bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of acute appendicitis among patient admitted for acute abdomen in Ethiopia: Systematic review and meta-analysis
Authors: Obsa Mohammed Suleiman , Adema Bulcha Guye , Shanka Getahun Mola , Lake Eyasu Alem , Azeze Gedion Asnake , Fite Robera Olana
Published: September 2020

ABSTRACT

Background:

Acute abdomen is an acute onset of abdominal disease entities that require immediate surgical intervention. It is one of the commonest surgical emergencies encountered both in developed and developing nations. This systemic review and meta-analysis was aimed at determining the pooled prevalence of acute appendicitis among acute abdomen patients in Ethiopia.

Materials and methods:

PubMed, Science Direct, Google Scholar and Excerpta Medica Database (EMBASE), AJOL, Web of Science, Mednar, and Chocrane library were searched. The data were extracted using Microsoft Excel and analyzed by using STATA version 14. Publication bias was checked by funnel plot and more objectively through Egger's regression test, with P > 0.05 considered to indicate absence publication bias. Heterogeneity of studies was checked using the I2 test. Pooled analysis was conducted. Subgroup analysis was done by region. Leave out one sensitivity analysis was employed to see the effect of single study on the overall estimation. STATA version 14 statistical software was used for meta-analysis.

Results:

The overall prevalence of acute appendicitis was 44.272% (95% CI: 38.366, 50.18.503; I2 = 93.9%). Based on the subgroup analysis, the prevalence of acute appendicitis was 53.2% in Tigrai, 46.54% in Oromia, 44.26% in SNNPR, 41.30% in Addis Ababa, and 36.81% in Amhara.

Conclusion:

The prevalence of acute appendicitis among acute abdomen patients is high. Therefore, close monitoring of the patient prognosis and appropriate prevention techniques is essential.

Highlights:
Gore‐Tex implant extrusion following revision medialization thyroplasty: Case report and review of the literature
Authors: Frost Ariel , Mirza Natasha
Published: September 2020

Objective

To review current literature and experience with Gore‐TexⓇ implant extrusion following medialization thyroplasty, as well as to report the unique case of Gore‐TexⓇ implant extrusion following revision medialization thyroplasty.

Methods

Review of existing literature and description of personal experience with unique case of Gore‐TexⓇ implant extrusion following revision medialization thyroplasty.

Results

Review of existing literature found no prior reported cases of Gore‐TexⓇ implant extrusion following revision medialization thyroplasty. Risk factors for implant extrusion include the pressure of the implant on insertion and the inability to secure the implant. Cases of implant extrusion can be managed operatively via an endoscopic or via an external open approach.

Conclusion

This is the first reported case of Gore‐TexⓇ implant extrusion following revision medialization thyroplasty. Careful consideration should be given in revision medialization thyroplasty as additional implant material may cause increased pressure, a risk factor for implant extrusion.
Talking about culturally responsive approaches to education: teacher professional learning, Indigenous learners and the politics of schooling
Authors: Bishop Michelle , Vass Greg
Published: September 2020

Abstract
Culturally responsive approaches to schooling (CRS) aim to address pervasive inequities that exist in education. More specifically, CRS practices seek to improve the experiences and academic achievements of marginalised and minoritised learners, such as those from culturally and linguistically diverse backgrounds. In this paper, we consider the possibilities for CRS in the context of Australia where Indigenous students (along with their parents, peers and teachers) are consistently reminded, courtesy of the deficit government policies and ‘close the gap’ rhetoric, that they have the worst educational outcomes of any settler society. This paper does not seek to offer fixed solutions in response to this. Rather, based on shared experience researching and teaching together that draw on CRS, the paper foregrounds a collaborative culturally responsive dialogue between the authors. Together we discuss, deliberate and despair about the state of the education system for Indigenous students, we also remain tentatively hopeful about how CRS might become embedded in teaching and learning, through teacher professional learning, in ways that are relevant to the Australian context.
Finding tight Hamilton cycles in random hypergraphs faster
Authors: Allen Peter , Koch Christoph , Parczyk Olaf , Person Yury
Published: September 2020

In an r-uniform hypergraph on n vertices, a tight Hamilton cycle consists of n edges such that there exists a cyclic ordering of the vertices where the edges correspond to consecutive segments of r vertices. We provide a first deterministic polynomial-time algorithm, which finds a.a.s. tight Hamilton cycles in random r-uniform hypergraphs with edge probability at least C log3n/n.

Our result partially answers a question of Dudek and Frieze, who proved that tight Hamilton cycles exist already for p = ω(1/n) for r = 3 and p = (e + o(1))/n for $r \ge 4$ using a second moment argument. Moreover our algorithm is superior to previous results of Allen, Böttcher, Kohayakawa and Person, and Nenadov and Škorić, in various ways: the algorithm of Allen et al. is a randomized polynomial-time algorithm working for edge probabilities $p \ge {n^{ - 1 + \varepsilon}}$, while the algorithm of Nenadov and Škorić is a randomized quasipolynomial-time algorithm working for edge probabilities $p \ge C\mathop {\log }\nolimits^8 n/n$.
Regional Sensitivities Strongly Affect Modeled Climate Extremes
Authors: Shultz David
Published: September 2020

