bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood abuse and neglect are prospectively associated with scripted attachment representations in young adulthood
Authors: Nivison Marissa D. , Facompré Christopher R. , Raby K. Lee , Simpson Jeffry A. , Roisman Glenn I. , Waters Theodore E. A.
Published: June 2020

Waters, Ruiz, and Roisman (2017) recently published evidence based on the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) that sensitive caregiving during childhood is associated with higher levels ofsecure base script knowledgeduring the Adult Attachment Interview (AAIsbs). At present, however, little is known about the role of variation inatypicalcaregiving, including abuse and/or neglect, in explaining individual differences in AAIsbs. This study revisited data from the MLSRA (N= 157) to examine the association between experiencing abuse and/or neglect in the first 17.5 years of life and secure base script knowledge measured at ages 19 and 26 years. Several aspects of abuse and/or neglect experiences were assessed, including perpetrator identity, timing, and type. Regressions revealed that childhood abuse and/or neglect was robustly associated with lower AAIsbsscores in young adulthood, above and beyond previously documented associations with maternal sensitivity and demographic covariates. Follow-up analyses provided evidence that the predictive significance of abuse for secure base script knowledge was specific to perpetration by parental figures, rather than non-caregivers. Exploratory analyses indicated that abuse and/or neglect: (a) in middle childhood and adolescence (but not infancy and early childhood) and (b) physical abuse (but not sexual abuse or neglect) were uniquely associated with lower AAIsbsscores.
Eulogy: Professor Milan Šamánek, DrSc, FESC (*09.05.1931 †29.04.2020) – legend from the East
Authors: Marek Jan , Janoušek Jan , Tůma Stanislav
Published: June 2020

This article is to commemorate and celebrate achievements of Professor Milan Šamánek who passed away on 29 April, 2020. Milan was an excellent and visionary paediatric cardiologist who helped to establish paediatric cardiology as a speciality in Czechoslovakia and several other east European countries in the late 1970s. Milan was also paramount for connecting the East and West, helping in no small way to establish the Association for European Paediatric Cardiology (AEPC) as the leading learned society in Europe.
Implementation of a standardised annual anticoagulation specialist review in primary care
Authors: Hutchinson-Jones Nathan W. , Didcott Sophie K. , Jones Matthew D. , Crowe Josephine N.
Published: June 2020

An increasing number of patients are being prescribed direct oral anticoagulants (DOACs), while the patients who remain on warfarin are becoming more complex. There is currently a lack of a standardised anticoagulation review for patients in primary care, resulting in potentially preventable harm events. Our aim was to implement a new service, where a standardised review is carried out by a specialist multidisciplinary secondary care anticoagulation team. Overall, the implementation of a standardised review resulted in better optimisation of anticoagulation management for patients taking either a DOAC or a warfarin. Of the 172 eligible patients prescribed warfarin, 47 (27%) chose to switch a DOAC. The average time in therapeutic range for patients on warfarin before and after the pilot increased from 73.5% to 75%. Of 482 patients taking a DOAC, 35 (7%) were found to be on incorrect dose. In 32 (91%) of 35 patients, the dose was amended after notifying the patient’s general practitioner. We also found a significant number of patients inappropriately prescribed concomitant medication such as antiplatelet or non-steroidal anti-inflammatory drugs, potentially putting the patients at an elevated risk of bleeding. While further research is needed; we believe the results of this pilot can be used to help build a case to influence the commissioning of anticoagulation services. Secondary care anticoagulation teams, like our own, may be well-placed to provide or support such services, by working across the primary care and secondary care interface to support our primary care colleagues.
Family dispute resolution and access to justice in Australia
Authors: Akin Ojelabi Lola , Gutman Judith
Published: June 2020

The context of this paper is the several innovative reforms since the Australian government changed the family-law system more than forty years ago with the enactment of the Family Law Act 1975 (Cth). Whilst no-fault divorce was introduced over four decades ago, the watershed effect of replacing a blaming culture with a collaborative problem-solving approach to family disputing has provided a stepping stone for a progressive pathway to less adversarialism in family conflict. This narrative resonates throughout the family-law system today. It also continues to guide the justice discourse in family matters. This paper focuses on developments in the family-law system canvassing several legislative amendments that demonstrate the use of alternative dispute resolution (ADR) as a means of improving access to justice in relation to family disputes in Australia. It is argued that, in the family-law system, justice and ADR are inextricably linked. In support of this contention, the growth, development and evaluation of family dispute resolution is considered; access to justice issues that arise are highlighted. Finally, it reviews ramifications for the future considering recommendations from the recent inquiry into the family-law system.
Germination and emergence of common beggar’s-tick (Bidens alba) seeds at two different stages of afterripening as affected by environmental factors
Authors: Yu Jialin , Sharpe Shaun M. , Boyd Nathan S.
Published: June 2020

