bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study and polygenic risk score analysis of esketamine treatment response
Authors: Li Qingqin S. , Wajs Ewa , Ochs-Ross Rachel , Singh Jaskaran , Drevets Wayne C. 
Published: July 2020

AbstractTo elucidate the genetic underpinnings of the antidepressant efficacy of S-ketamine (esketamine) nasal spray in major depressive disorder (MDD), we performed a genome-wide association study (GWAS) in cohorts of European ancestry (n = 527). This analysis was followed by a polygenic risk score approach to test for associations between genetic loading for psychiatric conditions, symptom profiles and esketamine efficacy. We identified a genome-wide significant locus in IRAK3 (p = 3.57 × 10–8, rs11465988, β = − 51.6, SE = 9.2) and a genome-wide significant gene-level association in NME7 (p = 1.73 × 10–6) for esketamine efficacy (i.e. percentage change in symptom severity score compared to baseline). Additionally, the strongest association with esketamine efficacy identified in the polygenic score analysis was from the genetic loading for depressive symptoms (p = 0.001, standardized coefficient β = − 3.1, SE = 0.9), which did not reach study-wide significance. Pathways relevant to neuronal and synaptic function, immune signaling, and glucocorticoid receptor/stress response showed enrichment among the suggestive GWAS signals.
The polyketide synthase PKS15 has a crucial role in cell wall formation in Beauveria bassiana
Authors: Udompaisarn Somsiri , Toopaang Wachiraporn , Sae-Ueng Udom , Srisuksam Chettida , Wichienchote Nuchnudda , Wasuwan Rudsamee , Nahar Nur Amalina Shamsun , Tanticharoen Morakot , Amnuaykanjanasin Alongkorn 
Published: July 2020

AbstractEntomopathogenic fungi utilize specific secondary metabolites to defend against insect immunity, thereby enabling colonization of their specific hosts. We are particularly interested in the polyketide synthesis gene pks15, which is involved in metabolite production, and its role in fungal virulence. Targeted disruption of pks15 followed by genetic complementation with a functional copy of the gene would allow for functional characterization of this secondary metabolite biosynthesis gene. Using a Beauveria bassiana ∆pks15 mutant previously disrupted by a bialophos-resistance (bar) cassette, we report here an in-cis complementation at bar cassette using CRISPR/Cas9 gene editing. A bar-specific short guide RNA was used to target and cause a double-strand break in bar, and a donor DNA carrying a wild-type copy of pks15 was co-transformed with the guide RNA. Isolate G6 of ∆pks15 complemented with pks15 was obtained and verified by PCR, Southern analyses and DNA sequencing. Compared to ∆pks15 which showed a marked reduction in sporulation and insect virulence, the complementation in G6 restored with insect virulence, sporulation and conidial germination to wild-type levels. Atomic force and scanning electron microscopy revealed that G6 and wild-type conidial wall surfaces possessed the characteristic rodlet bundles and rough surface while ∆pks15 walls lacked the bundles and were relatively smoother. Conidia of ∆pks15 were larger and more elongated than that of G6 and the wild type, indicating changes in their cell wall organization. Our data indicate that PKS15 and its metabolite are likely not only important for fungal virulence and asexual reproduction, but also cell wall formation.
Effects of amines on the formation and photodegradation of DCNM under UV/chlorine disinfection
Authors: Deng Lin , Liao Xueying , Shen Jiaxin , Xu Bohui 
Published: July 2020

AbstractInvestigations were conducted to examine the effects of amine type and initial concentration, free chlorine concentration, UV light intensity, pH and tert-butyl alcohol (TBA) on the formation of dichloronitromethane (DCNM) under UV/chlorine. Methylamine (MA), dimethylamine (DMA) and poly-dimethyl diallyl ammonium chloride (PolyDADMAC) were selected as the amine precursors of DCNM. And the reaction products of amines were explored through observing the contents of various nitrogen under UV/chlorine. Experimental results indicated that the higher of the intensity of UV light, the concentration of amines and free chlorine, the greater of the amount of DCNM formation; the amine substance with simple structure is more likely oxidized to form DCNM, so the potential of MA to form DCNM is the largest among three amines; the formation of DCNM decreased with increasing pH from 6.0 to 8.0; due to adding TBA into the reaction solution, halogen and hydroxyl radicals were restrained which resulted the DCNM formation decreased. In the reaction process, the formation of DCNM from amines increased at the beginning, then decreased and almost disappeared due to photodegradation. During the formation and photodegradation of DCNM, the dissolved organic nitrogen could be transformed into the ammonia-nitrogen (NH3-N) and nitrate-nitrogen (NO3−-N).
EGCG impedes human Tau aggregation and interacts with Tau
Authors: Sonawane Shweta Kishor , Chidambaram Hariharakrishnan , Boral Debjyoti , Gorantla Nalini Vijay , Balmik Abhishek Ankur , Dangi Abha , Ramasamy Sureshkumar , Marelli Udaya Kiran , Chinnathambi Subashchandrabose 
Published: July 2020

