bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation and characterization of iPSC-derived renal proximal tubule-like cells with extended stability
Authors: Chandrasekaran Vidya , Carta Giada , da Costa Pereira Daniel , Gupta Rajinder , Murphy Cormac , Feifel Elisabeth , Kern Georg , Lechner Judith , Cavallo Anna Lina , Gupta Shailesh , Caiment Florian , Kleinjans Jos C. S. , Gstraunthaler Gerhard , Jennings Paul , Wilmes Anja 
Published: June 2021

AbstractThe renal proximal tubule is responsible for re-absorption of the majority of the glomerular filtrate and its proper function is necessary for whole-body homeostasis. Aging, certain diseases and chemical-induced toxicity are factors that contribute to proximal tubule injury and chronic kidney disease progression. To better understand these processes, it would be advantageous to generate renal tissues from human induced pluripotent stem cells (iPSC). Here, we report the differentiation and characterization of iPSC lines into proximal tubular-like cells (PTL). The protocol is a step wise exposure of small molecules and growth factors, including the GSK3 inhibitor (CHIR99021), the retinoic acid receptor activator (TTNPB), FGF9 and EGF, to drive iPSC to PTL via cell stages representing characteristics of early stages of renal development. Genome-wide RNA sequencing showed that PTL clustered within a kidney phenotype. PTL expressed proximal tubular-specific markers, including megalin (LRP2), showed a polarized phenotype, and were responsive to parathyroid hormone. PTL could take up albumin and exhibited ABCB1 transport activity. The phenotype was stable for up to 7 days and was maintained after passaging. This protocol will form the basis of an optimized strategy for molecular investigations using iPSC derived PTL.
High burden of cerebral white matter lesion in 9 Asian cities
Authors: Lam Bonnie Yin Ka , Yiu Brian , Ampil Encarnita , Chen Christopher Li-Hsian , Dikot Yustiani , Dominguez Jacqueline C. , Ganeshbhai Patel Vishal , Hilal Saima , Kandiah Nagaendran , Kim SangYun , Lee Jun-Young , Ong Anam Paulus , Senanarong Vorapun , Leung Kam Tat , Wang Huali , Yang Yuan-Han , Yong Tingting , Arshad Faheem , Alladi Suvarna , Wong Samuel , Ko Ho , Lau Alexander Yuk Lun , Mok Vincent Chung Tong 
Published: June 2021

AbstractAge-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer’s disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.
Impact of kidney transplantation on the risk of retinal vein occlusion in end-stage renal disease
Authors: Lee Jangwook , Choe Hye Rim , Park Sang Hyun , Do Han Kyung , Kim Dong Ki , Joo Kwon Wook , Kim Yon Su , Lee Eun Kyoung , Park Un Chul , Yu Hyeong Gon , Lee Hajeong , Kim Yong Chul , Oh Baek-Lok 
Published: June 2021

AbstractIt has been known that retinal vein occlusion (RVO) is associated with chronic kidney disease, especially end-stage renal disease (ESRD). However, little is known about the effect of kidney transplantation (KT) on RVO incidence in ESRD patients. This study aimed to compare the incidence of RVO in KT recipients (n = 10,498), matched ESRD patients (n = 10,498), and healthy controls (HCs, n = 10,498), using a long-term population-based cohort. The incidence of RVO was 2.74, 5.68, and 1.02 per 1000 patient-years, for the KT group, the ESRD group, and the HCs group, respectively. Adjusted hazard ratios for RVO development compared to the HCs group, were 1.53 and 3.21, in the KT group and the ESRD group, respectively. In the KT group, multivariable regression analysis indicated that an age over 50, a Charlson Comorbidity Index score over 4, and a history of desensitization therapy were associated with an increased risk of RVO. In summary, KT recipients have a lower risk for development of RVO than ESRD patients treated with dialysis. However, the risk is still higher compared to healthy people who have normal kidney functions.
Development of a reference standard for the detection and quantification of Mycobacterium avium subsp. paratuberculosis by quantitative PCR
Authors: Beinhauerova Monika , Beinhauerova Martina , McCallum Sarah , Sellal Eric , Ricchi Matteo , O’Brien Rory , Blanchard Beatrice , Slana Iva , Babak Vladimir , Kralik Petr 
Published: June 2021

