bluuebunny/crossref_metadata_2025 huggingface dataset:
Parent Decision-Making About Support for Siblings of Children With Cancer: Sociodemographic Influences
Authors: Oberoi Anjali R. , Cardona Nicole D. , Davis Kathryn A. , Pariseau Emily M. , Berk Deborah , Muriel Anna C. , Long Kristin A.
Published: June 2020

Background: Siblings of children with cancer have elevated psychosocial risk. Sociodemographic factors (e.g., non-White race, low income, and low caregiver education) are associated with increased risk. Little is known about how sociodemographic factors influence families’ decisions to participate in sibling support services. This convergent mixed-methods study characterizes how sociodemographic factors influence parent decision-making to engage siblings in support. Method: A purposive sample of parents of children with cancer ( N = 28) participated in semistructured interviews that queried their perceptions of sibling support, including preferences for ideal support and perceived barriers to accessing support. Qualitative findings were merged with quantitative data to stratify by sociodemographic categories (ethnicity, parent-reported financial hardship, parent education). Applied thematic analysis was used to distill findings. Results: Sociodemographic differences emerged across parents’ decision-making on whether to engage with sibling support services. Some cross-cutting barriers to accessing sibling support were described by all groups. However, differences across sociodemographic groups emerged for other barriers to care and for preferences for sibling support. Conclusions: These findings inform the design and implementation of sibling support programs. Providers can work with families to craft individualized sibling support plans that align with the family’s preferences and circumvent perceived barriers, which may improve acceptability and use of support programming and ultimately improve siblings’ psychosocial outcomes.

Implications for Impact Statement

This article offers an overview of sociodemographic variables (ethnicity, financial hardship, parent education) associated with parents’ decision to engage in support for siblings of children of cancer. An understanding of these factors can support clinicians in the design and implementation of programs that are acceptable and accessible for all families of children with cancer.
Bosutinib for pretreated patients with chronic phase chronic myeloid leukemia: primary results of the phase 4 BYOND study
Authors: Hochhaus Andreas , Gambacorti-Passerini Carlo , Abboud Camille , Gjertsen Bjørn Tore , Brümmendorf Tim H. , Smith B. Douglas , Ernst Thomas , Giraldo-Castellano Pilar , Olsson-Strömberg Ulla , Saussele Susanne , Bardy-Bouxin Nathalie , Viqueira Andrea , Leip Eric , Russell-Smith T. Alexander , Leone Jocelyn , Rosti Gianantonio , Watts Justin , Giles Francis J. ,   on behalf of the BYOND Study Investigators, Abruzzese E. , Akard L. P. , Bosi A. , Cervantes F. , Charbonnier A. , Di Raimondo F. , Etienne G. , Garcia Gutierrez V. , Guerci-Bresler A. P. , Hjorth-Hansen H , Karsenti J. M. , Kelly K. R. , Le Coutre P. , Martinez Chamorro C. , Oehler V. G. , Orti Pascual G. , Petzer A. , Pungolino E. , Rege-Cambrin G. , Rigal-Huguet F. , Roboz G. J. , Rousselot P. , Sanchez-Guijo F. M. , Sanz Santillana G. , Schafhausen P. , Scheid C. , Schmidt S. , Specchia G. , Steegmann J. L. , Stenke L.
Published: June 2020

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.
Functional genomics identifies new synergistic therapies for retinoblastoma
Authors: Aubry Arthur , Pearson Joel D. , Huang Katherine , Livne-bar Izhar , Ahmad Mohammad , Jagadeesan Madhavan , Khetan Vikas , Ketela Troy , Brown Kevin R. , Yu Tao , Lu Suying , Wrana Jeffrey L. , Moffat Jason , Bremner Rod
Published: June 2020

Local intravitreal or intra-arterial chemotherapy has improved therapeutic success for the pediatric cancer retinoblastoma (RB), but toxicity remains a major caveat. RB initiates primarily withRB1loss or, rarely,MYCNamplification, but the critical downstream networks are incompletely understood. We set out to uncover perturbed molecular hubs, identify synergistic drug combinations to target these vulnerabilities, and expose and overcome drug resistance. We applied dynamic transcriptomic analysis to identify network hubs perturbed in RB versus normal fetal retina, and performed in vivo RNAi screens inRB1nullandRB1wt;MYCNamporthotopic xenografts to pinpoint essential hubs. We employed in vitro and in vivo studies to validate hits, define mechanism, develop new therapeutic modalities, and understand drug resistance. We identified BRCA1 and RAD51 as essential for RB cell survival. Their oncogenic activity was independent of BRCA1 functions in centrosome, heterochromatin, or ROS regulation, and instead linked to DNA repair. RAD51 depletion or inhibition with the small molecule inhibitor, B02, killed RB cells in a Chk1/Chk2/p53-dependent manner. B02 further synergized with clinically relevant topotecan (TPT) to engage this pathway, activating p53–BAX mediated killing of RB but not human retinal progenitor cells. Paradoxically, a B02/TPT-resistant tumor exhibited more DNA damage than sensitive RB cells. Resistance reflected dominance of the p53–p21 axis, which mediated cell cycle arrest instead of death. Deleting p21 or applying the BCL2/BCL2L1 inhibitor Navitoclax re-engaged the p53–BAX axis, and synergized with B02, TPT or both to override resistance. These data expose new synergistic therapies to trigger p53-induced killing in diverse RB subtypes.
YES1 amplification confers trastuzumab–emtansine (T-DM1) resistance in HER2-positive cancer
Authors: Wang Lei , Wang Quanren , Xu Piaopiao , Fu Li , Li Yun , Fu Haoyu , Quan Haitian , Lou Liguang
Published: June 2020

Background

Trastuzumab–emtansine (T-DM1), one of the most potent HER2-targeted drugs, shows impressive efficacy in patients with HER2-positive breast cancers. However, resistance inevitably occurs and becomes a critical clinical problem.