Experiments were conducted to determine the effect of various environmental factors and burial depth on germination and seedling emergence of common beggar’s-tick [Bidens alba (L.) DC.] seeds at two different stages of afterripening. Mature B. alba seeds were stored at 4 C for 3 to 5 mo (new seed lot) and 13 to 15 mo (old seed lot) until experiment initiation. Germination exponentially decreased with increasing moisture stress. Germination rate decreased from 87 ± 2.9% to 13 ± 6.1% as osmotic potential decreased from 0 to −0.5 MPa and was completely inhibited at osmotic potentials below −0.83 MPa. A large portion of the new seeds tested positively photoblastic, but seeds that had afterripened for 1 additional year were partially desensitized to the light requirement. New and old seeds still germinated to a greater percentage in the presence of light than under continuous dark at temperatures ranging from 15 to 35 C. Both new and old seeds germinated over a range of temperatures from 5 to 35 C, but the optimum temperatures for germination was 15 to 30 C in the presence of light. Regardless of seed lot, seedling emergence was the greatest when seeds were sown at the soil surface. Seedling emergence was abruptly reduced when burial depth was 1 cm or greater. Based on these results, we conclude that shallow cultivation could effectively suppress this population of B. alba from emerging when incorporated into an integrated control strategy. The information obtained in this research identifies some important factors that facilitate the widespread presence of B. alba in Florida and may contribute to weed management programs.
The Magnitude of Regional‐Scale Tree Mortality Caused by the Invasive Pathogen Phytophthora ramorum
Authors: Cobb Richard C. , Haas Sarah E. , Kruskamp Nicholas , Dillon Whalen W. , Swiecki Tedmund J. , Rizzo David M. , Frankel Susan J. , Meentemeyer Ross K.
Published: June 2020

Forest pathogens are important drivers of tree mortality across the globe, but it is exceptionally challenging to gather and build unbiased quantitative models of their impacts. Here we harness the rare data set matching the spatial scale of pathogen invasion, host, and disease heterogeneity to estimate infection and mortality for the four most susceptible host species of Phytophthora ramorum, an invasive pathogen that drives the most important biological cause of tree mortality in a broad geographic region of coastal California and southwest Oregon. As of 2012, the most current field survey year, we estimate 17.5 (±4.6, 95% CI [confidence interval]) million tanoak (Notholithocarpus densiflorus) stems were pathogen killed with an additional 71 (±21.5) million infected. We estimated 9.0 million (±2.2) coast live oak (Quercus agrifolia) and 1.7 million (±0.5) California black oak (Quercus kelloggii) stems are disease impacted (mortality and infection combined). Lastly, our estimates suggest infection in 95.2 million (±8.6) California bay laurel (Umbellularia californica), which does not suffer mortality from infection and represents a critical source of continued spread. Prevalent infection as of 2012 suggests the cumulative number of disease‐killed stems likely increased from 20.8 to 42.8 million between 2012 and 2019 for all species. While these impacts are substantial, most host populations occur in a yet to be invaded region of northern California indicating that the disease will intensify in the coming decades.
Oceanic Changes Correlate with Methane Seepage
Authors: Thomasy Hannah
Published: June 2020

Changes in sea level and organic carbon burial may have affected seafloor methane seepage over the past 150 million years.
Short-term trends in the prevalence, awareness, treatment, and control of arterial hypertension in Peru
Authors: Villarreal-Zegarra David , Carrillo-Larco Rodrigo M. , Bernabe-Ortiz Antonio
Published: June 2020

The prevalence of hypertension has been declining in low- and middle-income countries (LMIC), particularly in Latin America and the Caribbean. However, we have not identified studies that evaluate trends for awareness, treatment, and control of hypertension in LMIC. We aimed to describe the trends in the prevalence, awareness, treatment, and control of hypertension in Peru. A cross-sectional analysis was conducted using secondary data (4 years) of the Demographic and Health Survey of Peru (ENDES, Spanish acronym), which is conducted annually and is representative at the country level. The age-standardized prevalence was estimated using the World Health Organization population as the reference population. The trend over time was evaluated with the score test for trend of odds. A total of 109,401 participants were included. In Peru, from 2015 to 2018, the age-standardized prevalence of hypertension increased (p < 0.001), while the proportion of people with disease awareness (p < 0.001) and controlled hypertension decreased (p = 0.01). During that same period, the proportion of people with treatment for hypertension did not vary over time (p = 0.13). In 2018, the age-standardized prevalence of hypertension was 20.6%, and the proportion of people with disease awareness, treatment, and control of arterial hypertension was 43.5%, 20.6%, 5.3%, respectively. People with low socioeconomic status and people living in rural areas have the lowest proportion of awareness, treatment, and control of hypertension.
The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation
Authors: La Rosée F. , Bremer H. C. , Gehrke I. , Kehr A. , Hochhaus A. , Birndt S. , Fellhauer M. , Henkes M. , Kumle B. , Russo S. G. , La Rosée P.
Published: June 2020

A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th, 2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).
Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer
Authors: Fong Winnie , Li Qing , Yu Jun
Published: June 2020

Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.
Immunomodulatory effects of platelets on the severity of hand, foot, and mouth disease infected with enterovirus 71
Authors: Li Qianwen , Wang Yimeng , Xue Wenyao , Bian Zhengying , Gao Yue , Zeng Yu , Tang Lei , Tang Tiejun , Tian Ye , Guo Wei
Published: June 2020

Background

Enterovirus 71 (EV71) infection contributes to hand, foot, and mouth disease (HFMD) with severe neurogenic complications, leading to higher morbidity. In addition to their typical roles in coagulation, platelets could serve as essential immune regulatory cells to play a key role in the pathogenesis of this viral infection.