Analysis of temperature and precipitation extremes in two generations of CMIP climate models revealed similarities in regional climate sensitivities, contrasting with divergent global sensitivities.
40Ar/39Ar Thermochronology for Submilligram Samples Using a Ta Platform Microfurnace, With Illustrations From the Bushveld Complex
Authors: Setera Jacob B. , Turrin Brent D. , Herzog Gregory F. , VanTongeren Jill A. , Delaney Jeremy S. , Swisher Carl C.
Published: September 2020

We present a method for40Ar/39Ar step‐heating measurements on anhydrous K‐bearing minerals. Samples placed in dimples on Ta foil platforms are heated indirectly with a laser while temperatures are measured with a two‐color pyrometer. The system provides a simple, inexpensive, and reliable means for the heating of samples as small as a few to tens of micrograms. Results for plagioclase separates from the Rustenburg Layered Suite of the circa 2.06 Ga Bushveld Complex closely match previously published data.
Simultaneous Observations of Geoelectric and Geomagnetic Fields Produced by Magnetospheric ULF Waves
Authors: Hartinger M. D. , Shi X. , Lucas G. M. , Murphy B. S. , Kelbert A. , Baker J. B. H. , Rigler E. J. , Bedrosian P. A.
Published: September 2020

Geomagnetic perturbations (BGEO) related to magnetospheric ultralow frequency (ULF) waves induce electric fields within the conductive Earth—geoelectric fields (EGEO)—that in turn drive geomagnetically induced currents. Though numerous past studies have examined ULF wave BGEO from a space weather perspective, few studies have linked ULF waves with EGEO. Using recently available magnetotelluric impedance and EGEO measurements in the contiguous United States, we explore the relationship between ULF waves and EGEO. We use satellite, ground‐based radar, BGEO, and EGEO measurements in a case study of a plasmaspheric virtual resonance (PVR), demonstrating that the PVR EGEO has significant spatial variation in contrast to a relatively uniform BGEO, consistent with spatially varying Earth conductivity. We further show ULF wave EGEO measurements during two moderate storms of ∼1 V/km. We use both results to highlight the need for more research characterizing ULF wave EGEO.
Seasonality of Dissolved Organic Carbon Exchange Across the Strait of Gibraltar
Authors: Álvarez‐Salgado X. A. , Otero J. , Flecha S. , Huertas I. E.
Published: September 2020

Exchange of mass, heat, and solutes across the Strait of Gibraltar is fundamental to understand the circulation and biogeochemistry of the Mediterranean. Here we focus on the exchange of dissolved organic carbon (DOC) using data from 12 surveys conducted between 2008 and 2015. DOC exchange exhibits a marked bimodal distribution with minima in late June and late October and maxima in mid‐April and late August. This pattern is mainly due to seasonal variation of the DOC gradient between the Atlantic Surface Water entering the Mediterranean and the deep opposite flow of Mediterranean Overflow Water. The gradient is controlled by the different seasonal cycles followed by the DOC in the two layers. Annual average DOC import from the Atlantic is equivalent to 4.2 ± 1.5 Tg C yr−1, which represents 53% of the external DOC inputs and contributes to support 32% of the net heterotrophy of the Mediterranean.
Applying a Deep Learning Algorithm to Tsunami Inundation Database of Megathrust Earthquakes
Authors: Mulia Iyan E. , Gusman Aditya Riadi , Satake Kenji
Published: September 2020

We explore recent developments in computer science on deep learning to estimate high‐resolution tsunami inundation from a quick low‐resolution computation result. Deep network architecture is capable of storing large information acquired via a training/learning process by pairing low‐ and high‐resolution deterministic simulation results from precalculated hypothetical scenarios. In a real case, with a real‐time source estimate and linear simulation computed on a relatively low‐grid resolution, optimized network parameters can be used to rapidly and accurately transform low‐resolution simulation outputs to higher‐resolution grids. We generate 532 source scenarios of interplate earthquakes (Mw 8–9) along the Japan Trench subduction zone to simulate tsunamis and utilize a precalculated library for deep learning. To test the proposed method, we consider a realistic source model inferred from static ground displacements and offshore tsunami data presumably available in real‐time and compare forecasted inundation heights against observations in Rikuzentakata and Otsuchi cities associated with the 2011 Tohoku‐oki tsunami. Our results show that the proposed method exhibits comparable accuracy to the conventional physics‐based simulation but achieves approximately 90% reduction of real‐time computational efforts. Thus, it has good potential as a future tsunami forecasting algorithm.
The Performance of CMIP6 Versus CMIP5 in Simulating Temperature Extremes Over the Global Land Surface
Authors: Fan Xuewei , Miao Chiyuan , Duan Qingyun , Shen Chenwei , Wu Yi
Published: September 2020

Simulations from the models participating in the sixth phase of the Coupled Model Intercomparison Project (CMIP6), which represent the most recent generation of climate models, are now available. Understanding the performance of these models in simulating historical climate extremes can provide a basis for producing reliable future climate projections. Here, we assess the simulation of 16 indices of temperature extremes defined by the Expert Team on Climate Change Detection and Indices using results from 24 CMIP6 models as compared with results from CMIP5. Comparisons with observations and reanalyses indicate that the CMIP6 models could capture the spatial patterns and temporal variations of the observed temperature extremes well for some indices, although less well for others. Based on spatial and temporal skill scores, CMIP6 ensemble means were more skillful in simulating absolute and threshold indices of extreme temperature than CMIP5 ensemble means were, but the performances of both the CMIP5 and CMIP6 ensemble means in simulating the spatial patterns for duration and percentile indices were relatively unsatisfactory (spatial skill scores S < 0.3). Furthermore, our results suggest that there have been improvements in spatial pattern skill scores in some individual CMIP6 models relative to CMIP5 model scores for summer days, tropical nights, cold spell duration, and diurnal temperature range.
Managing Financial Risk Trade‐Offs for Hydropower Generation Using Snowpack‐Based Index Contracts
Authors: Hamilton Andrew L. , Characklis Gregory W. , Reed Patrick M.
Published: September 2020

