bluuebunny/crossref_metadata_2025 huggingface dataset:
Delirium in the intensive care setting dependent on the Richmond Agitation and Sedation Scale (RASS): Inattention and visuo-spatial impairment as potential screening domains
Authors: Boettger Soenke , Meyer Rafael , Richter André , Rudiger Alain , Schubert Maria , Jenewein Josef , Nuñez David Garcia
Published: September 2019

Objective

In the intensive care setting, delirium is a common occurrence; however, the impact of the level of alertness has never been evaluated. Therefore, this study aimed to assess the delirium characteristics in the drowsy, as well as the alert and calm patient.

Method

In this prospective cohort study, 225 intensive care patients with Richmond Agitation and Sedation Scale (RASS) scores of −1 — drowsy and 0 — alert and calm were evaluated with the Delirium Rating Scale-Revised-1998 (DRS-R-98) and the Diagnostic and Statistical Manual 4th edition text revision (DSM-IV-TR)-determined diagnosis of delirium.

Results

In total, 85 drowsy and 140 alert and calm patients were included. Crucial items for the correct identification of delirium were sleep–wake cycle disturbances, language abnormalities, thought process alterations, psychomotor retardation, disorientation, inattention, short- and long-term memory, as well as visuo-spatial impairment, and the temporal onset. Conversely, perceptual disturbances, delusions, affective lability, psychomotor agitation, or fluctuations were items, which identified delirium less correctly. Further, the severities of inattentiveness and visuo-spatial impairment were indicative of delirium in both alert- or calmness and drowsiness.

Significance of results

The impairment in the cognitive domain, psychomotor retardation, and sleep–wake cycle disturbances correctly identified delirium irrespective of the level alertness. Further, inattentiveness and — to a lesser degree — visuo-spatial impairment could represent a specific marker for delirium in the intensive care setting meriting further evaluation.
Fighting on Christmas: brawling as self-governance in rural Peru
Authors: Escalante Edwar E. , March Raymond J.
Published: September 2019

This paper analyzes the Peruvian highland tradition of Takanakuy, a public brawling ritual occurring each Christmas to resolve conflicts between local community members. We argue that Takanakuy provides an effective way for locals to resolve disputes that Peru's formal judicial system is unable or unwilling to settle. Using insights from ethnographic fieldwork, journalistic articles, reports, and academic sources, we find that brawling during Takanakuy encourages social cooperation by preventing potential violence and offering community members a credible mechanism of law enforcement in an orderly fashion with social acceptance.
African, Religious, and Tolerant? How Religious Diversity Shapes Attitudes Toward Sexual Minorities in Africa
Authors: Dreier Sarah K. , Long James D. , Winkler Stephen J.
Published: September 2019

Despite trends towards greater LGBTQ (lesbian, gay, bisexual, transgender, and queer) rights in industrialized democracies, the rights of sexual minorities have become increasingly politicized and restricted throughout Africa. Recognizing religion's central role in shaping attitudes toward gays and lesbians, we hypothesize that local religious diversity could expose individuals to alternative religious perspectives, engender tolerance toward marginalized communities, and therefore dislodge dogmatic beliefs about social issues. Employing cross-national Afrobarometer survey data from 33 countries with an index of district-level religious concentration, we find that respondents living in religiously pluralistic communities are 4–5 points more likely to express tolerance of homosexual neighbors (50% increase) compared to those in homogeneous locales. This effect is not driven by outlier countries, the existence of specific religious affiliations within diverse communities, respondents' religiosity, or other observable and latent factors at the country, sub-national, district, and individual level. Further robustness checks address potential threats to validity. We conclude that religious diversity can foster inclusion of sexual minorities in Africa.
An X-band magnetic dipole quasi-Yagi antenna based on a dielectric resonator
Authors: Qian Zhong-Yu , Sun Wen-Jian , Zhang Xue-Feng , Chen Jian-Xin
Published: September 2019

A magnetic dipole quasi-Yagi antenna based on a dielectric resonator (DR) is proposed in this letter. The dominate TE1δ1 mode of the rectangular DR is used as a magnetic dipole which can be differentially fed by the coplanar strip line (CPS). Thanks to the DR employment, the proposed antenna has several advantages such as compact size and flexible design which means the 3-D dimensions of the DR can be easily adjusted to cater for various applications. Meanwhile, the gain of the proposed DR quasi-Yagi antenna is higher than that of traditional electric dipole counterparts. Furthermore, since the DR driver is horizontally polarized, both the metal strip and DR can be used as a director for enhancing the end-fire gain. To verify the design concept, a prototype operating at the X-band is fabricated and measured. Good agreement between the simulated and measured results can be observed.
Union Leader Talks Coal and Climate
Authors: Showstack Randy
Published: September 2019

President of mine workers’ union says that combatting climate change is important but it can’t come at the cost of mining jobs.
Effects of empagliflozin on nondiabetic salt-sensitive hypertension in uninephrectomized rats
Authors: Kim Sua , Jo Chor Ho , Kim Gheun-Ho
Published: September 2019