Methods

Platelet parameters were measured using an automatic hematology analyzer. T-helper type 1 (Th1) and Th2 cells were analyzed by flow cytometry. The levels of cytokines and key transcription factors were determined.

Results

The levels of platelet count and plateletcrit were positively associated with the severity of HFMD. Th1 and Th2 cells as well as their corresponding cytokines were increased in the severe group compared to the healthy volunteers. Moreover, the levels of platelets were negatively correlated with the level of interferon-γ (IFN-γ), but positively correlated with the frequency of Th1 cells. Coculture of platelets and naive CD4+ T cells showed that platelets from mild patients promote Th1 cell differentiation and IFN-γ secretion.

Conclusions

Our study has shown for the first time that the distinct roles of platelets are responsible for the regulation of pathogenic CD4+ T cell differentiation and function in the pathogenesis of HFMD caused by EV71.

Impact

Our study has shown for the first time that the distinct roles of platelets are responsible for the regulation of pathogenic CD4+ T cell differentiation and function in the pathogenesis of HFMD caused by EV71.

For the first time, we have discovered the role of platelets in children’s HFMD caused by EV71 infection, which may provide a better treatment for HFMD in the future.

This article describes new discoveries in platelet immunity.
Genomic and physiological resilience in extreme environments are associated with a secure attachment style
Authors: Caputo Viviana , Pacilli Maria Giuseppina , Arisi Ivan , Mazza Tommaso , Brandi Rossella , Traversa Alice , Casasanta Giampietro , Pisa Edoardo , Sonnessa Michele , Healey Beth , Moggio Lorenzo , D’Onofrio Mara , Alleva Enrico , Macrì Simone
Published: June 2020

Understanding individual capability to adjust to protracted confinement and isolation may inform adaptive plasticity and disease vulnerability/resilience, and may have long-term implications for operations requiring prolonged presence in distant and restricted environments. Individual coping depends on many different factors encompassing psychological dispositional traits, endocrine reactivity and their underlying molecular mechanisms (e.g. gene expression). A positive view of self and others (secure attachment style) has been proposed to promote individual resilience under extreme environmental conditions. Here, we tested this hypothesis and investigated the underlying molecular mechanisms in 13 healthy volunteers confined and isolated for 12 months in a research station located 1670 km away from the south geographic pole on the Antarctic Plateau at 3233 m above sea level. Study participants, stratified for attachment style, were characterised longitudinally (before, during and after confinement) for their psychological appraisal of the stressful nature of the expedition, diurnal fluctuations in endocrine stress reactivity, and gene expression profiling (transcriptomics). Predictably, a secure attachment style was associated with reduced psychological distress and endocrine vulnerability to stress. In addition, while prolonged confinement and isolation remarkably altered overall patterns of gene expression, such alteration was largely reduced in individuals characterised by a secure attachment style. Furthermore, increased resilience was associated with a reduced expression of genes involved in energy metabolism (mitochondrial function and oxidative phosphorylation). Ultimately, our data indicate that a secure attachment style may favour individual resilience in extreme environments and that such resilience can be mapped onto identifiable molecular substrates.
Shared polygenic risk for ADHD, executive dysfunction and other psychiatric disorders
Authors: Chang Suhua , Yang Li , Wang Yufeng , Faraone Stephen V.
Published: June 2020

Many psychiatric disorders are associated with impaired executive functioning (EF). The associated EF component varies by psychiatric disorders, and this variation might be due to genetic liability. We explored the genetic association between five psychiatric disorders and EF in clinically-recruited attention deficit hyperactivity disorder (ADHD) children using polygenic risk score (PRS) methodology. Genome-wide association study (GWAS) summary data for ADHD, major depressive disorder (MDD), schizophrenia (SZ), bipolar disorder (BIP) and autism were used to calculate the PRSs. EF was evaluated by the Stroop test for inhibitory control, the trail-making test for cognitive flexibility, and the digital span test for working memory in a Chinese ADHD cohort (n = 1147). Exploratory factor analysis of the three measures identified one principal component for EF (EF-PC). Linear regression models were used to analyze the association between each PRS and the EF measures. The role of EF measures in mediating the effects of the PRSs on ADHD symptoms was also analyzed. The result showed the PRSs for MDD, ADHD and BIP were all significantly associated with the EF-PC. For each EF component, the association results were different for the PRSs of the five psychiatric disorders: the PRSs for ADHD and MDD were associated with inhibitory control (adjusted P = 0.0183 and 0.0313, respectively), the PRS for BIP was associated with working memory (adjusted P = 0.0416), and the PRS for SZ was associated with cognitive flexibility (adjusted P = 0.0335). All three EF measures were significantly correlated with ADHD symptoms. In mediation analyses, the ADHD and MDD PRSs, which were associated with inhibitory control, had significant indirect effects on ADHD symptoms through the mediation of inhibitory control. These findings indicate that the polygenic risks for several psychiatric disorders influence specific executive dysfunction in children with ADHD. The results helped to clarify the relationship between risk genes of each mental disorder and the intermediate cognitive domain, which may further help elucidate the risk genes and motivate efforts to develop EF measures as a diagnostic marker and future treatment target.
LncRNA FOXC2-AS1 enhances FOXC2 mRNA stability to promote colorectal cancer progression via activation of Ca2+-FAK signal pathway
Authors: Pan Ke , Xie Yong
Published: June 2020