Methods

We modelled the development of acquired resistance by exposing HER2-positive cells to escalating concentrations of T-DM1. Signalling pathways activation was detected by western blotting, gene expression was analysed by qRT-PCR and gene copy numbers were determined by qPCR. The role of Yes on resistance was confirmed by siRNA-mediated knockdown and stable transfection-mediated overexpression. The in vivo effects were tested in xenograft model.

Results

We found that Yes is overexpressed in T-DM1–resistant cells owing to amplification of chromosome region 18p11.32, where theYES1gene resides. Yes activated multiple proliferation-related signalling pathways, including EGFR, PI3K and MAPK, and led to cross-resistance to all types of HER2-targeted drugs, including antibody-drug conjugate, antibody and small molecule inhibitor. The outcome of this cross-resistance may be a clinically incurable condition. Importantly, we found that inhibiting Yes with dasatinib sensitised resistant cells in vitro and in vivo.

Conclusions

Our study revealed thatYES1amplification conferred resistance to HER2-targeted drugs and suggested the potential application of the strategy of combining HER2 and Yes inhibition in the clinic.
SIX1 cooperates with RUNX1 and SMAD4 in cell fate commitment of Müllerian duct epithelium
Authors: Terakawa Jumpei , Serna Vanida A. , Nair Devi M. , Sato Shigeru , Kawakami Kiyoshi , Radovick Sally , Maire Pascal , Kurita Takeshi
Published: June 2020

During female mammal reproductive tract development, epithelial cells of the lower Müllerian duct are committed to become stratified squamous epithelium of the vagina and ectocervix, when the expression of ΔNp63 transcription factor is induced by mesenchymal cells. The absence of ΔNp63 expression leads to adenosis, the putative precursor of vaginal adenocarcinoma. Our previous studies with genetically engineered mouse models have established that fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP)/SMAD, and activin A/runt-related transcription factor 1 (RUNX1) signaling pathways are independently required for ΔNp63 expression in Müllerian duct epithelium (MDE). Here, we report that sine oculis homeobox homolog 1 (SIX1) plays a critical role in the activation of ΔNp63 locus in MDE as a downstream transcription factor of mesenchymal signals. In the developing mouse reproductive tract, SIX1 expression was restricted to MDE within the future cervix and vagina. SIX1 expression was totally absent in SMAD4 null MDE and was reduced in RUNX1 null and FGFR2 null MDE, indicating that SIX1 is under the control of vaginal mesenchymal factors: BMP4, activin A and FGF7/10. Furthermore, Six1, Runx1, and Smad4 gene-dose-dependently activated ΔNp63 expression in MDE within the vaginal fornix. Using a mouse model of diethylstilbestrol (DES)-associated vaginal adenosis, we found DES action through epithelial estrogen receptor α (ESR1) inhibits activation of ΔNp63 locus in MDE by transcriptionally repressing SIX1 and RUNX1 in the vaginal fornix.
Formation of ammonia–helium compounds at high pressure
Authors: Shi Jingming , Cui Wenwen , Hao Jian , Xu Meiling , Wang Xianlong , Li Yinwei
Published: June 2020

Uranus and Neptune are generally assumed to have helium only in their gaseous atmospheres. Here, we report the possibility of helium being fixed in the upper mantles of these planets in the form of NH3–He compounds. Structure predictions reveal two energetically stable NH3–He compounds with stoichiometries (NH3)2He and NH3He at high pressures. At low temperatures, (NH3)2He is ionic with NH3 molecules partially dissociating into (NH2)− and (NH4)+ ions. Simulations show that (NH3)2He transforms into intermediate phase at 100 GPa and 1000 K with H atoms slightly vibrate around N atoms, and then to a superionic phase at  ~2000 K with H and He exhibiting liquid behavior within the fixed N sublattice. Finally, (NH3)2He becomes a fluid phase at temperatures of 3000 K. The stability of (NH3)2He at high pressure and temperature could contribute to update models of the interiors of Uranus and Neptune.
Author Correction: HIF1α inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis
Authors: Liang Chao , Li Jie , Lu Cheng , Xie Duoli , Liu Jin , Zhong Chuanxin , Wu Xiaohao , Dai Rongchen , Zhang Huarui , Guan Daogang , Guo Baosheng , He Bing , Li Fangfei , He Xiaojuan , Zhang Wandong , Zhang Bao-Ting , Zhang Ge , Lu Aiping
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The genome of Prasinoderma coloniale unveils the existence of a third phylum within green plants
Authors: Li Linzhou , Wang Sibo , Wang Hongli , Sahu Sunil Kumar , Marin Birger , Li Haoyuan , Xu Yan , Liang Hongping , Li Zhen , Cheng Shifeng , Reder Tanja , Çebi Zehra , Wittek Sebastian , Petersen Morten , Melkonian Barbara , Du Hongli , Yang Huanming , Wang Jian , Wong Gane Ka-Shu , Xu Xun , Liu Xin , Van de Peer Yves , Melkonian Michael , Liu Huan
Published: June 2020

