bluuebunny/crossref_metadata_2025 huggingface dataset:
CSVS, a crowdsourcing database of the Spanish population genetic variability
Authors: Peña-Chilet María , Roldán Gema , Perez-Florido Javier , Ortuño Francisco M , Carmona Rosario , Aquino Virginia , Lopez-Lopez Daniel , Loucera Carlos , Fernandez-Rueda Jose L , Gallego Asunción , García-Garcia Francisco , González-Neira Anna , Pita Guillermo , Núñez-Torres Rocío , Santoyo-López Javier , Ayuso Carmen , Minguez Pablo , Avila-Fernandez Almudena , Corton Marta , Moreno-Pelayo Miguel Ángel , Morin Matías , Gallego-Martinez Alvaro , Lopez-Escamez Jose A , Borrego Salud , Antiñolo Guillermo , Amigo Jorge , Salgado-Garrido Josefa , Pasalodos-Sanchez Sara , Morte Beatriz ,   The Spanish Exome Crowdsourcing Consortium, Al-Shahrour Fátima , Artuch Rafael , Benitez Javier , Castaño Luis Antonio , Castillo Ignacio del , Delmiro Aitor , Espinos Carmina , González Roser , Grinberg Daniel , Guillén Encarnación , Lapunzina Pablo , Lopez Esther , Martí Ramón , Milá Montserrat , Millán José Mª , Nunes Virginia , Palau Francesc , Perez Belen , Jurado Luis Pérez , Perona Rosario , Pujol Aurora , Ramos Feliciano , Ribes Antonia , Rosell Jordi , Rovira Eulalia , Surrallés Jordi , Tejada Isabel , Ugarte Magdalena , Carracedo Ángel , Alonso Ángel , Dopazo Joaquín
Published: September 2020

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variability worldwide. CSVS is also part of the GA4GH Beacon network.

CSVS can be accessed at: http://csvs.babelomics.org/.
Current situation and perspectives of ready-to-eat food/meal suppliers
Authors: Sakata Takashi ,   for Working Group 2 of the Healthy Diet Research Committee of International Life Sciences Institute, Japan
Published: September 2020

Working Group 2 of the Healthy Diet Research Committee of International Life Sciences Institute Japan (WG2) assessed the concept and practice of healthy eating in the ready-to-eat food/meal industry in Japan. WG2 interviewed 14 arbitrarily selected member companies that included “health” or “nutrition” in their management policy, and sent a questionnaire to 338 member companies of the Japan Ready-Made Meal Association. Ready-to-eat food/meal suppliers mainly referred to Dietary Reference Intakes for Japanese, the Japanese Food Guide, and/or Healthy Japan 21 for their menu construction. They increased dietary fiber, variety, vegetables, whole-grain cereals, millet rice, and soy bean products; and reduced energy, carbohydrates, and salt in “healthy” food. They tended to avoid making direct appeals to health. Many companies reduced the salt content without drawing attention to the practice. They continually strive to improve flavor as the single most important factor for selling healthy food. The cycling of menus is used to increase diversity in food consumption. These industries require both academia and the government to define priorities for increasing and decreasing particular nutrients as the main targets and to establish the maximum time for balancing each nutrient.
What is the scientific definition of the Japanese diet from the viewpoint of nutrition and health?
Authors: Sasaki Satoshi ,   for Working Group 1 of the Healthy Diet Research Committee of International Life Sciences Institute, Japan
Published: September 2020

The Japanese people have enjoyed longevity for several decades, and Japanese dietary habits are considered to contribute to this longevity. The scientific definition of the Japanese diet, however, is not yet fully established. The Working Group 1 of the Healthy Diet Research Committee of the International Life Sciences Institute Japan reviewed the literature to collect definitions of the Japanese diet appearing in articles in the fields of diet, nutrition, foods, and human health. This report addresses the definitions and the questions raised by these definitions. Among 283 relevant articles identified, 116 were carefully screened and included in the analysis. In most of the articles, the authors self-defined the Japanese diet; some studies used a government-proposed definition. This review revealed no systematic approach to define the Japanese diet from the viewpoints of nutrition and health. Before conducting studies to determine whether the Japanese diet is healthy, it is important to address the question of what the Japanese diet is from the viewpoint of human nutrition rather than culinary culture.
Personalized nutrition and healthy aging
Authors: Ordovas Jose M , Berciano Silvia
Published: September 2020

The human lifespan and quality of life depend on complex interactions among genetic, environmental, and lifestyle factors. Aging research has been remarkably advanced by the development of high-throughput “omics” technologies. Differences between chronological and biological ages, and identification of factors (eg, nutrition) that modulate the rate of aging can now be assessed at the individual level on the basis of telomere length, the epigenome, and the metabolome. Nevertheless, the understanding of the different responses of people to dietary factors, which is the focus of precision nutrition research, remains incomplete. The lack of reliable dietary assessment methods constitutes a significant challenge in nutrition research, especially in elderly populations. For practical and successful personalized diet advice, big data techniques are needed to analyze and integrate the relevant omics (ie, genomic, epigenomic, metabolomics) with an objective and longitudinal capture of individual nutritional and environmental information. Application of such techniques will provide the scientific evidence and knowledge needed to offer actionable, personalized health recommendations to transform the promise of personalized nutrition into reality.
Grapevine U-Box E3 Ubiquitin Ligase VlPUB38 Negatively Regulates Fruit Ripening by Facilitating Abscisic-Aldehyde Oxidase Degradation
Authors: Yu Yihe , Meng Xiangxuan , Guo Dalong , Yang Shengdi , Zhang Guohai , Liang Zhenchang
Published: September 2020