Long noncoding RNAs (lncRNAs) have been confirmed, which are involved in tumorigenesis and metastasis in colorectal cancer (CRC). FOXC2 antisense RNA 1 (FOXC2-AS1) was reported, facilitating the proliferation and progression in several cancers. However, the role of FOXC2-AS1 in CRC cell migration and metastasis is not unclear. In this study, we observed that lncRNA FOXC2-AS1 was upregulated in CRC tissues, and its high expression indicated the poor survival in CRC patients. Meanwhile, FOXC2-AS1 was higher in CRC tissues with metastasis than that of nonmetastatic tumor tissues. We found that FOXC2-AS1 was predominately expressed in the nucleus of tissues and cells. FOXC2-AS1 knockdown suppressed CRC cell growth, invasion, and metastasis in vitro and in vivo. Moreover, FOXC2-AS1 could positively regulate the neighboring gene FOXC2 and stabilized FOXC2 mRNA by forming a RNA duplex. Meanwhile, ectopic expression of FOXC2 could obviously alleviate the suppressed effects caused by silencing FOXC2-AS1. For the mechanism, FOXC2-AS1 knockdown could reduce intracellular Ca2+ levels, inhibited FA formation and FAK signaling, and these suppressed effects were mitigated by increasing FOXC2 expression. These results demonstrated that FOXC2-AS1 enhances FOXC2 mRNA stability to promote CRC proliferation, migration, and invasion by activation of Ca2+-FAK signaling, which implicates that FOXC2-AS1 may represent a latent effective therapeutic target for CRC progression.
ADP binding by the Culex quinquefasciatus mosquito D7 salivary protein enhances blood feeding on mammals
Authors: Martin-Martin Ines , Paige Andrew , Valenzuela Leon Paola Carolina , Gittis Apostolos G. , Kern Olivia , Bonilla Brian , Chagas Andrezza Campos , Ganesan Sundar , Smith Leticia Barion , Garboczi David N. , Calvo Eric
Published: June 2020

During blood-feeding, mosquito saliva is injected into the skin to facilitate blood meal acquisition. D7 proteins are among the most abundant components of the mosquito saliva. Here we report the ligand binding specificity and physiological relevance of two D7 long proteins from Culex quinquefasciatus mosquito, the vector of filaria parasites or West Nile viruses. CxD7L2 binds biogenic amines and eicosanoids. CxD7L1 exhibits high affinity for ADP and ATP, a binding capacity not reported in any D7. We solve the crystal structure of CxD7L1 in complex with ADP to 1.97 Å resolution. The binding pocket lies between the two protein domains, whereas all known D7s bind ligands either within the N- or the C-terminal domains. We demonstrate that these proteins inhibit hemostasis in ex vivo and in vivo experiments. Our results suggest that the ADP-binding function acquired by CxD7L1 evolved to enhance blood-feeding in mammals, where ADP plays a key role in platelet aggregation.
Structural distortion and electron redistribution in dual-emitting gold nanoclusters
Authors: Li Qi , Zhou Dongming , Chai Jinsong , So Woong Young , Cai Tong , Li Mingxing , Peteanu Linda A. , Chen Ou , Cotlet Mircea , Wendy Gu X. , Zhu Haiming , Jin Rongchao
Published: June 2020

Deciphering the complicated excited-state process is critical for the development of luminescent materials with controllable emissions in different applications. Here we report the emergence of a photo-induced structural distortion accompanied by an electron redistribution in a series of gold nanoclusters. Such unexpected slow process of excited-state transformation results in near-infrared dual emission with extended photoluminescent lifetime. We demonstrate that this dual emission exhibits highly sensitive and ratiometric response to solvent polarity, viscosity, temperature and pressure. Thus, a versatile luminescent nano-sensor for multiple environmental parameters is developed based on this strategy. Furthermore, we fully unravel the atomic-scale structural origin of this unexpected excited-state transformation, and demonstrate control over the transition dynamics by tailoring the bi-tetrahedral core structures of gold nanoclusters. Overall, this work provides a substantial advance in the excited-state physical chemistry of luminescent nanoclusters and a general strategy for the rational design of next-generation nano-probes, sensors and switches.
Quantifying the drivers and predictability of seasonal changes in African fire
Authors: Yu Yan , Mao Jiafu , Thornton Peter E. , Notaro Michael , Wullschleger Stan D. , Shi Xiaoying , Hoffman Forrest M. , Wang Yaoping
Published: June 2020

