bluuebunny/crossref_metadata_2025 huggingface dataset:
Tabletop Application of SALT Triage to 10, 100, and 1000 Pediatric Victims
Authors: McGlynn Nicholas , Claudius Ilene , Kaji Amy H. , Fisher Emilia H. , Shaban Alaa , Cicero Mark X. , Santillanes Genevieve , Gausche-Hill Marianne , Chang Todd P. , Donofrio-Odmann J. Joelle
Published: February 2020

Introduction:

The Sort, Access, Life-saving interventions, Treatment and/or Triage (SALT) mass-casualty incident (MCI) algorithm is unique in that it includes two subjective questions during the triage process: “Is the victim likely to survive given the resources?” and “Is the injury minor?”

Hypothesis/Problem:

Given this subjectivity, it was hypothesized that as casualties increase, the inter-rater reliability (IRR) of the tool would decline, due to an increase in the number of patients triaged as Minor and Expectant.

Methods:

A pre-collected dataset of pediatric trauma patients age <14 years from a single Level 1 trauma center was used to generate “patients.” Three trained raters triaged each patient using SALT as if they were in each of the following scenarios: 10, 100, and 1,000 victim MCIs. Cohen’s kappa test was used to evaluate IRR between the raters in each of the scenarios.

Results:

A total of 247 patients were available for triage. The kappas were consistently “poor” to “fair:” 0.37 to 0.59 in the 10-victim scenario; 0.13 to 0.36 in the 100-victim scenario; and 0.05 to 0.36 in the 1,000-victim scenario. There was an increasing percentage of subjects triaged Minor as the number of estimated victims increased: 27.8% increase from 10- to 100-victim scenario and 7.0% increase from 100- to 1,000-victim scenario. Expectant triage categorization of patients remained stable as victim numbers increased.

Conclusion:

Overall, SALT demonstrated poor IRR in this study of increasing casualty counts while triaging pediatric patients. Increased casualty counts in the scenarios did lead to increased Minor but not Expectant categorizations.
Economics is not statistics (and vice versa)
Authors: Leeson Peter T.
Published: February 2020

Economic analysis is a theoretical approach, not an empirical one. It is a way of thinking, not a way of testing. An analysis that has an empirical component can be economic without being quantitative: economics is not statistics. An atheoretical analysis can never be economic, no matter how impressive its regressions: statistics is not economics.
Changing Rainfall Patterns Over the Western Lake Erie Basin (1975–2017): Effects on Tributary Discharge and Phosphorus Load
Authors: Williams Mark R. , King Kevin W.
Published: February 2020

In agricultural watersheds, shifting climate and hydrologic patterns present an immediate and future risk to both farm productivity and downstream aquatic ecosystems. Here, our objective was to evaluate long‐term spatiotemporal trends in rainfall amount and intensity within the Maumee River‐Lake Erie system and quantify the effects of rainfall patterns on streamflow and phosphorus loading. Across the watershed, annual rainfall increased by 102 ± 115 mm (11 ± 13%) from 1975–2017. Heavy (25.4–76.2 mm) and very heavy (>76.2 mm) rainfall accounted for most of the increase in total rainfall, with observed increases of 45 ± 32% that occurred primarily during spring and summer. Trends in streamflow for 12 monitored subwatersheds generally followed patterns in rainfall, as discharge increased by 19 ± 32%. Discharge‐to‐rainfall ratio increased in 9 of 12 subwatersheds despite no change or increases in watershed storage capacity, suggesting that increasing rainfall intensity that exceeds short‐term watershed storage capacity (i.e., during/immediately following the rainfall event) may control patterns of discharge more than long‐term gains in watershed storage (i.e., changes in soil water holding capacity). Long‐term trends in phosphorus (total phosphorus and soluble reactive phosphorus) load indicate that changes in rainfall amount and intensity have substantially contributed to increased loading through increased discharge volumes. Differences in total phosphorus and soluble reactive phosphorus concentration trends also highlight how concomitant changes in rainfall and land management practices have influenced loading. Findings therefore suggest that changing patterns in rainfall amount and intensity have and will likely continue to pose a significant challenge to conservation efforts in agricultural landscapes aiming to decrease phosphorus delivery to surface waters.
Numerical Study of Solute Transport in Heterogeneous Beach Aquifers Subjected to Tides
Authors: Geng Xiaolong , Boufadel Michel C. , Rajaram Harihar , Cui Fangda , Lee Kenneth , An Chunjiang
Published: February 2020