The plant U-box E3 ubiquitin ligase-mediated ubiquitin/26S proteasome degradation system plays a key role in plant growth and development. Previously identified as a member of the grape PUB gene family, PUB38 was shown to participate in the berry-ripening progress. Here, we demonstrate that the E3 ligase VlPUB38 mediates abscisic acid (ABA) synthesis via 26S proteasome degradation and its involvement in regulating fruit-ripening processes. Strawberry-overexpressing VlPUB38 lines displayed obvious inhibition of mature phenotype, and this was rescued by exogenous ABA treatment and MG132. Post-ABA treatment, expression levels of ABA response-related genes in VlPUB38-overexpressed Arabidopsis significantly exceeded controls. Strawberry and Arabidopsis ectopic expression assays suggest that VlPUB38 negatively regulates fruit ripening in an ABA-dependent manner. Moreover, VlPUB38 has ubiquitin ligase activity, which depends on the U-box-conserved domain. VlPUB38 interacts with abscisic-aldehyde oxidase (VlAAO), targeting VlAAO proteolysis via the 26S proteasome system. These results indicate that VlPUB38 negatively regulates grape fruit ripening by mediating the degradation of key factor VlAAO in the ABA synthesis pathway.
The Role of Identity Prioritization
Authors: Hickel Flavio R , Alamillo Rudy , Oskooii Kassra A R , Collingwood Loren
Published: September 2020

Social Identity Theory suggests that individuals are motivated to support/oppose policies and politicians that benefit/harm members of their ingroup as a means of protecting their social status. Since the Republican Party’s rhetoric against immigrants in recent decades has often been viewed as an assault upon those of Latinx descent, it is not surprising that strong majorities oppose restrictionist immigration policies and support the Democratic Party. However, the existing literature has overlooked why a sizeable minority of Latinx voters express support for restrictionist immigration policies and the politicians who espouse them. Our analysis of Latinx voters with the 2012 and 2016 American National Election Studies (ANES) demonstrates that the degree to which individuals prioritize their US American identity over their Latinx identity has a significant influence over support for conservative immigration policies and GOP candidates. This relationship emerges above and beyond partisanship, ideology, and other key explanatory factors. Such attitudes likely represent an individual social mobility strategy in which members of a social group attempt to “pass” as a member of a higher-status group. Prioritizing a US American identity, supporting the Republican Party, and expressing hostility toward the interests of undocumented immigrants are a means of distinguishing themselves from a social group that has become increasingly associated with negative stereotypes. In contrast, those who are unwilling or unable to make this transition are likely pursuing a collective social mobility strategy (e.g., linked fate) whereby they attempt to enhance their individual status by elevating that of the entire social group.
Exposure totert-Butylphenyl Diphenyl Phosphate, an Organophosphate Ester Flame Retardant and Plasticizer, Alters Hedgehog Signaling in Murine Limb Bud Cultures
Authors: Yan Han , Hales Barbara F
Published: September 2020

Organophosphate esters have become widely used as flame retardants since the phase out of polybrominated diphenyl ethers. Previously, we demonstrated that some organophosphate esters, such as tert-butylphenyl diphenyl phosphate (BPDP), were more detrimental to endochondral ossification in murine limb bud cultures than one of the major polybrominated diphenyl ethers that they replaced, 2,2′,4,4′-tetrabromodiphenyl ether. Here, we used a transcriptomic approach to elucidate the mechanism of action of BPDP in the developing limb. Limb buds collected from gestation day 13 CD1 mouse embryos were cultured for 3 or 24 h in the presence of vehicle, 1 μM, or 10 μM BPDP. RNA sequencing analyses revealed that exposure to 1 µM BPDP for 24 h increased the expression of 5 transcripts, including Ihh, and decreased 14 others, including Gli1, Ptch1, Ptch2, and other targets of Hedgehog (Hh) signaling. Pathway analysis predicted the inhibition of Hh signaling. Attenuation of Hh signaling activity began earlier and reached a greater magnitude after exposure to 10 µM BPDP. Because this pathway is part of the regulatory network governing endochondral ossification, we used a known Hh agonist, purmorphamine, to determine the contribution of Hh signaling inhibition to the negative impact of BPDP on endochondral ossification. Cotreatment of limbs with purmorphamine rescued the detrimental morphological changes in the cartilage template induced by BPDP exposure though it did not restore the expression of key transcription factors, Runx2 and Sp7, to control levels. These data highlight Hh signaling as a developmentally important pathway vulnerable to environmental chemical exposures.
Development of a Diagnostic Assay for Race Differentiation of Podosphaera macularis
Authors: Block Mary , Knaus Brian J. , Wiseman Michele S. , Grünwald Niklaus J. , Gent David H.
Published: September 2020

