabetes risk. Sex-related differences observed suggest that males and females are either subject to different risk factor exposures or have different responses to them.
Age dependency of plasma vitamin B12 status markers in Dutch children and adolescents
Authors: Heiner-Fokkema M. Rebecca , Riphagen Ineke J. , Wiersema Nicole S. , van Zanden Jelmer J. , Kootstra-Ros Jenny E. , Pinxterhuis Tineke H. , Hooimeijer H. Louise , van Spronsen Francjan J. , Muller Kobold Anneke C. , de Jong Wilhelmina H. A. 
Published: February 2021

Abstract
Background
Vitamin B12 deficiency in children may be associated with (severe) neurological manifestations, therefore recognition is important. Diagnosing vitamin B12 deficiency in children is challenging. This study aimed to investigate plasma methylmalonic acid, holotranscobalamin, and total cobalamin in children 0–18 years of age and to estimate age-dependent reference intervals.

Methods
Plasma vitamin B12 markers were measured in collected plasma samples of 170 children 0–18 years visiting a local primary care laboratory. All had within-reference hemoglobin and MCV values. Pediatric plasma vitamin B12 biomarkers were measured and reference values were derived thereof.

Results
Plasma methylmalonic acid was higher in young children, in particular between 1 and 6 months of age; total cobalamin and holotranscobalamin were highest from 0.5 to 4 years and decreased till 10 years of age. Plasma holotranscobalamin was highly correlated with plasma total cobalamin; their ratio was independent of age. Plasma methylmalonic acid was slightly more related to total cobalamin than to holotranscobalamin. A large proportion of mainly young children would be misclassified when adult references are applied.

Conclusions
Pediatric reference values for cobalamin markers are necessary to allow for early recognition and monitoring of children suspect of (clinical) cobalamin deficiency.

Impact

We analyzed three plasma vitamin B12 status markers, i.e., total cobalamin, holotranscobalamin, and methylmalonic acid, in the plasma of 170 children 0–18 years of age and were able to derive reference intervals thereof. Recognition of vitamin B12 deficiency in children is important but challenging as pediatric reference intervals for plasma vitamin B12 status markers, particularly plasma holotranscobalamin, are not well described. We think that our results may help early recognition and monitoring of children suspect of (clinical) vitamin B12 deficiency.
Molecular medicine tumor board: whole-genome sequencing to inform on personalized medicine for a man with advanced prostate cancer
Authors: Armstrong Andrew J. , Li Xiaotong , Tucker Matthew , Li Shantao , Mu Xinmeng Jasmine , Eng Kenneth Wha , Sboner Andrea , Rubin Mark , Gerstein Mark 
Published: February 2021

Abstract
Purpose
Molecular profiling of cancer is increasingly common as part of routine care in oncology, and germline and somatic profiling may provide insights and actionable targets for men with metastatic prostate cancer. However, all reported cases are of deidentified individuals without full medical and genomic data available in the public domain.

Patient and methods
We present a case of whole-genome tumor and germline sequencing in a patient with advanced prostate cancer, who has agreed to make his genomic and clinical data publicly available.

Results
We describe an 84-year-old Caucasian male with a Gleason 10 oligometastastic hormone-sensitive prostate cancer. Whole-genome sequencing provided insights into his tumor’s underlying mutational processes and the development of an SPOP mutation. It also revealed an androgen-receptor dependency of his cancer which was reflected in his durable response to radiation and hormonal therapy. Potentially actionable genomic lesions in the tumor were identified through a personalized medicine approach for potential future therapy, but at the moment, he remains in remission, illustrating the hormonal sensitivity of his SPOP-driven prostate cancer. We also placed this patient in the context of a large prostate-cancer cohort from the PCAWG (Pan-cancer Analysis of Whole Genomes) group. In this comparison, the patient’s cancer appears typical in terms of the number and type of somatic mutations, but it has a somewhat larger contribution from the mutational process associated with aging.

Conclusion
We combined the expertise of medical oncology and genomics approaches to develop a molecular tumor board to integrate the care and study of this patient, who continues to have an outstanding response to his combined modality treatment. This identifiable case potentially helps overcome barriers to clinical and genomic data sharing.
AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development
Authors: Wan Xiaofeng , Zhou Meng , Huang Fuqiang , Zhao Na , Chen Xu , Wu Yuncui , Zhu Wanhui , Ni Zhaofei , Jin Fuquan , Wang Yani , Hu Zhongdong , Chen Xianguo , Ren Min , Zhang Hongbing , Zha Xiaojun 
Published: February 2021

AbstractAs evidenced by the behavior of loss-of-function mutants of PTEN in the context of a gain-of-function mutation of AKT1, the PTEN-AKT1 signaling pathway plays a critical role in human cancers. In this study, we demonstrated that a deficiency in PTEN or activation of AKT1 potentiated the expression of platelet-derived growth factor receptor α (PDGFRα) based on studies on Pten−/− mouse embryonic fibroblasts, human cancer cell lines, the hepatic tissues of Pten conditional knockout mice, and human cancer tissues. Loss of PTEN enhanced PDGFRα expression via activation of the AKT1-CREB signaling cascade. CREB transactivated PDGFRα expression by direct binding of the promoter of the PDGFRα gene. Depletion of PDGFRα attenuated the tumorigenicity of Pten-null cells in nude mice. Moreover, the PI3K-AKT signaling pathway has been shown to positively correlate with PDGFRα expression in multiple cancers. Augmented PDGFRα was associated with poor survival of cancer patients. Lastly, combination treatment with the AKT inhibitor MK-2206 and the PDGFR inhibitor CP-673451 displayed synergistic anti-tumor effects. Therefore, activation of the AKT1-CREB-PDGFRα signaling pathway contributes to the tumor growth induced by PTEN deficiency and should be targeted for cancer treatment.
Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway
Authors: Liu Xiaoli , Yin Zuwei , Xu Linping , Liu Huaimin , Jiang Lifeng , Liu Shuochuan , Sun Xu 
Published: February 2021