Genome analysis of the pico-eukaryotic marine green algaPrasinoderma colonialeCCMP 1413 unveils the existence of a novel phylum within green plants (Viridiplantae), the Prasinodermophyta, which diverged before the split of Chlorophyta and Streptophyta. Structural features of the genome and gene family comparisons revealed an intermediate position of theP. colonialegenome (25.3 Mb) between the extremely compact, small genomes of picoplanktonic Mamiellophyceae (Chlorophyta) and the larger, more complex genomes of early-diverging streptophyte algae. Reconstruction of the minimal core genome of Viridiplantae allowed identification of an ancestral toolkit of transcription factors and flagellar proteins. Adaptations ofP. colonialeto its deep-water, oligotrophic environment involved expansion of light-harvesting proteins, reduction of early light-induced proteins, evolution of a distinct type of C4photosynthesis and carbon-concentrating mechanism, synthesis of the metal-complexing metabolite picolinic acid, and vitamin B1, B7and B12auxotrophy. TheP. colonialegenome provides first insights into the dawn of green plant evolution.
Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder
Authors: Gerasimenko Maria , Cherepanov Stanislav M. , Furuhara Kazumi , Lopatina Olga , Salmina Alla B. , Shabalova Anna A. , Tsuji Chiharu , Yokoyama Shigeru , Ishihara Katsuhiko , Brenner Charles , Higashida Haruhiro
Published: June 2020

Oxytocin (OT) is a critical molecule for social recognition and memory that mediates social and emotional behaviours. In addition, OT acts as an anxiolytic factor and is released during stress. Based on the activity of CD38 as an enzyme that produces the calcium-mobilizing second messenger cyclic ADP-ribose (cADPR), CD157, a sister protein of CD38, has been considered a candidate mediator for the production and release of OT and its social engagement and anti-anxiety functions. However, the limited expression of CD157 in the adult mouse brain undermined confidence that CD157 is an authentic and/or actionable molecular participant in OT-dependent social behaviour. Here, we show that CD157 knockout mice have low levels of circulating OT in cerebrospinal fluid, which can be corrected by the oral administration of nicotinamide riboside, a recently discovered vitamin precursor of nicotinamide adenine dinucleotide (NAD). NAD is the substrate for the CD157- and CD38-dependent production of cADPR. Nicotinamide riboside corrects social deficits and fearful and anxiety-like behaviours in CD157 knockout males. These results suggest that elevating NAD levels with nicotinamide riboside may allow animals with cADPR- and OT-forming deficits to overcome these deficits and function more normally.
Dietary protein restriction deciphers new relationships between lifespan, fecundity and activity levels in fruit flies Drosophila melanogaster
Authors: Krittika Sudhakar , Yadav Pankaj
Published: June 2020

Drosophila melanogaster has been used in Diet Restriction (DR) studies for a few decades now, due to easy diet implementation and its short lifespan. Since the concentration of protein determines the trade-offs between lifespan and fecundity, it is important to understand the level of protein and the extent of its influence on lifespan, fecundity and activity of fruit flies. In this study, we intend to assess the effect of a series of protein restricted diets from age 1 day of the adult fly on these traits to understand the possible variations in trade-off across tested diets. We found that lifespan under different protein concentrations remains unaltered, even though protein restricted diets exerted an age-specific influence on fecundity. Interestingly, there was no difference in lifetime activity of the flies in most of the tested protein restricted (PR) diets, even though a sex-dependent influence of protein concentrations was observed. Additionally, we report that not all concentrations of PR diet increase activity, thereby suggesting that the correlation between lifespan and the lifetime activity can be challenged under protein-restricted condition. Therefore, the PR does not need to exert its effect on lifespan and fecundity only but can also influence activity levels of the flies, thereby emphasizing the role of nutrient allotment between lifespan, fecundity and activity.
Sequential delithiation behavior and structural rearrangement of a nanoscale composite-structured Li1.2Ni0.2Mn0.6O2 during charge–discharge cycles
Authors: Shimoda Keiji , Yazawa Koji , Matsunaga Toshiyuki , Murakami Miwa , Yamanaka Keisuke , Ohta Toshiaki , Matsubara Eiichiro , Ogumi Zempachi , Abe Takeshi
Published: June 2020

Lithium- and manganese-rich layered oxides (LMRs) are promising positive electrode materials for next-generation rechargeable lithium-ion batteries. Herein, the structural evolution of Li1.2Ni0.2Mn0.6O2 during the initial charge–discharge cycle was examined using synchrotron-radiation X-ray diffraction, X-ray absorption spectroscopy, and nuclear magnetic resonance spectroscopy to elucidate the unique delithiation behavior. The pristine material contained a composite layered structure composed of Ni-free and Ni-doped Li2MnO3 and LiMO2 (M = Ni, Mn) nanoscale domains, and Li ions were sequentially and inhomogeneously extracted from the composite structure. Delithiation from the LiMO2 domain was observed in the potential slope region associated with the Ni2+/Ni4+ redox couple. Li ions were then extracted from the Li2MnO3 domain during the potential plateau and remained mostly in the Ni-doped Li2MnO3 domain at 4.8 V. In addition, structural transformation into a spinel-like phase was partly observed, which is associated with oxygen loss and cation migration within the Li2MnO3 domain. During Li intercalation, cation remigration and mixing resulted in a domainless layered structure with a chemical composition similar to that of LiNi0.25Mn0.75O2. After the structural activation, the Li ions were reversibly extracted from the newly formed domainless structure.
Synchronization of the circadian clock by time-restricted feeding with progressive increasing calorie intake. Resemblances and differences regarding a sustained hypocaloric restriction
Authors: García-Gaytán Ana Cristina , Miranda-Anaya Manuel , Turrubiate Isaías , López-De Portugal Leonardo , Bocanegra-Botello Guadalupe Nayeli , López-Islas Amairani , Díaz-Muñoz Mauricio , Méndez Isabel
Published: June 2020