Impaired pressure natriuresis (PN) underlies salt-sensitive hypertension, and renal inflammation and hypoxia-inducible factor-1 (HIF-1) have been implicated in the modulation of systemic hypertension. Although sodium–glucose cotransporter-2 (SGLT2) inhibitors were reported to lower blood pressure (BP) in type 2 diabetes mellitus, whether they have a role in nondiabetic hypertensive kidney diseases is unclear. The present study was undertaken to investigate whether nondiabetic salt-sensitive hypertension and accompanying renal inflammation are ameliorated by SGLT2 inhibition. Male Sprague-Dawley rats were randomly divided into three groups: sham controls (SCs), uninephrectomized controls (UCs), and empagliflozin-treated rats (ETs). All rats were fed a rodent diet with 8% NaCl throughout the study period. Empagliflozin was orally administered for 3 weeks after uninephrectomy. Systolic blood pressure was recorded weekly, and kidneys were harvested for immunoblotting, immunohistochemistry, and quantitative PCR analysis at the end of the animal experiment. Systolic BP was significantly decreased in ETs that were orally given empagliflozin for 3 weeks after uninephrectomy. Although ETs did not show any increase in weekly measured urine sodium, the right-shifted PN relationship in UCs was improved by empagliflozin treatment. The expression of HIF-1α was increased in the renal outer medulla of ETs. Consistent with this, HIF prolyl-hydroxylase-2 protein and mRNA were decreased in ETs. The abundance of CD3 and ED-1 immunostaining in UCs was reduced by empagliflozin treatment. The increased IL-1ß, gp91phox, and NOX4 mRNA levels in UCs were also reversed. Empagliflozin restored impaired PN in nondiabetic hypertensive kidney disease in association with increased renal medullary expression of HIF-1α and amelioration of renal inflammation.
An African Salmonella Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host adaptation
Authors: Van Puyvelde Sandra , Pickard Derek , Vandelannoote Koen , Heinz Eva , Barbé Barbara , de Block Tessa , Clare Simon , Coomber Eve L. , Harcourt Katherine , Sridhar Sushmita , Lees Emily A. , Wheeler Nicole E. , Klemm Elizabeth J. , Kuijpers Laura , Mbuyi Kalonji Lisette , Phoba Marie-France , Falay Dadi , Ngbonda Dauly , Lunguya Octavie , Jacobs Jan , Dougan Gordon , Deborggraeve Stijn
Published: September 2019

Bloodstream infections bySalmonella entericaserovar Typhimurium constitute a major health burden in sub-Saharan Africa (SSA). These invasive non-typhoidal (iNTS) infections are dominated by isolates of the antibiotic resistance-associated sequence type (ST) 313. Here, we report emergence of ST313 sublineage II.1 in the Democratic Republic of the Congo. Sublineage II.1 exhibits extensive drug resistance, involving a combination of multidrug resistance, extended spectrum β-lactamase production and azithromycin resistance. ST313 lineage II.1 isolates harbour an IncHI2 plasmid we name pSTm-ST313-II.1, with one isolate also exhibiting decreased ciprofloxacin susceptibility. Whole genome sequencing reveals that ST313 II.1 isolates have accumulated genetic signatures potentially associated with altered pathogenicity and host adaptation, related to changes observed in biofilm formation and metabolic capacity. Sublineage II.1 emerged at the beginning of the 21st century and is involved in on-going outbreaks. Our data provide evidence of further evolution within the ST313 clade associated with iNTS in SSA.
Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle
Authors: Brouwer Philip J. M. , Antanasijevic Aleksandar , Berndsen Zachary , Yasmeen Anila , Fiala Brooke , Bijl Tom P. L. , Bontjer Ilja , Bale Jacob B. , Sheffler William , Allen Joel D. , Schorcht Anna , Burger Judith A. , Camacho Miguel , Ellis Daniel , Cottrell Christopher A. , Behrens Anna-Janina , Catalano Marco , del Moral-Sánchez Iván , Ketas Thomas J. , LaBranche Celia , van Gils Marit J. , Sliepen Kwinten , Stewart Lance J. , Crispin Max , Montefiori David C. , Baker David , Moore John P. , Klasse Per Johan , Ward Andrew B. , King Neil P. , Sanders Rogier W.
Published: September 2019

The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.
Disposable ultrasound-sensing chronic cranial window by soft nanoimprinting lithography
Authors: Li Hao , Dong Biqin , Zhang Xian , Shu Xiao , Chen Xiangfan , Hai Rihan , Czaplewski David A. , Zhang Hao F. , Sun Cheng
Published: September 2019

Chronic cranial window (CCW) is an essential tool in enabling longitudinal imaging and manipulation of various brain activities in live animals. However, an active CCW capable of sensing the concealed in vivo environment while simultaneously providing longitudinal optical access to the brain is not currently available. Here we report a disposable ultrasound-sensing CCW (usCCW) featuring an integrated transparent nanophotonic ultrasonic detector fabricated using soft nanoimprint lithography process. We optimize the sensor design and the associated fabrication process to significantly improve detection sensitivity and reliability, which are critical for the intend longitudinal in vivo investigations. Surgically implanting the usCCW on the skull creates a self-contained environment, maintaining optical access while eliminating the need for external ultrasound coupling medium for photoacoustic imaging. Using this usCCW, we demonstrate photoacoustic microscopy of cortical vascular network in live mice over 28 days. This work establishes the foundation for integrating photoacoustic imaging with modern brain research.
Inferring neural signalling directionality from undirected structural connectomes
Authors: Seguin Caio , Razi Adeel , Zalesky Andrew
Published: September 2019