A numerical study, based on a variably saturated groundwater flow model within a Monto Carlo framework, was conducted to investigate flow and solute transport in a heterogeneous beach aquifer subjected to tides. The numerical simulations were conducted based on our previous tracer experiments performed in a laboratory beach. Heterogeneity is assumed to be multifractal generated using the Universal Multifractal model. Our results show that heterogeneity greatly alters temporal and spatial evolution of the tracer plume migrating in the beach. The spreading coefficient of the plume shows very dynamic response to tides; it increases as the tidally driven recirculation cell overlaps with the plume and decreases as the recirculation cell moves far from the plume with tides. Descriptive statistics suggests that heterogeneity enhances spreading of the plume in the beach in an ensemble sense along with significant spatial and temporal variation. Due to heterogeneity, high spots of the pore water velocity are formed within the recirculation cell, creating transient preferential flow paths in the beach in response to tides. Contours of the Okubo‐Weiss (OW) parameter show that coupling with tides, heterogeneity creates vorticity‐dominated flow regions and also expands strain‐dominated flow regions more downward, indicating complex local‐scale mixing in the beach, compared to corresponding homogeneous case. Geologic heterogeneity also alters the spatial extent of the recirculating cell and induces highly variable transit time along the recirculating flow paths. The results provide insights into effects of geologic heterogeneity on seawater‐groundwater mixing and associated solute transport processes in tidally influenced coastal aquifers.
microRNA-378a-5p iS a novel positive regulator of melanoma progression
Authors: Tupone Maria Grazia , D’Aguanno Simona , Di Martile Marta , Valentini Elisabetta , Desideri Marianna , Trisciuoglio Daniela , Donzelli Sara , Sacconi Andrea , Buglioni Simonetta , Ercolani Cristiana , Biagioni Alessio , Fibbi Gabriella , Fattore Luigi , Mancini Rita , Ciliberto Gennaro , Blandino Giovanni , Del Bufalo Donatella
Published: February 2020

Evaluating the expression levels of miR-378a-5p both in a large melanoma patient cohort from The Cancer Genome Atlas database and in melanoma patients from our Institute, we found that miR-378a-5p is upregulated in metastatic melanoma specimens. miR-378a-5p expression was also increased in melanoma cells resistant to target therapy, and decreased in response to drug treatment. We also demonstrated that overexpression of miR-378a-5p enhances in vitro cell invasion and migration, and facilitates the ability of melanoma cells to form de novo vasculogenic structures. While performing downstream targeting studies, we confirmed the ability of miR-378a-5p to modulate the expression of known target genes, such as SUFU, FUS-1, and KLF9. Luciferase-3′UTR experiments also identified STAMBP and HOXD10 as new miR-378a-5p target genes. MMP2 and uPAR, two HOXD10 target genes, were positively regulated by miR-378a-5p. Genetic and pharmacologic approaches inhibiting uPAR expression and activity evidenced that the in vitro tumor-promoting functions of miR-378a-5p, were in part mediated by uPAR. Of note miR-378a-5p was also able to increase VEGF, as well as in vitro and in vivo angiogenesis. Finally, genetic and pharmacologic modulation of Bcl-2 evidenced Bcl-2 ability to regulate miR-378a-5p expression. In conclusion, to the best of our knowledge, this is the first study demonstrating that miR-378a-5p acts as an oncogenic microRNA in melanoma.
Liquids relax and unify strain in graphene
Authors: Belyaeva Liubov A. , Jiang Lin , Soleimani Alireza , Methorst Jeroen , Risselada H. Jelger , Schneider Grégory F.
Published: February 2020

Solid substrates often induce non-uniform strain and doping in graphene monolayer, therefore altering the intrinsic properties of graphene, reducing its charge carrier mobilities and, consequently, the overall electrical performance. Here, we exploit confocal Raman spectroscopy to study graphene directly free-floating on the surface of water, and show that liquid supports relief the preexisting strain, have negligible doping effect and restore the uniformity of the properties throughout the graphene sheet. Such an effect originates from the structural adaptability and flexibility, lesser contamination and weaker intermolecular bonding of liquids compared to solid supports, independently of the chemical nature of the liquid. Moreover, we demonstrate that water provides a platform to study and distinguish chemical defects from substrate-induced defects, in the particular case of hydrogenated graphene. Liquid supports, thus, are advantageous over solid supports for a range of applications, particularly for monitoring changes in the graphene structure upon chemical modification.
Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency
Authors: Álvarez-Quilón Alejandro , Terrón-Bautista José , Delgado-Sainz Irene , Serrano-Benítez Almudena , Romero-Granados Rocío , Martínez-García Pedro Manuel , Jimeno-González Silvia , Bernal-Lozano Cristina , Quintero Cristina , García-Quintanilla Lourdes , Cortés-Ledesma Felipe
Published: February 2020

The ATM kinase is a master regulator of the DNA damage response to double-strand breaks (DSBs) and a well-established tumour suppressor whose loss is the cause of the neurodegenerative and cancer-prone syndrome Ataxia-Telangiectasia (A-T). A-T patients and Atm−/− mouse models are particularly predisposed to develop lymphoid cancers derived from deficient repair of RAG-induced DSBs during V(D)J recombination. Here, we unexpectedly find that specifically disturbing the repair of DSBs produced by DNA topoisomerase II (TOP2) by genetically removing the highly specialised repair enzyme TDP2 increases the incidence of thymic tumours in Atm−/− mice. Furthermore, we find that TOP2 strongly colocalizes with RAG, both genome-wide and at V(D)J recombination sites, resulting in an increased endogenous chromosomal fragility of these regions. Thus, our findings demonstrate a strong causal relationship between endogenous TOP2-induced DSBs and cancer development, confirming these lesions as major drivers of ATM-deficient lymphoid malignancies, and potentially other conditions and cancer types.
Glass transition temperature from the chemical structure of conjugated polymers
Authors: Xie Renxuan , Weisen Albree R. , Lee Youngmin , Aplan Melissa A. , Fenton Abigail M. , Masucci Ashley E. , Kempe Fabian , Sommer Michael , Pester Christian W. , Colby Ralph H. , Gomez Enrique D.
Published: February 2020

