bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning analysis of pregnancy data enables early identification of a subpopulation of newborns with ASD
Authors: Caly Hugues , Rabiei Hamed , Coste-Mazeau Perrine , Hantz Sebastien , Alain Sophie , Eyraud Jean-Luc , Chianea Thierry , Caly Catherine , Makowski David , Hadjikhani Nouchine , Lemonnier Eric , Ben-Ari Yehezkel 
Published: March 2021

AbstractTo identify newborns at risk of developing ASD and to detect ASD biomarkers early after birth, we compared retrospectively ultrasound and biological measurements of babies diagnosed later with ASD or neurotypical (NT) that are collected routinely during pregnancy and birth. We used a supervised machine learning algorithm with a cross-validation technique to classify NT and ASD babies and performed various statistical tests. With a minimization of the false positive rate, 96% of NT and 41% of ASD babies were identified with a positive predictive value of 77%. We identified the following biomarkers related to ASD: sex, maternal familial history of auto-immune diseases, maternal immunization to CMV, IgG CMV level, timing of fetal rotation on head, femur length in the 3rd trimester, white blood cell count in the 3rd trimester, fetal heart rate during labor, newborn feeding and temperature difference between birth and one day after. Furthermore, statistical models revealed that a subpopulation of 38% of babies at risk of ASD had significantly larger fetal head circumference than age-matched NT ones, suggesting an in utero origin of the reported bigger brains of toddlers with ASD. Our results suggest that pregnancy follow-up measurements might provide an early prognosis of ASD enabling pre-symptomatic behavioral interventions to attenuate efficiently ASD developmental sequels.
High frequency SD-OCT follow-up leading to up to biweekly intravitreal ranibizumab treatment in neovascular age-related macular degeneration
Authors: Tuerksever Cengiz , Pruente Christian , Hatz Katja 
Published: March 2021

AbstractA remarkable proportion of neovascular age-related macular degeneration (nAMD) patients respond rather poorly to ranibizumab treatment, in spite of the minimum 4-week follow-up and treatment interval. Usually, retreatments are based on nAMD activity as evaluated by Spectral-domain Optical coherence Tomography (SD-OCT), biomicroscopic fundus examination and visual acuity changes. In this prospective pilot study, we aimed to study SD-OCT changes in a high-frequent follow-up manner (weekly (month 0–6), biweekly (month 7–12)) throughout the first year, which consequently led to intravitreal ranibizumab being administered up to biweekly. Best corrected visual acuity (BCVA) was already significantly improved at week 2. Central retinal thickness (CRT), intraretinal and subretinal fluid (SRF) were significantly improved from week 1 onwards. Half of the patients showed nAMD activity at week 2 or 3 and received the first retreatment earlier than 4 weeks after baseline injection. In total, 46% of retreatments were already applied 2 or 3 weeks after the previous treatment. Greater range of CRT and SRF fluctuation during follow-up was associated with lower final BCVA. Lower baseline BCVA and better SRF improvement at week 2 was associated with greater BCVA improvement. In conclusion, high-frequency SD-OCT follow-up provided a good option for adapting treatment in nAMD individually.
Genotoxic and oxidative effect of duloxetine on mouse brain and liver tissues
Authors: Álvarez-González Isela , Camacho-Cantera Scarlett , Gómez-González Patricia , Barrón Michael J. Rendón , Morales-González José A. , Madrigal-Santillán Eduardo O. , Paniagua-Pérez Rogelio , Madrigal-Bujaidar Eduardo 
Published: March 2021