AbstractLong noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.
Alternative splicing of ceramide synthase 2 alters levels of specific ceramides and modulates cancer cell proliferation and migration in Luminal B breast cancer subtype
Authors: Pani Trishna , Rajput Kajal , Kar Animesh , Sharma Harsh , Basak Rituparna , Medatwal Nihal , Saha Sandhini , Dev Gagan , Kumar Sharwan , Gupta Siddhi , Mukhopadhyay Arnab , Malakar Dipankar , Maiti Tushar Kanti , Arimbasseri Aneeshkumar G. , Deo S. V. S. , Sharma Ravi Datta , Bajaj Avinash , Dasgupta Ujjaini 
Published: February 2021

AbstractGlobal dysregulation of RNA splicing and imbalanced sphingolipid metabolism has emerged as promoters of cancer cell transformation. Here, we present specific signature of alternative splicing (AS) events of sphingolipid genes for each breast cancer subtype from the TCGA-BRCA dataset. We show thatceramide synthase 2(CERS2) undergoes a unique cassette exon event specifically in Luminal B subtype tumors. We validated this exon 8 skipping event in Luminal B cancer cells compared to normal epithelial cells, and in patient-derived tumor tissues compared to matched normal tissues. Differential AS-based survival analysis shows that this AS event ofCERS2is a poor prognostic factor for Luminal B patients. As Exon 8 corresponds to catalytic Lag1p domain, overexpression of AS transcript ofCERS2in Luminal B cancer cells leads to a reduction in the level of very-long-chain ceramides compared to overexpression of protein-coding (PC) transcript ofCERS2. We further demonstrate that this AS event-mediated decrease of very-long-chain ceramides leads to enhanced cancer cell proliferation and migration. Therefore, our results show subtype-specific AS of sphingolipid genes as a regulatory mechanism that deregulates sphingolipids like ceramides in breast tumors, and can be explored further as a suitable therapeutic target.
BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism
Authors: Luo Lifang , Sun Wenjing , Zhu Weijian , Li Shuhan , Zhang Wenqi , Xu Xiaohui , Fang Daoquan , Grahn Tan Hooi Min , Jiang Lei , Zheng Yihu 
Published: February 2021

AbstractCisplatin is one of the most effective chemotherapy drugs and is widely used in the treatment of cancer, including hepatocellular carcinoma (HCC) and cervical cancer, but its therapeutic benefit is limited by the development of resistance. Our previous studies demonstrated that BCAT1 promoted cell proliferation and decreased cisplatin sensitivity in HCC cells. However, the exact role and mechanism of how BCAT1 is involved in cisplatin cytotoxicity remain undefined. In this study, we revealed that cisplatin triggered autophagy in cancer cells, with an increase in BCAT1 expression. The cisplatin-induced up-regulation of BCAT1 decreased the cisplatin sensitivity by regulating autophagy through the mTOR signaling pathway. In addition, branched-chain amino acids or leucine treatment inhibited cisplatin- or BCAT1-mediated autophagy and increased cisplatin sensitivity by activating mTOR signaling in cancer cells. Moreover, inhibition of autophagy by chloroquine increased cisplatin sensitivity in vivo. Also, the knockdown of BCAT1 or the administration of leucine activated mTOR signaling, inhibited autophagy, and increased cisplatin sensitivity in cancer cells in vivo. These findings demonstrate a new mechanism, revealing that BCAT1 decreases cisplatin sensitivity in cancer cells by inducing mTOR-mediated autophagy via branched-chain amino acid leucine metabolism, providing an attractive pharmacological target to improve the effectiveness of chemotherapy.
IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury
Authors: Mo Guixi , Liu Xin , Zhong Yiyue , Mo Jian , Li Zhiyi , Li Daheng , Zhang Liangqing , Liu Yijun 
Published: February 2021

AbstractIntracellular ion channel inositol 1,4,5-triphosphate receptor (IP3R1) releases Ca2+ from endoplasmic reticulum. The disturbance of IP3R1 is related to several neurodegenerative diseases. This study investigated the mechanism of IP3R1 in myocardial ischemia/reperfusion (MI/R). After MI/R modeling, IP3R1 expression was silenced in myocardium of MI/R rats to explore its role in the concentration of myocardial enzymes, infarct area, Ca2+ level, NLRP3/Caspase-1, and pyroptosis markers and inflammatory factors. The adult rat cardiomyocytes were isolated and cultured to establish hypoxia/reperfusion (H/R) cell model. The expression of IP3R1 was downregulated or ERP44 was overexpressed in H/R-induced cells. Nifedipine D6 was added to H/R-induced cells to block Ca2+ channel or Nigericin was added to activate NLRP3. IP3R1 was highly expressed in myocardium of MI/R rats, and silencing IP3R1 alleviated MI/R injury, reduced Ca2+ overload, inflammation and pyroptosis in MI/R rats, and H/R-induced cells. The binding of ERP44 to IP3R1 inhibited Ca2+ overload, alleviated cardiomyocyte inflammation, and pyroptosis. The increase of intracellular Ca2+ level caused H/R-induced cardiomyocyte pyroptosis through the NLRP3/Caspase-1 pathway. Activation of NLRP3 pathway reversed the protection of IP3R1 inhibition/ERP44 overexpression/Nifedipine D6 on H/R-induced cells. Overall, ERP44 binding to IP3R1 inhibits Ca2+ overload, thus alleviating pyroptosis and MI/R injury.