AbstractQuantitative PCR (qPCR) has become a frequently employed direct method for the detection and quantification of Mycobacterium avium subsp. paratuberculosis (MAP). The quantity of MAP determined by qPCR, however, may be affected by the type of qPCR quantification standard used (PCR product, plasmid, genomic DNA) and the way in which standard DNA quantity is determined (absorbance, fluorescence). In practice, this can be reflected in the inability to properly compare quantitative data from the same qPCR assays in different laboratories. Thus, the aim of this study was to prepare a prototype of an international MAP reference standard, which could be used to calibrate routinely used qPCR quantification standards in various laboratories to promote clinical data comparability. Considering stability, storage and shipment issues, a lyophilised fecal suspension artificially contaminated with a MAP reference strain was chosen as the most suitable form of the standard. The effect of five types of lyophilisation matrices on standard stability was monitored on 2-weeks interval basis for 4 months by F57 qPCR. The lyophilisation matrix with 10% skimmed milk provided the best recovery and stability in time and was thus selected for subsequent comparative testing of the standard involving six diagnostic and research laboratories, where DNA isolation and qPCR assay procedures were performed with the parallel use of the identical supplied genomic DNA solution. Furthermore, the effect of storage conditions on the standard stability was tested for at least 6 months. The storage at room temperature in the dark and under light, at + 4 °C, − 20 °C and − 80 °C showed no significant changes in the stability, and also no substantial changes in MAP viability were found using phage amplification assay. The prepared MAP quantification standard provided homogeneous and reproducible results demonstrating its suitability for utilisation as an international reference qPCR standard.
Global climate shift in 1970s causes a significant worldwide increase in precipitation extremes
Authors: Sarkar Subharthi , Maity Rajib 
Published: June 2021

AbstractThe shift in climate regimes around 1970s caused an overall enhancement of precipitation extremes across the globe with a specific spatial distribution pattern. We used gridded observational-reanalysis precipitation dataset and two important extreme precipitation measures, namely Annual Maximum Daily Precipitation (AMDP) and Probable Maximum Precipitation (PMP). AMDP is reported to increase for almost two-third of the global land area. The variability of AMDP is found to increase more than its mean that eventually results in increased PMP almost worldwide, less near equator and maximum around mid-latitudes. Continent-wise, such increase in AMDP and PMP is true for all continents except some parts of Africa. The zone-wise analysis (dividing the globe into nine precipitation zones) reveals that zones of ‘moderate precipitation’ and ‘moderate seasonality’ exhibit the maximum increases in PMP. Recent increased in pole-ward heat and moisture transport as a result of Arctic Amplification may be associated with such spatial redistribution of precipitation extremes in the northern hemisphere.
Lipid profile of bovine grade-1 blastocysts produced either in vivo or in vitro before and after slow freezing process
Authors: Janati Idrissi Sarah , Le Bourhis Daniel , Lefevre Antoine , Emond Patrick , Le Berre Laurene , Desnoës Olivier , Joly Thierry , Buff Samuel , Maillard Virginie , Schibler Laurent , Salvetti Pascal , Elis Sebastien 
Published: June 2021

AbstractCurrently, in vitro embryo production (IVP) is successfully commercially applied in cattle. However, the high sensitivity of embryos to cryopreservation in comparison to in vivo (IVD) embryos slows the dissemination of this biotechnology. Reduced cryotolerance is frequently associated with lipid accumulation in the cytoplasm mainly due to in vitro culture conditions. The objective of this study was to evaluate the lipid composition of biopsied and sexed embryos, produced either in vivo or in vitro from the same Holstein heifers before and after a slow freezing protocol. Lipid extracts were analysed by liquid chromatography-high resolution mass spectrometry, which enabled the detection of 496 features. Our results highlighted a lipid enrichment of IVP embryos in triglycerides and oxidised glycerophospholipids and a reduced abundance in glycerophospholipids. The slow freezing process affected the lipid profiles of IVP and IVD embryos similarly. Lysophosphatidylcholine content was reduced when embryos were frozen/thawed. In conclusion, the embryonic lipid profile is impacted by IVP and slow freezing protocols but not by sex. Lysophosphatidylcholine seemed highly sensitive to cryopreservation and might contribute to explain the lower quality of frozen embryos. Further studies are required to improve embryo freezability by modulating the lipidome.
Mycoplasma pneumoniae CARDS toxin exploits host cell endosomal acidic pH and vacuolar ATPase proton pump to execute its biological activities
Authors: Ramasamy Kumaraguruparan , Balasubramanian Sowmya , Kirkpatrick Alejandra , Szabo Daniel , Pandranki Lavanya , Baseman Joel B. , Kannan T. R. 
Published: June 2021

