bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Partitioning of Meridional Heat Transport from the Last Glacial Maximum to CO2 Quadrupling in Coupled Climate Models
Authors: Donohoe Aaron , Armour Kyle C. , Roe Gerard H. , Battisti David S. , Hahn Lily 
Published: February 2020

AbstractMeridional heat transport (MHT) is analyzed in ensembles of coupled climate models simulating climate states ranging from the Last Glacial Maximum (LGM) to quadrupled CO2. MHT is partitioned here into atmospheric (AHT) and implied oceanic (OHT) heat transports. In turn, AHT is partitioned into dry and moist energy transport by the meridional overturning circulation (MOC), transient eddy energy transport (TE), and stationary eddy energy transport (SE) using only monthly averaged model output that is typically archived. In all climate models examined, the maximum total MHT (AHT + OHT) is nearly climate-state invariant, except for a modest (4%, 0.3 PW) enhancement of MHT in the Northern Hemisphere (NH) during the LGM. However, the partitioning of MHT depends markedly on the climate state, and the changes in partitioning differ considerably among different climate models. In response to CO2 quadrupling, poleward implied OHT decreases, while AHT increases by a nearly compensating amount. The increase in annual-mean AHT is a smooth function of latitude but is due to a spatially inhomogeneous blend of changes in SE and TE that vary by season. During the LGM, the increase in wintertime SE transport in the NH midlatitudes exceeds the decrease in TE resulting in enhanced total AHT. Total AHT changes in the Southern Hemisphere (SH) are not significant. These results suggest that the net top-of-atmosphere radiative constraints on total MHT are relatively invariant to climate forcing due to nearly compensating changes in absorbed solar radiation and outgoing longwave radiation. However, the partitioning of MHT depends on detailed regional and seasonal factors.
Formation of Recirculating Cores in Convectively Breaking Internal Solitary Waves of Depression Shoaling over Gentle Slopes in the South China Sea
Authors: Rivera-Rosario Gustavo , Diamessis Peter J. , Lien Ren-Chieh , Lamb Kevin G. , Thomsen Greg N. 
Published: February 2020

AbstractThe formation of a recirculating subsurface core in an internal solitary wave (ISW) of depression, shoaling over realistic bathymetry, is explored through fully nonlinear and nonhydrostatic two-dimensional simulations. The computational approach is based on a high-resolution/accuracy deformed spectral multidomain penalty-method flow solver, which employs the recorded bathymetry, background current, and stratification profile in the South China Sea. The flow solver is initialized using a solution of the fully nonlinear Dubreil–Jacotin–Long equation. During shoaling, convective breaking precedes core formation as the rear steepens and the trough decelerates, allowing heavier fluid to plunge forward, forming a trapped core. This core-formation mechanism is attributed to a stretching of a near-surface background vorticity layer. Since the sign of the vorticity is opposite to that generated by the propagating wave, only subsurface recirculating cores can form. The onset of convective breaking is visualized, and the sensitivity of the core properties to changes in the initial wave, near-surface background shear, and bottom slope is quantified. The magnitude of the near-surface vorticity determines the size of the convective-breaking region, and the rapid increase of local bathymetric slope accelerates core formation. If the amplitude of the initial wave is increased, the subsequent convective-breaking region increases in size. The simulations are guided by field data and capture the development of the recirculating subsurface core. The analyzed parameter space constitutes a baseline for future three-dimensional simulations focused on characterizing the turbulent flow engulfed within the convectively unstable ISW.
A deep adversarial variational autoencoder model for dimensionality reduction in single-cell RNA sequencing analysis
Authors: Lin Eugene , Mukherjee Sudipto , Kannan Sreeram 
Published: February 2020

Abstract
Background
Single-cell RNA sequencing (scRNA-seq) is an emerging technology that can assess the function of an individual cell and cell-to-cell variability at the single cell level in an unbiased manner. Dimensionality reduction is an essential first step in downstream analysis of the scRNA-seq data. However, the scRNA-seq data are challenging for traditional methods due to their high dimensional measurements as well as an abundance of dropout events (that is, zero expression measurements).