AbstractTau aggregation and accumulation is a key event in the pathogenesis of Alzheimer’s disease. Inhibition of Tau aggregation is therefore a potential therapeutic strategy to ameliorate the disease. Phytochemicals are being highlighted as potential aggregation inhibitors. Epigallocatechin-3-gallate (EGCG) is an active phytochemical of green tea that has shown its potency against various diseases including aggregation inhibition of repeat Tau. The potency of EGCG in altering the PHF assembly of full-length human Tau has not been fully explored. By various biophysical and biochemical analyses like ThS fluorescence assay, MALDI-TOF analysis and Isothermal Titration Calorimetry, we demonstrate dual effect of EGCG on aggregation inhibition and disassembly of full-length Tau and their binding affinity. The IC50 for Tau aggregation by EGCG was found to be 64.2 μM.
A model for classification of invasive fungal rhinosinusitis by computed tomography
Authors: Slonimsky Guy , McGinn Johnathan D. , Goyal Neerav , Crist Henry , Hennessy Max , Gagnon Eric , Slonimsky Einat 
Published: July 2020

AbstractOur purpose was to classify acute invasive fungal rhinosinusitis (AIFR) caused by Mucor versus Aspergillus species by evaluating computed tomography radiological findings. Two blinded readers retrospectively graded radiological abnormalities of the craniofacial region observed on craniofacial CT examinations obtained during initial evaluation of 38 patients with eventually pathology-proven AIFR (13:25, Mucor:Aspergillus). Binomial logistic regression was used to analyze correlation between variables and type of fungi. Score-based models were implemented for analyzing differences in laterality of findings, including the ‘unilateral presence’ and ‘bilateral mean’ models. Binary logistic regression was used, with Score as the only predictor and Group (Mucor vs Aspergillus) as the only outcome. Specificity, sensitivity, positive predictive value, negative predictive value and accuracy were determined for the evaluated models. Given the low predictive value of any single evaluated anatomical site, a ‘bilateral mean’ score-based model including the nasal cavity, maxillary sinuses, ethmoid air cells, sphenoid sinus and frontal sinuses yielded the highest prediction accuracy, with Mucor induced AIFR correlating with higher prevalence of bilateral findings. The odds ratio for the model while integrating the above anatomical sites was 12.3 (p < 0.001). PPV, NPV, sensitivity, specificity and accuracy were 0.85, 0.82, 0.92, 0.69 and 0.84 respectively. The abnormal radiological findings on craniofacial CT scans of Mucor and Aspergillus induced AIFR could be differentiated based on laterality, with Mucor induced AIFR associated with higher prevalence of bilateral findings.
Relative efficacy of three approaches to mitigate Crown-of-Thorns Starfish outbreaks on Australia’s Great Barrier Reef
Authors: Westcott David A. , Fletcher Cameron S. , Kroon Frederieke J. , Babcock Russell C. , Plagányi Eva E. , Pratchett Morgan S. , Bonin Mary C. 
Published: July 2020

AbstractPopulation outbreaks of Crown-of-Thorns Starfish (COTS; Acanthaster spp.) are a major contributor to loss of hard coral throughout the Indo-Pacific. On Australia’s Great Barrier Reef (GBR), management interventions have evolved over four COTS outbreaks to include: (1) manual COTS control, (2) Marine Protected Area (MPA) zoning, and, (3) water quality improvement. Here we evaluate the contribution of these three approaches to managing population outbreaks of COTS to minimize coral loss. Strategic manual control at sites reduced COTS numbers, including larger, more fecund and damaging individuals. Sustained reduction in COTS densities and improvements in hard coral cover at a site were achieved through repeated control visits. MPAs influenced initial COTS densities but only marginally influenced final hard coral cover following COTS control. Water quality improvement programs have achieved only marginal reductions in river nutrient loads delivered to the GBR and the study region. This, a subsequent COTS outbreak, and declining coral cover across the region suggest their contributions are negligible. These findings support manual control as the most direct, and only effective, means of reducing COTS densities and improving hard coral cover currently available at a site. We provide recommendations for improving control program effectiveness with application to supporting reef resilience across the Indo-Pacific.
In vivo effect of magnetic microspheres loaded with E2-a in the treatment of alveolar echinococcosis
Authors: Li Zhi , Zhang Guochao , Luo Yanping , Gao Qi , Wang Jianghua , Chen Chong , Xu Xiaoying , Zhao Yingying , Li Tingting , Ma Xingming 
Published: July 2020