Neural information flow is inherently directional. To date, investigation of directional communication in the human structural connectome has been precluded by the inability of non-invasive neuroimaging methods to resolve axonal directionality. Here, we demonstrate that decentralized measures of network communication, applied to the undirected topology and geometry of brain networks, can infer putative directions of large-scale neural signalling. We propose the concept of send-receive communication asymmetry to characterize cortical regions as senders, receivers or neutral, based on differences between their incoming and outgoing communication efficiencies. Our results reveal a send-receive cortical hierarchy that recapitulates established organizational gradients differentiating sensory-motor and multimodal areas. We find that send-receive asymmetries are significantly associated with the directionality of effective connectivity derived from spectral dynamic causal modeling. Finally, using fruit fly, mouse and macaque connectomes, we provide further evidence suggesting that directionality of neural signalling is significantly encoded in the undirected architecture of nervous systems.
Activity in the dorsal ACC causes deterioration of sequential motor performance due to anxiety
Authors: Ganesh Gowrishankar , Minamoto Takehiro , Haruno Masahiko
Published: September 2019

Performance anxiety can profoundly affect motor performance, even in experts such as professional athletes and musicians. Previously, the neural mechanisms underlying anxiety-induced performance deterioration have predominantly been investigated for individual one-shot actions. Sports and music, however, are characterized by action sequences, where many individual actions are assembled to develop a performance. Here, utilizing a novel differential sequential motor learning paradigm, we first show that performance at the junctions between pre-learnt action sequences is particularly prone to anxiety. Next, utilizing functional magnetic resonance imaging (fMRI), we reveal that performance deterioration at the junctions is parametrically correlated with activity in the dorsal anterior cingulate cortex (dACC). Finally, we show that 1 Hz repetitive transcranial magnetic stimulation of the dACC attenuates the performance deterioration at the junctions. These results demonstrate causality between dACC activity and impairment of sequential motor performance due to anxiety, and suggest new intervention techniques against the deterioration.
Endosomal PI(3)P regulation by the COMMD/CCDC22/CCDC93 (CCC) complex controls membrane protein recycling
Authors: Singla Amika , Fedoseienko Alina , Giridharan Sai S. P. , Overlee Brittany L. , Lopez Adam , Jia Da , Song Jie , Huff-Hardy Kayci , Weisman Lois , Burstein Ezra , Billadeau Daniel D.
Published: September 2019

Protein recycling through the endolysosomal system relies on molecular assemblies that interact with cargo proteins, membranes, and effector molecules. Among them, the COMMD/CCDC22/CCDC93 (CCC) complex plays a critical role in recycling events. While CCC is closely associated with retriever, a cargo recognition complex, its mechanism of action remains unexplained. Herein we show that CCC and retriever are closely linked through sharing a common subunit (VPS35L), yet the integrity of CCC, but not retriever, is required to maintain normal endosomal levels of phosphatidylinositol-3-phosphate (PI(3)P). CCC complex depletion leads to elevated PI(3)P levels, enhanced recruitment and activation of WASH (an actin nucleation promoting factor), excess endosomal F-actin and trapping of internalized receptors. Mechanistically, we find that CCC regulates the phosphorylation and endosomal recruitment of the PI(3)P phosphatase MTMR2. Taken together, we show that the regulation of PI(3)P levels by the CCC complex is critical to protein recycling in the endosomal compartment.
Complex vectorial optics through gradient index lens cascades
Authors: He Chao , Chang Jintao , Hu Qi , Wang Jingyu , Antonello Jacopo , He Honghui , Liu Shaoxiong , Lin Jianyu , Dai Ben , Elson Daniel S. , Xi Peng , Ma Hui , Booth Martin J.
Published: September 2019

Graded index (GRIN) lenses are commonly used for compact imaging systems. It is not widely appreciated that the ion-exchange process that creates the rotationally symmetric GRIN lens index profile also causes a symmetric birefringence variation. This property is usually considered a nuisance, such that manufacturing processes are optimized to keep it to a minimum. Here, rather than avoiding this birefringence, we understand and harness it by using GRIN lenses in cascade with other optical components to enable extra functionality in commonplace GRIN lens systems. We show how birefringence in the GRIN cascades can generate vector vortex beams and foci, and how it can be used advantageously to improve axial resolution. Through using the birefringence for analysis, we show that the GRIN cascades form the basis of a new single-shot Müller matrix polarimeter with potential for endoscopic label-free cancer diagnostics. The versatility of these cascades opens up new technological directions.
Regulating the coordination structure of single-atom Fe-NxCy catalytic sites for benzene oxidation
Authors: Pan Yuan , Chen Yinjuan , Wu Konglin , Chen Zheng , Liu Shoujie , Cao Xing , Cheong Weng-Chon , Meng Tao , Luo Jun , Zheng Lirong , Liu Chenguang , Wang Dingsheng , Peng Qing , Li Jun , Chen Chen
Published: September 2019

Atomically dispersed metal-N-C structures are efficient active sites for catalyzing benzene oxidation reaction (BOR). However, the roles of N and C atoms are still unclear. We report a polymerization-regulated pyrolysis strategy for synthesizing single-atom Fe-based catalysts, and present a systematic study on the coordination effect of Fe-NxCycatalytic sites in BOR. The special coordination environment of single-atom Fe sites brings a surprising discovery: Fe atoms anchored by four-coordinating N atoms exhibit the highest BOR performance with benzene conversion of 78.4% and phenol selectivity of 100%. Upon replacing coordinated N atoms by one or two C atoms, the BOR activities decrease gradually. Theoretical calculations demonstrate the coordination pattern influences not only the structure and electronic features, but also the catalytic reaction pathway and the formation of key oxidative species. The increase of Fe-N coordination number facilitates the generation and activation of the crucial intermediate O=Fe=O species, thereby enhancing the BOR activity.
A qualitative investigation of the allergic rhinitis network from the perspective of the patient
Authors: Cvetkovski Biljana , Kritikos Vicky , Tan Rachel , Yan Kwok , Azzi Elizabeth , Srour Pamela , Bosnic-Anticevich Sinthia
Published: September 2019