Circadian rhythms are the product of the interaction of molecular clocks and environmental signals, such as light-dark cycles and eating-fasting cycles. Several studies have demonstrated that the circadian rhythm of peripheral clocks, and behavioural and metabolic mediators are re-synchronized in rodents fed under metabolic challenges, such as hyper- or hypocaloric diets and subjected to time-restricted feeding protocols. Despite the metabolic challenge, these approaches improve the metabolic status, raising the enquiry whether removing progressively the hypocaloric challenge in a  time-restricted feeding protocol leads to metabolic benefits by the synchronizing effect. To address this issue, we compared the effects of two time-restricted feeding protocols, one involved hypocaloric intake during the entire protocol (HCT) and the other implied a progressive intake accomplishing a normocaloric intake at the end of the protocol (NCT) on several behavioural, metabolic, and molecular rhythmic parameters. We observed that the food anticipatory activity (FAA) was driven and maintained in both HCT and NCT. Resynchronization of hepatic molecular clock, free fatty acids (FFAs), and FGF21 was elicited closely by HCT and NCT. We further observed that the fasting cycles involved in both protocols promoted ketone body production, preferentially beta-hydroxybutyrate in HCT, whereas acetoacetate was favoured in NCT before access to food. These findings demonstrate that time-restricted feeding does not require a sustained calorie restriction for promoting and maintaining the synchronization of the metabolic and behavioural circadian clock, and suggest that metabolic modulators, such as FFAs and FGF21, could contribute to FAA expression.
A new mechanism of strain transfer in polycrystals
Authors: Di Gioacchino F. , Edwards T. E. J. , Wells G. N. , Clegg W. J.
Published: June 2020

At the grain boundaries of plastically deforming polycrystals, strain transfer mechanisms can accommodate the shear strain carried by slip bands and mechanical twins to prevent stress build-ups and damage. So far, only the accommodation obtained through slip (and twinning) alone has been considered in the mechanism known as slip (and twin) transfer. Here, a strain transfer mechanism that also requires the rotation of the crystal lattice is demonstrated. A region of accumulated slip develops perpendicular to the active slip plane in the impinged grain. The slip gradients enable a localized lattice rotation that accommodates the shear strain in the incoming band, preventing the build-up of interfacial stresses. The mechanism operates preferentially at the boundaries between highly misoriented grains. Facilitating strain transfer at these interfaces opens up new possibilities to improve the mechanical properties of polycrystals, as discussed.
In-vivo anterior segment OCT imaging provides unique insight into cerulean blue-dot opacities and cataracts in Down syndrome
Authors: Little Julie-Anne , Mahil Aman-Deep S. , Richardson Patrick , Woodhouse J. Margaret , Vinuela-Navarro Valldeflors , Saunders Kathryn J.
Published: June 2020

Down syndrome (DS) is frequently associated with cataract, but there remains scant information about DS cataract morphology. Supra-nuclear cataracts in DS have been proposed as indicative of beta-amyloid (Aβ) aggregation and thus potential biomarkers for Alzheimer’s (AD). This study employed anterior segment OCT (AS-OCT) and slit-lamp (SL) photography to image the crystalline lens in DS, compared with adult controls. Lens images were obtained post-dilation. Using MATLAB, AS-OCT images were analysed and lens opacities calculated as pixel intensity and area ratios. SL images were classified using LOCS III. Subjects were n = 28 DS (mean ± SD 24.1 ± 14.3years), and n = 36 controls (54.0 ± 3.4years). For the DS group, AS-OCT imaging revealed the frequent presence of small dot opacities (27 eyes, 50%) in the cortex and nucleus of the lens, covering an area ranging from 0.2–14%. There was no relation with age or visual acuity and these dot opacities (p > 0.5) and they were not present in any control lenses. However, their location and morphology does not coincide with previous reports linking these opacities with Aβ accumulation and AD. Four participants (14%) in the DS group had clinically significant age-related cataracts, but there was no evidence of early onset of age-related cataracts in DS.
Novel in-office peroxide-free tooth-whitening gels: bleaching effectiveness, enamel surface alterations, and cell viability
Authors: Ribeiro Juliana Silva , Barboza Andressa da Silva , Cuevas-Suárez Carlos Enrique , da Silva Adriana Fernandes , Piva Evandro , Lund Rafael Guerra
Published: June 2020

To evaluate the bleaching ability, the effect on enamel surface and cytotoxicity of novel tooth-whitening formulations containing papain, ficin, or bromelain. Forty bovine dental discs (6 cm ×4 cm) were pigmentated and randomly allocated into the following groups (n = 10): Group 1, 20 wt% carbamide peroxide (control); group 2, 1% papain-based whitening; group 3, 1% ficin-based whitening; and group 4, 1% bromelain-based whitening. The whitening gels were prepared and applied on the enamel three times per day once a week, for 4 weeks. Color measurement was obtained by CIEDE2000. Enamel Knoop microhardness and roughness were evaluated. The WST-1 assay was used to evaluate the cell viability of mouse fibroblast cells (L929). Data were statistically analyzed by one-way analysis of variance (ANOVA) and Student Newman Keuls’s post hoc test at α = 0.05 significance level. Bromelain, ficin-based, and carbamide peroxide bleaching gels showed a similar color change (p < 0.001). Higher enamel hardness decrease and higher enamel roughness were caused by the carbamide peroxide (p < 0.05). The experimental whitening gels did not affect cell viability. Tooth bleaching gels containing bromelain, papain, or ficin have substantial clinical potential to be used in the development of peroxide-free tooth whitening gels.
Microevolution of Campylobacter jejuni during long-term infection in an immunocompromised host
Authors: Barker Clare R. , Painset Anaïs , Swift Craig , Jenkins Claire , Godbole Gauri , Maiden Martin C. J. , Dallman Timothy J.
Published: June 2020