Results
To overcome these difficulties, we propose DR-A (Dimensionality Reduction with Adversarial variational autoencoder), a data-driven approach to fulfill the task of dimensionality reduction. DR-A leverages a novel adversarial variational autoencoder-based framework, a variant of generative adversarial networks. DR-A is well-suited for unsupervised learning tasks for the scRNA-seq data, where labels for cell types are costly and often impossible to acquire. Compared with existing methods, DR-A is able to provide a more accurate low dimensional representation of the scRNA-seq data. We illustrate this by utilizing DR-A for clustering of scRNA-seq data.

Conclusions
Our results indicate that DR-A significantly enhances clustering performance over state-of-the-art methods.
Comparative analysis of ChIP-exo peak-callers: impact of data quality, read duplication and binding subtypes
Authors: Sharma Vasudha , Majumdar Sharmistha 
Published: February 2020

Abstract
Background
ChIP (Chromatin immunoprecipitation)-exo has emerged as an important and versatile improvement over conventional ChIP-seq as it reduces the level of noise, maps the transcription factor (TF) binding location in a very precise manner, upto single base-pair resolution, and enables binding mode prediction. Availability of numerous peak-callers for analyzing ChIP-exo reads has motivated the need to assess their performance and report which tool executes reasonably well for the task.

Results
This study has focussed on comparing peak-callers that report direct binding events with those that report indirect binding events. The effect of strandedness of reads and duplication of data on the performance of peak-callers has been investigated. The number of peaks reported by each peak-caller is compared followed by a comparison of the annotated motifs present in the reported peaks. The significance of peaks is assessed based on the presence of a motif in top peaks. Indirect binding tools have been compared on the basis of their ability to identify annotated motifs and predict mode of protein-DNA interaction.

Conclusion
By studying the output of the peak-callers investigated in this study, it is concluded that the tools that use self-learning algorithms, i.e. the tools that estimate all the essential parameters from the aligned reads, perform better than the algorithms which require formation of peak-pairs. The latest tools that account for indirect binding of TFs appear to be an upgrade over the available tools, as they are able to reveal valuable information about the mode of binding in addition to direct binding. Furthermore, the quality of ChIP-exo reads have important consequences on the output of data analysis.
FastMM: an efficient toolbox for personalized constraint-based metabolic modeling
Authors: Li Gong-Hua , Dai Shaoxing , Han Feifei , Li Wenxing , Huang Jingfei , Xiao Wenzhong 
Published: February 2020

Abstract
Background
Constraint-based metabolic modeling has been applied to understand metabolism related disease mechanisms, to predict potential new drug targets and anti-metabolites, and to identify biomarkers of complex diseases. Although the state-of-art modeling toolbox, COBRA 3.0, is powerful, it requires substantial computing time conducting flux balance analysis, knockout analysis, and Markov Chain Monte Carlo (MCMC) sampling, which may limit its application in large scale genome-wide analysis.

Results
Here, we rewrote the underlying code of COBRA 3.0 using C/C++, and developed a toolbox, termed FastMM, to effectively conduct constraint-based metabolic modeling. The results showed that FastMM is 2~400 times faster than COBRA 3.0 in performing flux balance analysis and knockout analysis and returns consistent outputs. When applied to MCMC sampling, FastMM is 8 times faster than COBRA 3.0. FastMM is also faster than some efficient metabolic modeling applications, such as Cobrapy and Fast-SL. In addition, we developed a Matlab/Octave interface for fast metabolic modeling. This interface was fully compatible with COBRA 3.0, enabling users to easily perform complex applications for metabolic modeling. For example, users who do not have deep constraint-based metabolic model knowledge can just type one command in Matlab/Octave to perform personalized metabolic modeling. Users can also use the advance and multiple threading parameters for complex metabolic modeling. Thus, we provided an efficient and user-friendly solution to perform large scale genome-wide metabolic modeling. For example, FastMM can be applied to the modeling of individual cancer metabolic profiles of hundreds to thousands of samples in the Cancer Genome Atlas (TCGA).