AbstractThe alveolar echinococcosis of human is a severe helminthic disease caused by the larva of Echinococcus multilocularis tapeworms. Novel compounds or therapy strategies for the treatment of alveolar echinococcosis are urgently needed due to the limitation of the widely used albendazole. Magnetic microspheres as drug carriers in magnetically targeted therapy of tumor have gained growing interests advantaged by delivering the drug to the aimed site, achieving localized therapeutic effect effectively under the influence of an external magnetic field. In this study, we formulated magnetic microspheres loaded with E2-a (PLGA-Fe-E2-a) and identified the activity in E. multilocularis-infected mice which infected with 3,000 protoscoleces intraperitoneally. Compared with the untreated control, with the help of a magnet, there was a significant reduction in parasite burden with PLGA-Fe-E2-a treatment and similar reduction observed with albendazole. PLGA-Fe-E2-a treatment group also showed a significant increase in the IFN-γ level and impaired morphological and ultrastructural alterations. Most importantly, one-third concentrations of E2-a from PLGA-Fe-E2 based on the release profile of E2-a was equally effective in inhibiting metacestode growth as E2-a treated group, supporting efficacy and bioavailability of a drug. It will be an alternative treatment for alveolar echinococcosis using magnetic microspheres as drug carriers.
Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing
Authors: Nanki Yoshiko , Chiyoda Tatsuyuki , Hirasawa Akira , Ookubo Aki , Itoh Manabu , Ueno Masaru , Akahane Tomoko , Kameyama Kaori , Yamagami Wataru , Kataoka Fumio , Aoki Daisuke 
Published: July 2020

AbstractThe use of primary patient-derived organoids for drug sensitivity and resistance testing could play an important role in precision cancer medicine. We developed expandable ovarian cancer organoids in < 3 weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumours. Seven pairs of organoids (3 high-grade serous, 1 clear cell, 3 endometrioid) and original tumours shared 59.5% (36.1–73.1%) of the variants identified. Copy number variations were also similar among organoids and primary tumours. The organoid that harboured the BRCA1 pathogenic variant (p.L63*) showed a higher sensitivity to PARP inhibitor, olaparib, as well as to platinum drugs compared to the other organoids, whereas an organoid derived from clear cell ovarian cancer was resistant to conventional drugs for ovarian cancer, namely platinum drugs, paclitaxel, and olaparib. The overall success rate of primary organoid culture, including those of various histological subtypes, was 80% (28/35). Our data show that patient-derived organoids are suitable physiological ex vivo cancer models that can be used to screen effective personalised ovarian cancer drugs.
Extracellular gp96 is a crucial mediator for driving immune hyperactivation and liver damage
Authors: Guan Zeliang , Ding Yun , Liu Yongai , Zhang Yu , Zhao Jingmin , Li Changfei , Li Zihai , Meng Songdong 
Published: July 2020

AbstractLiver failure leads to the massive necrosis of hepatocytes, releasing large amounts of intracellular components including damage-associated molecular patterns (DAMPs). We found that extracellular gp96 levels in serum were elevated in patients with chronic hepatitis B infection (CHB) and acute-on-chronic liver failure (ACLF). Meanwhile, the gp96 level positively correlated with hepatic necroinflammation. We employed two mouse liver damage and liver failure models induced by lipopolysaccharide (LPS) plus d-galactosamine (d-Galn), and concanavalin A (ConA) to identify the function of extracellular gp96. As a result, the inhibition of extracellular gp96 by a specific peptide efficiently mitigated both LPS/d-Galn- and ConA-induced liver injury and immune hyperactivation, whereas exogenous gp96 aggravated the symptoms of hepatic injury in mice but not in Kupffer cells-ablated mice. The exposure of Kupffer cells to gp96 induced the secretion of pro-inflammatory cytokines. Collectively, our data demonstrate that gp96 released from necrotic hepatocytes aggravates immune hyperactivation and promotes liver damage and possibly the development of liver failure mainly by activating Kupffer cells.
Colonization history affects heating rates of invasive cane toads
Authors: Kosmala Georgia K. , Brown Gregory P. , Shine Richard 
Published: July 2020