The glass transition temperature (Tg) is a key property that dictates the applicability of conjugated polymers. TheTgdemarks the transition into a brittle glassy state, making its accurate prediction for conjugated polymers crucial for the design of soft, stretchable, or flexible electronics. Here we show that a single adjustable parameter can be used to build a relationship between theTgand the molecular structure of 32 semiflexible (mostly conjugated) polymers that differ drastically in aromatic backbone and alkyl side chain chemistry. An effective mobility value,ζ, is calculated using an assigned atomic mobility value within each repeat unit. The only adjustable parameter in the calculation ofζis the ratio of mobility between conjugated and non-conjugated atoms. We show thatζcorrelates strongly to theTg, and that this simple method predicts theTgwith a root-mean-square error of 13 °C for conjugated polymers with alkyl side chains.
MYCN amplification and ATRX mutations are incompatible in neuroblastoma
Authors: Zeineldin Maged , Federico Sara , Chen Xiang , Fan Yiping , Xu Beisi , Stewart Elizabeth , Zhou Xin , Jeon Jongrye , Griffiths Lyra , Nguyen Rosa , Norrie Jackie , Easton John , Mulder Heather , Yergeau Donald , Liu Yanling , Wu Jianrong , Van Ryn Collin , Naranjo Arlene , Hogarty Michael D. , Kamiński Marcin M. , Valentine Marc , Pruett-Miller Shondra M. , Pappo Alberto , Zhang Jinghui , Clay Michael R. , Bahrami Armita , Vogel Peter , Lee Seungjae , Shelat Anang , Sarthy Jay F. , Meers Michael P. , George Rani E. , Mardis Elaine R. , Wilson Richard K. , Henikoff Steven , Downing James R. , Dyer Michael A.
Published: February 2020

Aggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating mutations in tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene and inactivation of the ATRX tumor-suppressor gene correlate with high-risk disease and poor prognosis. Here we show that ATRX mutations and MYCN amplification are mutually exclusive across all ages and stages in neuroblastoma. Using human cell lines and mouse models, we found that elevated MYCN expression and ATRX mutations are incompatible. Elevated MYCN levels promote metabolic reprogramming, mitochondrial dysfunction, reactive-oxygen species generation, and DNA-replicative stress. The combination of replicative stress caused by defects in the ATRX–histone chaperone complex, and that induced by MYCN-mediated metabolic reprogramming, leads to synthetic lethality. Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.
A square-root topological insulator with non-quantized indices realized with photonic Aharonov-Bohm cages
Authors: Kremer Mark , Petrides Ioannis , Meyer Eric , Heinrich Matthias , Zilberberg Oded , Szameit Alexander
Published: February 2020

Topological Insulators are a novel state of matter where spectral bands are characterized by quantized topological invariants. This unique quantized nonlocal property commonly manifests through exotic bulk phenomena and corresponding robust boundary effects. In our work we study a system where the spectral bands are associated with non-quantized indices, but nevertheless possess robust boundary states. We present a theoretical analysis, where we show that the square of the Hamiltonian exhibits quantized indices. The findings are experimentally demonstrated by using photonic Aharonov-Bohm cages.
Tracking attosecond electronic coherences using phase-manipulated extreme ultraviolet pulses
Authors: Wituschek Andreas , Bruder Lukas , Allaria Enrico , Bangert Ulrich , Binz Marcel , Borghes Roberto , Callegari Carlo , Cerullo Giulio , Cinquegrana Paolo , Giannessi Luca , Danailov Miltcho , Demidovich Alexander , Di Fraia Michele , Drabbels Marcel , Feifel Raimund , Laarmann Tim , Michiels Rupert , Mirian Najmeh Sadat , Mudrich Marcel , Nikolov Ivaylo , O’Shea Finn H. , Penco Giuseppe , Piseri Paolo , Plekan Oksana , Prince Kevin Charles , Przystawik Andreas , Ribič Primož Rebernik , Sansone Giuseppe , Sigalotti Paolo , Spampinati Simone , Spezzani Carlo , Squibb Richard James , Stranges Stefano , Uhl Daniel , Stienkemeier Frank
Published: February 2020

The recent development of ultrafast extreme ultraviolet (XUV) coherent light sources bears great potential for a better understanding of the structure and dynamics of matter. Promising routes are advanced coherent control and nonlinear spectroscopy schemes in the XUV energy range, yielding unprecedented spatial and temporal resolution. However, their implementation has been hampered by the experimental challenge of generating XUV pulse sequences with precisely controlled timing and phase properties. In particular, direct control and manipulation of the phase of individual pulses within an XUV pulse sequence opens exciting possibilities for coherent control and multidimensional spectroscopy, but has not been accomplished. Here, we overcome these constraints in a highly time-stabilized and phase-modulated XUV-pump, XUV-probe experiment, which directly probes the evolution and dephasing of an inner subshell electronic coherence. This approach, avoiding any XUV optics for direct pulse manipulation, opens up extensive applications of advanced nonlinear optics and spectroscopy at XUV wavelengths.
Structural insights into NDH-1 mediated cyclic electron transfer
Authors: Zhang Chunli , Shuai Jin , Ran Zhaoxing , Zhao Jiaohong , Wu Zhenfang , Liao Rijing , Wu Jian , Ma Weimin , Lei Ming
Published: February 2020