Patient self-selection of over-the-counter medicines for the management of allergic rhinitis is suboptimal. The mapping of the allergic rhinitis network demonstrates that patients’ decisions with regards to their allergic rhinitis management can be influenced by up to 11 individuals/resources (alters). This study aimed to identify the role of alters within the allergic rhinitis network and identify the factors that determined their degree of influence as perceived by the patient. This research was a qualitative exploration embedded in an empirical framework and social network theory. People with allergic rhinitis were interviewed about their network and transcripts were analysed deductively and inductively. Transcripts were coded by researchers independently and then discussed until agreement was reached. Forty-one participants described the roles of 17 alters on their allergic rhinitis management. The roles of alters fell within five categories: diagnosis, medication prescription/supply/administration, medication recommendation, information about allergic rhinitis and emotional support. Participant interactions with these alters were often acute and had a long standing effect, with the participants often navigating the long-term management on their own. The significance of the influence of each alter on their allergic rhinitis management was dependent on the level of trust in their relationship, impact of the role made to the participants’ day-to-day management of allergic rhinitis and/or the participant’s beliefs. Allergic rhinitis management was fragmented and had opportunity to be improved by developing strategies, resources and policies to support self-management in collaboration with patients and health-care professionals.
Learning and adaptation in speech production without a vocal tract
Authors: Thompson Megan M. C. , Houde John F. , Nagarajan Srikantan S.
Published: September 2019

How is the complex audiomotor skill of speaking learned? To what extent does it depend on the specific characteristics of the vocal tract? Here, we developed a touchscreen-based speech synthesizer to examine learning of speech production independent of the vocal tract. Participants were trained to reproduce heard vowel targets by reaching to locations on the screen without visual feedback and receiving endpoint vowel sound auditory feedback that depended continuously on touch location. Participants demonstrated learning as evidenced by rapid increases in accuracy and consistency in the production of trained targets. This learning generalized to productions of novel vowel targets. Subsequent to learning, sensorimotor adaptation was observed in response to changes in the location-sound mapping. These findings suggest that participants learned adaptable sensorimotor maps allowing them to produce desired vowel sounds. These results have broad implications for understanding the acquisition of speech motor control.
Functional organization of motor networks in the lumbosacral spinal cord of non-human primates
Authors: Toossi Amirali , Everaert Dirk G. , Perlmutter Steve I. , Mushahwar Vivian K.
Published: September 2019

Implantable spinal-cord-neuroprostheses aiming to restore standing and walking after paralysis have been extensively studied in animal models (mainly cats) and have shown promising outcomes. This study aimed to take a critical step along the clinical translation path of these neuroprostheses, and investigated the organization of the neural networks targeted by these implants in a non-human primate. This was accomplished by advancing a microelectrode into various locations of the lumbar enlargement of the spinal cord, targeting the ventral horn of the gray matter. Microstimulation in these locations produced a variety of functional movements in the hindlimb. The resulting functional map of the spinal cord in monkeys was found to have a similar overall organization along the length of the spinal cord to that in cats. This suggests that the human spinal cord may also be organized similarly. The obtained spinal cord maps in monkeys provide important knowledge that will guide the very first testing of these implants in humans.
A machine learning framework for automated diagnosis and computer-assisted planning in plastic and reconstructive surgery
Authors: Knoops Paul G. M. , Papaioannou Athanasios , Borghi Alessandro , Breakey Richard W. F. , Wilson Alexander T. , Jeelani Owase , Zafeiriou Stefanos , Steinbacher Derek , Padwa Bonnie L. , Dunaway David J. , Schievano Silvia
Published: September 2019

Current computational tools for planning and simulation in plastic and reconstructive surgery lack sufficient precision and are time-consuming, thus resulting in limited adoption. Although computer-assisted surgical planning systems help to improve clinical outcomes, shorten operation time and reduce cost, they are often too complex and require extensive manual input, which ultimately limits their use in doctor-patient communication and clinical decision making. Here, we present the first large-scale clinical 3D morphable model, a machine-learning-based framework involving supervised learning for diagnostics, risk stratification, and treatment simulation. The model, trained and validated with 4,261 faces of healthy volunteers and orthognathic (jaw) surgery patients, diagnoses patients with 95.5% sensitivity and 95.2% specificity, and simulates surgical outcomes with a mean accuracy of 1.1 ± 0.3 mm. We demonstrate how this model could fully-automatically aid diagnosis and provide patient-specific treatment plans from a 3D scan alone, to help efficient clinical decision making and improve clinical understanding of face shape as a marker for primary and secondary surgery.
Ki-67 assessment in early breast cancer: SAKK28/12 validation study on the IBCSG VIII and IBCSG IX cohort
Authors: Varga Zsuzsanna , Li Qiyu , Jochum Wolfram , Perriard Ulrike , Rau Tilman , Tille Jean-Christoph , Hawle Hanne , Klingbiel Dirk , Thuerlimann Beat , Ruhstaller Thomas
Published: September 2019

