bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substantial Increase in the Joint Occurrence and Human Exposure of Heatwave and High‐PM Hazards Over South Asia in the Mid‐21st Century
Authors: Xu Yangyang , Wu Xiaokang , Kumar Rajesh , Barth Mary , Diao Chenrui , Gao Meng , Lin Lei , Jones Bryan , Meehl Gerald A. 
Published: April 2020

AbstractExtreme heat occurrence worldwide has increased in the past decades. Greenhouse gas emissions, if not abated aggressively, will lead to large increases in frequency and intensity of heat extremes. At the same time, many cities are facing severe air pollution problems featuring high‐PM episodes that last from days to weeks. Based on a high‐resolution decadal‐long model simulation using a state‐of‐the‐science regional chemistry‐climate model that is bias corrected against reanalysis, here we show that when daily average wet‐bulb temperature of 25 °C is taken as the threshold for severe health impacts, heat extremes frequency averaged over South Asia increases from 45 ± 5 days/year in 1997–2004 to 78 ± 3 days/year in 2046–2054 under RCP8.5 scenario. With daily averaged PM2.5 surface concentration of 60 μg/m3 defined as the threshold for such “unhealthy” extremes, high‐PM extremes would occur 132 ± 8 days/year in the Decade 2050 under RCP8.5. Even more concerning, due to the potential health impacts of two stressors acting in tandem, is the joint occurrence of the heatwave and high‐PM hazard (HHH), which would have substantial increases of 175% in frequency and 79% in duration. This is in contrast to the 73–76% increase for heatwave or high PM when assessed individually. The fraction of land exposed to prolonged HHH increases by more than tenfold in 2050. The alarming increases in just a few decades pose great challenges to adaptation and call for more aggressive mitigation. For example, under a lower emission pathway, the frequency of HHH will only increase by 58% with a lower frequency of high‐PM extremes.
Surface Deformation and Induced Seismicity Due to Fluid Injection and Oil and Gas Extraction in Western Texas
Authors: Deng Fanghui , Dixon Timothy H. , Xie Surui 
Published: April 2020

AbstractTexas is experiencing increasing seismicity, likely related to the oil and gas production process. We used satellite InSAR (Interferometric Synthetic Aperture Radar) to monitor surface deformation at three study sites in western Texas with similar geologic characteristics. The deformation data were compared to earthquake distribution, groundwater changes, volumes of produced and injected fluid, and calculated pore pressure change and Coulomb failure stress change to assess causes of deformation and seismicity. Site 1 experienced surface uplift due to fluid injection but no increase in seismicity. The average media properties were estimated based on the deformation using a poroelastic model. Site 2 experienced subtle surface subsidence and elevated seismicity. Subsidence here might reflect groundwater withdrawal. Simulated pore pressure changes using MODFLOW suggest the earthquakes are likely induced by fluid injection. Site 3 experienced significant surface subsidence and seismicity. InSAR time series, water level data, and oil/gas extraction history suggest that subsidence in the northern part of this site reflects oil/gas extraction, while subsidence in the southern part is mainly due to groundwater withdrawal. An Okada tensile model was used to derive the equivalent source strength causing the subsidence, then Coulomb failure stress changes associated with this source were calculated. We found that pore pressure change (simulated using MODFLOW) due to fluid injection is likely the main contributor to elevated seismicity at this site. Variations in oil/gas production activity, seismicity, and surface deformation between our three sites suggest the importance of local rock structure and media properties in determining susceptibility to induced seismicity.
Differentiation of adipose-derived stem cells into functional chondrocytes by a small molecule that induces Sox9
Authors: Lee Jiyun , Lee Chang Youn , Park Jun-Hee , Seo Hyang-Hee , Shin Sunhye , Song Byeong-Wook , Kim Il-Kwon , Kim Sang Woo , Lee Seahyoung , Park Jong-Chul , Lim Soyeon , Hwang Ki-Chul 
Published: April 2020