NDH-1 is a key component of the cyclic-electron-transfer around photosystem I (PSI CET) pathway, an important antioxidant mechanism for efficient photosynthesis. Here, we report a 3.2-Å-resolution cryo-EM structure of the ferredoxin (Fd)-NDH-1L complex from the cyanobacterium Thermosynechococcus elongatus. The structure reveals three β-carotene and fifteen lipid molecules in the membrane arm of NDH-1L. Regulatory oxygenic photosynthesis-specific (OPS) subunits NdhV, NdhS and NdhO are close to the Fd-binding site whilst NdhL is adjacent to the plastoquinone (PQ) cavity, and they play different roles in PSI CET under high-light stress. NdhV assists in the binding of Fd to NDH-1L and accelerates PSI CET in response to short-term high-light exposure. In contrast, prolonged high-light irradiation switches on the expression and assembly of the NDH-1MS complex, which likely contains no NdhO to further accelerate PSI CET and reduce ROS production. We propose that this hierarchical mechanism is necessary for the survival of cyanobacteria in an aerobic environment.
Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors
Authors: Saito Yuki , Chikenji Takako S. , Matsumura Takashi , Nakano Masako , Fujimiya Mineko
Published: February 2020

Idiopathic inflammatory myopathies cause progressive muscle weakness and degeneration. Since high-dose glucocorticoids might not lead to full recovery of muscle function, physical exercise is also an important intervention, but some exercises exacerbate chronic inflammation and muscle fibrosis. It is unknown how physical exercise can have both beneficial and detrimental effects in chronic myopathy. Here we show that senescence of fibro-adipogenic progenitors (FAPs) in response to exercise-induced muscle damage is needed to establish a state of regenerative inflammation that induces muscle regeneration. In chronic inflammatory myopathy model mice, exercise does not promote FAP senescence or resistance against tumor necrosis factor–mediated apoptosis. Pro-senescent intervention combining exercise and pharmacological AMPK activation reverses FAP apoptosis resistance and improves muscle function and regeneration. Our results demonstrate that the absence of FAP senescence after exercise leads to muscle degeneration with FAP accumulation. FAP-targeted pro-senescent interventions with exercise and pharmacological AMPK activation may constitute a therapeutic strategy for chronic inflammatory myopathy.
Perovskite-molecule composite thin films for efficient and stable light-emitting diodes
Authors: Wang Heyong , Kosasih Felix Utama , Yu Hongling , Zheng Guanhaojie , Zhang Jiangbin , Pozina Galia , Liu Yang , Bao Chunxiong , Hu Zhangjun , Liu Xianjie , Kobera Libor , Abbrent Sabina , Brus Jiri , Jin Yizheng , Fahlman Mats , Friend Richard H. , Ducati Caterina , Liu Xiao-Ke , Gao Feng
Published: February 2020

Although perovskite light-emitting diodes (PeLEDs) have recently experienced significant progress, there are only scattered reports of PeLEDs with both high efficiency and long operational stability, calling for additional strategies to address this challenge. Here, we develop perovskite-molecule composite thin films for efficient and stable PeLEDs. The perovskite-molecule composite thin films consist of in-situ formed high-quality perovskite nanocrystals embedded in the electron-transport molecular matrix, which controls nucleation process of perovskites, leading to PeLEDs with a peak external quantum efficiency of 17.3% and half-lifetime of approximately 100 h. In addition, we find that the device degradation mechanism at high driving voltages is different from that at low driving voltages. This work provides an effective strategy and deep understanding for achieving efficient and stable PeLEDs from both material and device perspectives.
Bayesian Spatiotemporal Modeling of Routinely Collected Data to Assess the Effect of Health Programs in Malaria Incidence During Pregnancy in Burkina Faso
Authors: Rouamba Toussaint , Samadoulougou Sekou , Tinto Halidou , Alegana Victor A. , Kirakoya-Samadoulougou Fati
Published: February 2020

Control of malaria in pregnancy (MiP) remains a major challenge in Burkina Faso. Surveillance of the burden due to MiP based on routinely collected data at a fine-scale level, followed by an appropriate analysis and interpretation, may be crucial for evaluating and improving the effectiveness of existing control measures. We described the spatio-temporal dynamics of MiP at the community-level and assessed health program effects, mainly community-based health promotion, results-based financing, and intermittent-preventive-treatment with sulphadoxine-pyrimethamine (IPTp-SP). Community-aggregated monthly MiP cases were downloaded from Health Management Information System and combined with covariates from other sources. The MiP spatio-temporal pattern was decomposed into three components: overall spatial and temporal trends and space-time interaction. Bayesian hierarchical spatio-temporal Poisson models were used to fit the MiP incidence rate and assess health program effects. The overall annual incidence increased between 2015 and 2017. The findings reveal spatio-temporal heterogenicity throughout the year, which peaked during rainy season. From the model without covariates, 96 communities located mainly in the Cascades, South-West, Center-West, Center-East, and Eastern regions, exhibited significant relative-risk levels. The combined effect (significant reducing effect) of RBF, health promotion and IPTp-SP strategies was greatest in 17.7% (17/96) of high burden malaria communities. Despite intensification of control efforts, MiP remains high at the community-scale. The provided risk maps are useful tools for highlighting areas where interventions should be optimized, particularly in high-risk communities.
Concentration dependence of the sol-gel phase behavior of agarose-water system observed by the optical bubble pressure tensiometry
Authors: Ichinose Nobuyuki , Ura Hodaka
Published: February 2020