Africa contains some of the most vulnerable ecosystems to fires. Successful seasonal prediction of fire activity over these fire-prone regions remains a challenge and relies heavily on in-depth understanding of various driving mechanisms underlying fire evolution. Here, we assess the seasonal environmental drivers and predictability of African fire using the analytical framework of Stepwise Generalized Equilibrium Feedback Assessment (SGEFA) and machine learning techniques (MLTs). The impacts of sea-surface temperature, soil moisture, and leaf area index are quantified and found to dominate the fire seasonal variability by regulating regional burning condition and fuel supply. Compared with previously-identified atmospheric and socioeconomic predictors, these slowly evolving oceanic and terrestrial predictors are further identified to determine the seasonal predictability of fire activity in Africa. Our combined SGEFA-MLT approach achieves skillful prediction of African fire one month in advance and can be generalized to provide seasonal estimates of regional and global fire risk.
Multiplexed imaging of nucleome architectures in single cells of mammalian tissue
Authors: Liu Miao , Lu Yanfang , Yang Bing , Chen Yanbo , Radda Jonathan S. D. , Hu Mengwei , Katz Samuel G. , Wang Siyuan
Published: June 2020

The three-dimensional architecture of the genome affects genomic functions. Multiple genome architectures at different length scales, including chromatin loops, domains, compartments, and lamina- and nucleolus-associated regions, have been discovered. However, how these structures are arranged in the same cell and how they are mutually correlated in different cell types in mammalian tissue are largely unknown. Here, we develop Multiplexed Imaging of Nucleome Architectures that measures multiscale chromatin folding, copy numbers of numerous RNA species, and associations of numerous genomic regions with nuclear lamina, nucleoli and surface of chromosomes in the same, single cells. We apply this method in mouse fetal liver, and identify de novo cell-type-specific chromatin architectures associated with gene expression, as well as cell-type-independent principles of chromatin organization. Polymer simulation shows that both intra-chromosomal self-associating interactions and extra-chromosomal interactions are necessary to establish the observed organization. Our results illustrate a multi-faceted picture and physical principles of chromatin organization.
Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen
Authors: Wu Daichao , Gallagher D. Travis , Gowthaman Ragul , Pierce Brian G. , Mariuzza Roy A.
Published: June 2020

Adoptive cell therapy (ACT) with tumor-specific T cells can mediate cancer regression. The main target of tumor-specific T cells are neoantigens arising from mutations in self-proteins. Although the majority of cancer neoantigens are unique to each patient, and therefore not broadly useful for ACT, some are shared. We studied oligoclonal T-cell receptors (TCRs) that recognize a shared neoepitope arising from a driver mutation in the p53 oncogene (p53R175H) presented by HLA-A2. Here we report structures of wild-type and mutant p53–HLA-A2 ligands, as well as structures of three tumor-specific TCRs bound to p53R175H–HLA-A2. These structures reveal how a driver mutation in p53 rendered a self-peptide visible to T cells. The TCRs employ structurally distinct strategies that are highly focused on the mutation to discriminate between mutant and wild-type p53. The TCR–p53R175H–HLA-A2 complexes provide a framework for designing TCRs to improve potency for ACT without sacrificing specificity.
Synthesis and versatile reactivity of scandium phosphinophosphinidene complexes
Authors: Feng Bin , Xiang Li , McCabe Karl N. , Maron Laurent , Leng Xuebing , Chen Yaofeng
Published: June 2020

M=E/M≡E multiple bonds (M = transition metal, E = main group element) are of significant fundamental scientific importance and have widespread applications. Expanding the ranges of M and E represents grand challenges for synthetic chemists and will bring new horizons for the chemistry. There have been reports of M=E/M≡E multiple bonds for the majority of the transition metals, and even some actinide metals. In stark contrast, as the largest subgroup in the periodic table, rare-earth metals (Ln) were scarcely involved in Ln=E/Ln≡E multiple bonds. Until recently, there were a few examples of rare-earth monometallic alkylidene, imido and oxo complexes, featuring Ln=C/N/O bonds. What are in absence are rare-earth monometallic phosphinidene complexes with Ln=P bonds. Herein, we report synthesis and structure of rare-earth monometallic phosphinidene complexes, namely scandium phosphinophosphinidene complexes. Reactivity of scandium phosphinophosphinidene complexes is also mapped out, and appears to be easily tuned by the supporting ligand.
Deep Learning for Improved Risk Prediction in Surgical Outcomes
Authors: Jalali Ali , Lonsdale Hannah , Do Nhue , Peck Jacquelin , Gupta Monesha , Kutty Shelby , Ghazarian Sharon R. , Jacobs Jeffrey P. , Rehman Mohamed , Ahumada Luis M.
Published: June 2020