AbstractOsteoarthritis (OA) is a common joint disease that results from the disintegration of joint cartilage and the underlying bone. Because cartilage and chondrocytes lack the ability to self-regenerate, efforts have been made to utilize stem cells to treat OA. Although various methods have been used to differentiate stem cells into functional chondrocytes, the currently available methods cannot induce stem cells to undergo differentiation into chondrocyte-like cells without inducing characteristics of hypertrophic chondrocytes, which finally lead to cartilage disintegration and calcification. Therefore, an optimized method to differentiate stem cells into chondrocytes that do not display undesired phenotypes is needed. This study focused on differentiating adipose-derived stem cells (ASCs) into functional chondrocytes using a small molecule that regulated the expression of Sox9 as a key factor in cartilage development and then explored its ability to treat OA. We selected ellipticine (ELPC), which induces chondrocyte differentiation of ASCs, using a GFP-Sox9 promoter vector screening system. An in vivo study was performed to confirm the recovery rate of cartilage regeneration with ASC differentiation into chondrocytes by ELPC in a collagenase-induced animal model of OA. Taken together, these data indicate that ellipticine induces ASCs to differentiate into mature chondrocytes without hypertrophic chondrocytes in vitro and in vivo, thus overcoming a problem encountered in previous studies. These results indicate that ELPC is a novel chondrocyte differentiation-inducing drug that shows potential as a cell therapy for OA.
Tankyrase inhibition ameliorates lipid disorder via suppression of PGC-1α PARylation in db/db mice
Authors: Wang Hong , Kuusela Sara , Rinnankoski-Tuikka Rita , Dumont Vincent , Bouslama Rim , Ramadan Usama Abo , Waaler Jo , Linden Anni-Maija , Chi Nai-Wen , Krauss Stefan , Pirinen Eija , Lehtonen Sanna 
Published: April 2020

Abstract
Objective
Human TNKS, encoding tankyrase 1 (TNKS1), localizes to a susceptibility locus for obesity and type 2 diabetes mellitus (T2DM). Here, we addressed the therapeutic potential of G007-LK, a TNKS-specific inhibitor, for obesity and T2DM.

Methods
We administered G007-LK to diabetic db/db mice and measured the impact on body weight, abdominal adiposity, and serum metabolites. Muscle, liver, and white adipose tissues were analyzed by quantitative RT-PCR and western blotting to determine TNKS inhibition, lipolysis, beiging, adiponectin level, mitochondrial oxidative metabolism and mass, and gluconeogenesis. Protein interaction and PARylation analyses were carried out by immunoprecipitation, pull-down and in situ proximity ligation assays.

Results
TNKS inhibition reduced body weight gain, abdominal fat content, serum cholesterol levels, steatosis, and proteins associated with lipolysis in diabetic db/db mice. We discovered that TNKS associates with PGC-1α and that TNKS inhibition attenuates PARylation of PGC-1α, contributing to increased PGC-1α level in WAT and muscle in db/db mice. PGC-1α upregulation apparently modulated transcriptional reprogramming to increase mitochondrial mass and fatty acid oxidative metabolism in muscle, beiging of WAT, and raised circulating adiponectin level in db/db mice. This was in sharp contrast to the liver, where TNKS inhibition in db/db mice had no effect on PGC-1α expression, lipid metabolism, or gluconeogenesis.

Conclusion
Our study unravels a novel molecular mechanism whereby pharmacological inhibition of TNKS in obesity and diabetes enhances oxidative metabolism and ameliorates lipid disorder. This happens via tissue-specific PGC-1α-driven transcriptional reprogramming in muscle and WAT, without affecting liver. This highlights inhibition of TNKS as a potential pharmacotherapy for obesity and T2DM.
NUSAP1 potentiates chemoresistance in glioblastoma through its SAP domain to stabilize ATR
Authors: Zhao Yuzu , He Jiang , Li Yongsen , Lv Shengqing , Cui Hongjuan 
Published: April 2020

AbstractNUSAP1, which is a microtubule-associated protein involved in mitosis, plays essential roles in diverse biological processes, especially in cancer biology. In this study, NUSAP1 was found to be overexpressed in GBM tissues in a grade-dependent manner compared with normal brain tissues. NUSAP1 was also highly expressed in GBM patients, dead patients, and GBM cells. In addition, NUSAP1 was found to participate in cell proliferation, apoptosis, and DNA damage in GBM cells. Ataxia telangiectasia and Rad3-related protein (ATR) are a primary sensor of DNA damage, and ATR is also a promising target in cancer therapy. Here, we found that NUSAP1 positively regulated the expression of ATR. Mechanistically, NUSAP1 suppressed the ubiquitin-dependent proteolysis of ATR. The SAP (SAF-A/B, Acinus, and PIAS) domain is a common motif of many SUMO (small ubiquitin-like modifier) E3 ligases, and this domain is involved in substrate recognition and ligase activity. This study further demonstrated that the SAP domain of NUSAP1 promoted the sumoylation of ATR, and thereby antagonized the ubiquitination of ATR. These results suggest that NUSAP1 stabilizes ATR by sumoylation. Moreover, NUSAP1 potentiated chemotherapeutic resistance to temozolomide (TMZ) and doxorubicin (DOX) through its SAP domain. Overall, this study indicates that NUSAP1 is a promising therapeutic target in GBM.
Association of cannabis with glutamatergic levels in patients with early psychosis: Evidence for altered volume striatal glutamate relationships in patients with a history of cannabis use in early psychosis
Authors: Sami Musa , Worker Amanda , Colizzi Marco , Annibale Luciano , Das Debasis , Kelbrick Marlene , Eranti Savitha , Collier Tracy , Onyejiaka Chidimma , O’Neill Aisling , Lythgoe David , McGuire Philip , Williams Steve C. R. , Kempton Matthew J. , Bhattacharyya Sagnik ,   Collaborators, Macherla Praveen , Prountzos Athanasios , Kitts Rachel , Vasicuro Loredana , Taousi Zohra , Tekfi Fatma 
Published: April 2020