The assessment of Ki-67 in early-stage breast cancer has become an important diagnostic tool in planning adjuvant therapy, particularly for the administration of additional chemotherapy to hormone-responsive patients. An accurate determination of the Ki-67 index is of the utmost importance; however, the reproducibility is currently unsatisfactory. In this study, we addressed the predictive/prognostic value of Ki-67 index assessed by using the most reproducible methods, which were identified in the pilot phase. Paraffin blocks obtained from patients with moderately differentiated, estrogen receptor (ER)-positive early-stage breast cancer in Switzerland, who were originally randomized to the treatment arms with and without chemotherapy in the IBCSG VIII-IX trials, were retrieved. Of these 344 randomized patients, we identified 158 patients (82 treated with and 76 treated without chemotherapy) for whom sufficient tumour tissue was available. The presence of Ki-67 was assessed visually by counting 2000 cells at the periphery (A) and estimating the number of positive cells in five different peripheral regions (C), which was determined to be the most reproducible method identified the pilot phase. The prognostic and predictive value was assessed by calculating the breast cancer-free interval (BCFI) and overall survival (OS) rate. Ki-67 was considered a numerical and categorical variable when different cut-off values were used (10%, 14%, 20% and 30%). An mRNA-based subtyping by using the MammaTyper kit with the application of a 20% Ki-67 immunohistochemistry (IHC) cut-off equivalent was also performed. 158 of 344 randomized patients could be included in the Ki-67 analysis. The mean Ki-67 values obtained by using the two methods differed (A: 21.32% and C: 16.07%). Ki-67 assessed by using method A with a cut-off of 10% was a predictive marker for OS, as the hazard ratio (>10% vs. <=10%) in patients with chemotherapy was 0.48 with a 95% confidence interval of [0.19–1.19]. Further, the HR of patients treated without chemotherapy was 3.72 with a 95% confidence interval of [1.16–11.96] (pinteraction=0.007). Higher Ki-67 index was not associated with outcome and using the 10% Ki-67 cut-off there was an opposite association for patients with and without chemotherapy. Ki-67 assessments with IHC significantly correlated with MammaTyper results (p=0.002). The exact counting method (A) performed via a light-microscope revealed the predictive value of Ki-67 assessment with a 10% cut-off value. Further analyses employing image analyses and/or mRNA-based-assessments in larger populations are warranted.
Process development for scale-up production of a therapeutic L-asparaginase by Streptomyces brollosae NEAE-115 from shake flasks to bioreactor
Authors: El-Naggar Noura El-Ahmady , Moawad Hassan , El-Shweihy Nancy M. , El-Ewasy Sara M. , Elsehemy Islam A. , Abdelwahed Nayera A. M.
Published: September 2019

L-asparaginase is a promising enzyme that has a wide range of significant applications including cancer therapy and starchy food industries. The statistical design of Plackett–Burman and face centered central composite design were employed to optimize L-asparaginase production by Streptomyces brollosae NEAE-115. As a result, a medium of the following formula is the optimum for producing L-asparaginase in the culture filtrate of Streptomyces brollosae NEAE-115: Dextrose 2 g, starch 20 g, L-asparagine 10 g, KNO3 1 g, K2HPO4 1 g, MgSO4.7H2O 0.5 g, NaCl 0.1 g, pH 7, fermentation period 7 days, temperature 30 °C, inoculum size 4%, v/v, agitation speed 150 rpm and inoculum age 48 h. The kinetics of cell growth, carbohydrates consumption and L- asparaginase production were studied in 7-L stirred tank bioreactor under different cultivation conditions. A significant increase in both cell growth and carbohydrate consumption was observed as the stirring speed increased from 200 to 600 rpm under uncontrolled pH. The highest L- asparaginase activity of 108.46 U/mL was obtained after 96 h at 400 rpm. On the other hand, the specific enzyme production (Yp/x) under uncontrolled pH reached its maximal value of about 20.3 U/mg cells. Further improvement of enzyme production was attained by controlling pH at 7 using the selected stirring speed of 400 rpm. Enzyme production of 162.11 U/mL obtained from the controlled pH cultures exceeded this value gained from uncontrolled pH (108.46 U/mL) by about 50%.
Calcium chloride and 1-methylcyclopropene treatments delay postharvest and reduce decay of New Queen melon
Authors: Zhang Qiang , Dai Wenting , Jin Xinwen , Li Jixin
Published: September 2019

In this study, newly harvested New Queen melons were treated with calcium chloride (CaCl2) and 1-methylcyclopropene (1-MCP) alone or in combination before storage. The results showed that the respiration rate, ethylene release, the activity and gene expression of pectinases such as polygalacturonase (PG), pectin methylesterase (PME) and pectate lyase (PL) in New Queen melons were dramatically decreased by treatments with 0.18 mol/L CaCl2 and/or 1 μL/L 1-MCP. Meanwhile, the climacteric behavior and flesh hardness reduction were inhibited. We also found that softer melon flesh was more conducive to the growth and reproduction of decay-causing microorganisms according to their growth curves in melons that were different in flesh hardness, suggesting inhibiting fruit softening can slow down the growth of microorganisms in fruit flesh, and thus reduce fruit decay rate. The combined use of CaCl2 and 1-MCP was more effective in suppressing respiration rate, ethylene release and protopectin hydrolysis, which could greatly delay the softening, reduce the decay rate, and extend the shelf life of New Queen melons.
The interactome of 2-Cys peroxiredoxins in Plasmodium falciparum
Authors: Brandstaedter Christina , Delahunty Claire , Schipper Susanne , Rahlfs Stefan , Yates John R. , Becker Katja
Published: September 2019