AbstractAmphibians in hot climates may be able to avoid high temperatures by controlling their rates of heating. In northern Australia, invasive cane toads (Rhinella marina) experience hot dry conditions in newly-colonized (western) sites but milder conditions in longer-occupied (eastern) sites. Under standardized conditions, toads from western sites heated less rapidly than did conspecifics from an eastern site. The availability of free water slowed heating rates of eastern but not western toads. Thus, the colonization of climatically extreme sites has been accompanied by a rapid shift in the toads’ ability to remain cool under hot conditions, even when free water is not available.
A comparison of the effectiveness of azelaic and pyruvic acid peels in the treatment of female adult acne: a randomized controlled trial
Authors: Chilicka Karolina , Rogowska Aleksandra M. , Szyguła Renata , Dzieńdziora-Urbińska Iwona , Taradaj Jakub 
Published: July 2020

AbstractChemical peels are widely used as therapeutic agents in dermatology and cosmetology. This study aims to explore the differences in the effectiveness of azelaic and pyruvic acid peels in the treatment of acne vulgaris. Eligibility criteria for participants were: female gender, 18–25 years of age, no dermatological treatment within the last 12 months and mild to moderate papulopustular acne. We treated 120 young women (with a mean age of 22 years old) with six peeling sessions at 2-week intervals. In the parallel clinical study design, one randomized group (n = 60, 50%) was treated using azelaic acid (AA), whereas the second group participated in pyruvic acid (PA) sessions. We evaluated the patients clinically twice (before and after treatment), using the Scale of Hellegren–Vincent Severity Symptoms to assess the acne diagnosis, and the Nati Analyzer to estimate the skin properties (oily skin, desquamation, porosity, and moisture). The clinical evaluation of the patients demonstrated a significant reduction of acne severity symptoms in both the AA and PA groups, after the peeling sessions. An effect was also found in terms of decreasing desquamation and the oiliness of the skin. PA showed a more significant reduction of greasy skin than AA. In conclusion, after the six peeling sessions using AA and PA, all patients showed better skin parameters in term of reduced oiliness and desquamation. Both AA and PA peelings are a safe and efficient treatment for mild acne, however, during the selection of one of the two acids, side effects, skin properties, and patients’ preferences should be taken into account. This study was registered in the ISRCTN registry (registration number ISRCTN79716614, 17/01/2020).
Great apes selectively retrieve relevant memories to guide action
Authors: Bobrowicz Katarzyna , Johansson Mikael , Osvath Mathias 
Published: July 2020

AbstractMemory allows us to draw on past experiences to inform behaviour in the present. However, memories rarely match the situation at hand exactly, and new situations regularly trigger multiple related memories where only some are relevant to act upon. The flexibility of human memory systems is largely attributed to the ability to disregard irrelevant, but salient, memories in favour of relevant ones. This is considered an expression of an executive function responsible for suppressing irrelevant memories, associated with the prefrontal cortex. It is unclear to what extent animals have access to this ability. Here, we demonstrate, in a series of tool-use tasks designed to evoke conflicting memories, that chimpanzees and an orangutan suffer from this conflict but overcome it in favour of a more relevant memory. Such mnemonic flexibility is among the most advanced expressions of executive function shown in animals to date and might explain several behaviours related to tool-use, innovation, planning and more.
Synthesis of nickel nanoparticles by a green and convenient method as a magnetic mirror with antibacterial activities
Authors: Ahghari Mohammad Reza , Soltaninejad Vahhab , Maleki Ali 
Published: July 2020