AbstractThe associative striatum, an established substrate in psychosis, receives widespread glutamatergic projections. We sought to see if glutamatergic indices are altered between early psychosis patients with and without a history of cannabis use and characterise the relationship to grey matter. 92 participants were scanned: Early Psychosis with a history of cannabis use (EPC = 29); Early Psychosis with minimal cannabis use (EPMC = 25); Controls with a history of cannabis use (HCC = 16) and Controls with minimal use (HCMC = 22). Whole brain T1 weighted MR images and localised proton MR spectra were acquired from head of caudate, anterior cingulate and hippocampus. We examined relationships in regions with known high cannabinoid 1 receptor (CB1R) expression (grey matter, cortex, hippocampus, amygdala) and low expression (white matter, ventricles, brainstem) to caudate Glutamine+Glutamate (Glx). Patients were well matched in symptoms, function and medication. There was no significant group difference in Glx in any region. In EPC grey matter volume explained 31.9% of the variance of caudate Glx (p = 0.003) and amygdala volume explained 36.9% (p = 0.001) of caudate Glx. There was no significant relationship in EPMC. The EPC vs EPMC interaction was significant (p = 0.042). There was no such relationship in control regions. These results are the first to demonstrate association of grey matter volume and striatal glutamate in the EPC group. This may suggest a history of cannabis use leads to a conformational change in distal CB1 rich grey matter regions to influence striatal glutamatergic levels or that such connectivity predisposes to heavy cannabis use.
Efficient option of industrial wastewater resources in cement mortar application with river-sand by microbial induced calcium carbonate precipitation
Authors: Huang Yi-Hsun , Chen How-Ji , Maity Jyoti Prakash , Chen Chien-Cheng , Sun An- Cheng , Chen Chien-Yen 
Published: April 2020

AbstractThe industrial wastewater disposal has been growing attention for environmental protection and resource substitution, current decades. Similarly, the durability enhancement of concrete has increased attention by microbial induced CaCO3 precipitation (MICP) process (biocalcification). However, ecofriendly utilization of industrial wastewater in concrete formation is unstudied so far. The present study was carried out to evaluate the effect of industrial wastewater on the formation of cement mortar, compressive strength and water absorption. The biocement mortar strength (y) increased (y = 0.5295×2 + 1.6019×+251.05; R2 = 0.9825) with increasing percentage of organic wastewater (x) (BM0 – BM100) by MICP, where highest strength (280.75 kgf/cm2) was observed on BM100 (100% wastewater), compared to control (252.05 kgf/cm2). The water absorption (y) of biocement mortar decreases (y = −0.0251×2–0.103× + 15.965; R2 = 0.9594) with increment of wastewater (x) (%) (BM0 – BM100), where a minimum-water-absorption (14.42%) observed on BM100, compared to control (15.89%). SEM micrograph and XRD shows the formation of most-distinctive CaCO3 crystallization (aragonite/calcite) (acicular, brick shape, massive and stacked structure) inside biocement mortar (BM100), which fills the pores within cement mortar to form a denser structure, by microbial organic wastewater. Thus, present findings implied a cost-effective of MICP technology to improve the concrete properties along with the mitigation of industrial wastewater pollution, which goes some way towards solving the problem of industrial wastewater pollution.
Hepatitis B: changes in epidemiological features of Afro-descendant communities in Central Brazil
Authors: Lima Livia Alves , Lago Bárbara Vieira do , Weis-Torres Sabrina Moreira dos Santos , Martins Regina Maria Bringel , Cesar Gabriela Alves , Bandeira Larissa Melo , Rezende Grazielli Rocha , Lindenberg Andrea de Siqueira Campos , Gomes Selma Andrade , Motta-Castro Ana Rita Coimbra 
Published: April 2020

