bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATF5, a putative therapeutic target for the mitochondrial DNA 3243A > G mutation-related disease
Authors: Gao Xinpei , Jiang Zhixin , Yan Xinfeng , Liu Jiping , Li Fengwen , Liu Peng , Li Jialu , Wei Yuehua , Sun Yi Eve , Zhang Yinan , Wang Congrong 
Published: July 2021

AbstractThe mitochondrial DNA m.3243A > G mutation is well-known to cause a variety of clinical phenotypes, including diabetes, deafness, and osteoporosis. Here, we report isolation and expansion of urine-derived stem cells (USCs) from patients carrying the m.3243A > G mutation, which demonstrate bimodal heteroplasmy. USCs with high levels of m.3243A > G mutation displayed abnormal mitochondrial morphology and function, as well as elevated ATF5-dependent mitochondrial unfolded protein response (UPRmt), together with reduced Wnt/β-catenin signaling and osteogenic potentials. Knockdown of ATF5 in mutant USCs suppressed UPRmt, improved mitochondrial function, restored expression of GSK3B and WNT7B, and rescued osteogenic potentials. These results suggest that ATF5-dependent UPRmt could be a core disease mechanism underlying mitochondrial dysfunction and osteoporosis related to the m.3243A > G mutation, and therefore could be a novel putative therapeutic target for this genetic disorder.
A major quantitative trait locus affecting resistance to Tilapia lake virus in farmed Nile tilapia (Oreochromis niloticus)
Authors: Barría Agustin , Trịnh Trọng Quốc , Mahmuddin Mahirah , Peñaloza Carolina , Papadopoulou Athina , Gervais Ophelie , Chadag V. Mohan , Benzie John A. H. , Houston Ross D. 
Published: July 2021

AbstractEnhancing host resistance to infectious disease has received increasing attention in recent years as a major goal of farm animal breeding programs. Combining field data with genomic tools can provide opportunities to understand the genetic architecture of disease resistance, leading to new opportunities for disease control. In the current study, a genome-wide association study was performed to assess resistance to the Tilapia lake virus (TiLV), one of the biggest threats affecting Nile tilapia (Oreochromis niloticus); a key aquaculture species globally. A pond outbreak of TiLV in a pedigreed population of the GIFT strain was observed, with 950 fish classified as either survivor or mortality, and genotyped using a 65 K SNP array. A significant QTL of large effect was identified on chromosomeOni22. The average mortality rate of tilapia homozygous for the resistance allele at the most significant SNP (Pvalue = 4.51E−10) was 11%, compared to 43% for tilapia homozygous for the susceptibility allele. Several candidate genes related to host response to viral infection were identified within this QTL, includinglgals17,vps52, andtrim29. These results provide a rare example of a major QTL affecting a trait of major importance to a farmed animal. Genetic markers from the QTL region have potential in marker-assisted selection to improve host resistance, providing a genetic solution to an infectious disease where few other control or mitigation options currently exist.
Advancing diagnostic performance and clinical usability of neural networks via adversarial training and dual batch normalization
Authors: Han Tianyu , Nebelung Sven , Pedersoli Federico , Zimmermann Markus , Schulze-Hagen Maximilian , Ho Michael , Haarburger Christoph , Kiessling Fabian , Kuhl Christiane , Schulz Volkmar , Truhn Daniel 
Published: July 2021

AbstractUnmasking the decision making process of machine learning models is essential for implementing diagnostic support systems in clinical practice. Here, we demonstrate that adversarially trained models can significantly enhance the usability of pathology detection as compared to their standard counterparts. We let six experienced radiologists rate the interpretability of saliency maps in datasets of X-rays, computed tomography, and magnetic resonance imaging scans. Significant improvements are found for our adversarial models, which are further improved by the application of dual-batch normalization. Contrary to previous research on adversarially trained models, we find that accuracy of such models is equal to standard models, when sufficiently large datasets and dual batch norm training are used. To ensure transferability, we additionally validate our results on an external test set of 22,433 X-rays. These findings elucidate that different paths for adversarial and real images are needed during training to achieve state of the art results with superior clinical interpretability.
Boosting photoelectrochemical efficiency by near-infrared-active lattice-matched morphological heterojunctions
Authors: Liu Guo-Qiang , Yang Yuan , Li Yi , Zhuang Taotao , Li Xu-Feng , Wicks Joshua , Tian Jie , Gao Min-Rui , Peng Jin-Lan , Ju Huan-Xin , Wu Liang , Pan Yun-Xiang , Shi Lu-An , Zhu Haiming , Zhu Junfa , Yu Shu-Hong , Sargent Edward H. 
Published: July 2021