The Norwood surgical procedure restores functional systemic circulation in neonatal patients with single ventricle congenital heart defects, but this complex procedure carries a high mortality rate. In this study we address the need to provide an accurate patient specific risk prediction for one-year postoperative mortality or cardiac transplantation and prolonged length of hospital stay with the purpose of assisting clinicians and patients’ families in the preoperative decision making process. Currently available risk prediction models either do not provide patient specific risk factors or only predict in-hospital mortality rates. We apply machine learning models to predict and calculate individual patient risk for mortality and prolonged length of stay using the Pediatric Heart Network Single Ventricle Reconstruction trial dataset. We applied a Markov Chain Monte-Carlo simulation method to impute missing data and then fed the selected variables to multiple machine learning models. The individual risk of mortality or cardiac transplantation calculation produced by our deep neural network model demonstrated 89 ± 4% accuracy and 0.95 ± 0.02 area under the receiver operating characteristic curve (AUROC). The C-statistics results for prediction of prolonged length of stay were 85 ± 3% accuracy and AUROC 0.94 ± 0.04. These predictive models and calculator may help to inform clinical and organizational decision making.
Jasmonic acid and methyl jasmonate modulate growth, photosynthetic activity and expression of photosystem II subunit genes in Brassica oleracea L
Authors: Sirhindi Geetika , Mushtaq Ruqia , Gill Sarvajeet Singh , Sharma Poonam , Abd_Allah Elsayed F. , Ahmad Parvaiz
Published: June 2020

The effects of jasmonic acid (JA) and methyl jasmonate (Me-JA) on photosynthetic efficiency and expression of some photosystem (PSII) related in different cultivars of Brassica oleracea L. (var. italica, capitata, and botrytis) were investigated. Plants raised from seeds subjected to a pre-sowing soaking treatment of varying concentrations of JA and Me-JA showed enhanced photosynthetic efficiency in terms of qP and chlorophyll fluorescence. Maximum quantum efficiency of PSII (Fv/Fm) was increased over that in the control seedlings. This enhancement was more pronounced in the Me-JA-treated seedlings compared to that in JA-treated ones. The expression of PSII genes was differentially regulated among the three varieties of B. oleracea. The gene PsbI up-upregulated in var. botrytis after treatment of JA and Me-JA, whereas PsbL up-regulated in capitata and botrytis after supplementation of JA. The gene PsbM showed many fold enhancements in these expressions in italica and botrytis after treatment with JA. However, the expression of the gene PsbM increased by both JA and Me-JA treatments. PsbTc(p) and PsbTc(n) were also found to be differentially expressed which revealed specificity with the variety chosen as well as JA or Me-JA treatments. The RuBP carboxylase activity remained unaffected by either JA or Me-JA supplementation in all three varieties of B. oleracea L. The data suggest that exogenous application of JA and Me-JA to seeds before germination could influence the assembly, stability, and repair of PS II in the three varieties of B. oleracea examined. Furthermore, this improvement in the PS II machinery enhanced the photosynthetic efficiency of the system and improved the photosynthetic productivity in terms of saccharides accumulation.
A novel culture medium with reduced nutrient concentrations supports the development and viability of mouse embryos
Authors: Ermisch Alison F. , Herrick Jason R. , Pasquariello Rolando , Dyer McKenna C. , Lyons Sarah M. , Broeckling Corey D. , Rajput Sandeep K. , Schoolcraft William B. , Krisher Rebecca L.
Published: June 2020

Further refinement of culture media is needed to improve the quality of embryos generated in vitro. Previous results from our laboratory demonstrated that uptake of nutrients by the embryo is significantly less than what is supplied in traditional culture media. Our objective was to determine the impact of reduced nutrient concentrations in culture medium on mouse embryo development, metabolism, and quality as a possible platform for next generation medium formulation. Concentrations of carbohydrates, amino acids, and vitamins could be reduced by 50% with no detrimental effects, but blastocyst development was impaired at 25% of standard nutrient provision (reduced nutrient medium; RN). Addition of pyruvate and L-lactate (+PL) to RN at 50% of standard concentrations restored blastocyst development, hatching, and cell number. In addition, blastocysts produced in RN + PL contained more ICM cells and ATP than blastocysts cultured in our control (100% nutrient) medium; however, metabolic activity was altered. Similarly, embryos produced in the RN medium with elevated (50% control) concentrations of pyruvate and lactate in the first step medium and EAA and Glu in the second step medium were competent to implant and develop into fetuses at a similar rate as embryos produced in the control medium. This novel approach to culture medium formulation could help define the optimal nutrient requirements of embryos in culture and provide a means of shifting metabolic activity towards the utilization of specific metabolic pathways that may be beneficial for embryo viability.
Association of body surface scanner-based abdominal volume with parameters of the Metabolic Syndrome and comparison with manually measured waist circumference
Authors: Jaeschke Lina , Steinbrecher Astrid , Hansen Guido , Sommer Stefan , Adler Carolin , Janke Jürgen , Pischon Tobias
Published: June 2020

To investigate abdominal volume determined by a new body scanner algorithm as anthropometric marker for Metabolic Syndrome (MetS) and its parameters compared to manually measured waist circumference (WC), we performed body scans in 411 participants (38% men, 20-81 years). WC and triglyceride, HDL-cholesterol, and fasting glucose concentrations, and blood pressure were assessed as MetS parameters. We used Spearman correlations and linear regression to investigate associations and goodness-of-fit (R², BIC) of abdominal volume and WC with MetS parameters, and logistic regression to analyse the discriminative power of WC and abdominal volume to assess likelihoods of MetS components and MetS. Correlations with triglyceride, HDL-cholesterol, and glucose concentration were slightly stronger for abdominal volume (r; 0.32, −0.32, and 0.34, respectively) than for WC (0.28, −0.28, and 0.29, respectively). Explained variances in MetS parameters were slightly higher and goodness-of-fit slightly better for abdominal volume than for WC, but differences were small. Exemplarily, glucose levels were 0.28 mmol/L higher (R² = 0.25; BIC = 945.5) per 1-SD higher  WC, and 0.35 mmol/L higher (R² = 0.28; BIC = 929.1) per 1-SD higher abdominal volume. The discriminative power to estimate MetS components was similar for WC and abdominal volume. Our data show that abdominal volume allows metabolic characterization comparable to established WC.
Unrevealed genetic diversity of GII Norovirus in the swine population of North East Italy
Authors: Cavicchio L. , Tassoni L. , Laconi A. , Cunial G. , Gagliazzo L. , Milani A. , Campalto M. , Di Martino G. , Forzan M. , Monne I. , Beato M. S.
Published: June 2020