We have studied an expansion behavior of pressurized bubbles at the orifice of a capillary inserted in gelator-solvent (agarose-water) mixtures as a function of the gelator concentration in which the phase transition points are included. The pressure (P) -dependence of the radius of the curvature (R) of the bubbles monitored by laser beam has shown a discontinuous decrease in the exponent (m) of the experimental power law R = KΔP−m (K: constant) from 1 to 1/2 and a discontinuous increase in the average surface tension (γave) obtained from the work-area plots of the mixtures exceeding that of pure water (72.6 mN/m) at 0.02 < [agarose] < 0.03 wt%, which is attributed to the disappearance of the fluidity. The apparent surface tension (γapp = ΔP/2 R) of the system in the concentration range of 0.03–0.20 wt% has been analyzed by a modified Shuttleworth equation γapp = σ0 + τln(A/A0), where σ0 is an isotropic constant component and the second term is a surface area (A) -dependent elastic component, in which τ is the coefficient and A0 is the area of the orifice. The analysis has indicated that σ0 coincides with the γapp value of the mixture of 0.02 wt% and the second term at >0.02 wt% is the dominant component. From the appearance of the elastic component and concentration dependence of τ, the plateau of τ for the agarose-water mixtures at 0.03–0.10 wt% (Region II) has been explained to the phase separation giving two-phase mixtures of 0.02 wt% sol and 0.10 wt% gel and the upward inflection of τ at 0.10 wt% has been assigned to an increase in the elasticity of the gel with the increase of the agarose concentration in the range of >0.10 wt% (Region III). On considering the concentration dependence of the surface tension of agarose-water mixtures, the discontinuous and inflection points were assigned to the 1st- and 2nd-order phase transition concentrations of the agarose gel, respectively. Given the results with our tensiometry based on the optical bubble pressure method, distinct gelation points for other systems could be determined both mechanically and thermodynamically which will provide a diagnostic criterion of sol-gel transitions.
Author Correction: Global phylogenetic analysis of Escherichia coli and plasmids carrying the mcr-1 gene indicates bacterial diversity but plasmid restriction
Authors: Matamoros Sébastien , van Hattem Jarne M. , Arcilla Maris S. , Willemse Niels , Melles Damian C. , Penders John , Vinh Trung Nguyen , Thi Hoa Ngo , Bootsma Martin C. J. , Genderen Perry J. van , Goorhuis Abraham , Grobusch Martin , Molhoek Nicky , Oude Lashof Astrid M. L. , Stobberingh Ellen E. , Verbrugh Henri A. , de Jong Menno D. , Schultsz Constance
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Bioprospecting desert plant Bacillus endophytic strains for their potential to enhance plant stress tolerance
Authors: Bokhari Ameerah , Essack Magbubah , Lafi Feras F. , Andres-Barrao Cristina , Jalal Rewaa , Alamoudi Soha , Razali Rozaimi , Alzubaidy Hanin , Shah Kausar H. , Siddique Shahid , Bajic Vladimir B. , Hirt Heribert , Saad Maged M.
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Surveillance-embedded genomic outbreak resolution of methicillin-susceptible Staphylococcus aureus in a neonatal intensive care unit
Authors: Cremers A. J. H. , Coolen J. P. M. , Bleeker-Rovers C. P. , van der Geest-Blankert A. D. J. , Haverkate D. , Hendriks H. , Henriet S. S. V. , Huynen M. A. , Kolwijck E. , Liem D. , Melchers W. J. G. , Rossen J. W. , Zoll J. , van Heijst A. , Hopman J. , Wertheim H. F. L.
Published: February 2020

We observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections at a Dutch neonatal intensive care unit. Weekly neonatal MSSA carriage surveillance and cross-sectional screenings of health care workers (HCWs) were available for outbreak tracing. Traditional clustering of MSSA isolates by spa typing and Multiple-Locus Variable number tandem repeat Analysis (MLVA) suggested that nosocomial transmission had contributed to the infections. We investigated whether whole-genome sequencing (WGS) of MSSA surveillance would provide additional evidence for transmission. MSSA isolates from neonatal infections, carriage surveillance, and HCWs were subjected to WGS and bioinformatic analysis for identification and localization of high-quality single nucleotide polymorphisms, and in-depth analysis of subsets of isolates. By measuring the genetic diversity in background surveillance, we defined transmission-level relatedness and identified isolates that had been unjustly assigned to clusters based on MLVA, while spa typing was concordant but of insufficient resolution. Detailing particular subsets of isolates provided evidence that HCWs were involved in multiple outbreaks, yet it alleviated concerns about one particular HCW. The improved resolution and accuracy of genomic outbreak analyses substantially altered the view on outbreaks, along with apposite measures. Therefore, inclusion of the circulating background population has the potential to overcome current issues in genomic outbreak inference.
Author Correction: The in vivo specificity of synaptic Gβ and Gγ subunits to the α2a adrenergic receptor at CNS synapses
Authors: Yim Yun Young , Betke Katherine M. , McDonald W. Hayes , Gilsbach Ralf , Chen Yunjia , Hyde Karren , Wang Qin , Hein Lutz , Hamm Heidi E.
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Frailness and resilience of gene networks predicted by detection of co-occurring mutations via a stochastic perturbative approach
Authors: Bersanelli Matteo , Mosca Ettore , Milanesi Luciano , Bazzani Armando , Castellani Gastone
Published: February 2020