AbstractWe evaluated the duloxetine DNA damaging capacity utilizing the comet assay applied to mouse brain and liver cells, as well as its DNA, lipid, protein, and nitric oxide oxidative potential in the same cells. A kinetic time/dose strategy showed the effect of 2, 20, and 200 mg/kg of the drug administered intraperitoneally once in comparison with a control and a methyl methanesulfonate group. Each parameter was evaluated at 3, 9, 15, and 21 h postadministration in five mice per group, except for the DNA oxidation that was examined only at 9 h postadministration. Results showed a significant DNA damage mainly at 9 h postexposure in both organs. In the brain, with 20 and 200 mg/kg we found 50 and 80% increase over the control group (p ≤ 0.05), in the liver, the increase of 2, 20, and 200 mg/kg of duloxetine was 50, 80, and 135% in comparison with the control level (p ≤ 0.05). DNA, lipid, protein and nitric oxide oxidation increase was also observed in both organs. Our data established the DNA damaging capacity of duloxetine even with a dose from the therapeutic range (2 mg/kg), and suggest that this effect can be related with its oxidative potential.
Population genetics of 30 insertion/deletion polymorphisms in the Bahraini population
Authors: Al-Snan Noora R. , Shabbir Sabah , Baksh Sahar S. , AlQerainees Mashael , Haidar Mahdi , Messaoudi Safia A. , Bakhiet Moiz 
Published: March 2021

AbstractThis paper evaluates the forensic utility of 30 insertion-deletion polymorphism (indel) markers in a sample from the Bahraini population using the Qiagen Investigator DIPplex Kit. Allele frequencies and forensic stats of the 30 indels were investigated in 293 unrelated individuals from different governorates of the Kingdom of Bahrain. None of the markers showed significant deviation from Hardy Weinberg equilibrium except for HLD88 locus and no linkage disequilibrium were detected between all possible pair of the indel loci, assuming that these markers are independent and their allele frequencies can be used to calculate the match probabilities in the Bahraini population. The high power of discrimination (CPD = 0.9999999999998110) and the low combined match probability (CPM = 1.89 × 10−13) indicate that these markers are informative and can be successfully used for human identification in terms of forensics and paternity. Genetic distances and relatedness were displayed through multidimensional plotting and phylogenetic tree using various populations in the region. Our study showed that the Bahraini population was clustered with neighboring countries such as Kuwait and Emirates which indicates that these closely geographical regions share similar allele frequencies and are more genetically related than other reference population studied.
Genome-wide association study and Mendelian randomization analysis provide insights for improving rice yield potential
Authors: Su Jing , Xu Kai , Li Zirong , Hu Yuan , Hu Zhongli , Zheng Xingfei , Song Shufeng , Tang Zhonghai , Li Lanzhi 
Published: March 2021

AbstractRice yield per plant has a complex genetic architecture, which is mainly determined by its three component traits: the number of grains per panicle (GPP), kilo-grain weight (KGW), and tillers per plant (TP). Exploring ideotype breeding based on selection for genetically less complex component traits is an alternative route for further improving rice production. To understand the genetic basis of the relationship between rice yield and component traits, we investigated the four traits of two rice hybrid populations (575 + 1495 F1) in different environments and conducted meta-analyses of genome-wide association study (meta-GWAS). In total, 3589 significant loci for three components traits were detected, while only 3 loci for yield were detected. It indicated that rice yield is mainly controlled by minor-effect loci and hardly to be identified. Selecting quantitative trait locus/gene affected component traits to further enhance yield is recommended. Mendelian randomization design is adopted to investigate the genetic effects of loci on yield through component traits and estimate the genetic relationship between rice yield and its component traits by these loci. The loci for GPP or TP mainly had a positive genetic effect on yield, but the loci for KGW with different direction effects (positive effect or negative effect). Additionally, TP (Beta = 1.865) has a greater effect on yield than KGW (Beta = 1.016) and GPP (Beta = 0.086). Five significant loci for component traits that had an indirect effect on yield were identified. Pyramiding superior alleles of the five loci revealed improved yield. A combination of direct and indirect effects may better contribute to the yield potential of rice. Our findings provided a rationale for using component traits as indirect indices to enhanced rice yield, which will be helpful for further understanding the genetic basis of yield and provide valuable information for improving rice yield potential.
The enrichment of neutrophil extracellular traps impair the placentas of systemic lupus erythematosus through accumulating decidual NK cells
Authors: Jiang Meng , Shen Nan , Zhou Haibo , Wang You , Lin Sihan , Wu Jiayue , Di Wen 
Published: March 2021