Campylobacteriosis typically manifests as a short-lived, self-limiting gastrointestinal infection in humans, however prolonged infection can be seen in cases with underlying immunodeficiency. Public Health England received 25 isolates of Campylobacter jejuni from an individual with combined variable immunodeficiency over a period of 15 years. All isolates were typed and archived at the time of receipt. Whole genome sequencing (WGS) and antimicrobial susceptibility testing were performed to examine the relatedness of the isolates and to investigate the changes in the genome that had taken place over the course of the infection. Genomic typing methods were compared to conventional phenotypic methods, and revealed that the infection was caused by a single, persistent strain of C. jejuni belonging to clonal complex ST-45, with evidence of adaptation and selection in the genome over the course of the infection. Genomic analysis of sequence variants associated with antimicrobial resistance identified the genetic background behind rRNA gene mutations causing variable levels of resistance to erythromycin. This application of WGS to examine a persistent case of campylobacteriosis provides insight into the mutations and selective pressures occurring over the course of an infection, some of which have important clinical relevance.
Author Correction: Optimization of Molecules via Deep Reinforcement Learning
Authors: Zhou Zhenpeng , Kearnes Steven , Li Li , Zare Richard N. , Riley Patrick
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
An integrative DNA barcoding framework of ladybird beetles (Coleoptera: Coccinellidae)
Authors: Huang Weidong , Xie Xiufeng , Huo Lizhi , Liang Xinyue , Wang Xingmin , Chen Xiaosheng
Published: June 2020

Even though ladybirds are well known as economically important biological control agents, an integrative framework of DNA barcoding research was not available for the family so far. We designed and present a set of efficient mini-barcoding primers to recover full DNA barcoding sequences for Coccinellidae, even for specimens collected 40 years ago. Based on these mini-barcoding primers, we obtained 104 full DNA barcode sequences for 104 species of Coccinellidae, in which 101 barcodes were newly reported for the first time. We also downloaded 870 COI barcode sequences (658 bp) from GenBank and BOLD database, belonging to 108 species within 46 genera, to assess the optimum genetic distance threshold and compare four methods of species delimitation (GMYC, bPTP, BIN and ABGD) to determine the most accurate approach for the family. The results suggested the existence of a ‘barcode gap’ and that 3% is likely an appropriate genetic distance threshold to delimit species of Coccinellidae using DNA barcodes. Species delimitation analyses confirm ABGD as an accurate and efficient approach, more suitable than the other three methods. Our research provides an integrative framework for DNA barcoding and descriptions of new taxa in Coccinellidae. Our results enrich DNA barcoding public reference libraries, including data for Chinese coccinellids. This will facilitate taxonomic identification and biodiversity monitoring of ladybirds using metabarcoding.
Arterial pulsations drive oscillatory flow of CSF but not directional pumping
Authors: Kedarasetti Ravi Teja , Drew Patrick J. , Costanzo Francesco
Published: June 2020

The brain lacks a traditional lymphatic system for metabolite clearance. The existence of a “glymphatic system” where metabolites are removed from the brain’s extracellular space by convective exchange between interstitial fluid (ISF) and cerebrospinal fluid (CSF) along the paravascular spaces (PVS) around cerebral blood vessels has been controversial. While recent work has shown clear evidence of directional flow of CSF in the PVS in anesthetized mice, the driving force for the observed fluid flow remains elusive. The heartbeat-driven peristaltic pulsation of arteries has been proposed as a probable driver of directed CSF flow. In this study, we use rigorous fluid dynamic simulations to provide a physical interpretation for peristaltic pumping of fluids. Our simulations match the experimental results and show that arterial pulsations only drive oscillatory motion of CSF in the PVS. The observed directional CSF flow can be explained by naturally occurring and/or experimenter-generated pressure differences.
Novel insights on demographic history of tribal and caste groups from West Maharashtra (India) using genome-wide data
Authors: Debortoli Guilherme , Abbatangelo Cristina , Ceballos Francisco , Fortes-Lima Cesar , Norton Heather L. , Ozarkar Shantanu , Parra Esteban J. , Jonnalagadda Manjari
Published: June 2020

The South Asian subcontinent is characterized by a complex history of human migrations and population interactions. In this study, we used genome-wide data to provide novel insights on the demographic history and population relationships of six Indo-European populations from the Indian State of West Maharashtra. The samples correspond to two castes (Deshastha Brahmins and Kunbi Marathas) and four tribal groups (Kokana, Warli, Bhil and Pawara). We show that tribal groups have had much smaller effective population sizes than castes, and that genetic drift has had a higher impact in tribal populations. We also show clear affinities between the Bhil and Pawara tribes, and to a lesser extent, between the Warli and Kokana tribes. Our comparisons with available modern and ancient DNA datasets from South Asia indicate that the Brahmin caste has higher Ancient Iranian and Steppe pastoralist contributions than the Kunbi Marathas caste. Additionally, in contrast to the two castes, tribal groups have very high Ancient Ancestral South Indian (AASI) contributions. Indo-European tribal groups tend to have higher Steppe contributions than Dravidian tribal groups, providing further support for the hypothesis that Steppe pastoralists were the source of Indo-European languages in South Asia, as well as Europe.
The Impact of Bt Corn on Aflatoxin-Related Insurance Claims in the United States
Authors: Yu Jina , Hennessy David A. , Wu Felicia
Published: June 2020