In recent years complex networks have been identified as powerful mathematical frameworks for the adequate modeling of many applied problems in disparate research fields. Assuming a Master Equation (ME) modeling the exchange of information within the network, we set up a perturbative approach in order to investigate how node alterations impact on the network information flow. The main assumption of the perturbed ME (pME) model is that the simultaneous presence of multiple node alterations causes more or less intense network frailties depending on the specific features of the perturbation. In this perspective the collective behavior of a set of molecular alterations on a gene network is a particularly adapt scenario for a first application of the proposed method, since most diseases are neither related to a single mutation nor to an established set of molecular alterations. Therefore, after characterizing the method numerically, we applied as a proof of principle the pME approach to breast cancer (BC) somatic mutation data downloaded from Cancer Genome Atlas (TCGA) database. For each patient we measured the network frailness of over 90 significant subnetworks of the protein-protein interaction network, where each perturbation was defined by patient-specific somatic mutations. Interestingly the frailness measures depend on the position of the alterations on the gene network more than on their amount, unlike most traditional enrichment scores. In particular low-degree mutations play an important role in causing high frailness measures. The potential applicability of the proposed method is wide and suggests future development in the control theory context.
Cold plasma treatment to release dormancy and improve growth in grape buds: a promising alternative to natural chilling and rest breaking chemicals
Authors: Mujahid Z. , Tounekti T. , Khemira H.
Published: February 2020

Winter dormancy of temperate zone perennial plant species is commonly released by chilling temperature. If the duration of the cold weather is not adequate, plant growth becomes disorganized leading to reduced growth, spread out flowering and fruit maturation and often reduced yield. In mild-winter regions, growers commonly resort to spraying their trees with chemicals such as hydrogen cyanamide to compensate for the lack of chilling to ensure good growth and yield. Although effective, most of these chemicals are highly toxic; unfortunately, there is no effective and environmentally friendly alternative which can be used to release dormancy. In this work, we present a cold plasma treatment-based method which can effectively release the dormancy of grape buds. We have found that exposing grape buds to plasma provides improvement of several growth parameters including higher, faster and more synchronous budbreak and more vigorous vegetative growth, comparatively similar to or better than natural chilling. Biochemical analyses of bud tissue suggest that the plasma treatment triggered a marked transient oxidative stress as indicated by the increase in the concentrations of free proline, malondialdehyde (MDA) and hydrogen peroxide (H2O2). Proline appears to have played a key role; as a compatible osmolyte, it may have protected cellular structures against free radicals and as a signaling molecule, it may have induced the events leading to dormancy release. We anticipate that our work will provide a starting point for the development of novel plasma-based tools and methods to treat dormant plants. The plasma treatment method may allow higher agricultural production in several regions of the world at risk of becoming marginal for the cultivation of certain crops due to global warming.
Extract from used Xpert MTB/RIF Ultra cartridges is useful for accurate second-line drug-resistant tuberculosis diagnosis with minimal rpoB-amplicon cross-contamination risk
Authors: Venter Rouxjeane , Minnies Stephanie , Derendinger Brigitta , Tshivhula Happy , de Vos Margaretha , Dolby Tania , Ruiters Ashley , Warren Robin M. , Theron Grant
Published: February 2020

Xpert MTB/RIF Ultra (Ultra) detects Mycobacterium tuberculosis and rifampicin resistance. Follow-on drug susceptibility testing (DST) requires additional sputum. Extract from the diamond-shaped chamber of the cartridge (dCE) of Ultra’s predecessor, Xpert MTB/RIF (Xpert), is useful for MTBDRsl-based DST but this is unexplored with Ultra. Furthermore, whether CE from non-diamond compartments is useful, the performance of FluoroType MTBDR (FT) on  CE, and rpoB cross-contamination risk associated with the extraction procedure are unknown. We tested MTBDRsl, MTBDRplus, and FT on CEs from chambers from cartridges (Ultra, Xpert) tested on bacilli dilution series. MTBDRsl on Ultra dCE on TB-positive sputa (n = 40) was also evaluated and, separately, rpoB amplicon cross-contamination risk . MTBDRsl on Ultra dCE from dilutions ≥103 CFU/ml (CTmin <25, >“low semi-quantitation”) detected fluoroquinolone (FQ) and second-line injectable (SLID) susceptibility and resistance correctly (some SLIDs-indeterminate). At the same threshold (at which ~85% of Ultra-positives in our setting would be eligible), 35/35 (100%) FQ and 34/35 (97%) SLID results from Ultra dCE were concordant with sputa results. Tests on other chambers were unfeasible. No tubes open during 20 batched extractions had FT-detected rpoB cross-contamination. False-positive Ultra rpoB results was observed when dCE dilutions ≤10−3 were re-tested. MTBDRsl on Ultra dCE is concordant with isolate results. rpoB amplicon cross-contamination is unlikely. These data mitigate additional specimen collection for second-line DST and cross-contamination concerns.
Appraising the potential of Zr-based biomedical alloys to reduce magnetic resonance imaging artifacts
Authors: Suzuki Anderson Kiyoshi , Campo Kaio Niitsu , Fonseca Eduardo Bertoni , Araújo Luana Caldeira , Gandra Flávio César Guimarães , Lopes Éder Sócrates Najar
Published: February 2020