AbstractDespite the advances made in the management of pregnancies in women with systemic lupus erythematosus (SLE), the rate of adverse pregnancy outcomes is still higher than that in the general population. In the last few years, neutrophil extracellular traps (NETs) were proven to be detrimental in both autoimmune diseases and placental injury. We investigated whether NETs could be detected in the placentas of pregnant individuals with SLE and explored the relationship between NETs and decidual natural killer cells (dNKs), which comprise the majority of immune cells at the maternal–fetal interface, using clinical samples and animal models. In this study, we found that the infiltration of NETs and dNKs, especially CD56+CD16+ NK cells, was significantly increased in pregnant individuals with SLE with placental insufficiency. In the murine models of SLE, the number of dNKs was significantly decreased due to the decreased formation of NETs affected by Ly6G. Moreover, the histopathological placental injury was reduced, with a remarkable increase in fetal birth weight. This study shows that NETs may contribute to immunological disorder in the placenta and the pathological changes in pregnancies with SLE, which provides a research basis for further explorations of the mechanism of SLE in placental impairment.
Mercury content in the Siberian tiger (Panthera tigris altaica Temminck, 1844) from the coastal and inland areas of the Russia
Authors: Poddubnaya N. Ya. , Salkina G. P. , Eltsova L. S. , Ivanova E. S. , Oleynikov A. Yu. , Pavlov D. D. , Kryukov V. Kh. , Rumyantseva O. Yu. 
Published: March 2021

AbstractBeing a global pollutant, mercury can originate from both natural as well as anthropogenic sources. Coastal marine atmospheric fog is considered a potential source of ocean-derived monomethylmercury (MMHg) to coastal terrestrial ecosystems. However, the ratio between mercury appearing through natural processes and that from the results of human activity is unclear. We assumed that the total mercury content in the fur of tigers would differ depending on the distance from the sea. Here we show that the average mercury content in tigers from the coast (0.435 ± 0.062 mg kg−1) is significantly different from tigers from the inland area (0.239 ± 0.075 mg kg−1), (p = 0.02). We found that the content of mercury in the fur of tigers is largely dependent of natural processes rather than human activity. We assume that the levels of mercury in coastal ecosystems in the south of the Russian Far East reflect the position of the region relative to the deep faults of the East Pacific Platform. Obtained data indicate that environmental risks associated with mercury pollution currently exist, but do not pose a serious threat to Siberian tigers.
Optimal treatment recommendations for diabetes patients using the Markov decision process along with the South Korean electronic health records
Authors: Oh Sang-Ho , Lee Su Jin , Noh Juhwan , Mo Jeonghoon 
Published: March 2021

AbstractThe extensive utilization of electronic health records (EHRs) and the growth of enormous open biomedical datasets has readied the area for applications of computational and machine learning techniques to reveal fundamental patterns. This study’s goal is to develop a medical treatment recommendation system using Korean EHRs along with the Markov decision process (MDP). The sharing of EHRs by the National Health Insurance Sharing Service (NHISS) of Korea has made it possible to analyze Koreans’ medical data which include treatments, prescriptions, and medical check-up. After considering the merits and effectiveness of such data, we analyzed patients’ medical information and recommended optimal pharmaceutical prescriptions for diabetes, which is known to be the most burdensome disease for Koreans. We also proposed an MDP-based treatment recommendation system for diabetic patients to help doctors when prescribing diabetes medications. To build the model, we used the 11-year Korean NHISS database. To overcome the challenge of designing an MDP model, we carefully designed the states, actions, reward functions, and transition probability matrices, which were chosen to balance the tradeoffs between reality and the curse of dimensionality issues.
Deep viral blood metagenomics reveals extensive anellovirus diversity in healthy humans
Authors: Cebriá-Mendoza María , Arbona Cristina , Larrea Luís , Díaz Wladimiro , Arnau Vicente , Peña Carlos , Bou Juan Vicente , Sanjuán Rafael , Cuevas José M. 
Published: March 2021