Hop powdery mildew (caused by Podosphaera macularis) was confirmed in the Pacific Northwest in 1996. Before 2012, the most common race of P. macularis was able to infect plants that possessed powdery mildew resistance based on the R-genes Rb, R3, and R5. After 2012, two additional races of P. macularis were discovered that can overcome the resistance gene R6 and the partial resistance found in the cultivar Cascade. These three races now occur throughout the region, which can complicate management and research efforts because of uncertainty on which race(s) may be present in the region and able to infect susceptible hop genotypes. Current methods for determining the races of P. macularis are labor intensive, costly, and typically require more than 14 days to obtain results. We sought to develop a molecular assay to differentiate races of the fungus possessing virulence on plants with R6, referred to as V6-virulent, from other races. The transcriptomes of 46 isolates of P. macularis were sequenced to identify loci and variants unique to V6 isolates. Fourteen primer pairs were designed for 10 candidate loci that contained single nucleotide polymorphisms (SNP) and short insertion-deletion polymorphisms. Two differentially labeled locked nucleic acid probes were designed for a contig that contained a conserved SNP associated with V6-virulence. The resulting duplexed real-time PCR assay was validated against 46 V6 and 54 non-V6 P. macularis isolates collected from the United States and Europe. The assay had perfect discrimination of V6-virulence among isolates of P. macularis originating from the western U.S. but failed to predict V6-virulence in three isolates collected from Europe. The specificity of the assay was tested with different species of powdery mildew fungi and other microorganisms associated with hop. Weak nonspecific amplification occurred with powdery mildew fungi collected from Vitis vinifera, Fragaria sp., and Zinnia sp.; however, nonspecification amplification is not a concern when differentiating pathogen race from colonies on hop. The assay has practical applications in hop breeding, epidemiological studies, and other settings where rapid confirmation of pathogen race is needed.
Perspectives on Global Mycotoxin Issues and Management From the MycoKey Maize Working Group
Authors: Logrieco Antonio , Battilani Paola , Leggieri Marco Camardo , Jiang Yu , Haesaert Geert , Lanubile Alessandra , Mahuku George , Mesterházy Akos , Ortega-Beltran Alejandro , Pasti Marco , Smeu Irina , Torres Adriana , Xu Jing , Munkvold Gary
Published: September 2020

During the last decade, there have been many advances in research and technology that have greatly contributed to expanded capabilities and knowledge in detection and measurement, characterization, biosynthesis, and management of mycotoxins in maize. MycoKey, an EU‐funded Horizon 2020 project, was established to advance knowledge and technology transfer around the globe to address mycotoxin impacts in key food and feed chains. MycoKey included several working groups comprising international experts in different fields of mycotoxicology. The MycoKey Maize Working Group recently convened to gather information and strategize for the development and implementation of solutions to the maize mycotoxin problem in light of current and emerging technologies. This feature summarizes the Maize WG discussion and recommendations for addressing mycotoxin problems in maize. Discussions focused on aflatoxins, deoxynivalenol, fumonisins, and zearalenone, which are the most widespread and persistently important mycotoxins in maize. Although regional differences were recognized, there was consensus about many of the priorities for research and effective management strategies. For preharvest management, genetic resistance and selecting adapted maize genotypes, along with insect management, were among the most fruitful strategies identified across the mycotoxin groups. For postharvest management, the most important practices included timely harvest, rapid grain drying, grain cleaning, and carefully managed storage conditions. Remediation practices such as optical sorting, density separation, milling, and chemical detoxification were also suggested. Future research and communication priorities included advanced breeding technologies, development of risk assessment tools, and the development and dissemination of regionally relevant management guidelines.
Influence of Single and Combined Mixtures of Metal Oxide Nanoparticles on Eggplant Growth, Yield, and Verticillium Wilt Severity
Authors: Elmer Wade H. , de la Torre-Roche Roberto , Zuverza-Mena Nubia , Adisa Ishaq H. , Dimkpa Christian , Gardea-Torresdey Jorge , White Jason C.
Published: September 2020

Verticillium wilt, caused by Verticillium dahliae, is one of the major diseases of eggplants. Nanoparticles (NPs) of CuO, Mn2O3, and ZnO were sprayed alone onto leaves of young eggplants and in different combinations and rates, and then seedlings were transplanted into soil infested with V. dahliae in the greenhouse and field between 2015 and 2018. All combinations of NPs were consistently less effective than CuO NPs applied alone at 500 µg/ml at increasing disease suppression, biomass, and fruit yield. CuO NPs were associated with an increase in fruit yield (17 and 33% increase) and disease suppression (28 and 22% reduction) in 2016 and 2017, respectively, when compared with untreated controls. However, this effect was negated in the greenhouse and field experiments when CuO NPs were combined with Mn2O3. Combining NPs of CuO with ZnO resulted in variable effects; amendments increased growth and suppressed disease in greenhouse experiments, but results were mixed in the field. Leaf tissue analyses from the greenhouse experiments showed that Cu concentration in leaves was reduced when CuO NPs were combined with other NPs, even when application rates were the same amount. A simple competition for entry sites may explain why combinations of CuO NPs and Mn2O3 NPs reduced efficacy but does not explain the lack of inhibition between Cu and Zn. NPs of CuO performed better than their larger bulk equivalent, and studies on application rate found 500 µg/ml was optimal. No phytotoxicity, as determined, by leaf burning, necrotic spots, or dead apical buds was noted even at the highest combined rates of 1,500 µg/ml.
Discrete-Event Simulation Modeling of Critical Care Flow: New Hospital, Old Challenges
Authors: Williams Elizabeth , Szakmany Tamas , Spernaes Izabela , Muthuswamy Babu , Holborn Penny
Published: September 2020