Previous field studies have reached no collective consensus on whether Bt corn, one of the most commonly planted transgenic crops worldwide, has significantly lower aflatoxin levels than non-Bt isolines. Aflatoxin, a mycotoxin contaminating corn and other commodities, causes liver cancer in humans and can pose severe economic losses to farmers. We found that from 2001–2016, a significant inverse correlation existed between Bt corn planting and aflatoxin-related insurance claims in the United States, when controlling for temperature and drought. Estimated benefits of aflatoxin reduction resulting from Bt corn planting are about $120 million to $167 million per year over 16 states on average. These results suggest that Bt corn use is an important strategy in reducing aflatoxin risk, with corresponding economic benefits. If the same principles hold true in other world regions, then Bt corn hybrids adapted to diverse agronomic regions may have a role in reducing aflatoxin in areas prone to high aflatoxin contamination, and where corn is a dietary staple.
Alcohol consumption before pregnancy causes detrimental fetal development and maternal metabolic disorders
Authors: Lee Yoo Jeong , Kim Ji Yeon , Lee Dae Yeon , Park Keon Jae , Kim Gyu Hee , Kim Jeong Eun , Roh Gu Seob , Lim Joong Yeon , Koo Seul , Lim Nam Kyoo , Park Hyun Young , Kim Won-Ho
Published: June 2020

Alcohol consumption before or during pregnancy poses serious health risks to the fetus; however, the underlying mechanisms involved remain obscure. Here, we investigated whether ethanol consumption before pregnancy affects maternal or fetal health and whether pharmacological inhibition of CYP2E1, a major ethanol oxidation enzyme, by 4-methylpyrazole (4-MP) has therapeutic effects. We found that ethanol consumption (5%) 2 weeks before pregnancy resulted in a decrease in the number of viable fetuses and abnormal fetal development, and these effects were accompanied by impaired maternal glucose homeostasis and hepatic steatosis during pregnancy. Neonates of ethanol-fed mice had postnatal macrosomia and significantly decreased growth rates during the lactation period. However, treatment with 4-MP, a CYP2E1 inhibitor, markedly ameliorated the reduction in insulin action and glucose disposal responsiveness in the livers of ethanol-fed mice. Blockage of CYP2E1 significantly reduced the alteration in hepatic lipid deposition, fatty acid oxidation, mitochondrial energy status, and macrophage infiltration observed in ethanol-fed mice. Finally, there was a positive correlation between postnatal macrosomia or growth retardation and increased inflammatory responses. Collectively, our study suggests that even moderate ethanol intake may be detrimental to fetal development and may cause growth retardation through maternal metabolic disorders.
Streptomyces sp SM01 isolated from Indian soil produces a novel antibiotic picolinamycin effective against multi drug resistant bacterial strains
Authors: Maiti Pulak Kumar , Das Sujoy , Sahoo Prithidipa , Mandal Sukhendu
Published: June 2020

A Kashmir Himalayan (India) soil isolate, Streptomyces sp. SM01 was subjected to small scale fermentation for the production of novel antimicrobials, picolinamycin (SM1). The production has been optimized which found to be maximum while incubated in AIA medium (pH 7) for 7 days at 30 °C. Seven days grew crude cell-free culture media (50 µL) showed a larger zone of inhibition against Staphylococcus aureus compared to streptomycin (5 µg) and ampicillin (5 µg). Extraction, purification, and chemical analysis of the antimicrobial component has been proved to be a new class of antibiotic with 1013 dalton molecular weight. We have named this new antibiotic as picolinamycin for consisting picolinamide moiety in the center of the molecule and produced by a Streptomyces sp. In general, the antimicrobial potency of this newly characterized antibiotic found to be higher against Gram-positive organisms than the tested Gram-negative organisms. The MIC of this antimicrobial compound was found to be 0.01 µg/ml for tested Gram-positive organisms and 0.02 to 5.12 µg/ml for Gram-negative organisms. Furthermore, it showed strong growth impairments of several multidrug resistance (MDR) strains, including methicillin-resistant strains of Staphylococci and Enterococci with the MIC value of 0.04 to 5.12 µg/ml and MDR (but methicillin-sensitive) strains of S. aureus with the MIC value of 0.084 µg/ml. It also showed anti-mycobacterial potential in higher concentrations (MIC is 10.24 µg/ml). Picolinamycin however did not show toxicity against tested A549 human cell line indicating that the spectrum of its activity limited within bacteria only.
Impact of hearing loss on the performance of auditory processing measured by questionnaires in Korean adolescents
Authors: Ahn Joong Ho , Oh Seung-Ha , Jang Hyunsook , Lee Jung-Bok , Chung Jong Woo
Published: June 2020