AbstractHuman blood metagenomics has revealed the presence of different types of viruses in apparently healthy subjects. By far, anelloviruses constitute the viral family that is more frequently found in human blood, although amplification biases and contaminations pose a major challenge in this field. To investigate this further, we subjected pooled plasma samples from 120 healthy donors in Spain to high-speed centrifugation, RNA and DNA extraction, random amplification, and massive parallel sequencing. Our results confirm the extensive presence of anelloviruses in such samples, which represented nearly 97% of the total viral sequence reads obtained. We assembled 114 different viral genomes belonging to this family, revealing remarkable diversity. Phylogenetic analysis of ORF1 suggested 28 potentially novel anellovirus species, 24 of which were validated by Sanger sequencing to discard artifacts. These findings underscore the importance of implementing more efficient purification procedures that enrich the viral fraction as an essential step in virome studies and question the suggested pathological role of anelloviruses.
Relationship between post-traumatic amnesia and white matter integrity in traumatic brain injury using tract-based spatial statistics
Authors: Cho Min Jye , Jang Sung Ho 
Published: March 2021

AbstractThis study used tract-based spatial statistics to examine the relationship between post-traumatic amnesia (PTA) and white matter integrity in patients with a traumatic brain injury (TBI). Forty-seven patients with TBI in the chronic stage and 47 age- and sex-matched normal control subjects were recruited to the study. Correlation coefficients were calculated to observe the relationships among the PTA duration, white matter fractional anisotropy (FA) values, and mini-mental state examination (MMSE) results in the patient group. Both before and after Benjamini–Hochberg (BH) corrections, FA values of 46 of the 48 regions of interests of the patient group were lower than those of the control group. The FA values of column and body of fornix, left crus of fornix, left uncinate fasciculus, right hippocampus part of cingulum, left medial lemniscus, right superior cerebellar peduncle, left superior cerebellar peduncle, and left posterior thalamic radiation (after BH correction: the uncinate fasciculus and right hippocampus part of cingulum) in the patient group were negatively correlated with PTA duration. PTA duration was related to the injury severity of eight neural structures, each of which is involved in the cognitive functioning of patients with TBI. Therefore, PTA duration can indicate injury severity of the above neural structures in TBI patients.
Projecting changes in extreme rainfall from three tropical cyclones using the design-rainfall approach
Authors: Jalowska Anna M. , Spero Tanya L. , Bowden Jared H. 
Published: March 2021

AbstractIn the past quarter-century, Eastern North Carolina (ENC) experienced several devastating tropical cyclones that led to widespread flooding and damage. Historical climate records reflect an increasing trend in the frequency and intensity of extreme rainfall events across the eastern U.S., which is projected to continue to increase throughout the twenty-first century. Potential changes to extreme rainfall across ENC are explored and quantified for 2025–2100 for three tropical cyclones using an approach based on relative changes in future extreme rainfall frequencies (return periods) from dynamically downscaled projections. Maximum rainfall intensities at ‘2100’ could increase locally by 168%, with widespread regional increases in total rainfall up to 44%. Although these magnitudes exceed the consensus in the literature, the values here are comparable to the most extreme rainfall events observed in the U.S. during the early twenty-first century, which suggests that the intensity of projected future events is already a present-day reality.
Structure analysis suggests Ess1 isomerizes the carboxy-terminal domain of RNA polymerase II via a bivalent anchoring mechanism
Authors: Namitz Kevin E. W. , Zheng Tongyin , Canning Ashley J. , Alicea-Velazquez Nilda L. , Castañeda Carlos A. , Cosgrove Michael S. , Hanes Steven D. 
Published: March 2021