Objectives:

As the demand for critical care beds rises each year, hospitals must be able to adapt. Delayed transfer of care reduces available critical care capacity and increases occupancy. The use of mathematic modeling within healthcare systems has the ability to aid planning of resources. Discrete-event simulation models can determine the optimal number of critical care beds required and simulate different what-if scenarios.

Design:

Complex discrete-event simulation model was developed using a warm-up period of 30 days and ran for 30 trials against a 2-year period with the mean calculated for the runs. A variety of different scenarios were investigated to determine the effects of increasing capacity, increasing demand, and reduction of proportion and length of delayed transfer of care out of the ICU.

Setting:

Combined data from two ICUs in United Kingdom.

Patients:

The model was developed using 1,728 patient records and was validated against an independent dataset of 2,650 patients.

Interventions:

None.

Measurements and Main Results:

During model validation, the average bed utilization and admittance rate were equal to the real-world data. In the what-if scenarios, we found that increasing bed numbers from 23 to 28 keeping the arrival rate stable reduces the average occupancy rate to 70%. We found that the projected 4% yearly increase in admissions could overwhelm even the 28-bedded unit, without change in the delayed transfer of care episodes. Reduction in the proportion of patients experiencing delayed transfer of care had the biggest effect on occupancy rates, time spent at full capacity, and average bed utilization.

Conclusions:

Using discrete-event simulation of commonly available baseline patient flow and patient care data produces reproducible models. Reducing the proportion of patients with delayed transfer of care had a greater effect in reducing occupancy levels than simply increasing bed numbers even when demand is increased.
COVID-19 in pregnancy
Authors: Martini Anne E.
Published: September 2020

Evidence continues to emerge on the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) in pregnancy. Compared with previous coronavirus outbreaks (severe acute respiratory syndrome and Middle East respiratory syndrome), recent reports suggest that pregnant women who contract SARS-CoV-2 have lower rates of maternal and fetal complications; however, the incidence of preterm birth remains elevated. The potential for vertical transmission is still under investigation. Universal testing of women admitted to labor and delivery is being encouraged in most centers.
Nurse-driven Clinical Pathway Based on an Innovative Asthma Score Reduces Admission Time for Children
Authors: Sjoerdsma Machtelt H. , Bongaerts Thom H.G. , van Lente Lidy , Kamps Arvid W.A.
Published: September 2020

Objective:

We recently demonstrated that an innovative asthma score independent of auscultation could accurately predict the requirement for bronchodilator nebulization compared to the physician’s routine clinical judgment to administer bronchodilators. We aimed to standardize inpatient care for children with acute asthma by implementing a clinical pathway based on this innovative asthma score.

Methods:

We designed a nurse-driven clinical pathway. This pathway included standardized respiratory assessments and a protocol for the nursing staff to administer bronchodilators without a specific order from the physician. We compared the length of stay and the number of readmissions to a historical cohort.

Results:

Seventy-nine patients with moderate acute asthma completed the pathway. We obtained a total of 858 Childhood asthma scores in these patients, with a median of 11 scores per patient (interquartile range 8–17). Patients treated according to the nurse-driven protocol were 3.3 times more likely to be discharged earlier (hazard ratio, 3.29; 95% confidence interval, 2.33–4.66; P < 0.05), and length of stay was significantly reduced (median 28 versus 53 h) compared to the historical standard practice. On request, the attending physician assessed the patient’s respiratory status 42 times (4.9% of all childhood asthma score assessments). Patient safety was not compromised, and none of the patients were removed from the pathway. In each group, we readmitted two (2.5%) patients within 1 week after discharge.

Conclusion:

This nurse-driven clinical pathway for children with acute asthma based on an asthma score independent of auscultation findings significantly decreased length of stay without compromising patient safety.
Iterative Ring Artifact Removal Method for Helical Computed Tomography Scans
Authors: Balogh Zsolt Adam , Huszar Tamas , Kis Benedek Janos
Published: September 2020

Objective

In this article, a statistical-based iterative ring removal (IRR) algorithm that effectively removes ring artifacts generated by defective detector cells is proposed.

Methods

The physical state of computed tomography (CT) detector elements can change dynamically owing to their temperature dependence and the varying irradiation caused by focal spot movements. This variation in the properties of cells may cause false pixel values in sinograms, resulting in rings or segments of rings in reconstructed images. In this article, the proposed algorithm is studied on clinical CT. Two patients were scanned using a clinical CT scanner (AnyScan SPECT/CT, Mediso). Artificial rings and band rings were generated on the real sinogram data to examine the algorithm in different cases. The method was performed also on real ring artifacts.