Peroxiredoxins (Prxs) are crucially involved in maintaining intracellular H2O2 homeostasis via their peroxidase activity. However, more recently, this class of proteins was found to also transmit oxidizing equivalents to selected downstream proteins, which suggests an important function of Prxs in the regulation of cellular protein redox relays. Using a pull-down assay based on mixed disulfide fishing, we characterized the thiol-dependent interactome of cytosolic Prx1a and mitochondrial Prx1m from the apicomplexan malaria parasite Plasmodium falciparum (Pf). Here, 127 cytosolic and 20 mitochondrial proteins that are components of essential cellular processes were found to interact with PfPrx1a and PfPrx1m, respectively. Notably, our data obtained with active-site mutants suggests that reducing equivalents might also be transferred from Prxs to target proteins. Initial functional analyses indicated that the interaction with Prx can strongly impact the activity of target proteins. The results provide initial insights into the interactome of Prxs at the level of a eukaryotic whole cell proteome. Furthermore, they contribute to our understanding of redox regulatory principles and thiol-dependent redox relays of Prxs in subcellular compartments.
Genome-wide analysis of Corsican population reveals a close affinity with Northern and Central Italy
Authors: Tamm Erika , Di Cristofaro Julie , Mazières Stéphane , Pennarun Erwan , Kushniarevich Alena , Raveane Alessandro , Semino Ornella , Chiaroni Jacques , Pereira Luisa , Metspalu Mait , Montinaro Francesco
Published: September 2019

Despite being the fourth largest island in the Mediterranean basin, the genetic variation of Corsica has not been explored as exhaustively as Sardinia, which is situated only 11 km South. However, it is likely that the populations of the two islands shared, at least in part, similar demographic histories. Moreover, the relative small size of the Corsica may have caused genetic isolation, which, in turn, might be relevant under medical and translational perspectives. Here we analysed genome wide data of 16 Corsicans, and integrated with newly (33 individuals) and previously generated samples from West Eurasia and North Africa. Allele frequency, haplotype-based, and ancient genome analyses suggest that although Sardinia and Corsica may have witnessed similar isolation and migration events, the latter is genetically closer to populations from continental Europe, such as Northern and Central Italians.
Brain atrophy and patch-based grading in individuals from the CIMA-Q study: a progressive continuum from subjective cognitive decline to AD
Authors: Marcotte Christine , Potvin Olivier , Collins D. Louis , Rheault Sylvie , Duchesne Simon
Published: September 2019

It has been proposed that individuals developing Alzheimer’s disease (AD) first experience a phase expressing subjective complaints of cognitive decline (SCD) without objective cognitive impairment. Using magnetic resonance imaging (MRI), our objective was to verify whether SNIPE probability grading, a new MRI analysis technique, would distinguish between clinical dementia stage of AD: Cognitively healthy controls without complaint (CH), SCD, mild cognitive impairment, and AD. SNIPE score in the hippocampus and entorhinal cortex was applied to anatomical T1-weighted MRI of 143 participants from the Consortium pour l’identification précoce de la maladie Alzheimer - Québec (CIMA-Q) study and compared to standard atrophy measures (volumes and cortical thicknesses). Compared to standard atrophy measures, SNIPE score appeared more sensitive to differentiate clinical AD since differences between groups reached a higher level of significance and larger effect sizes. However, no significant difference was observed between SCD and CH groups. Combining both types of measures did not improve between-group differences. Further studies using a combination of biomarkers beyond anatomical MRI might be needed to identify individuals with SCD who are on the beginning of the clinical continuum of AD.
Interactions between Kuroshio Extension and Central Tropical Pacific lead to preferred decadal-timescale oscillations in Pacific climate
Authors: Joh Youngji , Di Lorenzo Emanuele
Published: September 2019

The Kuroshio Extension (KE) exhibits prominent decadal fluctuations that enhance the low-frequency variability of North Pacific climate. Using available observations, we show evidence that a preferred decadal timescale in the KE emerges from the interaction between KE and the central tropical Pacific via Meridional Modes. Specifically, we show that changes in the KE states apply a persistent downstream atmospheric response (e.g. wind stress curl, 0–12 months timescales) that projects on the atmospheric forcing of the Pacific Meridional Modes (PMM) over 9 months timescales. Subsequently, the PMM energizes the central tropical Pacific El Niño Southern Oscillation (CP-ENSO) and its atmospheric teleconnections back to the Northern Hemisphere (1–3 months timescale), which in turn excites oceanic Rossby waves in the central/eastern North Pacific that propagate westward changing the KE (~3 years timescales). Consistent with this hypothesis, the cross-correlation function between the KE and the PMM/CP-ENSO indices exhibits a significant sinusoidal shape corresponding to a preferred spectral power at decadal timescales (~10 years). This dynamics pathway (KE→PMM/CP-ENSO→KE) may provide a new mechanistic basis to explain the preferred decadal-timescale of the North Pacific and enhance decadal predictability of Pacific climate.
Elucidating the putative link between prefrontal neurotransmission, functional connectivity, and affective symptoms in irritable bowel syndrome
Authors: Icenhour Adriane , Tapper Sofie , Bednarska Olga , Witt Suzanne T. , Tisell Anders , Lundberg Peter , Elsenbruch Sigrid , Walter Susanna
Published: September 2019