Hydrologic variability poses an important source of financial risk for hydropower‐reliant electric utilities, particularly in snow‐dominated regions. Drought‐related reductions in hydropower production can lead to decreased electricity sales or increased procurement costs to meet firm contractual obligations. This research contributes a methodology for characterizing the trade‐offs between cash flows and debt burden for alternative financial risk management portfolios, and applies it to a hydropower producer in the Sierra Nevada mountains (San Francisco Public Utilities Commission). A newly designed financial contract, based on a snow water equivalent depth (SWE) index, provides payouts to hydropower producers in dry years in return for the producers making payments in wet years. This contract, called a capped contract for differences (CFD), is found to significantly reduce cash flow volatility and is considered within a broader risk management portfolio that also includes reserve funds and debt issuance. Our results show that solutions relying primarily on a reserve fund can manage risk at low cost but may require a utility to take on significant debt during severe droughts. More risk‐averse utilities with less access to debt should combine a reserve fund with the proposed CFD instrument in order to better manage the financial losses associated with extreme droughts. Our results show that the optimal risk management strategies and resulting outcomes are strongly influenced by the utility's fixed cost burden and by CFD pricing, while interest rates are found to be less important. These results are broadly transferable to hydropower systems in snow‐dominated regions facing significant revenue volatility.
Measuring Fracture Flow Changes in a Bedrock Aquifer Due to Open Hole and Pumped Conditions Using Active Distributed Temperature Sensing
Authors: Munn J. D. , Maldaner C. H. , Coleman T. I. , Parker B. L.
Published: September 2020

Efficiently measuring groundwater flow in bedrock aquifers is inherently challenging due to the irregular distribution and fine scale of fractures. Recent advances in Active Distributed Temperature Sensing (A‐DTS) in boreholes temporarily sealed with liners have made it possible to quantify flow rates in such aquifers at many different depths using heat as a tracer, but until now only data collected under a single hydraulic condition have been published. This paper presents the first field data from multiple A‐DTS field tests conducted under different hydraulic conditions to quantify groundwater flow redistribution within a bedrock aquifer. Three separate quasi steady state A‐DTS tests were collected in a sealed borehole: (1) natural gradient condition where all boreholes were sealed with flexible and impermeable liners, (2) cross‐connected condition where a nearby borehole was open allowing vertical flow within the borehole, and (3) forced gradient condition where the nearby open borehole was pumped at a constant rate of 54 L/min. The depth‐discrete hydraulic head responses were also measured during the three tests using a string of transducers in a sealed borehole. Results provide quantifiable insights as to how the bedrock aquifer responds, including A‐DTS‐derived measurements of flow changes in fractures at multiple depths driven by changes in gradients. The results confirm that a single open borehole or long‐screened well can significantly alter the site hydraulics and demonstrate that not all large or transmissive fractures show evidence of active flow and thus, transmissivity and aperture should not be used alone to infer active flow zones.
Comments on “Bayesian Update and Method of Distributions: Application to Leak Detection in Transmission Mains” by Alawadhi and Tartakovsky
Authors: Wang Xun , Che Tong‐Chuan , Ghidaoui Mohamed S.
Published: September 2020

In a recent paper (Alawadhi & Tartakovsky, 2020, https://doi.org/10.1029/2019WR025879), Alawadhi and Tartakovsky proposed an interesting, novel, efficient, and potentially powerful Bayesian‐based approach to cope with the uncertainty in initial flow velocity when using transient waves to detect leaks in pressurized pipes. In this discussion, we illustrate that the uncertainty in initial flow velocity has negligible effect on the accuracy of transient‐based leak detection methods. On the other hand, uncertainties in the wave speed have significant effects on the leak detection accuracy. Unfortunately, it appears that the proposed approach cannot be easily, if at all, extended to deal with uncertainties in wave speed and one may have to resort to classical Bayesian approaches which could be computationally intensive.
Light-modulated vertical heterojunction phototransistors with distinct logical photocurrents
Authors: Han Jiayue , He Meiyu , Yang Ming , Han Qi , Wang Fang , Zhong Fang , Xu Mengjian , Li Qing , Zhu He , Shan Chongxin , Hu Weida , Chen Xiaoqing , Wang Xinran , Gou Jun , Wu Zhiming , Wang Jun
Published: September 2020