Noroviruses (NoVs) are one of the major causative agents of non-bacterial gastroenteritis in humans worldwide. NoVs, belonging to Caliciviridae, are classified into ten genogroups (G) and eight P-groups based on major capsid protein (VP1) and of the RNA-dependent-RNA-polymerase (RdRp), respectively. In swine, the main genogroup and P-group identified are GII and GII.P; which can infect humans too. To date, only one case of GIIP.11 have been identified in swine in Italy while the circulation of other P-types is currently unknown. In the present study, 225 swine faecal samples were collected from 74 swine herds in Veneto region through on-farm monitoring. NoV circulation was particularly high in older pigs. The phylogenetic analysis showed the co-circulation of NoVs belonging to two different P-types: GII.P11 and GII.P18, here described for the first time in Italy, presenting an extensive genetic diversity, never described before worldwide. Distinct NoV genetic subgroups and unique amino acid mutations were identified for each P-type for the first time. This study demonstrated the co-circulation of diverse swine NoVs subgroups in Italy, raising questions on the origin of such diversity and suggesting that continuous monitoring of swine NoVs is needed to track the emergence of potentially zoonotic viruses by recombination events.
Identifying the role of PrimPol in TDF-induced toxicity and implications of its loss of function mutation in an HIV+ patient
Authors: Duong Vincent N. , Zhou Lei , Martínez-Jiménez María I. , He Linh , Cosme Moises , Blanco Luis , Paintsil Elijah , Anderson Karen S.
Published: June 2020

A key component of antiretroviral therapy (ART) for HIV patients is the nucleoside reverse transcriptase inhibitor (NRTI) is tenofovir. Recent reports of tenofovir toxicity in patients taking ART for HIV cannot be explained solely on the basis of off-target inhibition of mitochondrial DNA polymerase gamma (Polγ). PrimPol was discovered as a primase-polymerase localized to the mitochondria with repriming and translesion synthesis capabilities and, therefore, a potential contributor to mitochondrial toxicity. We established a possible role of PrimPol in tenofovir-induced toxicity in vitro and show that tenofovir-diphosphate incorporation by PrimPol is dependent on the n-1 nucleotide. We identified and characterized a PrimPol mutation, D114N, in an HIV+ patient on tenofovir-based ART with mitochondrial toxicity. This mutant form of PrimPol, targeting a catalytic metal ligand, was unable to synthesize primers, likely due to protein instability and weakened DNA binding. We performed cellular respiration and toxicity assays using PrimPol overexpression and shRNA knockdown strains in renal proximal tubular epithelial cells. The PrimPol-knockdown strain was hypersensitive to tenofovir treatment, indicating that PrimPol protects against tenofovir-induced mitochondrial toxicity. We show that a major cellular role of PrimPol is protecting against toxicity caused by ART and individuals with inactivating mutations may be predisposed to these effects.
Frontoparietal connectivity correlates with working memory performance in multiple sclerosis
Authors: Figueroa-Vargas Alejandra , Cárcamo Claudia , Henríquez-Ch Rodrigo , Zamorano Francisco , Ciampi Ethel , Uribe-San-Martin Reinaldo , Vásquez Macarena , Aboitiz Francisco , Billeke Pablo
Published: June 2020

Working Memory (WM) impairment is the most common cognitive deficit of patients with Multiple Sclerosis (MS). However, evidence of its neurobiological mechanisms is scarce. Here we recorded electroencephalographic activity of twenty patients with relapsing-remitting MS and minimal cognitive deficit, and 20 healthy control (HC) subjects while they solved a WM task. In spite of similar performance, the HC group demonstrated both a correlation between temporoparietal theta activity and memory load, and a correlation between medial frontal theta activity and successful memory performances. MS patients did not show theses correlations leading significant differences between groups. Moreover, cortical connectivity analyses using granger causality and phase-amplitude coupling between theta and gamma revealed that HC group, but not MS group, presented a load-modulated progression of the frontal-to-parietal connectivity. This connectivity correlated with working memory capacity in MS groups. This early alterations in the oscillatory dynamics underlaying working memory could be useful for plan therapeutic interventions.
Light-enhanced incoherence of electronic transport in quantum cascade lasers
Authors: Kolek Andrzej
Published: June 2020