Altered neural mechanisms are well-acknowledged in irritable bowel syndrome (IBS), a disorder of brain-gut-communication highly comorbid with anxiety and depression. As a key hub in corticolimbic inhibition, medial prefrontal cortex (mPFC) may be involved in disturbed emotion regulation in IBS. However, aberrant mPFC excitatory and inhibitory neurotransmission potentially contributing to psychological symptoms in IBS remains unknown. Using quantitative magnetic resonance spectroscopy (qMRS), we compared mPFC glutamate + glutamine (Glx) and γ-aminobutyric acid (GABA+) concentrations in 64 women with IBS and 32 age-matched healthy women (HCs) and investigated their association with anxiety and depression in correlational and subgroup analyses. Applying functional magnetic resonance imaging (fMRI), we explored whether altered neurotransmission was paralleled by aberrant mPFC resting-state functional connectivity (FC). IBS patients did not differ from HCs with respect to mPFC GABA+ or Glx levels. Anxiety was positively associated with mPFC GABA+ concentrations in IBS, whereas Glx was unrelated to psychological or gastrointestinal symptoms. Subgroup comparisons of patients with high or low anxiety symptom severity and HCs revealed increased GABA+ in patients with high symptom severity, and lower mPFC FC with adjacent anterior cingulate cortex (ACC), a crucial region of emotion modulation. Our findings provide novel evidence that altered prefrontal inhibitory neurotransmission may be linked to anxiety in IBS.
Novel breast cancer screening: combined expression of miR-21 and MMP-1 in urinary exosomes detects 95% of breast cancer without metastasis
Authors: Ando Wataru , Kikuchi Kiyoshi , Uematsu Takayuki , Yokomori Hiroaki , Takaki Takashi , Sogabe Masaya , Kohgo Yutaka , Otori Katsuya , Ishikawa Shigemi , Okazaki Isao
Published: September 2019

Serum and tissue miR-21 expression in patients with breast cancer (BC) is a useful biomarker for cancer diagnosis, progression, and treatment. Matrix metalloproteinase-1 (MMP-1) is also important in breast cancer carcinogenesis. However, miR-21 and MMP-1/CD63 in urine exosomes in these patients have not been examined. Urine samples were collected from patients with BC and 26 healthy females. Urinary exosomes were isolated and confirmed by western blotting with anti-CD63 antibody and electron microscopy observation. MiR-21 and MMP-1/CD63 expression was examined by quantitative RT-PCR and western blotting, respectively. Patients with very early stage breast cancer were evaluated. MiR-21 expression in the patients was 0.26 [95% CI: 0.20–0.78], which was significant lower than in the 26 controls (1.00 [95% CI: 1.01–3.37], p = 0.0947). MMP-1/CD63 expression in patients was significantly higher than in controls (1.74 [95% CI: 0.86–5.08] vs 0.535 [95% CI: −0.01–2.81], p = 0.0001). Sensitivity and specificity were 0.708 and 0.783 for miR-21 and 0.792 and 0.840 for MMP-1/CD63, respectively. Sensitivity and specificity of combined expression were 95% and 79%, respectively. The sensitivity of MMP-1/CD63 expression in urinary exosomes was better than that of miR-21 expression. Thus, miR-21 and MMP/CD63 may be useful markers for BC screening.
Quantum nanoconstrictions fabricated by cryo-etching in encapsulated graphene
Authors: Clericò V. , Delgado-Notario J. A. , Saiz-Bretín M. , Malyshev A. V. , Meziani Y. M. , Hidalgo P. , Méndez B. , Amado M. , Domínguez-Adame F. , Diez E.
Published: September 2019

We report on a novel implementation of the cryo-etching method, which enabled us to fabricate low-roughness hBN-encapsulated graphene nanoconstrictions with unprecedented control of the structure edges; the typical edge roughness is on the order of a few nanometers. We characterized the system by atomic force microscopy and used the measured parameters of the edge geometry in numerical simulations of the system conductance, which agree quantitatively with our low temperature transport measurements. The quality of our devices is confirmed by the observation of well defined quantized 2e2/h conductance steps at zero magnetic field. To the best of our knowledge, such an observation reports the clearest conductance quantization in physically etched graphene nanoconstrictions. The fabrication of such high quality systems and the scalability of the cryo-etching method opens a novel promising possibility of producing more complex truly-ballistic devices based on graphene.
Photo-modulated nanozymes for biosensing and biomedical applications
Authors: Wu Shihong , Zhang Jinyi , Wu Peng
Published: September 2019

The current status of the use of light for the modulation of nanozyme activity and selectivity was summarized.
The effects of active site and support on hydrogen elimination over transition-metal-functionalized yttria-decorated metal–organic frameworks
Authors: Yang Bo , Sharkas Kamal , Gagliardi Laura , Truhlar Donald G.
Published: September 2019

Transition-metal catalysts supported on a metal–organic framework have been screened computationally to reveal the best catalytic candidates for hydrogen elimination reactions, which are critical in many catalytic cycles.
Fiber all-optical light control with low-dimensional materials (LDMs): thermo-optic effect and saturable absorption
Authors: Shao Zhengpeng , Wang Cong , Wu Kan , Zhang Han , Chen Jianping
Published: September 2019