AbstractPhotoelectrochemical catalysis is an attractive way to provide direct hydrogen production from solar energy. However, solar conversion efficiencies are hindered by the fact that light harvesting has so far been of limited efficiency in the near-infrared region as compared to that in the visible and ultraviolet regions. Here we introduce near-infrared-active photoanodes that feature lattice-matched morphological hetero-nanostructures, a strategy that improves energy conversion efficiency by increasing light-harvesting spectral range and charge separation efficiency simultaneously. Specifically, we demonstrate a near-infrared-active morphological heterojunction comprised of BiSeTe ternary alloy nanotubes and ultrathin nanosheets. The heterojunction’s hierarchical nanostructure separates charges at the lattice-matched interface of the two morphological components, preventing further carrier recombination. As a result, the photoanodes achieve an incident photon-to-current conversion efficiency of 36% at 800 nm in an electrolyte solution containing hole scavengers without a co-catalyst.
An antisite defect mechanism for room temperature ferroelectricity in orthoferrites
Authors: Ning Shuai , Kumar Abinash , Klyukin Konstantin , Cho Eunsoo , Kim Jong Heon , Su Tingyu , Kim Hyun-Suk , LeBeau James M. , Yildiz Bilge , Ross Caroline A. 
Published: July 2021

AbstractSingle-phase multiferroic materials that allow the coexistence of ferroelectric and magnetic ordering above room temperature are highly desirable, motivating an ongoing search for mechanisms for unconventional ferroelectricity in magnetic oxides. Here, we report an antisite defect mechanism for room temperature ferroelectricity in epitaxial thin films of yttrium orthoferrite, YFeO3, a perovskite-structured canted antiferromagnet. A combination of piezoresponse force microscopy, atomically resolved elemental mapping with aberration corrected scanning transmission electron microscopy and density functional theory calculations reveals that the presence of YFe antisite defects facilitates a non-centrosymmetric distortion promoting ferroelectricity. This mechanism is predicted to work analogously for other rare earth orthoferrites, with a dependence of the polarization on the radius of the rare earth cation. Our work uncovers the distinctive role of antisite defects in providing a mechanism for ferroelectricity in a range of magnetic orthoferrites and further augments the functionality of this family of complex oxides for multiferroic applications.
Broadly cross-reactive human antibodies that inhibit genogroup I and II noroviruses
Authors: Alvarado Gabriela , Salmen Wilhelm , Ettayebi Khalil , Hu Liya , Sankaran Banumathi , Estes Mary K. , Venkataram Prasad B. V. , Crowe James E. 
Published: July 2021

AbstractThe rational development of norovirus vaccine candidates requires a deep understanding of the antigenic diversity and mechanisms of neutralization of the virus. Here, we isolate and characterize a panel of broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs and IgGs reactive with human norovirus (HuNoV) genogroup I or II (GI or GII). We note three binding patterns and identify monoclonal antibodies (mAbs) that neutralize at least one GI or GII HuNoV strain when using a histo-blood group antigen (HBGA) blocking assay. The HBGA blocking assay and a virus neutralization assay using human intestinal enteroids reveal that the GII-specific mAb NORO-320, mediates HBGA blocking and neutralization of multiple GII genotypes. The Fab form of NORO-320 neutralizes GII.4 infection more potently than the mAb, however, does not block HBGA binding. The crystal structure of NORO-320 Fab in complex with GII.4 P-domain shows that the antibody recognizes a highly conserved region in the P-domain distant from the HBGA binding site. Dynamic light scattering analysis of GII.4 virus-like particles with mAb NORO-320 shows severe aggregation, suggesting neutralization is by steric hindrance caused by multivalent cross-linking. Aggregation was not observed with the Fab form of NORO-320, suggesting that this clone also has additional inhibitory features.
Exposure–lag response of smoking prevalence on lung cancer incidence using a distributed lag non-linear model
Authors: Smith Daniel Robert , Behzadnia Alireza , Imawana Rabbiaatul Addawiyah , Solim Muzammil Nahaboo , Goodson Michaela Louise 
Published: July 2021