This study compared Zr-Mo alloys with commercial metallic biomaterials. It was observed that the Zr-Mo alloys exhibited favourable mechanical properties, particularly the Zr-10Mo alloy, which showed the highest strength to Young’s modulus ratio among all evaluated metals. These alloys also exhibited the lowest magnetic susceptibilities, which are important for magnetic resonance imaging (MRI). However, both Zr- and Ti-based metals yielded comparable artifacts. It was concluded that the magnetic susceptibility must differ considerably to afford significantly improved MRI quality owing to the increased importance of non-susceptibility-related artifacts when comparing materials with relatively similar magnetic susceptibilities.
Fractional Anisotropy changes in Parahippocampal Cingulum due to Alzheimer’s Disease
Authors: Dalboni da Rocha Josué Luiz , Bramati Ivanei , Coutinho Gabriel , Tovar Moll Fernanda , Sitaram Ranganatha
Published: February 2020

Current treatments for Alzheimer’s disease are only symptomatic and limited to reduce the progression rate of the mental deterioration. Mild Cognitive Impairment, a transitional stage in which the patient is not cognitively normal but do not meet the criteria for specific dementia, is associated with high risk for development of Alzheimer’s disease. Thus, non-invasive techniques to predict the individual’s risk to develop Alzheimer’s disease can be very helpful, considering the possibility of early treatment. Diffusion Tensor Imaging, as an indicator of cerebral white matter integrity, may detect and track earlier evidence of white matter abnormalities in patients developing Alzheimer’s disease. Here we performed a voxel-based analysis of fractional anisotropy in three classes of subjects: Alzheimer’s disease patients, Mild Cognitive Impairment patients, and healthy controls. We performed Support Vector Machine classification between the three groups, using Fisher Score feature selection and Leave-one-out cross-validation. Bilateral intersection of hippocampal cingulum and parahippocampal gyrus (referred as parahippocampal cingulum) is the region that best discriminates Alzheimer’s disease fractional anisotropy values, resulting in an accuracy of 93% for discriminating between Alzheimer’s disease and controls, and 90% between Alzheimer’s disease and Mild Cognitive Impairment. These results suggest that pattern classification of Diffusion Tensor Imaging can help diagnosis of Alzheimer’s disease, specially when focusing on the parahippocampal cingulum.
A Novel in situ Approach to Studying Detrusor Smooth Muscle Cells in Mice
Authors: Serdinšek Tamara , Lipovšek Saša , Leitinger Gerd , But Igor , Stožer Andraž , Dolenšek Jurij
Published: February 2020

The aim of our study was to develop a novel approach to investigating mouse detrusor smooth muscle cell (SMC) physiological activity, utilizing an acute tissue dissection technique and confocal calcium imaging. The bladder of a sacrificed adult female NMRI mouse was dissected. We used light and transmission electron microscopy to assess morphology of SMCs within the tissue. Calcium imaging in individual SMCs was performed using confocal microscopy during stimulation with increasing concentrations of carbamylcholine (CCh). SMCs were identified according to their morphology and calcium activity. We determined several parameters describing the SMC responses: delays to response, recruitment, relative activity, and contraction of the tissue. CCh stimulation revealed three different SMC phenotypes: spontaneously active SMCs with and without CCh-enhanced activity and SMCs with CCh-induced activity only. SMCs were recruited into an active state in response to CCh-stimulation within a narrow range (1–25 µM); causing activation of virtually all SMCs. Maximum calcium activity of SMCs was at about 25 µM, which coincided with a visible tissue contraction. Finally, we observed shorter time lags before response onsets with higher CCh concentrations. In conclusion, our novel in situ approach proved to be a robust and reproducible method to study detrusor SMC morphology and physiology.
Evaluating thyroid hormone disruption: investigations of long-term neurodevelopmental effects in rats after perinatal exposure to perfluorohexane sulfonate (PFHxS)
Authors: Ramhøj Louise , Hass Ulla , Gilbert Mary E. , Wood Carmen , Svingen Terje , Usai Diana , Vinggaard Anne Marie , Mandrup Karen , Axelstad Marta
Published: February 2020

Thyroid hormones are critical for mammalian brain development. Thus, chemicals that can affect thyroid hormone signaling during pregnancy are of great concern. Perfluorohexane sulfonate (PFHxS) is a widespread environmental contaminant found in human serum, breastmilk, and other tissues, capable of lowering serum thyroxine (T4) in rats. Here, we investigated its effects on the thyroid system and neurodevelopment following maternal exposure from early gestation through lactation (0.05, 5 or 25 mg/kg/day PFHxS), alone or in combination with a mixture of 12 environmentally relevant endocrine disrupting compounds (EDmix). PFHxS lowered thyroid hormone levels in both dams and offspring in a dose-dependent manner, but did not change TSH levels, weight, histology, or expression of marker genes of the thyroid gland. No evidence of thyroid hormone-mediated neurobehavioral disruption in offspring was observed. Since human brain development appear very sensitive to low T4 levels, we maintain that PFHxS is of potential concern to human health. It is our view that current rodent models are not sufficiently sensitive to detect adverse neurodevelopmental effects of maternal and perinatal hypothyroxinemia and that we need to develop more sensitive brain-based markers or measurable metrics of thyroid hormone-dependent perturbations in brain development.
Dynamic chiral magnetic effect and anisotropic natural optical activity of tilted Weyl semimetals
Authors: Dey Urmimala , Nandy S. , Taraphder A.
Published: February 2020