Conclusion
FastMM is an efficient and user-friendly toolbox for large-scale personalized constraint-based metabolic modeling. It can serve as a complementary and invaluable improvement to the existing functionalities in COBRA 3.0. FastMM is under GPL license and can be freely available at GitHub site: https://github.com/GonghuaLi/FastMM.
Heterosis analysis and underlying molecular regulatory mechanism in a wide-compatible neo-tetraploid rice line with long panicles
Authors: Ghaleb Mohammed Abdullah Abdulraheem , Li Cong , Shahid Muhammad Qasim , Yu Hang , Liang Junhong , Chen Ruoxin , Wu Jinwen , Liu Xiangdong 
Published: February 2020

Abstract
Background
Neo-tetraploid rice, which is a new germplasm developed from autotetraploid rice, has a powerful biological and yield potential and could be used for commercial utilization. The length of panicle, as a part of rice panicle architecture, contributes greatly to high yield. However, little information about long panicle associated with heterosis or hybrid vigor is available in neo-tetraploid rice.

Results
In the present study, we developed a neo-tetraploid rice line, Huaduo 8 (H8), with long panicles and harboring wide-compatibility genes for pollen and embryo sac fertility. All the hybrids generated by H8 produced significant high-parent yield heterosis and displayed long panicles similar to H8. RNA-seq analysis detected a total of 4013, 7050, 6787 and 6195 differentially expressed genes uniquely belonging to F1 and specifically (DEGFu-sp) associated with leaf, sheath, main panicle axis and spikelet in the two hybrids, respectively. Of these DEGFu-sp, 279 and 89 genes were involved in kinase and synthase, and 714 cloned genes, such as GW8, OsGA20ox1, Ghd8, GW6a, and LP1, were identified and validated by qRT-PCR. A total of 2925 known QTLs intervals, with an average of 1~100 genes per interval, were detected in both hybrids. Of these, 109 yield-related QTLs were associated with seven important traits in rice. Moreover, 1393 non-additive DEGs, including 766 up-regulated and 627 down-regulated, were detected in both hybrids. Importantly, eight up-regulated genes associated with panicle were detected in young panicles of the two hybrids compared to their parents by qRT-PCR. Re-sequencing analysis depicted that LP (a gene controlling long panicle) sequence of H8 was different from many other neo-tetraploid rice and most of the diploid and autotetraploid lines. The qRT-PCR results showed that LP was up-regulated in the hybrid compared to its parents at very young stage of panicle development.

Conclusions
These results suggested that H8 could overcome the intersubspecific autotetraploid hybrid rice sterility caused by embryo sac and pollen sterility loci. Notably, long panicles of H8 showed dominance phenomenon and played an important role in yield heterosis, which is a complex molecular mechanism. The neo-tetraploid rice is a useful germplasm to attain high yield of polyploid rice.
Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade
Authors: Zheng Qinghong , Peng Xiaohong , Zhang Yaqin 
Published: February 2020

Abstract
Background
Substantial clinical and preclinical evidence have indicated the association between amide-linked local anesthesia and the long-term outcomes of cancer patients. However, the potential effects of local anesthesia on cancer recurrence are inconclusive and the underlying mechanisms remain poorly understood.

Methods
We systematically examined the effects of three commonly used local anesthetics in melanoma cells and analyzed the underlying mechanisms focusing on small GTPases.

Results
Ropivacaine and lidocaine but not bupivacaine inhibited migration and proliferation, and induced apoptosis in melanoma cells. In addition, ropivacaine and lidocaine but not bupivacaine significantly augmented the in vitro efficacy of vemurafenib (a B-Raf inhibitor for melanoma with BRAF V600E mutation) and dacarbazine (a chemotherapeutic drug). Mechanistically, ropivacaine but not bupivacaine decreased the activities of Ras superfamily members with the dominant inhibitory effects on RhoA and Ras, independent of sodium channel blockade. Rescue studies using constitutively active Ras and Rho activator calpeptin demonstrated that ropivacaine inhibited migration mainly through RhoA whereas growth and survival were mainly inhibited through Ras in melanoma cells. We further detected a global reduction of downstream signaling of Ras and RhoA in ropivacaine-treated melanoma cells.