Results

The IRR can correct both single and band-like ring artifacts with one or more defective pixels. The proposed algorithm can detect the period when pixels contain false signals and only those periods are corrected. The IRR reduces ring artifacts, even in cases where low-contrast rings occur in the reconstructed image.

Conclusions

This statistical correction method efficiently detects and corrects false pixel values in the projection data without causing new artifacts in the reconstructed image. The algorithm is less sensitive to its parameters.
Timing of invasive mechanic ventilation in critically ill patients with coronavirus disease 2019
Authors: Zhang Qian , Shen Jun , Chen Liangkai , Li Sumeng , Zhang Wenkai , Jiang Cheng , Ma Haoli , Lin Lian , Zheng Xin , Zhao Yan
Published: September 2020

Background

Invasive mechanical ventilation (IMV) is a lifesaving strategy for critically ill patients with coronavirus disease 2019 (COVID-19). We aim to report the case series of critical patients receiving IMV in Wuhan and to discuss the timing of IMV in these patients.

Methods

Data of 657 patients admitted to emergency intensive care unit of Zhongnan Hospital and isolated isolation wards of Wuhan Union Hospital from January 1 to March 10, 2020, were retrospectively reviewed. All medical records of 40 COVID-19 patients who required IMV were collected at different time points, including baseline (at admission), before receiving IMV, and before death or hospital discharge.

Results

Among 40 COVID-19 patients with IMV, 31 died, and 9 survived and was discharged. The median age was 70 years (interquartile range [IQR], 62–76 years), and nonsurvivors were older than survivors. The median period from the noninvasive mechanic ventilation (NIV) or high-flow nasal cannula oxygen therapy (HFNC) to intubation was 7 hours (IQR, 2–42 hours) in IMV survivors and 54 hours (IQR, 28–143 hours) in IMV nonsurvivors. We observed that, when the time interval from NIV/HFNC to intubation was less than 50 hours (about 2 calendar days), together with Acute Physiology and Chronic Health Evaluation II (APACHE II) score of less than 10 or pneumonia severity index (PSI) score of less than 100, mortality can be reduced to 60% or less. Prolonged interval from NIV/HFNC to intubation and high levels of APACHE II and PSI before intubation were associated with higher mortality in critically ill patients. Multiple organ damage was common among these nonsurvivors in the course of treatment.

Conclusion

Early initial intubation after NIV/HFNC might have a beneficial effect in reducing mortality for critically ill patients meeting IMV indication. Considering APACHE II and PSI scores might help physicians in decision making about timing of intubation for curbing subsequent mortality.

Level of evidence

Therapeutic, level V.
Strain ATCC 4720T is the authentic type strain of Agrobacterium tumefaciens, which is not a later heterotypic synonym of Agrobacterium radiobacter
Authors: Velázquez Encarna , Flores-Félix José David , Sánchez-Juanes Fernando , Igual José M. , Peix Álvaro
Published: September 2020

The original type strains of

Agrobacterium radiobacter

and

Agrobacterium tumefaciens

recorded in the eighth edition of Bergey’s Manual of Determinative Bacteriology published in 1974 were NCIB 9042T and ATCC 4720T, respectively. However, in the list of the valid names of bacteria compiled in 1980, both strains were changed,

A. radiobacter

NCIB 9042T to ATCC 19358T and

A. tumefaciens

ATCC 4720T to ATCC 23308T. These changes were unjustified, particularly in the case of

A. tumefaciens

whose type strain was replaced by another strain from the same collection, although the original type strain ATCC 4720T was never lost and it is currently available in several culture collections. Therefore, we request that the type strain of

A. tumefaciens

be corrected from ATCC 23308T to ATCC 4720T.
Effect of combination antiretroviral therapy on human immunodeficiency virus 1 specific antibody responses in subtype-C infected children
Authors: Kumar Sanjeev , Batra Himanshu , Singh Swarandeep , Chawla Himanshi , Singh Ravinder , Katpara Sanket , Hussain Abdul Wahid , Das Bimal Kumar , Lodha Rakesh , Kabra Sushil Kumar , Luthra Kalpana
Published: September 2020

Protective antibody responses to human immunodeficiency virus (HIV)-1 infection evolve only in a fraction of infected individuals by developing broadly neutralizing antibodies (bnAbs) and/or effector functions such as antibody-dependent cellular cytotoxicity (ADCC). HIV-1 chronically infected adults and children on combination antiretroviral therapy (cART) showed a reduction in ADCC activity and improvement in HIV-1 specific neutralizing antibody (nAb) responses. Early initiation of cART in infected adults is found to be beneficial in reducing the viral load and delaying disease progression. Herein, we longitudinally evaluated the effect of cART on HIV-1 specific plasma ADCC and nAb responses in a cohort of 20 perinatally HIV-1 subtype-C infected infants and children ≤2 years of age, pre-cART and up to 1 year post-cART initiation. Significant reductions in HIV-1 specific plasma ADCC responses to subtype-C and subtype-B viruses and improvement in HIV-1 neutralization were observed in HIV-1 infected children 1 year post-cART initiation. A positive correlation between reduction in viral load and the loss of ADCC response was observed. This study provides information aiding the understanding of the effects of early initiation of cART on antibody effector functions and viral neutralization in HIV-1 infected children, which needs to be further evaluated in large cohorts of HIV-1 infected children on cART to plan future intervention strategies.
Distinct genetic bases for plant root responses to lipo-chitooligosaccharide signal molecules from distinct microbial origins
Authors: Bonhomme Maxime , Bensmihen Sandra , André Olivier , Amblard Emilie , Garcia Magali , Maillet Fabienne , Puech-Pagès Virginie , Gough Clare , Fort Sébastien , Cottaz Sylvain , Bécard Guillaume , Jacquet Christophe
Published: September 2020