The intriguing carrier dynamics in graphene heterojunctions have stimulated great interest in modulating the optoelectronic features to realize high-performance photodetectors. However, for most phototransistors, the photoresponse characteristics are modulated with an electrical gate or a static field. In this paper, we demonstrate a graphene/C60/pentacene vertical phototransistor to tune both the photoresponse time and photocurrent based on light modulation. By exploiting the power-dependent multiple states of the photocurrent, remarkable logical photocurrent switching under infrared light modulation occurs in a thick C60 layer (11 nm) device, which implies competition of the photogenerated carriers between graphene/C60 and C60/pentacene. Meanwhile, we observe a complete positive-negative alternating process under continuous 405 nm irradiation. Furthermore, infrared light modulation of a thin C60 (5 nm) device results in a photoresponsivity improvement from 3425 A/W up to 7673 A/W, and we clearly probe the primary reason for the distinct modulation results between the 5 and 11 nm C60 devices. In addition, the tuneable bandwidth of the infrared response from 10 to 3 × 103 Hz under visible light modulation is explored. Such distinct types of optical modulation phenomena and logical photocurrent inversion characteristics pave the way for future tuneable logical photocurrent switching devices and high-performance phototransistors with vertical graphene heterojunction structures.
Quorum sensing controls persistence, resuscitation, and virulence of Legionella subpopulations in biofilms
Authors: Personnic Nicolas , Striednig Bianca , Hilbi Hubert
Published: September 2020

The water-borne bacterium Legionella pneumophila is the causative agent of Legionnaires’ disease. In the environment, the opportunistic pathogen colonizes different niches, including free-living protozoa and biofilms. The physiological state(s) of sessile Legionella in biofilms and their functional consequences are not well understood. Using single-cell techniques and fluorescent growth rate probes as well as promoter reporters, we show here that sessile L. pneumophila exhibits phenotypic heterogeneity and adopts growing and nongrowing (“dormant”) states in biofilms and microcolonies. Phenotypic heterogeneity is controlled by the Legionella quorum sensing (Lqs) system, the transcription factor LvbR, and the temperature. The Lqs system and LvbR determine the ratio between growing and nongrowing sessile subpopulations, as well as the frequency of growth resumption (“resuscitation”) and microcolony formation of individual bacteria. Nongrowing L. pneumophila cells are metabolically active, express virulence genes and show tolerance toward antibiotics. Therefore, these sessile nongrowers are persisters. Taken together, the Lqs system, LvbR and the temperature control the phenotypic heterogeneity of sessile L. pneumophila, and these factors regulate the formation of a distinct subpopulation of nongrowing, antibiotic tolerant, virulent persisters. Hence, the biofilm niche of L. pneumophila has a profound impact on the ecology and virulence of this opportunistic pathogen.
The effect of intranasal oxytocin on visual processing and salience of human faces
Authors: Hovey Daniel , Martens Louise , Laeng Bruno , Leknes Siri , Westberg Lars
Published: September 2020

The mechanisms underlying the role of oxytocin (OT) as a regulator of social behavior in mammals are only partly understood. Recently, it has been proposed that OT increases the salience of social stimuli. We carried out a randomized, double-blind, cross-over study of the effects of OT on binocular rivalry, a visual phenomenon underpinned by the interplay of excitation and inhibition in the cortex. A final sample of 45 participants viewed images of social stimuli (faces with different emotional expressions) and non-social stimuli (houses and Gabor patches). We demonstrate a robust effect that intranasal OT increases the salience of human faces in binocular rivalry, such that dominance durations of faces are longer—this effect is not modulated by the facial expression. We tentatively show that OT treatment increases dominance durations for non-social stimuli. Our results lend support to the social salience hypothesis of OT, and in addition offer provisional support for the role of OT in influencing excitation-inhibition balance in the brain.
The prevalence of psychiatric symptoms of pregnant and non-pregnant women during the COVID-19 epidemic
Authors: Zhou Yongjie , Shi Hui , Liu Zhengkui , Peng Songxu , Wang Ruoxi , Qi Ling , Li Zezhi , Yang Jiezhi , Ren Yali , Song Xiuli , Zeng Lingyun , Qian Wei , Zhang Xiangyang
Published: September 2020

Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide, with a staggering number of cases and deaths. However, available data on the psychological impacts of COVID-19 on pregnant women are limited. The purposes of this study were to assess the prevalence of psychiatric symptoms among pregnant women, and to compare them with non-pregnant women. From February 28 to March 12, 2020, a cross-sectional study of pregnant and non-pregnant women was performed in China. The online questionnaire was used to collect information of participants. The mental health status was assessed by patient health questionnaire, generalized anxiety disorder scale, insomnia severity index, somatization subscale of the symptom checklist 90, and post-traumatic stress disorder (PTSD) checklist-5. Totally, 859 respondents were enrolled, including 544 pregnant women and 315 non-pregnant women. In this study, 5.3%, 6.8%, 2.4%, 2.6%, and 0.9% of pregnant women were identified to have symptoms of depression, anxiety, physical discomfort, insomnia, and PTSD, respectively. However, the corresponding prevalence rates among non-pregnant women were 17.5%, 17.5%, 2.5%, 5.4%, 5.7%, respectively. After adjusting for other covariates, we observed that pregnancy was associated a reduced risk of symptoms of depression (OR = 0.23; 95% CI: 0.12–0.45), anxiety (OR = 0.26; 95% CI: 0.16–0.42), insomnia (OR = 0.19; 95% CI: 0.06–0.58), and PTSD (OR = 0.15; 95% CI: 0.04–0.53) during the COVID-19 epidemic. Our results indicate that during the COVID-19 epidemic in China, pregnant women have an advantage of facing mental problems caused by COVID-19, showing fewer depression, anxiety, insomnia, and PTSD symptoms than non-pregnant women.
HOTAIR contributes to the carcinogenesis of gastric cancer via modulating cellular and exosomal miRNAs level
Authors: Zhang Jie , Qiu Wei-qing , Zhu Hongyi , Liu Hua , Sun Jian-hua , Chen Yuanwen , Shen Huojian , Qian Chang-lin , Shen Zhi-yong
Published: September 2020

Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs level in GC tissues were examined by qRT-PCR. MTT was used to determine cell viability. Flow cytometry was used to quantify the apoptotic cells. Transwell assay was used to examine the migration and invasion capacity. Dual-luciferase assay was used to examine the interaction between HOTAIR and miR-30a or -b. Capillary formation was used to determine the capillary formation capacity. Weak negative correlations were found between HOTAIR and miR-30a or -b in GC tissue samples. Interestingly, strong negative correlations were identified between the HOTAIR level in GC tissue samples and the miR-30a or -b levels in plasma exosomes. HOTAIR knockdown GC cells exhibited decreased migration, invasion, proliferation, and upregulated apoptosis, which released more miR-30a and -b into the exosomes. KRAS was upregulated when co-cultured with exosomes from HOTAIR overexpressed cells, and promoted GC cells proliferation, migration, and invasion. Meanwhile, HUVEC cells expressed increased VEGF-A and formatted more capillaries. Subsequently, we identified a 10mer target site of miR-30a or -b in HOTAIR sequence, and the overexpression of HOTAIR induced the degradation of miR-30a or -b, indicating a ceRNA role of HOTAIR. We report the negative correlation between the plasma miRNAs level and GC tissue HOTAIR expression for the first time and unveiled the ceRNA role of HOTAIR in GC. HOTAIR functions as an onco-lncRNA regulating the level of miR-30a and -b in both GC cells and exosomes. These findings may give insight into understanding the mechanism of GC pathogenesis and provide new biomarkers for clinical diagnosis.
Optical gap and fundamental gap of oligoynes and carbyne
Authors: Zirzlmeier Johannes , Schrettl Stephen , Brauer Jan C. , Contal Emmanuel , Vannay Laurent , Brémond Éric , Jahnke Eike , Guldi Dirk M. , Corminboeuf Clémence , Tykwinski Rik R. , Frauenrath Holger
Published: September 2020

The optoelectronic properties of various carbon allotropes and nanomaterials have been well established, while the purely sp-hybridized carbyne remains synthetically inaccessible. Its properties have therefore frequently been extrapolated from those of defined oligomers. Most analyses have, however, focused on the main optical transitions in UV-Vis spectroscopy, neglecting the frequently observed weaker optical bands at significantly lower energies. Here, we report a systematic photophysical analysis as well as computations on two homologous series of oligoynes that allow us to elucidate the nature of these weaker transitions and the intrinsic photophysical properties of oligoynes. Based on these results, we reassess the estimates for both the optical and fundamental gap of carbyne to below 1.6 eV, significantly lower than previously suggested by experimental studies of oligoynes.
Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture
Authors: Zhang Qian , Sidorenko Julia , Couvy-Duchesne Baptiste , Marioni Riccardo E. , Wright Margaret J. , Goate Alison M. , Marcora Edoardo , Huang Kuan-lin , Porter Tenielle , Laws Simon M. ,   Australian Imaging Biomarkers and Lifestyle (AIBL) Study, Masters Colin L. , Bush Ashley I. , Fowler Christopher , Darby David , Pertile Kelly , Restrepo Carolina , Roberts Blaine , Robertson Jo , Rumble Rebecca , Ryan Tim , Collins Steven , Thai Christine , Trounson Brett , Lennon Kate , Li Qiao-Xin , Ugarte Fernanda Yevenes , Volitakis Irene , Vovos Michael , Williams Rob , Baker Jenalle , Russell Alyce , Peretti Madeline , Milicic Lidija , Lim Lucy , Rodrigues Mark , Taddei Kevin , Taddei Tania , Hone Eugene , Lim Florence , Fernandez Shane , Rainey-Smith Stephanie , Pedrini Steve , Martins Ralph , Doecke James , Bourgeat Pierrick , Fripp Jurgen , Gibson Simon , Leroux Hugo , Hanson David , Dore Vincent , Zhang Ping , Burnham Samantha , Rowe Christopher C. , Villemagne Victor L. , Yates Paul , Pejoska Sveltana Bozin , Jones Gareth , Ames David , Cyarto Elizabeth , Lautenschlager Nicola , Barnham Kevin , Cheng Lesley , Hill Andy , Killeen Neil , Maruff Paul , Silbert Brendan , Brown Belinda , Sohrabi Harmid , Savage Greg , Vacher Michael , Sachdev Perminder S. , Mather Karen A. , Armstrong Nicola J. , Thalamuthu Anbupalam , Brodaty Henry , Yengo Loic , Yang Jian , Wray Naomi R. , McRae Allan F. , Visscher Peter M.
Published: September 2020

Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimalP-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.
Macrophage secretion of miR-106b-5p causes renin-dependent hypertension
Authors: Oh J. , Matkovich S. J. , Riek A. E. , Bindom S. M. , Shao J. S. , Head R. D. , Barve R. A. , Sands M. S. , Carmeliet G. , Osei-Owusu P. , Knutsen R. H. , Zhang H. , Blumer K. J. , Nichols C. G. , Mecham R. P. , Baldán Á , Benitez B. A. , Sequeira-Lopez M. L. , Gomez R. A. , Bernal-Mizrachi C.
Published: September 2020