AbstractHepatitis B virus (HBV) infection is still a concern in vulnerable populations. In a study performed by our team in 1999–2003 in two Afro-Brazilian communities, Furnas dos Dionísios (FD) and São Benedito (SB), high prevalence rates of HBV exposure (42.7% and 16.0%, respectively), high susceptibility to HBV (55.3% and 63.0%) and low HBV vaccination like profile rates (2.0% and 21.0%) were observed. In 2015–2016, we reassessed HBV epidemiological and molecular features in these two communities to verify the impact of health actions adopted in the last years. The prevalence rate of HBV exposure among the enrolled 331 subjects was 35.3% in FD and 21.8% in SB. HBV chronic infection (5.8% in FD, 4.9% in SB) remained high. The rate of HBV vaccination like profile increased from 10.7% to 43.5% (2.0% to 45.9% in FD, 21.0% to 39.5% in SB) while susceptible subjects declined from 58.9% to 26.3% (55.3% to 18.8% in FD, 63.0% to 38.7% in SB). Among 18 HBsAg positive samples, 13 were successfully sequenced (pre-S/S region). Phylogenetic analyses showed that all isolates belong to HBV subgenotype A1, clustering within the Asian-American clade. Despite the maintenance of high prevalence rate of HBV exposure over these 13 years of surveillance, significant improvements were observed, reinforcing the importance of facilitated HBV vaccination to difficult-to-access population to close gaps in prevention.
Immune priming with inactive dengue virus during the larval stage of Aedes aegypti protects against the infection in adult mosquitoes
Authors: Vargas Valeria , Cime-Castillo Jorge , Lanz-Mendoza Humberto 
Published: April 2020

AbstractSeveral studies have observed that the immune response in insects can be conserved, a phenomenon known as immune priming, which has been mostly tested in adult stages. However, it is unknown if induction of immune priming in larval stages protects against dengue virus (DENV) infections in adult mosquitoes. In this work, we primed larval instar 3rd of Aedes aegypti with inactive dengue virus, producing adult mosquitoes with i) an enhanced antiviral-immune response; ii) a reduction in the load and replication of RNA of dengue virus (DENV); iii) a decline in viral infective particles production. Adult mosquitoes previously primed during larval stages over-expressed RNA interference (RNAi) markers Argonaute-2 (AGO-2) and Dicer-2 (DCR-2). We also observed inter-individual variations of DENV infection in adult mosquitoes, indicating a heterogeneous response to DENV infection in the same mosquito strain. However, mosquitoes primed during larval stages appear to control the infection, reducing the viral load. The over-expression of interferon-like factors (VAGO) and AGO-2 in the pupa stage suggests a fast activation of antiviral mechanisms after immune priming in larvae, creating a condition in which adult mosquitoes are resistant to the pathogen in the posterior exposure.
Identification of tipifarnib sensitivity biomarkers in T-cell acute lymphoblastic leukemia and T-cell lymphoma
Authors: Alonso-Alonso Ruth , Mondéjar Rufino , Martínez Nerea , García-Diaz Nuria , Pérez Cristina , Merino David , Rodríguez Marta , Esteve-Codina Anna , Fuste Berta , Gut Marta , Burrows Francis , Scholz Catherine , Vaqué Jose Pedro , Gualberto Antonio , Piris Miguel Ángel 
Published: April 2020

AbstractPatients diagnosed with T-cell leukemias and T-cell lymphomas (TCLs) still have a poor prognosis and an inadequate response to current therapies, highlighting the need for targeted treatments. We have analyzed the potential therapeutic value of the farnesyltransferase inhibitor, tipifarnib, in 25 TCL cell lines through the identification of genomic and/or immunohistochemical markers of tipifarnib sensitivity. More than half of the cell lines (60%) were considered to be sensitive. Tipifarnib reduced cell viability in these T-cell leukemia and TCL cell lines, induced apoptosis and modified the cell cycle. A mutational study showed TP53, NOTCH1 and DNMT3 to be mutated in 84.6%, 69.2% and 30.0% of sensitive cell lines, and in 62.5%, 0% and 0% of resistant cell lines, respectively. An immunohistochemistry study showed that p-ERK and RelB were associated as potential biomarkers of tipifarnib sensitivity and resistance, respectively. Data from RNA-seq show that tipifarnib at IC50 after 72 h downregulated a great variety of pathways, including those controlling cell cycle, metabolism, and ribosomal and mitochondrial activity. This study establishes tipifarnib as a potential therapeutic option in T-cell leukemia and TCL. The mutational state of NOTCH1, p-ERK and RelB could serve as potential biomarkers of tipifarnib sensitivity and resistance.
Serial optical coherence microscopy for label-free volumetric histopathology
Authors: Min Eunjung , Ban Sungbea , Lee Junwon , Vavilin Andrey , Baek Songyee , Jung Sunwoo , Ahn Yujin , Park Kibeom , Shin Sungwon , Han SoHyun , Cho Hyungjoon , Lee-Kwon Whaseon , Kim Jeehyun , Lee C. Justin , Jung Woonggyu 
Published: April 2020