Lipo-chitooligosaccharides (LCOs) were originally found as symbiotic signals called Nod Factors (Nod-LCOs) controlling nodulation of legumes by rhizobia. More recently LCOs were also found in symbiotic fungi and, more surprisingly, very widely in the kingdom fungi including in saprophytic and pathogenic fungi. The LCO-V(C18:1, Fuc/MeFuc), hereafter called Fung-LCOs, are the LCO structures most commonly found in fungi. This raises the question of how legume plants, such asMedicago truncatula, can perceive and discriminate between Nod-LCOs and these Fung-LCOs.

To address this question, we performed a Genome Wide Association Study on 173 natural accessions ofMedicago truncatula, using a root branching phenotype and a newly developed local score approach.

Both Nod- and Fung-LCOs stimulated root branching in most accessions but there was very little correlation in the ability to respond to these types of LCO molecules. Moreover, heritability of root response was higher for Nod-LCOs than for Fung-LCOs. We identified 123 loci for Nod-LCO and 71 for Fung-LCO responses, but only one was common.

This suggests that Nod- and Fung-LCOs both control root branching but use different molecular mechanisms. The tighter genetic constraint of the root response to Fung-LCOs possibly reflects the ancestral origin of the biological activity of these molecules.
Using very high-resolution satellite imagery and deep learning to detect and count African elephants in heterogeneous landscapes
Authors: Duporge Isla , Isupova Olga , Reece Steven , Macdonald David W. , Wang Tiejun
Published: September 2020

Satellites allow large-scale surveys to be conducted in short time periods with repeat surveys possible <24hrs. Very high-resolution satellite imagery has been successfully used to detect and count a number of wildlife species in open, homogeneous landscapes and seascapes where target animals have a strong contrast with their environment. However, no research to date has detected animals in complex heterogeneous environments or detected elephants from space using very high-resolution satellite imagery and deep learning.

In this study we apply a Convolution Neural Network (CNN) model to automatically detect and count African elephants in a woodland savanna ecosystem in South Africa. We use WorldView-3 and 4 satellite data – the highest resolution satellite imagery commercially available. We train and test the model on eleven images from 2014-2019. We compare the performance accuracy of the CNN against human accuracy. Additionally, we apply the model on a coarser resolution satellite image (GeoEye-1) captured in Kenya to test if the algorithm can generalise to an elephant population outside of the training area.

Our results show the CNN performs with high accuracy, comparable to human detection capabilities. The detection accuracy (i.e., F2 score) of the CNN models was 0.78 in heterogeneous areas and 0.73 in homogenous areas. This compares with the detection accuracy of the human labels with an averaged F2 score 0.77 in heterogeneous areas and 0.80 in homogenous areas. The CNN model can generalise to detect elephants in a different geographical location and from a lower resolution satellite.

Our study demonstrates the feasibility of applying state-of-the-art satellite remote sensing and deep learning technologies for detecting and counting African elephants in heterogeneous landscapes. The study showcases the feasibility of using high resolution satellite imagery as a promising new wildlife surveying technique. Through creation of a customised training dataset and application of a Convolutional Neural Network, we have automated the detection of elephants in satellite imagery with as high accuracy as human detection capabilities. The success of the model to detect elephants outside of the training data site demonstrates the generalisability of the technique.
Nicotine dosimetry and stability in Cambridge Filter PADs (CFPs) following different smoking regimen protocols and condition storage
Authors: Zuccarello Pietro , Rust Sonja , Caruso Massimo , Emma Rosalia , Pulvirenti Roberta , Favara Claudia , Polosa Riccardo , Volti Giovanni Li , Ferrante Margherita
Published: September 2020

Despite the growing numbers of studies with cigarettes and other electronic nicotine delivery products (ENDs), there is no standard covering nicotine dosimetry and its stability in various matrix. The aim of the present study was to provide a protocol to normalize nicotine concentration adsorbed in Cambridge Filter PADs (CFPs) and their storage method. Smoke/vapor generated by a reference tobacco cigarette (1R6F) and ENDs with different exposure regimes (ISO, HCI and CRM81) was collected in CFPs. For each exposure, some CFPs were analyzed at time zero, whereas the others were stored under different conditions for nicotine assessment after 30 days. Principal Component Analysis (PCA) was also performed to establish the best parameter for nicotine normalization. PCA showed the best correlation between nicotine in CFPs and TPM. Our results showed differences between products and puffing regimes, but storage of CFPs at −80°C was always effective in maintaining the nicotine content. In conclusion, this study highlights that different exposure regimens and products can affect the preservation of nicotine titer in CFPs and samples storage at −80°C may prevent the loss of nicotine. These conditions are recommended and should be adopted for Inter-laboratory comparison studies on ENDs to ensure harmonization between participating laboratories.
Substantial gene flow caused by long-term translocation between wild populations of the Peruvian scallop (Argopecten purpuratus) is supported by RAD-Seq analyses
Authors: Velez-Zuazo Ximena , Barahona Sergio P. , Melo Omar G. , Hanschke Eric , Hanschke Ian , Santa-Maria Monica C.
Published: September 2020