Myeloid cells are known mediators of hypertension, but their role in initiating renin-induced hypertension has not been studied. Vitamin D deficiency causes pro-inflammatory macrophage infiltration in metabolic tissues and is linked to renin-mediated hypertension. We tested the hypothesis that impaired vitamin D signaling in macrophages causes hypertension using conditional knockout of the myeloid vitamin D receptor in mice (KODMAC). These mice develop renin-dependent hypertension due to macrophage infiltration of the vasculature and direct activation of renal juxtaglomerular (JG) cell renin production. Induction of endoplasmic reticulum stress in knockout macrophages increases miR-106b-5p secretion, which stimulates JG cell renin production via repression of transcription factors E2f1 and Pde3b. Moreover, in wild-type recipient mice of KODMAC/miR106b−/− bone marrow, knockout of miR-106b-5p prevents the hypertension and JG cell renin production induced by KODMAC macrophages, suggesting myeloid-specific, miR-106b-5p-dependent effects. These findings confirm macrophage miR-106b-5p secretion from impaired vitamin D receptor signaling causes inflammation-induced hypertension.
Conversion of anilines to chiral benzylic amines via formal one-carbon insertion into aromatic C–N bonds
Authors: Li Lei , Yang Min , He Qiuqin , Fan Renhua
Published: September 2020

Insertion of atoms into aromatic carbon-nitrogen bonds is an appealing method for the synthesis of nitrogen-containing molecules and it has the advantage of the availability and abundance of anilines. However, the direct cleavage of aromatic carbon-nitrogen bonds is challenging due to the particularly inert and stable nature of these bonds. Here we report a formal, enantioselective one-carbon insertion into an aromatic carbon-nitrogen bond via an aromaticity dissembly-reconstruction process to directly convert anilines to chiral α-branched benzylic amines. The process involves oxidative dearomatization of para-substituted anilines, chiral sulfur ylide-mediated asymmetric aziridination, and subsequent rearrangement. Chiral sulfur ylides serve as one-carbon insertion units.
Author Correction: The REGγ inhibitor NIP30 increases sensitivity to chemotherapy in p53-deficient tumor cells
Authors: Gao Xiao , Wang Qingwei , Wang Ying , Liu Jiang , Liu Shuang , Liu Jian , Zhou Xingli , Zhou Li , Chen Hui , Pan Linian , Chen Jiwei , Wang Da , Zhang Qing , Shen Shihui , Xiao Yu , Wu Zhipeng , Cheng Yiyun , Chen Geng , Kubra Syeda , Qin Jun , Huang Lan , Zhang Pei , Wang Chuangui , Moses Robb E. , Lonard David M. , O’ Malley Bert W. , Fares Fuad , Zhang Bianhong , Li Xiaotao , Li Lei , Xiao Jianru
Published: September 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Structural characterization of a neutralizing mAb H16.001, a potent candidate for a common potency assay for various HPV16 VLPs
Authors: Huang Weijin , He Maozhou , Ning Tingting , Nie Jianhui , Zhang Feng , Zheng Qingbing , Zhang Rui , Xu Ying , Gu Ying , Li Shaowei , Wang Youchun
Published: September 2020

With more human papillomavirus (HPV) virus-like particle (VLP) vaccines to hit the market in future, a monoclonal antibody (mAb) with preferably comparable reactivity against vaccines from different expression systems and bioprocesses is urgently needed for the potency characterization. Among all mAbs against HPV16 collected, rabbit mAb H16.001 is potently neutralizing with the highest affinity, recognizes an immune-dominant epitope, and can comparably react with HPV16 vaccines from various sources. Cryo-electron microscopic (cryo-EM) structure demonstrated that 360 H16.001 Fabs could bind to HPV16 capsid in preferable binding manner without steric hindrance between neighboring Fabs, potentially supporting its identification for VLP structural integrity and utility in monitoring VLP structural probity. This structural analysis indicated that mAb H16.001 afforded unbiased potency characterization for various HPV16 vaccines and was potential for use in vaccine regulation practice. This study also showed a model process for selecting suitable mAbs for potency assays of other vaccines.
Hourly 5-km surface total and diffuse solar radiation in China, 2007–2018
Authors: Jiang Hou , Lu Ning , Qin Jun , Yao Ling
Published: September 2020

Surface solar radiation is an indispensable parameter for numerical models, and the diffuse component contributes to the carbon uptake in ecosystems. We generated a 12-year (2007–2018) hourly dataset from Multi-functional Transport Satellite (MTSAT) satellite observations, including surface total solar radiation (Rs) and diffuse radiation (Rdif), with 5-km spatial resolution through deep learning techniques. The used deep network tacks the integration of spatial pattern and the simulation of complex radiation transfer by combining convolutional neural network and multi-layer perceptron. Validation against ground measurements shows the correlation coefficient, mean bias error and root mean square error are 0.94, 2.48 W/m2 and 89.75 W/m2 for hourly Rs and 0.85, 8.63 W/m2 and 66.14 W/m2 for hourly Rdif, respectively. The correlation coefficient of Rs and Rdif increases to 0.94 (0.96) and 0.89 (0.92) at daily (monthly) scales, respectively. The spatially continuous hourly maps accurately reflect regional differences and restore the diurnal cycles of solar radiation at fine resolution. This dataset can be valuable for studies on regional climate changes, terrestrial ecosystem simulations and photovoltaic applications.
Crop climate suitability mapping on the cloud: a geovisualization application for sustainable agriculture
Authors: Peter Brad G. , Messina Joseph P. , Lin Zihan , Snapp Sieglinde S.
Published: September 2020