In this paper, we review the recent studies on all-optical light control based on two main nonlinear mechanisms in LDMs: the thermo-optic effect and saturable absorption.
Epitaxial growth and defect repair of heterostructured CuInSexS2−x/CdSeS/CdS quantum dots
Authors: Wang Chao , Barba David , Zhao Haiguang , Tong Xin , Wang Zhiming , Rosei Federico
Published: September 2019

Heterostructured quantum dots (hetero-QDs) have outstanding optical properties and chemical/photostability, which make them promising building blocks for use in various optoelectronic devices.
A self-assembly of an active tumor-targeted photothermal agent for enhanced anti-inflammatory cancer therapy
Authors: Wang Hongyu , Chang Jinjie , Pan Wei , Li Na , Tang Bo
Published: September 2019

A self-assembly of an active tumor-targeted organic photothermal agent, functionalized with a cyclic Arg-Gly-Asp (cRGD) peptide and ibuprofen, for efficiently killing cancer cells and eliciting anti-inflammatory responses was successfully developed.
Synthesis and properties of porous CLEAs lipase by the calcium carbonate template method and its application in biodiesel production
Authors: Miao Changlin , Li Huiwen , Zhuang Xinshu , Wang Zhongming , Yang Lingmei , Lv Pengmei , Luo Wen
Published: September 2019

Porous cross-linked enzyme aggregates (p-CLEAs) were synthesized. This p-CLEAs presented a complete structure with abundant channels, large specific surface and more efficient catalytic effect compared with conventional CLEAs.
Novel camphor-based pyrimidine derivatives induced cancer cell death through a ROS-mediated mitochondrial apoptosis pathway
Authors: Zhang Yan , Wang Yunyun , Zhao Yuxun , Gu Wen , Zhu Yongqiang , Wang Shifa
Published: September 2019

A series of novel camphor-based pyrimidine derivatives were synthesized and characterized. We found the compound 3f exhibited strongest anti-tumor activity via ROS-mediated mitochondrial apoptosis pathway.
Alleviation of symptoms of Alzheimer's disease by diminishing Aβ neurotoxicity and neuroinflammation
Authors: Yang Tao , Zhu Zhenzhu , Yin Enmao , Wang Yanqing , Zhang Changli , Yuan Hao , Zhang Hongmei , Jin Suxing , Guo Zijian , Wang Xiaoyong
Published: September 2019

Neuromodulator BIBA inhibits Aβ aggregation and suppresses neuroinflammation in vitro and in vivo, showing prominent anti-AD potential through a synergistic mechanism.
Photoinduced chitosan–PEG hydrogels with long-term antibacterial properties
Authors: Sautrot-Ba P. , Razza N. , Breloy L. , Andaloussi S. Abbad , Chiappone A. , Sangermano M. , Hélary C. , Belbekhouche S. , Coradin T. , Versace D.-L.
Published: September 2019

The photo-induced synthesis of chitosan–PEG hydrogels with tremendous antibacterial and anti-adhesive properties even after 6 months’ storage.
Hydrophobic hBN-coated surface-enhanced Raman scattering sponge sensor for simultaneous separation and detection of organic pollutants
Authors: Jung Ho Sang , Koh Eun Hye , Mun ChaeWon , Min Jeongho , Sohng Woosuk , Chung Hoeil , Yang Jun-Yeong , Lee Seunghun , Kim Hyo Jung , Park Sung-Gyu , Lee Min-Young , Kim Dong-Ho
Published: September 2019

A sponge-based surface-enhanced Raman scattering (SERS) sensor composed of silver nanowires (AgNWs) coated with hydrophobic hexagonal boron nitride (hBN) was prepared for the simultaneous separation and detection of organic pollutants.
Accuracy of matrix-assisted LASER desorption ionization–time of flight mass spectrometry for identification of Candida
Authors: Xie Tian-Ao , Liu Ye-Ling , Liang Chuan , Huang Yuan-Yuan , Li Jin-Wei , Li Zhong-Wei , Fan Shu-Jin , Chen Jin-Tao , Xia Yong , Li Xiao-Yan , Ouyang Shi , Ji Tian-Xing , Guo Xu-Guang
Published: September 2019

Background: Candida is a fungus that causes various types of candidemia, which is the fourth major infectious disease of the blood system. MALDI-TOF-MS is a simple and rapid detection instrument. The aim of the present study was to verify the accuracy of MALDI-TOF-MS in detecting Candida.

Method: A pooled analysis of articles on MALDI-TOF-MS for diagnosis of candidemia was performed. The quality of original research was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Stata 12.0 software was used to merge the correct identification rates of Candida and Candida subspecies and obtain pooled sensitivity and specificity of the diagnostic methods. Heterogeneity was found in the subgroup analysis of the included articles. Hence, we explored the factors causing the heterogeneity and its impact on the overall situation. Sensitivity analysis was used to examine the effect of Candida level on total response. Egger’s test was used to evaluate the publication bias of the included articles.

Results: A total of 16 articles in Pubmed, 79 articles in Embase, 1 article in Cochrane Library, 30 articles in Web of Science and 3 from other sources were identified, of which 10 articles were included based on the inclusion and exclusion criteria. The overall identification accuracy was 100%.

Conclusion: The accuracy of MALDI-TOF-MS for the identification of Candida was 100%. Further research is necessary to determine whether MALDI-TOF-MS can be used as a clinical diagnostic standard for the identification of Candida.