The Peruvian scallop (Argopecten purpuratus, Lamarck 1989) is a marine bivalve of high commercial value in the aquaculture industry, with wild populations distributing from northern Peru to Chile. Its growing demand in the world aquaculture markets and limited availability of hatchery-based seeds, caused long-term seed translocations among wild populations to recover depleted local populations and for production needs. We investigated long-term translocations effects on the genetic diversity and structure of wild populations using next-generation RAD sequencing. We sampled individuals from Sechura, Lobos de Tierra, Samanco and Bahia Independencia in Peru, and La Rinconada in Northern Chile. We identified 6275 polymorphic RAD tags and 8345 SNPs for the five populations. We estimated high observed heterozygosity for all populations and high SNP frequency compared to similar studies on marine bivalves. We detected no spatial divergence among populations in Peru (pairwise FST ranged from 0 to 0.003), but strong differentiation with the population in Chile. Migration rate estimates suggested asymmetric directionality of seed translocation. Overall, our results support a remnant effect of an intense historic translocation and on-going gene flow among wild populations in Peru, challenging the identification of outlier loci and certification of sustainable origin of cultured scallops using genetic markers.
Chromosome-level Genome Assembly of a Regenerable Maize Inbred Line A188
Authors: Lin Guifang , He Cheng , Zheng Jun , Koo Dal-Hoe , Le Ha , Zheng Huakun , Tamang Tej Man , Lin Jinguang , Liu Yan , Zhao Mingxia , Hao Yangfan , McFraland Frank , Wang Bo , Qin Yang , Tang Haibao , McCarty Donald R , Wei Hairong , Cho Myeong-Je , Park Sunghun , Kaeppler Heidi , Kaeppler Shawn M , Liu Yunjun , Springer Nathan , Schnable Patrick S , Wang Guoying , White Frank F , Liu Sanzhen
Published: September 2020

The highly embryogenic and transformable maize inbred line A188 is an attractive model for analyzing maize gene function. Here we constructed a chromosome-level genome assembly of A188 using long reads and optical maps. Genome comparison of A188 with the reference line B73 identified pervasive structural variation, including a 1.8 Mb duplication on theGametophyte factor1locus for unilateral cross-incompatibility and six inversions of 0.7 Mb or greater. Increased copy number of the gene,carotenoid cleavage dioxygenase 1(ccd1) in A188 is associated with elevated expression during seed development. Highccd1expression together with low expression ofyellow endosperm 1(y1) condition reduced carotenoid accumulation, which accounts for the white seed phenotype of A188 that contrasts with the yellow seed of B73 that has high expression ofy1and low expression of the single-copyccd1. Further, transcriptome and epigenome analyses with the A188 reference genome revealed enhanced expression of defense pathways and altered DNA methylation patterns of embryonic callus.
Identifiability of Tissue Material Parameters from Uniaxial Tests using Multi-start Optimization
Authors: Safa Babak N. , Santare Michael H. , Ethier C. Ross , Elliott Dawn M.
Published: September 2020

Determining tissue biomechanical material properties from mechanical test data is frequently required in a variety of applications, e.g. tissue engineering. However, the validity of the resulting constitutive model parameters is the subject of debate in the field. Common methods to perform fitting, such as nonlinear least-squares, are known to be subject to several limitations, most notably the uniqueness of the fitting results. Parameter optimization in tissue mechanics often comes down to the “identifiability” or “uniqueness” of constitutive model parameters; however, despite advances in formulating complex constitutive relations and many classic and creative curve-fitting approaches, there is no accessible framework to study the identifiability of tissue material parameters. Our objective was to assess the identifiability of material parameters for established constitutive models of fiber-reinforced soft tissues, biomaterials, and tissue-engineered constructs. To do so, we generated synthetic experimental data by simulating uniaxial tension and compression tests, commonly used in biomechanics. We considered tendon and sclera as example tissues, using constitutive models that describe these fiber-reinforced tissues. We demonstrated that not all of the model parameters of these constitutive models were identifiable from uniaxial mechanical tests, despite achieving virtually identical fits to the stress-stretch response. We further show that when the lateral strain was considered as an additional fitting criterion, more parameters are identifiable, but some remain unidentified. This work provides a practical approach for addressing parameter identifiability in tissue mechanics.