Conclusion
Our study is the first to demonstrate the anti-melanoma activity of ropivacaine and lidocaine but not bupivacaine, via targeting small GTPases. Our findings provide preclinical evidence on how amide-linked local anesthetics could affect melanoma patients.
Sepsis in cancer patients residing in Zimbabwe: spectrum of bacterial and fungal aetiologies and their antimicrobial susceptibility patterns
Authors: Chinowaita Frank , Chaka Wendy , Nyazika Tinashe K. , Maboreke Tendai C. , Tizauone Emmanuel , Mapondera Prichard , Chitsike Inam , Cakana Andrew Z. , Mavenyengwa Rooyen T. 
Published: February 2020

Abstract
Background
Cancer and sepsis comorbidity is a major public health problem in most parts of the world including Zimbabwe. The microbial aetiologies of sepsis and their antibiograms vary with time and locations. Knowledge on local microbial aetiologies of sepsis and their susceptibility patterns is critical in guiding empirical antimicrobial treatment choices.

Methods
This was a descriptive cross-sectional study which determined the microbial aetiologies of sepsis from blood cultures of paediatric and adult cancer patients obtained between July 2016 and June 2017. The TDR-X120 blood culture system and TDR 300B auto identification machine were used for incubation of blood culture bottles and identification plus antimicrobial susceptibility testing, respectively.

Results
A total of 142 participants were enrolled; 50 (35.2%) had positive blood cultures, with 56.0% Gram positive, 42.0% Gram-negative bacteria and 2.0% yeast isolated. Common species isolated included coagulase negative Staphylococcus spp. (CoNS) (22.0%), E. coli (16.0%), K. pneumoniae (14.0%), E. faecalis (14.0%) and S. aureus (8.0%). Gram-negative isolates exhibited high resistance to gentamicin (61.9%) and ceftriaxone (71.4%) which are the empiric antimicrobial agents used in our setting. Amikacin and meropenem showed 85.7 and 95.2% activity respectively against all Gram-negative isolates, whilst vancomycin and linezolid were effective against 96.2 and 100.0% of all Gram-positive isolates respectively. We isolated 10 (66.7%) extended spectrum β-lactamase (ESBL) amongst the E. coli and K. pneumoniae isolates. Ten (66.7%) of the Staphylococcus spp. were methicillin resistant.

Conclusions
CoNS, E. coli, K. pneumoniae, E. faecalis and S. aureus were the major microbial drivers of sepsis amongst cancer patients in Zimbabwe. Most isolates were found to be resistant to commonly used empirical antibiotics, with isolates exhibiting high levels of ESBL and methicillin resistance carriage. A nationwide survey on microbial aetiologies of sepsis and their susceptibility patterns would assist in the guidance of effective sepsis empiric antimicrobial treatment among patients with cancer.
Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene
Authors: Iqbal Nida S. , Jascur Thomas A. , Harrison Steven M. , Edwards Angelena B. , Smith Luke T. , Choi Erin S. , Arevalo Michelle K. , Chen Catherine , Zhang Shaohua , Kern Adam J. , Scheuerle Angela E. , Sanchez Emma J. , Xing Chao , Baker Linda A. 
Published: February 2020

Abstract
Background
Prune belly syndrome (PBS) is a rare, multi-system congenital myopathy primarily affecting males that is poorly described genetically. Phenotypically, its morbidity spans from mild to lethal, however, all isolated PBS cases manifest three cardinal pathological features: 1) wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, 2) urinary tract dilation with poorly contractile smooth muscle, and 3) intra-abdominal undescended testes. Despite evidence for a genetic basis, previously reported PBS autosomal candidate genes only account for one consanguineous family and single cases.

Methods
We performed whole exome sequencing (WES) of two maternal adult half-brothers with syndromic PBS (PBS + Otopalatodigital spectrum disorder [OPDSD]) and two unrelated sporadic individuals with isolated PBS and further functionally validated the identified mutations.

Results
We identified three unreported hemizygous missense point mutations in the X-chromosome gene Filamin A (FLNA) (c.4952 C > T (p.A1448V), c.6727C > T (p.C2160R), c.5966 G > A (p.G2236E)) in two related cases and two unrelated sporadic individuals. Two of the three PBS mutations map to the highly regulatory, stretch-sensing Ig19–21 region of FLNA and enhance binding to intracellular tails of the transmembrane receptor β-integrin 1 (ITGβ1).