AbstractThe observation of histopathology using optical microscope is an essential procedure for examination of tissue biopsies or surgically excised specimens in biological and clinical laboratories. However, slide-based microscopic pathology is not suitable for visualizing the large-scale tissue and native 3D organ structure due to its sampling limitation and shallow imaging depth. Here, we demonstrate serial optical coherence microscopy (SOCM) technique that offers label-free, high-throughput, and large-volume imaging of ex vivo mouse organs. A 3D histopathology of whole mouse brain and kidney including blood vessel structure is reconstructed by deep tissue optical imaging in serial sectioning techniques. Our results demonstrate that SOCM has unique advantages as it can visualize both native 3D structures and quantitative regional volume without introduction of any contrast agents.
Five serum fatty acids are associated with subclinical hypothyroidism in a Chinese pregnant population
Authors: Zhang Ting , Xia Yinyin , Han Ting-Li , Zhang Hua , Baker Philip N. 
Published: April 2020

AbstractSubclinical hypothyroidism (SCH) is a common endocrine disorder affecting women of reproductive age. Although SCH and abnormal fatty acid composition are often associated with adverse pregnancy outcomes and metabolic syndrome later in maternal and fetal life, the longitudinal relationship between SCH and serum fatty acids during pregnancy has rarely been studied. Therefore, the aim of this study was to investigate the association between SCH and maternal serum fatty acids throughout gestation. A total of 240 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included in our study. Clinical information and maternal serum samples were collected at three time points during pregnancy: 11–14th, 22–28th, and 32–34th weeks of gestation. Twenty serum fatty acids were quantified using gas chromatography-mass spectrometry (GC-MS) analysis. A majority of the 20 serum fatty acids increased as gestation progressed in women with a normal pregnancy and women experiencing SCH. Levels of arachidic acid, docosahexaenoic acid, and eicosenoic acid were significantly higher in the serum of women with SCH when compared to women with a normal pregnancy, in the second trimester. On the other hand, the levels of eicosadienoic acid and octadecanoic acid were significantly higher in SCH in the third trimester. Our findings demonstrate that serum fatty acid composition during the second and third trimesters was significantly associated with SCH in pregnant Chinese women.
Rates and trends of childhood acute lymphoblastic leukaemia: an epidemiology study
Authors: Kakaje Ameer , Alhalabi Mohammad Marwan , Ghareeb Ayham , Karam Bahjat , Mansour Bassam , Zahra Bayan , Hamdan Othman 
Published: April 2020

AbstractAcute lymphoblastic leukaemia (ALL) is the most common childhood cancer and has a high survival rate when properly managed. Prognosis is correlated with many factors such as age, gender, white blood cell (WBC) count, CD10, French-American-British (FAB) classification, and many others. Many of these factors are included in this study as they play a major role in establishing the best treatment protocol. This study aims to demonstrate clinical and laboratory features of childhood ALL in Syria. They were treated at Children’s University Hospital, the only working major cancer centre in Syria at the time of the study. Data of 203 patients who aged 0–14 years were obtained for this study. Most patients (48.8%) aged (5–9) years with a male predominance (60.9%). The major features for ALL included lymphadenopathy (82.9%), presenting with systemic symptoms (74.9%), T-ALL subclass (20.2%), L2 FAB classification (36.1%), low educational levels for fathers (53%) and mothers (56.2%), having a high risk (48.4%), and having a duration of symptoms before evaluation for more than 4 weeks (42.6%). Only three (1.5%) patients had normal full blood counts (FBC) and only one (0.5%) patient had an isolated high WBC count at time of presentation. Most patients had either abnormal platelet count (89.3%) or low haemoglobin level (88.8%) when presenting with only (2.0%) having normal levels for both. This suggests that having normal haemoglobin and platelet count can be used for quick screening in crisis time like in Syria for prioritising patients. Many prognostic factors were significantly different from medical literature which emphasises the importance of local studies in the developping countries. This study included a high prevalence of T-all, L2 FAB classification, high-risk and other variables which require further studies to evaluate the aetiology of these features, especially that treatment protocols may have a higher mortality in developing countries when not adjusted to local variables.