AbstractThe prevalence of smokers is a major driver of lung cancer incidence in a population, though the “exposure–lag” effects are ill-defined. Here we present a multi-country ecological modelling study using a 30-year smoking prevalence history to quantify the exposure–lag response. To model the temporal dependency between smoking prevalence and lung cancer incidence, we used a distributed lag non-linear model (DLNM), controlling for gender, age group, country, outcome year, and population at risk, and presented the effects as the incidence rate ratio (IRR) and cumulative incidence rate ratio (IRRcum). The exposure–response varied by lag period, whilst the lag–response varied according to the magnitude and direction of changes in smoking prevalence in the population. For the cumulative lag–response, increments above and below the reference level was associated with an increased and decreased IRRcum respectively, with the magnitude of the effect varying across the lag period. Though caution should be exercised in interpretation of the IRR and IRRcum estimates reported herein, we hope our work constitutes a preliminary step towards providing policy makers with meaningful indicators to inform national screening programme developments. To that end, we have implemented our statistical model a shiny app and provide an example of its use.
C-terminal domain small phosphatase 1 (CTDSP1) regulates growth factor expression and axonal regeneration in peripheral nerve tissue
Authors: Gervasi Noreen M. , Dimtchev Alexander , Clark Desraj M. , Dingle Marvin , Pisarchik Alexander V. , Nesti Leon J. 
Published: July 2021

AbstractPeripheral Nerve Injury (PNI) represents a major clinical and economic burden. Despite the ability of peripheral neurons to regenerate their axons after an injury, patients are often left with motor and/or sensory disability and may develop chronic pain. Successful regeneration and target organ reinnervation require comprehensive transcriptional changes in both injured neurons and support cells located at the site of injury. The expression of most of the genes required for axon growth and guidance and for synapsis formation is repressed by a single master transcriptional regulator, the Repressor Element 1 Silencing Transcription factor (REST). Sustained increase of REST levels after injury inhibits axon regeneration and leads to chronic pain. As targeting of transcription factors is challenging, we tested whether modulation of REST activity could be achieved through knockdown of carboxy-terminal domain small phosphatase 1 (CTDSP1), the enzyme that stabilizes REST by preventing its targeting to the proteasome. To test whether knockdown of CTDSP1 promotes neurotrophic factor expression in both support cells located at the site of injury and in peripheral neurons, we transfected mesenchymal progenitor cells (MPCs), a type of support cells that are present at high concentrations at the site of injury, and dorsal root ganglion (DRG) neurons with REST or CTDSP1 specific siRNA. We quantified neurotrophic factor expression by RT-qPCR and Western blot, and brain-derived neurotrophic factor (BDNF) release in the cell culture medium by ELISA, and we measured neurite outgrowth of DRG neurons in culture. Our results show that CTDSP1 knockdown promotes neurotrophic factor expression in both DRG neurons and the support cells MPCs, and promotes DRG neuron regeneration. Therapeutics targeting CTDSP1 activity may, therefore, represent a novel epigenetic strategy to promote peripheral nerve regeneration after PNI by promoting the regenerative program repressed by injury-induced increased levels of REST in both neurons and support cells.
Inference of malaria reproduction numbers in three elimination settings by combining temporal data and distance metrics
Authors: Routledge Isobel , Unwin H. Juliette T. , Bhatt Samir 
Published: July 2021