Conclusions
FLNA is a regulatory actin-crosslinking protein that functions in smooth muscle cells as a mechanosensing molecular scaffold, transmitting force signals from the actin-myosin motor units and cytoskeleton via binding partners to the extracellular matrix. This is the first evidence for an X-linked cause of PBS in multiple unrelated individuals and expands the phenotypic spectrum associated with FLNA in males surviving even into adulthood.
Maternal and child-health outcomes in pregnancies following Assisted Reproductive Technology (ART): a prospective cohort study
Authors: da Silva Shana Ginar , da Silveira Mariângela Freitas , Bertoldi Andréa Dâmaso , Domingues Marlos Rodrigues , dos Santos Iná da Silva 
Published: February 2020

Abstract
Background
Studies comparing the outcome of spontaneous versus assisted reproductive technologies (ART) pregnancies report heterogeneous results. Despite the success of ART to overcome infertility, concern is growing regarding both its safety and its effect on maternal and child health. The objective of this study was to compare maternal and child-health outcomes after ART relative to natural conception.

Methods
A population-based birth cohort study was carried out among pregnant women expected to deliver in 2015 in Pelotas, southern Brazil. Maternal outcomes included pregnancy complications and gestational weight gain. Gestational age, weight, intrauterine growth restriction, length and head circumference, and 1-min and 5-min Apgar, as well as health problems at birth and breastfeeding were defined as offspring outcomes. Statistical analyses were performed using linear and logistic regression. G-formula was used to perform mediation analysis.

Results
The study included 4252 babies born by spontaneously pregnancies and 23 babies born after ART. Adjusted analyses showed that children conceived from ART presented lower means of gestational age (p = 0.001), birth weight (p = 0.002), length (p < 0.001), and head circumference at birth (p = 0.02). However, more than 90% of the effect of ART over these outcomes was mediated by multiple pregnancy.

Conclusion
Our findings suggest that the possible negative effect on the child-health outcomes is due mainly to the higher incidence of multiple pregnancies and not because of ART. The reasons for the increase in adverse pregnancy outcomes associated with ART singleton pregnancies are still uncertain and warrants further research. Further large-population studies are needed to confirm these results.
Maternal coffee intake and the risk of bleeding in early pregnancy: a cross-sectional analysis
Authors: Choi Hansol , Koo Seul , Park Hyun-Young 
Published: February 2020

Abstract
Background
Caffeine can easily cross the placenta, and maternal caffeine intake, thus, has an effect on fetal growth. However, it is still unclear whether coffee consumption is an independent risk factor for bleeding in early pregnancy. The objective of this study was to examine the association between pre-pregnancy coffee consumption patterns and the risk of bleeding in early pregnancy.

Methods
A cross-sectional analysis was conducted among 3510 pregnant women from the Korean Pregnancy Outcome Study who underwent baseline examination and for whom the results of the pregnancy were available. Coffee consumption patterns before pregnancy were examined using a questionnaire. The participants were classified according to the frequency of coffee consumption into seldom (< 1 cup/week), light (< 1 cup/day), moderate (1 cup/day), and heavy coffee drinker (≥2 cups/day) groups. Bleeding in early pregnancy was defined as the occurrence of vaginal bleeding in the first 20 weeks of pregnancy. Multiple logistic regression models were applied to examine the association between pre-pregnancy coffee consumption and the risk of bleeding in early pregnancy, after adjusting for age, body mass index (BMI), systolic blood pressure, cigarette smoking and alcohol consumption behavior, previous and current physical activity levels, stress levels, history of depression, antenatal depressive symptoms during the first trimester, type of emesis, parity, and the number of livebirths, stillbirths, miscarriages, and abortions.

Results
Women who were light, moderate, and heavy coffee drinkers before pregnancy had adjusted ORs of 1.086, 1.225, and 1.358, respectively, for bleeding in early pregnancy. In a fully adjusted model, heavy coffee drinkers showed a significantly higher risk of bleeding in early pregnancy, even in women aged 35 years and younger (OR 1.680) and in those with a normal body mass index (OR 1.389), who were at relatively low risk for pregnancy-related complications.

Conclusions
Our results showed that heavy coffee drinking was independently associated with a higher risk of bleeding in early pregnancy among pregnant Korean women, suggesting that caffeine intake before conception and during pregnancy should be reduced. Our study highlights the need for nutritional interventions for healthy coffee drinking among pregnant women in Korea.