We study the dynamic chiral magnetic conductivity (DCMC) and natural optical activity in an inversion-broken tilted Weyl semimetal (WSM). Starting from the Kubo formula, we derive the analytical expressions for the DCMC for two different directions of the incident electromagnetic wave. We show that the angle of rotation of the plane of polarization of the transmitted wave exhibits remarkable anisotropy and is larger along the tilt direction. This striking anisotropy of DCMC results in anisotropic optical activity and rotary power, which can be experimentally observed as a topological magneto-electric effect of inversion-broken tilted WSMs. Finally, using the low energy Hamiltonian, we show that the DCMC follows the universal $$\frac{{\bf{1}}}{{{\boldsymbol{\omega }}}^{{\bf{2}}}}$$

1

ω

2

decay in the high frequency regime. In the low frequency regime, however, the DCMC shows sharp peaks at the tilt dependent effective chemical potentials of the left-handed and right-handed Weyl points. This can serve as a signature to distinguish between the type-I and type-II Weyl semimetals.
Single-molecular real-time deep sequencing reveals the dynamics of multi-drug resistant haplotypes and structural variations in the hepatitis C virus genome
Authors: Yamashita Taiki , Takeda Haruhiko , Takai Atsushi , Arasawa Soichi , Nakamura Fumiyasu , Mashimo Yoichi , Hozan Miyuki , Ohtsuru Shigeru , Seno Hiroshi , Ueda Yoshihide , Sekine Akihiro
Published: February 2020

While direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have dramatically progressed, patients still suffer from treatment failures. For the radical eradication of HCV, a deeper understanding of multiple resistance-associated substitutions (RASs) at the single-clone level is essential. To understand HCV quasispecies and their dynamics during DAA treatment, we applied single-molecule real-time (SMRT) deep sequencing on sera from 12 patients with genotype-1b HCV infections with DAA treatment failures, both pre- and post-treatment. We identified >3.2 kbp sequences between NS3 and NS5A genes of 187,539 clones in total, classifying into haplotype codes based on the linkage of seven RAS loci. The number of haplotype codes during the treatment, per sample, significantly decreased from 14.67 ± 9.12 to 6.58 ± 7.1, while the number of nonsynonymous codons on the seven RAS loci, per clone, significantly increased from 1.50 ± 0.92 to 3.64 ± 0.75. In five cases, the minority multi-drug resistant haplotypes at pre-treatment were identical to the major haplotypes at relapse. Moreover, various structural variations (SVs) were detected and their dynamics analysed. These results suggest that SMRT deep sequencing is useful for detecting minority haplotypes and SVs, and to evaluate the dynamics of viral genomes at the single-clone level.
Impact of pulsed electric fields and mechanical compressions on the permeability and structure of Chlamydomonas reinhardtii cells
Authors: Bensalem Sakina , Pareau Dominique , Cinquin Bertrand , Français Olivier , Le Pioufle Bruno , Lopes Filipa
Published: February 2020

Current research findings clearly reveal the role of the microalga’s cell wall as a key obstacle to an efficient and optimal compound extraction. Such extraction process is therefore closely related to the microalga species used. Effects of electrical or mechanical constraints on C. reinhardtii’s structure and particularly its cell wall and membrane, is therefore investigated in this paper using a combination of microscopic tools. Membrane pores with a radius between 0.77 and 1.59 nm were determined for both reversible (5 kV∙cm−1) and irreversible (7 kV∙cm−1) electroporation with a 5 µs pulse duration. Irreversible electroporation with longer pulses (10 µs) lead to the entry of large molecules (at least 5.11 nm). Additionally, for the first time, the effect of pulsed electric fields on the cell wall was observed. The combined electrical and mechanical treatment showed a significant impact on the cell wall structure as observed under Transmission Electron Microscopy. This treatment permits the penetration of larger molecules (at least 5.11 nm) within the cell, shown by tracking the penetration of dextran molecules. For the first time, the size of pores on the cell membrane and the structural changes on the microalgae cell wall induced by electrical and mechanical treatments is reported.
Globe thermometer free convection error potentials
Authors: Teitelbaum Eric , Chen Kian Wee , Meggers Forrest , Guo Hongshan , Houchois Nicholas , Pantelic Jovan , Rysanek Adam
Published: February 2020

For thermal comfort research, globe thermometers have become the de facto tool for mean radiant temperature,tr, measurement. They provide a quick means to survey the radiant environment in a space with nearly a century of trials to reassure researchers. However, as more complexity is introduced to built environments, we must reassess the accuracy of globe measurements. In particular, corrections for globe readings taking wind into account rely on a forced convection heat transfer coefficient. In this study, we investigate potential errors introduced by buoyancy driven flow, or free convection, induced by radiant forcing of a black globe’s surface to a temperature different from the air. We discovered this error in an experimental radiant cooling system with high separation of air to radiant temperature. Empirical simulations and the data collected in a radiant cooling setup together demonstrate the influence of free convection on the instrument’s readings. Initial simulation and data show thattrmeasurements neglecting free convection when calculatingtrfrom air temperatures of 2 K abovetrcould introduce a mechanism for globe readings to incorrectly track air temperatures. The experimental data constructed to test this hypothesis showed the standard correction readings are 1.94 ± 0.90 °C higher than the ground truth readings for all measurements taken in the experiment. The proposed mixed convection correction is 0.51 ± 1.07 °C higher than the ground truth, and is most accurate at low air speeds, within 0.25 ± 0.60 °C. This implies a potential systematic error in millions of measurements over the past 30 years of thermal comfort research. Future work will be carried out to experimentally validate this framework in a controlled climate chamber environment, examining the tradeoffs between accuracy and precision with globe thermometer measurements.