AbstractIn this work, a simple protocol was described for the synthesis of nickel magnetic mirror nanoparticles (NMMNPs) including antibacterial activities. The identification of NMNPs was carried out by field-emission scanning electron microscopy (FESEM) images, energy-dispersive X-ray (EDX) analysis, X-ray diffraction (XRD) pattern, transmission electron microscopy (TEM) images and vibrating sample magnetometer (VSM) curve. The antibacterial activities are investigated against S. aureus and E. coli as the Gram-positive and Gram-negative bacteria, respectively. The UV–Vis absorption was also studied in the present of NMMNPs at different time intervals that disclosed decreasing of the bacterial concentration. More than 80% of the bacteria were disappeared after treating in the presence of NMMNPs for 18 h. The Ni-NPs revealed an excellent mirror attribute with a well-controlled transmission (7%). A better light-reflectivity over conventional glass or a mercury mirror proved their utility for domestic uses in comparison with conventional mirrors as rather toxic materials like mercury. Owing to its magnetic properties, this kind of mirror can be easily made onto glass by using an external magnet. An ordered crystalline structure, admissible magnetic properties, substantial antibacterial activities, tunable mirror properties, mild reaction conditions, and overall, the facile synthesis are the specific features of the present protocol for the possible uses of NMMNPs in diverse applications.
Endogenous NUCB2/Nesfatin-1 Regulates Energy Homeostasis Under Physiological Conditions in Male Rats
Authors: Wilz Anna-Maria , Wernecke Kerstin , Appel Lena , Kahrs Johanna , Dore Riccardo , Jöhren Olaf , Lehnert Hendrik , Schulz Carla 
Published: July 2020

AbstractNesfatin-1 is the proteolytic cleavage product of Nucleobindin 2, which is expressed both in a number of brain nuclei (e. g., the paraventricular nucleus of the hypothalamus) and peripheral tissues. While Nucleobindin 2 acts as a calcium binding protein, nesfatin-1 was shown to affect energy homeostasis upon central nervous administration by decreasing food intake and increasing thermogenesis. In turn, Nucleobindin 2 mRNA expression is downregulated in starvation and upregulated in the satiated state. Still, knowledge about the physiological role of endogenous Nucleobindin 2/nesfatin-1 in the control of energy homeostasis is limited and since its receptor has not yet been identified, rendering pharmacological blockade impossible. To overcome this obstacle, we tested and successfully established an antibody-based experimental model to antagonize the action of nesfatin-1. This model was then employed to investigate the physiological role of endogenous Nucleobindin 2/nesfatin-1. To this end, we applied nesfatin-1 antibody into the paraventricular nucleus of satiated rats to antagonize the presumably high endogenous Nucleobindin 2/nesfatin-1 levels in this feeding condition. In these animals, nesfatin-1 antibody administration led to a significant decrease in thermogenesis, demonstrating the important role of endogenous Nucleobindin 2/nesfatin-1in the regulation of energy expenditure. Additionally, food and water intake were significantly increased, confirming and complementing previous findings. Moreover, neuropeptide Y was identified as a major downstream target of endogenous Nucleobindin 2/nesfatin-1.
Amniotic-Umbilical-to-Cerebral Ratio – A Novel Ratio Combining Doppler Parameters and Amniotic Fluid Volume to Predict Adverse Perinatal Outcome in SGA Fetuses At Term
Authors: Stumpfe Florian Matthias , Faschingbauer Florian , Kehl Sven , Pretscher Jutta , Emons Julius , Gass Paul , Mayr Andreas , Schmid Matthias , Beckmann Matthias Wilhelm , Stelzl Patrick 
Published: July 2020

Abstract
Purpose Introduction of a novel ratio – the amniotic-umbilical-to-cerebral ratio (AUCR) – to predict adverse perinatal outcome in SGA fetuses at term and comparison of its predictive accuracy with established parameters.
Materials and Methods This retrospective cohort study included 165 singleton pregnancies with SGA fetuses (birth weight < 10th percentile) at term. Cases with planned vaginal delivery and documented pulsatility indices (PI) of the umbilical artery (UA), middle cerebral artery (MCA), and single deepest pocket (SDP) were included. CPR was calculated as the ratio between MCA PI and UA PI, UCR as the ratio between UA PI and MCA PI. AUCR was defined as follows: SDP/(UA PI/MCA PI). Adverse perinatal outcomes were defined as operative intervention (OI), OI due to fetal distress, admission to the neonatal intensive care unit (NICU), and composite adverse perinatal outcome (CAPO). Associations between Doppler parameters and these outcomes were estimated using regression analyses.
Results OI was statistically significantly associated with UCR, SDP, and AUCR, whereas no association was observed for UA PI, MCA PI, and CPR. Fetuses requiring OI due to fetal distress revealed a significantly higher UA PI and UCR as well as a lower MCA PI, CPR, and AUCR. With regard to NICU admission and CAPO, a significantly higher UA PI and lower CPR were found. Furthermore, a significant association was shown for SDP, UCR, and AUCR. AUCR achieved the best area under the curve for all outcome parameters.
Conclusion AUCR leads to an improvement in the prediction of unfavorable outcome in SGA fetuses at term. Furthermore, results of our study show that UCR might be superior to CPR.