AbstractAccurate gene transcription in eukaryotes depends on isomerization of serine-proline bonds within the carboxy-terminal domain (CTD) of RNA polymerase II. Isomerization is part of the “CTD code” that regulates recruitment of proteins required for transcription and co-transcriptional RNA processing.Saccharomyces cerevisiaeEss1 and its human ortholog, Pin1, are prolyl isomerases that engage the long heptad repeat (YSPTSPS)26of the CTD by an unknown mechanism. Here, we used an integrative structural approach to decipher Ess1 interactions with the CTD. Ess1 has a rigid linker between its WW and catalytic domains that enforces a distance constraint for bivalent interaction with the ends of long CTD substrates (≥4–5 heptad repeats). Our binding results suggest that the Ess1 WW domain anchors the proximal end of the CTD substrate during isomerization, and that linker divergence may underlie evolution of substrate specificity.
Structure of the p53/RNA polymerase II assembly
Authors: Liou Shu-Hao , Singh Sameer K. , Singer Robert H. , Coleman Robert A. , Liu Wei-Li 
Published: March 2021

AbstractThe tumor suppressor p53 protein activates expression of a vast gene network in response to stress stimuli for cellular integrity. The molecular mechanism underlying how p53 targets RNA polymerase II (Pol II) to regulate transcription remains unclear. To elucidate the p53/Pol II interaction, we have determined a 4.6 Å resolution structure of the human p53/Pol II assembly via single particle cryo-electron microscopy. Our structure reveals that p53’s DNA binding domain targets the upstream DNA binding site within Pol II. This association introduces conformational changes of the Pol II clamp into a further-closed state. A cavity was identified between p53 and Pol II that could possibly host DNA. The transactivation domain of p53 binds the surface of Pol II’s jaw that contacts downstream DNA. These findings suggest that p53’s functional domains directly regulate DNA binding activity of Pol II to mediate transcription, thereby providing insights into p53-regulated gene expression.
Bacteria-specific pro-photosensitizer kills multidrug-resistant Staphylococcus aureus and Pseudomonas aeruginosa
Authors: Lu Min , Li Yongli , Wu Mei X. 
Published: March 2021

AbstractThe emergence of multidrug-resistant bacteria has become a real threat and we are fast running out of treatment options. A combinatory strategy is explored here to eradicate multidrug-resistant Staphlococcus aureus and Pseudomonas aeruginosa including planktonic cells, established biofilms, and persisters as high as 7.5 log bacteria in less than 30 min. Blue-laser and thymol together rapidly sterilized acute infected or biofilm-associated wounds and successfully prevented systematic dissemination in mice. Mechanistically, blue-laser and thymol instigated oxidative bursts exclusively in bacteria owing to abundant proporphyrin-like compounds produced in bacteria over mammalian cells, which transformed harmless thymol into blue-laser sensitizers, thymoquinone and thymohydroquinone. Photo-excitations of thymoquinone and thymohydroquinone augmented reactive oxygen species production and initiated a torrent of cytotoxic events in bacteria while completely sparing the host tissue. The investigation unravels a previously unappreciated property of thymol as a pro-photosensitizer analogous to a prodrug that is activated only in bacteria.
Water scarcity will constrain the formation of a world-class megalopolis in North China
Authors: Zhang Zhuoying , Shi Minjun , Chen Kevin Z. , Yang Hong , Wang Shouyang 
Published: March 2021

AbstractThe formation of world-class megalopolises has been a goal of urban development agencies around the world owing to their economic advantages. On their bids of becoming a world-class megalopolis, water availability is a factor that requires consideration. China has set an ambitious goal of developing a world-class megalopolis in the water-scarce Beijing-Tianjin-Hebei (BTH) region. This study investigates the water challenge the BTH region faces and the effects of main water conservation measures in the region towards the goal. An inter-city input–output model was constructed for identifying the water gap in the region and analyzing the effectiveness of main water conservation measures under various scenarios. The results indicate a significant gap between the water required to achieve the goal of becoming a world-class megalopolis and the region’s available water resources. Although proposed water conservation measures of improving water use efficiency and reducing agricultural water use provide a modest improvement, the amount of water required for urban development still exceeds the availability. The study emphasizes the significance of agricultural water use reduction in Hebei through crop system replacement from water-intensive winter wheat to water-saving crops. The study also proposes an alternative option of adjusting the development plan through redefining the boundary of the BTH megalopolis by excluding part of cities in Hebei. The results of this study contribute to a better understanding of the effect of water scarcity on urban development and thus provide references for other water-scarce regions with ambitious urban development goals.