AbstractMycoplasma pneumoniae is the leading cause of bacterial community-acquired pneumonia among hospitalized children in the United States. It is also responsible for a spectrum of other respiratory tract disorders and extrapulmonary manifestations in children and adults. The main virulence factor of M. pneumoniae is a 591 amino acid multifunctional protein called Community Acquired Respiratory Distress Syndrome (CARDS) toxin. The amino terminal region of CARDS toxin (N-CARDS) retains ADP-ribosylating activity and the carboxy region (C-CARDS) contains the receptor binding and vacuolating activities. After internalization, CARDS toxin is transported in a retrograde manner from endosome through the Golgi complex into the endoplasmic reticulum. However, the mechanisms and criteria by which internalized CARDS toxin is transported and activated to execute its cytotoxic effects remain unknown. In this study, we used full-length CARDS toxin and its mutant and truncated derivatives to analyze how pharmacological drugs that alter pH of intracellular vesicles and electrical potential across vesicular membranes affect translocation of CARDS toxin in mammalian cells. Our results indicate that an acidic environment is essential for CARDS toxin retrograde transport to endoplasmic reticulum. Moreover, retrograde transport facilitates toxin clipping and is required to induce vacuole formation. Additionally, toxin-mediated cell vacuolation is strictly dependent on the function of vacuolar type-ATPase.
The international ENIGMA-II substudy on postoperative cognitive disorders (ISEP)
Authors: Haller Guy , Chan Matthew T. V. , Combescure Christophe , Lopez Ursula , Pichon Isabelle , Licker Marc , Fournier Roxane , Myles Paul 
Published: June 2021

AbstractThere is a large controversy as to whether nitrous oxide (N2O) added to the anaesthetic gas mixture is harmful or harmless for postoperative cognitive function recovery. We performed a nested study in the ENIGMA-II trial and compared postoperative neurocognitive recovery of patients randomly receiving N2O (70%) or Air (70%) in 30% O2 during anesthesia. We included adults having non cardiac surgery. We compared recovery scores for episodic memory, decision making/processing speed and executive functions measured with the computerised Cambridge Neuropsychological Test Automated Battery (CANTAB). Assessments were performed at baseline, seven and ninety days. At first interim analysis, following recruitment of 140 participants, the trial was suspended. We found that the mean (95%CI) changes of scores for episodic memory were in the Pocock futility boundaries. Decision making/processing speed did not differ either between groups (P > 0.182). But for executive functions at seven days, the mean number (95% CI) of problems successfully solved and the number of correct box choices made was higher in the N2O group, P = 0.029. N2O with the limitations of an interim analysis appears to have no harmful effect on cognitive functions (memory/processing speed). It may improve the early recovery process of executive functions. This preliminary finding warrants further investigations.
Common neurobiological correlates of resilience and personality traits within the triple resting-state brain networks assessed by 7-Tesla ultra-high field MRI
Authors: Altinok Dilsa Cemre Akkoc , Rajkumar Ravichandran , Nießen Dominik , Sbaihat Hasan , Kersey Margo , Shah N. Jon , Veselinović Tanja , Neuner Irene 
Published: June 2021