Climate change, food security, and environmental sustainability are pressing issues faced by today’s global population. As production demands increase and climate threatens crop productivity, agricultural research develops innovative technologies to meet these challenges. Strategies include biodiverse cropping arrangements, new crop introductions, and genetic modification of crop varieties that are resilient to climatic and environmental stressors. Geography in particular is equipped to address a critical question in this pursuit—when and where can crop system innovations be introduced? This manuscript presents a case study of the geographic scaling potential utilizing common bean, delivers an open access Google Earth Engine geovisualization application for mapping the fundamental climate niche of any crop, and discusses food security and legume biodiversity in Sub-Saharan Africa. The application is temporally agile, allowing variable growing season selections and the production of ‘living maps’ that are continually producible as new data become available. This is an essential communication tool for the future, as practitioners can evaluate the potential geographic range for newly-developed, experimental, and underrepresented crop varieties for facilitating sustainable and innovative agroecological solutions.
Prospective associations of the infant gut microbiome and microbial function with social behaviors related to autism at age 3 years
Authors: Laue Hannah E. , Korrick Susan A. , Baker Emily R. , Karagas Margaret R. , Madan Juliette C.
Published: September 2020

The hypothesized link between gut bacteria and autism spectrum disorder (ASD) has been explored through animal models and human studies with microbiome assessment after ASD presentation. We aimed to prospectively characterize the association between the infant/toddler gut microbiome and ASD-related social behaviors at age 3 years. As part of an ongoing birth cohort gut bacterial diversity, structure, taxa, and function at 6 weeks (n = 166), 1 year (n = 158), 2 years (n = 129), and 3 years (n = 140) were quantified with 16S rRNA gene and shotgun metagenomic sequencing (n = 101 six weeks, n = 103 one year). ASD-related social behavior was assessed at age 3 years using Social Responsiveness Scale (SRS-2) T-scores. Covariate-adjusted linear and permutation-based models were implemented. Microbiome structure at 1 year was associated with SRS-2 total T-scores (p = 0.01). Several taxa at 1, 2, and 3 years were associated with SRS-2 performance, including many in the Lachnospiraceae family. Higher relative abundance of Adlercreutzia equolifaciens and Ruminococcus torques at 1 year related to poorer SRS-2 performance. Two functional pathways, l-ornithine and vitamin B6 biosynthesis, were associated with better social skills at 3 years. Our results support potential associations between early-childhood gut microbiome and social behaviors. Future mechanistic studies are warranted to pinpoint sensitive targets for intervention.
Live-cell imaging with Aspergillus fumigatus-specific fluorescent siderophore conjugates
Authors: Pfister Joachim , Lichius Alexander , Summer Dominik , Haas Hubertus , Kanagasundaram Thines , Kopka Klaus , Decristoforo Clemens
Published: September 2020

Live-cell imaging allows the in vivo analysis of subcellular localisation dynamics of physiological processes with high spatial–temporal resolution. However, only few fluorescent dyes have been custom-designed to facilitate species-specific live-cell imaging approaches in filamentous fungi to date. Therefore, we developed fluorescent dye conjugates based on the sophisticated iron acquisition system of Aspergillus fumigatus by chemical modification of the siderophore triacetylfusarinine C (TAFC). Various fluorophores (FITC, NBD, Ocean Blue, BODIPY 630/650, SiR, TAMRA and Cy5) were conjugated to diacetylfusarinine C (DAFC). Gallium-68 labelling enabled in vitro and in vivo characterisations. LogD, uptake assays and growth assays were performed and complemented by live-cell imaging in different Aspergillus species. Siderophore conjugates were specifically recognised by the TAFC transporter MirB and utilized as an iron source in growth assays. Fluorescence microscopy revealed uptake dynamics and differential subcellular accumulation patterns of all compounds inside fungal hyphae.[Fe]DAFC-NBD and -Ocean Blue accumulated in vacuoles, whereas [Fe]DAFC-BODIPY, -SiR and -Cy5 localised to mitochondria. [Fe]DAFC -FITC showed a uniform cytoplasmic distribution, whereas [Fe]DAFC-TAMRA was not internalised at all. Co-staining experiments with commercially available fluorescent dyes confirmed these findings. Overall, we developed a new class of fluorescent dyes that vary in intracellular fungal targeting , thereby providing novel tools for live-cell imaging applications for Aspergillus fumigatus.
Play fighting social networks do not predict injuries from later aggression
Authors: Turner Simon P. , Weller Jennifer E. , Camerlink Irene , Arnott Gareth , Choi Taegyu , Doeschl-Wilson Andrea , Farish Marianne , Foister Simone
Published: September 2020

Early play fighting mimics later aggression in many species, and may, therefore, be expected to reduce costs from later aggressive interactions. Using social network analysis (SNA) the effect of a central play fighting network position on later skin lesions from aggression was assessed in domestic pigs. Piglets (n = 263) were kept in litter groups or socialised pre-weaning with another litter to enhance play fighting experience. Play fighting was recorded for 1.5 h per day over 6 days pre-weaning. Play fighting network centrality was quantified using measures of individual network position and entire network structure (degree, eigenvector, betweenness, clustering coefficient). Skin lesions from aggression were counted after a dyadic contest and at 24 h and 3 weeks following group mixing. Pigs with play fighting interactions with many partners experienced fewer lesions from the dyadic contest (in-degree, p = 0.01) and tended to received fewer lesions 3 weeks after group mixing (degree, p = 0.088) but no other play fighting centrality measures affected the number of lesions at any point. The benefits of play fighting were therefore limited to specific aggressive social contexts. The tendency of socialised piglets to play fight with non-littermates did not affect subsequent lesions. We advocate the use of SNA over approaches that only consider dyadic interactions to further our understanding of the influence of early social group interactions on later life experience.
Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring
Authors: Gui Yuzhou , Lu Youli , Li Shuijun , Zhang Mengqi , Duan Xiaokun , Liu Charles C. , Jia Jingying , Liu Gangyi
Published: September 2020