AbstractIndividual-level geographic information about malaria cases, such as the GPS coordinates of residence or health facility, is often collected as part of surveillance in near-elimination settings, but could be more effectively utilised to infer transmission dynamics, in conjunction with additional information such as symptom onset time and genetic distance. However, in the absence of data about the flow of parasites between populations, the spatial scale of malaria transmission is often not clear. As a result, it is important to understand the impact of varying assumptions about the spatial scale of transmission on key metrics of malaria transmission, such as reproduction numbers. We developed a method which allows the flexible integration of distance metrics (such as Euclidian distance, genetic distance or accessibility matrices) with temporal information into a single inference framework to infer malaria reproduction numbers. Twelve scenarios were defined, representing different assumptions about the likelihood of transmission occurring over different geographic distances and likelihood of missing infections (as well as high and low amounts of uncertainty in this estimate). These scenarios were applied to four individual level datasets from malaria eliminating contexts to estimate individual reproduction numbers and how they varied over space and time. Model comparison suggested that including spatial information improved models as measured by second order AIC (ΔAICc), compared to time only results. Across scenarios and across datasets, including spatial information tended to increase the seasonality of temporal patterns in reproduction numbers and reduced noise in the temporal distribution of reproduction numbers. The best performing parameterisations assumed long-range transmission (> 200 km) was possible. Our approach is flexible and provides the potential to incorporate other sources of information which can be converted into distance or adjacency matrices such as travel times or molecular markers.
Silica nanoparticles as pesticide against insects of different feeding types and their non-target attraction of predators
Authors: Thabet Ahmed F. , Boraei Hessien A. , Galal Ola A. , El-Samahy Magdy F. M. , Mousa Kareem M. , Zhang Yao Z. , Tuda Midori , Helmy Eman A. , Wen Jian , Nozaki Tsubasa 
Published: July 2021

AbstractThe agricultural use of silica (SiO2) nanoparticles (NPs) has the potential to control insect pests while the safety and tritrophic effects on plants and beneficial natural enemies remains unknown. Here, we evaluate the effects of silica NPs on insect pests with different feeding niches, natural enemies, and a plant. Silica NPs were applied at different concentrations (75–425 mg/L) on field-cultivated faba bean and soybean for two growing seasons. The faba bean pests, the cowpea aphidAphis craccivoraand the American serpentine leafminerLiriomyza trifolii, and the soybean pest, the cotton leafwormSpodoptera littoralis, were monitored along with their associated predators. Additional laboratory experiments were performed to test the effects of silica NPs on the growth of faba bean seedlings and to determine whether the rove beetlePaederus fuscipesis attracted to cotton leafworm-infested soybean treated with silica NPs. In the field experiments, silica NPs reduced the populations of all three insect pests and their associated predators, including rove beetles, as the concentration of silica NPs increased. In soybean fields, however, the total number of predators initially increased after applying the lowest concentration. An olfactometer-based choice test found that rove beetles were more likely to move towards an herbivore-infested plant treated with silica NPs than to a water-treated control, suggesting that silica NPs enhance the attraction of natural enemies via herbivore-induced plant volatiles. In the laboratory, while silica NPs inhibited the development of faba bean roots at 400 mg/L, they did not affect germination percentage, germination time, shoot length, or vigor index compared to the control.
Substrate reduction therapy for Krabbe disease and metachromatic leukodystrophy using a novel ceramide galactosyltransferase inhibitor
Authors: Babcock Michael C. , Mikulka Christina R. , Wang Bing , Chandriani Sanjay , Chandra Sundeep , Xu Yue , Webster Katherine , Feng Ying , Nelvagal Hemanth R. , Giaramita Alex , Yip Bryan K. , Lo Melanie , Jiang Xuntian , Chao Qi , Woloszynek Josh C. , Shen Yuqiao , Bhagwat Shripad , Sands Mark S. , Crawford Brett E. 
Published: July 2021

AbstractKrabbe disease (KD) and metachromatic leukodystrophy (MLD) are caused by accumulation of the glycolipids galactosylceramide (GalCer) and sulfatide and their toxic metabolites psychosine and lysosulfatide, respectively. We discovered a potent and selective small molecule inhibitor (S202) of ceramide galactosyltransferase (CGT), the key enzyme for GalCer biosynthesis, and characterized its use as substrate reduction therapy (SRT). Treating a KD mouse model with S202 dose-dependently reduced GalCer and psychosine in the central (CNS) and peripheral (PNS) nervous systems and significantly increased lifespan. Similarly, treating an MLD mouse model decreased sulfatides and lysosulfatide levels. Interestingly, lower doses of S202 partially inhibited CGT and selectively reduced synthesis of non-hydroxylated forms of GalCer and sulfatide, which appear to be the primary source of psychosine and lysosulfatide. Higher doses of S202 more completely inhibited CGT and reduced the levels of both non-hydroxylated and hydroxylated forms of GalCer and sulfatide. Despite the significant benefits observed in murine models of KD and MLD, chronic CGT inhibition negatively impacted both the CNS and PNS of wild-type mice. Therefore, further studies are necessary to elucidate the full therapeutic potential of CGT inhibition.
Aerosol microphysics and chemistry reveal the COVID19 lockdown impact on urban air quality
Authors: Eleftheriadis Konstantinos , Gini Maria I. , Diapouli Evangelia , Vratolis Stergios , Vasilatou Vasiliki , Fetfatzis Prodromos , Manousakas Manousos I. 
Published: July 2021