AbstractDespite numerous studies investigating resilience and personality trials, a paucity of information regarding their neurobiological commonalities at the level of the large resting-state networks (rsNWs) remains. Here we address this topic using the advantages of ultra-high-field (UHF) 7T-MRI, characterized by higher signal-to-noise ratio and increased sensitivity. The association between resilience, personality traits and three fMRI measures (fractional amplitude of low-frequency fluctuations (fALFF), degree centrality (DC) and regional homogeneity (ReHo)) determined for three core rsNWs (default mode (DMN), salience (SN), and central executive network (CEN)) were examined in 32 healthy volunteers. The investigation revealed a significant role of SN in both resilience and personality traits and a tight association of the DMN with resilience. DC in CEN emerged as a significant moderator for the correlations of resilience with the personality traits of neuroticism and extraversion. Our results indicate that the common neurobiological basis of resilience and the Big Five personality traits may be reflected at the level of the core rsNWs.
Pure hydroxyapatite synthesis originating from amorphous calcium carbonate
Authors: Sawada Michika , Sridhar Kandi , Kanda Yasuharu , Yamanaka Shinya 
Published: June 2021

AbstractWe report a synthesis strategy for pure hydroxyapatite (HAp) using an amorphous calcium carbonate (ACC) colloid as the starting source. Room-temperature phosphorylation and subsequent calcination produce pure HAp via intermediate amorphous calcium phosphate (ACP). The pre-calcined sample undergoes a competitive transformation from ACC to ACP and crystalline calcium carbonate. The water content, ACC concentration, Ca/P molar ratio, and pH during the phosphorylation reaction play crucial roles in the final phase of the crystalline phosphate compound. Pure HAp is formed after ACP is transformed from ACC at a low concentration (1 wt%) of ACC colloid (1.71 < Ca/P < 1.88), whereas Ca/P = 1.51 leads to pure β-tricalcium phosphate. The ACP phases are precursors for calcium phosphate compounds and may determine the final crystalline phase.
Circulation derived from 4D flow MRI correlates with right ventricular dysfunction in patients with tetralogy of Fallot
Authors: Tsuchiya Nanae , Nagao Michinobu , Shiina Yumi , Miyazaki Shohei , Inai Kei , Murayama Sadayuki , Sakai Shuji 
Published: June 2021

AbstractWe used 4D-flow MRI to investigate circulation, an area integral of vorticity, in the main pulmonary artery (MPA) as a new hemodynamic parameter for assessing patients with a repaired Tetralogy of Fallot (TOF). We evaluated the relationship between circulation, right ventricular (RV) function and the pulmonary regurgitant fraction (PRF). Twenty patients with a repaired TOF underwent cardiac MRI. Flow-sensitive 3D-gradient sequences were used to obtain 4D-flow images. Vortex formation in the MPA was visualized, with short-axis and longitudinal vorticities calculated by software specialized for 4D flow. The RV indexed end-diastolic/end-systolic volumes (RVEDVi/RVESVi) and RV ejection fraction (RVEF) were measured by cine MRI. The PR fraction (PRF) and MPA area were measured by 2D phase-contrast MRI. Spearman ρ values were determined to assess the relationships between circulation, RV function, and PRF. Vortex formation in the MPA occurred in 15 of 20 patients (75%). The longitudinal circulation (11.7 ± 5.1 m2/s) was correlated with the RVEF (ρ = − 0.85, p = 0.0002), RVEDVi (ρ = 0.62, p = 0.03), and RVESVi (ρ = 0.76, p = 0.003) after adjusting for the MPA size. The short-axis circulation (9.4 ± 3.4 m2/s) in the proximal MPA was positively correlated with the MPA area (ρ = 0.61, p = 0.004). The relationships between the PRF and circulation or RV function were not significant. Increased longitudinal circulation in the MPA, as demonstrated by circulation analysis using 4D flow MRI, was related to RV dysfunction in patients with a repaired TOF.
Metabolomics analysis of the soapberry (Sapindus mukorossi Gaertn.) pericarp during fruit development and ripening based on UHPLC-HRMS
Authors: Xu Yuanyuan , Gao Yuan , Chen Zhong , Zhao Guochun , Liu Jiming , Wang Xin , Gao Shilun , Zhang Duanguang , Jia Liming 
Published: June 2021