Increasing use of personal listening devices has been accompanied by increase in the prevalence of hearing loss (HL) among youth in Korea, as in other countries. Auditory processing disorder (APD) is one of the main factors affecting academic achievement at school. This study aimed to investigate the prevalence of HL in students attending general middle- and high schools and compare the findings with the APD survey results. From June 1 to December 31, 2016, Korean adolescents (n = 2,791) in the first years of middle- and high school underwent audiometric testing and otologic examination and completed questionnaires on APD. The survey was sponsored by the Korean Society of Otolaryngology-Head and Neck Surgery and the Korean Otology Society. The prevalence of speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL) in the poorer ear was 11.6% and 10.3%, respectively, among Korean adolescents. We analysed data from the Scale of Auditory Behaviors, Fisher’s Auditory Problems Checklist, and KNISE-Auditory Behavioral Checklist and compared these with the results of hearing tests. We observed positive correlations among the APD questionnaire results and mean hearing levels. This study suggested that hearing loss, especially bilateral high-frequency hearing loss, may affect central auditory processing.
A longitudinal observational retrospective study on risk factors and predictive model of PICC associated thrombosis in cancer patients
Authors: Song Xiaomin , Lu Hong , Chen Fang , Bao Zuowei , Li Shanquan , Li Siqin , Peng Yinghua , Liu Qiao , Chen Xiaohui , Li Jingzhen , Zhang Weimin
Published: June 2020

To analyze the incidence of PICC associated venous thrombosis. To predict the risk factors of thrombosis. To validate the best predictive model in predicting PICC associated thrombosis. Consecutive oncology cases in 341 who initially naive intended to be inserted central catheter for chemotherapy, were recruited to our dedicated intravenous lab. All patients used the same gauge catheter, Primary endpoint was thrombosis formation, the secondary endpoint was infusion termination without thrombosis. Two patients were excluded. 339 patients were divided into thrombosis group in 59 (17.4%) and non-thrombosis Group in 280 (82.6%), retrospectively. Tumor, Sex, Age, Weight, Height, BMI, BSA, PS, WBC, BPC, PT, D-dimer, APTT, FIB, Smoking history, Location, Catheter length, Ratio and Number as independent variables were analyzed by Fisher’s scoring, then Logistic risk regression, ROC analysis and nomogram was introduced. Total incidence was 17.4%. Venous mural thrombosis in 2 (3.4%), “fibrin sleeves” in 55 (93.2%), mixed thrombus in 2 (3.4%), symptomatic thrombosis in 2 (3.4%), asymptomatic thrombosis in 57 (96.6%), respectively. Height (χ² = 4.48, P = 0.03), D-dimer (χ² = 37.81, P < 0.001), Location (χ² = 7.56, P = 0.006), Number (χ² = 43.64, P < 0.001), Ratio (χ² = 4.38, P = 0.04), and PS (χ² = 58.78, P < 0.001), were statistical differences between the two groups analyzed by Fisher’s scoring. Logistic risk regression revealed that Height (β = −0.05, HR = 0.95, 95%CI: 0.911–0.997, P = 0.038), PS (β = 1.07, HR = 2.91, 95%CI: 1.98–4.27, P < 0.001), D-dimer (β0.11, HR = 1.12, 95%CI: 1.045–1.200, P < 0.001), Number (β = 0.87, HR = 2.38, 95% CI: 1.619–3.512, P < 0.001) was independently associated with PICC associated thrombosis. The best prediction model, D-dimer + Number as a novel co-variable was validated in diagnosing PICC associated thrombosis before PICC. Our research revealed that variables PS, Number, D-dimer and Height were risk factors for PICC associated thrombosis, which were slightly associated with PICC related thrombosis, in which, PS was the relatively strongest independent risk factor of PICC related thrombosis.
Long-term morphologic fundus and optic nerve head pattern of progressive myopia in congenital glaucoma distinguished by age at first surgery
Authors: Lee Eun Jung , Han Jong Chul , Park Do Young , Kee Changwon
Published: June 2020

The purpose of this study was to investigate the preservation of round optic nerve head (ONH) shape in myopic eyes of surgically treated congenital glaucoma patients, with regard to factors associated with intraocular pressure (IOP) elevation-induced peripapillary scleral (PPS) deformation. Using optical coherence tomography (OCT) on the ONH and macula, we identified myopic eyes with round ONH and internally oblique border tissue and those with non-round ONH. We investigated differences in clinical factors between the two groups. We included 51 eyes of 34 patients. Age at first surgery (2.8 vs. 15.2 months, P < 0.001) was significantly different between the two groups. Axial length was also significantly longer (P = 0.004) in the non-round group, but multiple logistic regression analysis revealed age as the only significant factor (P < 0.05) in ONH roundness. Interestingly, the round ONH group also had non-curved fundus morphology and a thick choroid, while the non-round ONH group showed diverse degrees of disc tilt and posterior pole curvature, and a thin choroid. In conclusion, in eyes with congenital glaucoma, age at first surgery, particularly when older than 6 months, was associated with round ONH and emmetropia-like fundus despite high myopia. The findings may indicate two different changes in the posterior sclera and the neural canal in response to the increased IOP.
Gut Microbiota Profiles of Treated Metabolic Syndrome Patients and their Relationship with Metabolic Health
Authors: Wutthi-in Montree , Cheevadhanarak Supapon , Yasom Sakawdaurn , Kerdphoo Sasiwan , Thiennimitr Parameth , Phrommintikul Arintaya , Chattipakorn Nipon , Kittichotirat Weerayuth , Chattipakorn Siriporn
Published: June 2020