Statement of Significance

Data fitting is a powerful technique commonly used to extract tissue material parameters from experimental data, and which thus has applications in tissue biomechanics and engineering. However, the problem of “uniqueness” or “identifiability” of the fit parameters is a significant issue, limiting the fit results’ validity. Here we provide a novel method to evaluate data fitting and assess the uniqueness of results in the tissue mechanics constitutive models. Our results indicate that the uniaxial stress-stretch experimental data are not adequate to identify all the tissue material parameters. This study is of potential interest to a wide range of readers because of its application for the characterization of other engineering materials, while addressing the problem of uniqueness of the fitted results.
A smartphone app for individual anesthetic calculation decreased anesthesia-related mortality in mice
Authors: Jara Carlos Poblete , Carraro Rodrigo S , Zanesco Ariane , Andrade Beatriz , Moreira Karina , Nogueira Guilherme , Souza Bruno L. , Prado Thais Paulino , Póvoa Valeria , Velloso Licio A. , Araújo Eliana P.
Published: September 2020

Annually, millions of animals are used for experimental purposes. Despite the recommended anesthetic doses being well-known worldwide, the final amounts applied to mice could be different than those calculated. Here, we developed, tested, and validated a mobile app where researchers and operators were able to use personal devices to process body weight, calculate a master anesthetic cocktail, and then apply the individual volume to each mouse. Our objective was to refine anesthesia procedures using information technologies. Our data showed that the “Labinsane” mobile app decreased anesthetic-related deaths upon using weight-adjusted doses of ketamine and xylazine. Also, we validated that the Labinsane mobile app matched all calculations of anesthetic doses. To our knowledge, this is the first report with hundreds of anesthetized mice records and validation and implementation of a mobile app to solve an old but transversal challenge for researchers working with experimental mice.
Effects of Long-Term Meditation Practices on Sensorimotor Rhythm Based BCI Learning
Authors: Jiang Xiyuan , Lopez Emily , Stieger James , Greco Carol , He Bin
Published: September 2020

Sensorimotor rhythm (SMR) based brain-computer interfaces (BCIs) provide an alternative pathway for users to perform motor control using motor imagery (MI). Despite the non-invasiveness, ease of use and low cost, this kind of BCI has limitation due to long training times and BCI inefficiency— where a subpopulation cannot generate decodable EEG signals to perform the control task. Meditation is a mental training method to improve mindfulness and awareness, and is reported to have a positive effect on one’s mental state. Here we investigate the behavioral and electrophysiological differences between experienced meditators and meditation naïve subjects in 1-dimensional and 2-dimensional cursor control tasks. We found that within subjects who have room for improvement, meditators outperformed control subjects in both tasks, and there were fewer BCI insufficient subjects in the meditator group. Finally, we also explored the neurophysiological difference between the two groups, and showed that meditators had higher SMR predictor and were better able to generate decodable EEG signals to achieve SMR BCI control.
Robust Preclinical Evidence in Somatic Cell Genome Editing: A Key Driver of Responsible and Efficient Therapeutic Innovations
Authors: Bittlinger Merlin , Schwietering Johannes , Strech Daniel
Published: September 2020

Somatic cell genome editing (SCGE) is highly promising for therapeutic innovation. Multifold financial and academic incentives exist for the quickest possible translation from preclinical to clinical studies. This study demonstrates that the majority of 46 preclinical SCGE studies discussed in expert reviews as particularly promising for clinical translation do not report on seven key elements for robust and confirmatory research practices: (1) randomization, (2) blinding, (3) sample size calculation, (4) data handling, (5) pre-registration, (6) multi-centric study design, and (7) independent confirmation. Against the background of the high incentives for clinical translation and recent concerns about the reproducibility of published preclinical evidence, we present the here examined reporting standards (1-4) and the new NIH funding criteria for SCGE research (6-7) as a viable solution to protect this promising field from backlashes. We argue that the implementation of the novel methodological standards, e.g. “confirmation” and “pre-registration”, is promising for preclinical SCGE research and provides an opportunity to become a lighthouse example for trust-worthy and useful translational research.
Incorporation of Heterogeneity in a Case-Control Study Through a Mixture Model
Authors: Paul Subrata , Santorico Stephanie A.
Published: September 2020

Most common human diseases and complex traits are etiologically heterogeneous. Genome-wide Association Studies (GWAS) aim to discover common genetic variants that are associated with complex traits, typically without considering heterogeneity. Heterogeneity, as well as im-precise phenotyping, significantly reduces the power to find genetic variants associated with human diseases and complex traits. Disease subtyping through unsupervised clustering techniques such as latent class analysis can explain some of the heterogeneity; however, subtyping methods do not typically incorporate heterogeneity into the association framework. Here, we use a finite mixture model with logistic regression to incorporate heterogeneity into the association testing framework for a case-control study. In the proposed method, the disease outcome is modeled as a mixture of two binomial distributions. One of the component distributions refers to the subgroup of the population for which the genetic variant is not associated with the disease outcome and another component distribution corresponds to the subgroup for which the genetic variant is associated with the disease outcome. The mixing parameter corresponds to the proportion of the population for which the genetic variant is associated with the disease outcome. A simulation study of a trait with differing levels of prevalence, SNP minor allele frequency, and odds ratio was performed, and effect size estimates compared between the models with and without incorporating heterogeneity. The proposed mixture model yields lower bias of odds ratios while having comparable power compared to classical logistic regression.