AbstractSoapberry (Sapindus mukorossi Gaertn.) is a multi-functional tree with widespread application in toiletries, biomedicine, biomass energy, and landscaping. The pericarp of soapberry can be used as a medicine or detergent. However, there is currently no systematic study on the chemical constituents of soapberry pericarp during fruit development and ripening, and the dynamic changes in these constituents still unclear. In this study, a non-targeted metabolomics approach using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to comprehensively profile the variations in metabolites in the soapberry pericarp at eight fruit growth stages. The metabolome coverage of UHPLC-HRMS on a HILIC column was higher than that of a C18 column. A total of 111 metabolites were putatively annotated. Principal component analysis and hierarchical clustering analysis of pericarp metabolic composition revealed clear metabolic shifts from early (S1–S2) to late (S3–S5) development stages to fruit ripening stages (S6–S8). Furthermore, pairwise comparison identified 57 differential metabolites that were involved in 18 KEGG pathways. Early fruit development stages (S1–S2) were characterized by high levels of key fatty acids, nucleotides, organic acids, and phosphorylated intermediates, whereas fruit ripening stages (S6–S8) were characterized by high contents of bioactive and valuable metabolites, such as troxipide, vorinostat, furamizole, alpha-tocopherol quinone, luteolin, and sucrose. S8 (fully developed and mature stage) was the most suitable stage for fruit harvesting to utilize the pericarp. To the best of our knowledge, this was the first metabolomics study of the soapberry pericarp during whole fruit growth. The results could offer valuable information for harvesting, processing, and application of soapberry pericarp, as well as highlight the metabolites that could mediate the biological activity or properties of this medicinal plant.
Effects of human serum albumin on post-mortem changes of malathion
Authors: Yamagishi Yoshikazu , Iwase Hirotaro , Ogra Yasumitsu 
Published: June 2021

AbstractMalathion, diethyl 2-[(dimethoxyphosphinothioyl)thio]butanedioate, is one of most widely used organophosphoryl pesticide, and it has been detected in several clinical cases of accidental exposure and suicide. It is reported that the observed malathion concentration in blood of persons who suffer from malathion poisoning is smaller than the expected concentration. Because malathion is bound to human serum albumin (HSA), recovery of malathion in the free form is insufficient. We detected malathion adducts in HSA by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF–MS). The mass spectra showed that malathion was preferably bound to the lysine (K) and cysteinylproline (CP) residues of HSA. The K- and CP-adducts of malathion were increased in vitro with a dose-dependent fashion when its concentration was smaller than the lethal dose. Further, the K-adduct was also detected in post-mortem blood of an autopsied subject suffering from intentional malathion ingestion. These results suggest that the K-adduct seems to be available to use a biomarker of malathion poisoning, and the determination of the K-adduct could make possible to estimate the amount of malathion ingestion.
IKKε isoform switching governs the immune response against EV71 infection
Authors: Chang Ya-Ling , Liao Yu-Wen , Chen Min-Hsuan , Chang Sui-Yuan , Huang Yao-Ting , Ho Bing-Ching , Yu Sung-Liang 
Published: June 2021

AbstractThe reciprocal interactions between pathogens and hosts are complicated and profound. A comprehensive understanding of these interactions is essential for developing effective therapies against infectious diseases. Interferon responses induced upon virus infection are critical for establishing host antiviral innate immunity. Here, we provide a molecular mechanism wherein isoform switching of the host IKKε gene, an interferon-associated molecule, leads to alterations in IFN production during EV71 infection. We found that IKKε isoform 2 (IKKε v2) is upregulated while IKKε v1 is downregulated in EV71 infection. IKKε v2 interacts with IRF7 and promotes IRF7 activation through phosphorylation and translocation of IRF7 in the presence of ubiquitin, by which the expression of IFNβ and ISGs is elicited and virus propagation is attenuated. We also identified that IKKε v2 is activated via K63-linked ubiquitination. Our results suggest that host cells induce IKKε isoform switching and result in IFN production against EV71 infection. This finding highlights a gene regulatory mechanism in pathogen-host interactions and provides a potential strategy for establishing host first-line defense against pathogens.