Therapeutic drug monitoring (TDM) is necessary for the optimal administration of anti-arrhythmic drugs in the treatment of heart arrhythmia. The present study aimed to develop and validate a direct analysis in real time tandem mass spectrometry (DART–MS/MS) method for the rapid and simultaneous determination of five anti-arrhythmic drugs (metoprolol, diltiazem, amiodarone, propafenone, and verapamil) and one metabolite (5-hydroxy(OH)-propafenone) in human serum. After the addition of isotope-labeled internal standards and protein precipitation with acetonitrile, anti-arrhythmic drugs were ionized by DART in positive mode followed by multiple reaction monitoring (MRM) detection. The use of DART–MS/MS avoided the need for chromatographic separation and allowed rapid and ultrahigh throughput analysis of anti-arrhythmic drugs in a total run time of 30 s per sample. The DART–MS/MS method yielded satisfactory linearity (R2 ≥ 0.9906), accuracy (86.1–109.9%), and precision (≤ 14.3%) with minimal effect of biological matrixes. The method was successfully applied to analyzing 30 clinical TDM samples. The relative error (RE) of the concentrations obtained by DART–MS/MS and liquid chromatography-tandem mass spectrometry (LC–MS/MS) was within ± 13%. This work highlights the potential usefulness of DART for the rapid quantitative analysis of anti-arrhythmic drugs in human serum and gives rapid feedback in the clinical TDM practices.
Research on drinking-groundwater source safety management based on numerical simulation
Authors: Song Kai , Ren Xu , Mohamed Adam Khalifa , Liu Jian , Wang Fei
Published: September 2020

A drinking-groundwater source protection technology system based on a three-dimensional finite-difference groundwater model was constructed and applied to the safe management of drinking groundwater in the first terrace of Fujiang River. In the study area, the main type of groundwater is the quaternary systemic alluvial deposit loose rock pore water and the aquifer thickness varies between 20 and 35 m. Groundwater is the main source of water and is used for various purposes through two exploitation wells. The water volumes of 1# exploitation well (1#) and 2# exploitation well (2#) are 10,000 m3/day and 5000 m3/day, respectively. An analysis of 22 indicators from 11 groundwater samples showed that a higher concentration of chemical-oxygen-demand (CODMn) and ammonia–nitrogen (NH3–N), and they had a high correlation with most of the other water-quality factors. Therefore, CODMn and NH3–N were selected as indicator factors for model calibration and prediction. Twenty-two hydraulic head observation wells were used for flow-model calibration. The flow model indicated that a drop funnel formed with a maximum depth of 12 m, and the particle-capture zone in the original downstream direction of the south side extended to 1100 m because of groundwater exploitation. The solute-transport model showed that industrial pollution sources were the main factors that led to a deterioration of water quality. To analyze the necessity and effectiveness of remediation measures for the safety of drinking-water sources, two scenarios were considered to predict the concentration of NH3-N and CODMn in groundwater exploitation wells over 20 years. Scenario I, which considered that current conditions were maintained, predicted that the NH3-N would exceed the drinking-water quality standard of 0.5 mg/L after 16 years. Scenario II, in which industrial sewage treatment plants were installed outside the particle-trapped zone of the exploitation wells and strict anti-seepage measures were implemented, predicted that the peak concentrations of NH3-N and CODMn in the exploitation wells would be 0.26 mg/L and 1.33 mg/L, respectively, after 3 years of model operation. This study provides a theoretical basis for drinking-groundwater source protection that can be applied to safety management practices.
The effect of transcranial random noise stimulation (tRNS) over bilateral posterior parietal cortex on divergent and convergent thinking
Authors: Peña Javier , Sampedro Agurne , Ibarretxe-Bilbao Naroa , Zubiaurre-Elorza Leire , Aizpurua Aralar , Ojeda Natalia
Published: September 2020

Creativity pervades many areas of everyday life and is considered highly relevant in several human living domains. Previous literature suggests that the posterior parietal cortex (PPC) is related to creativity. However, none of previous studies have compared the effect of transcranial random noise stimulation (tRNS) over bilateral PPC on both verbal and visual divergent thinking (DT) and Remote Associates Test (RAT) in the same experimental design. Forty healthy participants were randomly assigned to tRNS (100–500 Hz) over bilateral PPC or sham group, for 15 min and current was set at 1.5 mA. Participants’ creativity skills were assessed before and after brain stimulation with the Unusual Uses and the Picture Completion subtests from the Torrance Test of Creative Thinking and the RAT. ANCOVA (baseline scores as covariate) results indicated that tRNS group had significantly higher scores at post-test in RAT and visual originality compared to sham group. Unusual Uses, on the other hand, was not significant. Improvement in RAT suggests the involvement of PPC during via insight solution which may reflect internally directed attention that helps the recombination of remotely associated information. The improvement in visual originality dimension from DT may be due to a higher internally directed attention while reducing externally oriented attention.