Metabolic syndrome (MetS) has become a worldwide health issue. Recent studies reveal that the human gut microbiota exerts a significant role in the pathogenesis of this disease. While drug treatments may greatly improve metabolic symptoms, little is known about the gut microbiota composition of these treated MetS patients. This study aimed to characterize the gut microbiota composition of treated-MetS patients and analyse the possibility of using gut microbiota as an indicator of metabolic conditions. 16S rRNA metagenomic sequencing approach was used to profile gut microbiota of 111 treated MetS patients from The Cohort of patients at a high Risk of Cardiovascular Events (CORE)-Thailand registry. Our results show that the gut microbiota profiles of MetS patients are diverse across individuals, but can be classified based on their similarity into three groups or enterotypes. We also showed several associations between species abundance and metabolic parameters that are enterotype specific. These findings suggest that information on the gut microbiota can be useful for assessing treatment options for MetS patients. In addition, any correlations between species abundance and human properties are likely specific to each microbial community.
Cellular polyamines condense hyperphosphorylated Tau, triggering Alzheimer’s disease
Authors: Ivanov Stefan M. , Atanasova Mariyana , Dimitrov Ivan , Doytchinova Irini A.
Published: June 2020

Many gaps in our understanding of Alzheimer’s disease remain despite intense research efforts. One such prominent gap is the mechanism of Tau condensation and fibrillization. One viewpoint is that positively charged Tau is condensed by cytosolic polyanions. However, this hypothesis is likely based on an overestimation of the abundance and stability of cytosolic polyanions and an underestimation of crucial intracellular constituents – the cationic polyamines. Here, we propose an alternative mechanism grounded in cellular biology. We describe extensive molecular dynamics simulations and analysis on physiologically relevant model systems, which suggest that it is not positively charged, unmodified Tau that is condensed by cytosolic polyanions but negatively charged, hyperphosphorylated Tau that is condensed by cytosolic polycations. Our work has broad implications for anti-Alzheimer’s research and drug development and the broader field of tauopathies in general, potentially paving the way to future etiologic therapies.
Minimal Hepatic Encephalopathy: Effect of H. pylori infection and small intestinal bacterial overgrowth treatment on clinical outcomes
Authors: Abid Shahab , Kamran Muhammad , Abid Adeel , Butt Nazish , Awan Safia , Abbas Zaigham
Published: June 2020

The effect Helicobacter pylori (Hp) infection and small intestinal bacterial over growth (SIBO) in minimal hepatic encephalopathy (MHE) is not well understood. The aim of the study was to determine the effect of eradication of Hp infection and SIBO treatment on MHE in patients with cirrhosis. Patients with cirrhosis were enrolled and MHE was determined by psychometric tests and critical flicker frequency analysis. Hp infection and SIBO were assessed by urea breath and Hydrogen breath tests respectively in patients with cirrhosis and in healthy volunteers. Patients with Hp infection and SIBO were given appropriate treatment. At six weeks follow-up, presence of Hp infection, SIBO and MHE status was reassessed. Ninety patients with cirrhosis and equal number of healthy controls were included. 55 (61.1%) patients in the cirrhotic group were diagnosed to have underlying MHE. Among cirrhotic group, Hp infection was present in 28 with MHE (50.9%) vs. in 15 without MHE (42.8%) (p = 0.45). Similarly, SIBO was present in 17 (30.9%) vs. 11 (31.4%) (p = 0.95) in patients with and without MHE respectively. In comparison with healthy controls, patients with cirrhosis were more frequently harboring Hp and SIBO (47.7% vs. 17.7% (p < 0.001) and 31.1% vs. 4.4% (p < 0.001) respectively. On follow-up, all patients showed evidence of eradication of Hp and SIBO infection. Treatment of SIBO significantly improved the state of MHE in cirrhotics, however eradication of Hp infection did not improve MHE significantly. Additionally, patients with low Model for End-Stage Liver Disease (MELD) score and belonging to Child class B had significantly better improvement in MHE. A large number of patients with cirrhosis had either active Hp infection or SIBO with or without MHE, compared to healthy controls. Treatment of SIBO significantly improved MHE in patients with cirrhosis, whereas eradication of Hp did not affect the outcome of MHE in these patients.
Formation of large area closely packed carbon onions film by plasma-based ion implantation
Authors: Matsumoto Naohiro , Kinoshita Hiroshi , Choi Junho , Kato Takahisa
Published: June 2020

A substantial quantity of carbon onions in a durable film state is indispensable for its applications. In this study, large area fabrication of closely packed homogeneous carbon onion nanoparticle film using plasma-based ion implantation was demonstrated. Ag film deposited on a Si substrate was used as the implantation target for the hydrocarbon ions accelerated at 20 kV. Nanoparticles with the mean diameter of 7.5 nm were formed at the grain boundary of the Ag film. Carbon onions with the mean diameter of 17.4 nm were synthesized and arranged to a closely packed nanoparticle film with the thickness of around 200 nm by gradual thermal vaporization of the Ag. The closely packed configuration was achieved due to the isolated growth of carbon onion nanoparticle and high uniformity of the diameter. This process can be used in principle large area formation compered to typical ion implantation technique of carbon onion nanoparticle film, which can be applicable for the practical use in mechanical and electrochemical applications.
Applying support-vector machine learning algorithms toward predicting host–guest interactions with cucurbit[7]uril
Authors: Tabet Anthony , Gebhart Thomas , Wu Guanglu , Readman Charlie , Pierson Smela Merrick , Rana Vijay K. , Baker Cole , Bulstrode Harry , Anikeeva Polina , Rowitch David H. , Scherman Oren A.
Published: June 2020

We evaluate the ability of support-vector machines to predict the equilibrium binding constant of small molecules to cucurbit[7]uril.