Since their invention in the middle of the 1990s, quantum cascade lasers (QCLs) attract increasing theoretical interest stimulated by their widening applications. One of the key theoretical issues is the optimization of electronic transport which in most of these devices is governed by the injection barrier of QCL heterostructure. In the paper, the nonequilibrium Green’s function formalism is used to study electronic transition through the injection barrier as a function of laser field in the cavity; for the increasing field, a crossover is observed from the strong coupling regime, in which electronic transport through the barrier is coherent, to the weak coupling regime, in which electronic transport gets incoherent. This crossover is characterized by gain recovery time, τrec, which takes sub-picosecond values for mid-IR QCLs operating at room temperature. This time is also important for the performance of devices under steady-state conditions; the maximum output power is obtained when the figure of merit, FOM = (g(0)/gth − 1)/gcτrec [g(0) is the linear response gain, gth is the threshold gain needed to compensate all losses, gc is the gain cross-section], reaches maximum. It is shown that the use of this optimization criterion can result in the structures essentially different from those which can be obtained when the optimized quantity is the linear response gain, g(0).
Discovery of new boron-rich chalcogenides: orthorhombic B6X (X=S, Se)
Authors: Cherednichenko Kirill A. , Mukhanov Vladimir A. , Wang Zhenhai , Oganov Artem R. , Kalinko Aleksandr , Dovgaliuk Iurii , Solozhenko Vladimir L.
Published: June 2020

New boron-rich sulfide B6S and selenide B6Se have been discovered by combination of high pressure – high temperature synthesis and ab initio evolutionary crystal structure prediction, and studied by synchrotron X-ray diffraction and Raman spectroscopy at ambient conditions. As it follows from Rietveld refinement of powder X-ray diffraction data, both chalcogenides have orthorhombic symmetry and belong to Pmna space group. All experimentally observed Raman bands have been attributed to the theoretically calculated phonon modes, and the mode assignment has been performed. Prediction of mechanical properties (hardness and elastic moduli) of new boron-rich chalcogenides has been made using ab initio calculations, and both compounds were found to be members of a family of hard phases.
Epidemiological Characteristics and Spatiotemporal Analysis of Acute Hemorrhagic Conjunctivitis from 2004 to 2018 in Chongqing, China
Authors: Jing Dan , Zhao Han , Ou Rong , Zhu Hua , Hu Ling , Giri Mohan , Ye Mengliang
Published: June 2020

Chongqing is one of the five provinces in China that has the highest incidence of acute hemorrhagic conjunctivitis (AHC). Data of AHC cases from 2004 to 2018 were obtained from National Notifiable Diseases Reporting Information System (NNDRIS). Descriptive statistical methods were used to analyze the epidemiological characteristics; incidence maps were used to reflect incidence trends in each district; spatial autocorrelation was used to identify hotspot regions and spatiotemporal patterns of AHC outbreaks; spatiotemporal scan were conducted to identify AHC clusters. A total of 30,686 cases were reported with an annual incidence of 7.04 per 100,000. The incidence rates were high in 2007 and 2014, and large epidemics were observed in 2010 with the seasonal peak in September. Individuals aged 10–19 years, males, students and farmers were the prime high-risk groups. Except for 2012 and 2013, the spatial distribution of AHC did not exhibit significant global spatial autocorrelation. Local indicators of spatial association showed that the high-risk regions are Chengkou and Wuxi. The spatiotemporal scan indicated that all clusters occurred in September 2010, and the high-incidence clusters were mainly distributed in the northeast of Chongqing. The results could assist public health agencies to consider effective preventive measures based on epidemiological factors and spatiotemporal clusters in different regions.
Author Correction: Diversity and characteristics of colonization of root-associated fungi of Vaccinium uliginosum
Authors: Yang Hongyi , Zhao Xingyu , Liu Changli , Bai Long , Zhao Min , Li Lili
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Classification and mutation prediction based on histopathology H&E images in liver cancer using deep learning
Authors: Chen Mingyu , Zhang Bin , Topatana Win , Cao Jiasheng , Zhu Hepan , Juengpanich Sarun , Mao Qijiang , Yu Hong , Cai Xiujun
Published: June 2020

Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, and assessing its histopathological grade requires visual inspection by an experienced pathologist. In this study, the histopathological H&E images from the Genomic Data Commons Databases were used to train a neural network (inception V3) for automatic classification. According to the evaluation of our model by the Matthews correlation coefficient, the performance level was close to the ability of a 5-year experience pathologist, with 96.0% accuracy for benign and malignant classification, and 89.6% accuracy for well, moderate, and poor tumor differentiation. Furthermore, the model was trained to predict the ten most common and prognostic mutated genes in HCC. We found that four of them, including CTNNB1, FMN2, TP53, and ZFX4, could be predicted from histopathology images, with external AUCs from 0.71 to 0.89. The findings demonstrated that convolutional neural networks could be used to assist pathologists in the classification and detection of gene mutation in liver cancer.
Defect compensation in the p-type transparent oxide Ba2BiTaO6
Authors: Dahliah Diana , Rignanese Gian-Marco , Hautier Geoffroy
Published: June 2020

Ba2BiTaO6 is a transparent p-type oxide recently discovered and exhibiting attractive hole mobility but low carrier concentration.