AbstractAir quality in urban areas and megacities is dependent on emissions, physicochemical process and atmospheric conditions in a complex manner. The impact on air quality metrics of the COVID-19 lockdown measures was evaluated during two periods in Athens, Greece. The first period involved stoppage of educational and recreational activities and the second severe restrictions to all but necessary transport and workplace activities. Fresh traffic emissions and their aerosol products in terms of ultrafine nuclei particles and nitrates showed the most significant reduction especially during the 2nd period (40–50%). Carbonaceous aerosol both from fossil fuel emissions and biomass burning, as well as aging ultrafine and accumulation mode particles showed an increase of 10–20% of average before showing a decline (5 to 30%). It is found that removal of small nuclei and Aitken modes increased growth rates and migration of condensable species to larger particles maintaining aerosol volume.
Impact of train/test sample regimen on performance estimate stability of machine learning in cardiovascular imaging
Authors: Singh Vikash , Pencina Michael , Einstein Andrew J. , Liang Joanna X. , Berman Daniel S. , Slomka Piotr 
Published: July 2021

AbstractAs machine learning research in the field of cardiovascular imaging continues to grow, obtaining reliable model performance estimates is critical to develop reliable baselines and compare different algorithms. While the machine learning community has generally accepted methods such as k-fold stratified cross-validation (CV) to be more rigorous than single split validation, the standard research practice in medical fields is the use of single split validation techniques. This is especially concerning given the relatively small sample sizes of datasets used for cardiovascular imaging. We aim to examine how train-test split variation impacts the stability of machine learning (ML) model performance estimates in several validation techniques on two real-world cardiovascular imaging datasets: stratified split-sample validation (70/30 and 50/50 train-test splits), tenfold stratified CV, 10 × repeated tenfold stratified CV, bootstrapping (500 × repeated), and leave one out (LOO) validation. We demonstrate that split validation methods lead to the highest range in AUC and statistically significant differences in ROC curves, unlike the other aforementioned approaches. When building predictive models on relatively small data sets as is often the case in medical imaging, split-sample validation techniques can produce instability in performance estimates with variations in range over 0.15 in the AUC values, and thus any of the alternate validation methods are recommended.
Fishers' perception of the interaction between the South American sea lions and the Chinook salmon fishery in southern Chile
Authors: Sanguinetti M. , Cid-Aguayo B. , Guerrero A. , Durán M. , Gomez-Uchida D. , Sepúlveda M. 
Published: July 2021

AbstractWe studied how the South American sea lion (SASL, Otaria flavescens) interacts with the operation of an artisanal fishery of Chinook salmon, a non-native species in Chile, using a combination of biological and social approaches, including a valuation by fishers about this interaction. During austral summer of 2019, an observer onboard artisanal fishing boats characterized the attack behavior of SASLs to gillnet-captured Chinook salmon during 33 hauls and analyzed which factors may affect the intensity of attacks. To analyze the relationship between fishers and SASLs, a Likert scale about the perception and views about nature was applied. A total of 23 interviews—including 35 open and 16 closed questions—with fishers were conducted to describe how they perceived the interactions with SASLs. Interactions with SASLs were recorded in 35% of the fishing events and varied depending on both operational factors, such as the number of boats, as well as environmental factors, such as moon’s luminosity. Even though SASL interactions resulted in seven fish (~ 70 kg) damaged of a total catch of 2815 kg (2.5%) during the survey, boats with a damaged catch by SASL lost up to 11% of their revenue. This is consistent with 87% of the interviewed fishers who considered that the conflict with the SASL negatively impacts their activity and results in economic losses. A negative perception towards SASLs likely results from personal experience and revenue loss, even though impacts of SASL interactions at the scale of the entire fishery may be less important. While older fishers with less formal education have a productivist and instrumental focus, younger fishers with a more sustainable and conservationist view of fishing offer an opportunity to lead an improved local understanding of the relationship between salmon, SASLs, and humans.