bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Multicentric Follow-up Study of Cochlear Implantation in Adults With Single-Sided Deafness: Tinnitus and Audiological Outcomes
Authors: Poncet-Wallet Christine , Mamelle Elisabeth , Godey Benoit , Truy Eric , Guevara Nicolas , Ardoint Marine , Gnansia Dan , Hoen Michel , Saaï Sonia , Mosnier Isabelle , Lescanne Emmanuel , Bakhos David , Vincent Christophe 
Published: December 2019

Objective:
This study investigated the audiological and tinnitus outcomes of cochlear implantation (CI) in adults with single-sided deafness (SSD) and tinnitus.

Study Design:
Multicentered prospective, non-randomized intervention study.

Setting:
Six French CI centers.

Patients:
Twenty-six patients with SSD and incapacitating tinnitus (Tinnitus Handicap Inventory [THI] >58) underwent cochlear implantation.

Interventions:
First, CIs delivered only masking white noise stimulation for 1 month and then standard CI stimulation.

Main Outcome Measures:
Before and after CI surgery, patients completed the THI, Tinnitus Reaction Questionnaire (TRQ), Subjective Tinnitus Severity Scale (STSS), and two visual analogue scales quantifying tinnitus loudness and annoyance. Speech perception in spatialized noise was tested at 13 months.

Results:
The first month of white noise stimulation triggered a significant improvement in THI scores (72 ± 9 to 55 ± 20, p < 0.05). No change was observed for the other measures. After 1 year of standard CI stimulation, 23 patients (92%) reported a significant improvement in tinnitus. This improvement started 1 to 2 months after CI and exceeded 40% improvement for 14 patients (54%). Average speech-in-noise perception after 1 year significantly improved for the 23 patients who completed these measures.

Conclusions:
CI is efficacious to reduce the handicap of patient with SSD and incapacitating tinnitus, leading to a decrease in reported tinnitus and partial restoration of binaural hearing abilities.
A Retrospective Analysis of Intervention for Testicular Torsion: Searching for a Hallmark of High Reliability
Authors: Calder Jennifer K. , Calder Bennett W. , Arbra Chase A. , Cina Robert A. 
Published: December 2019

Introduction:
Consistent delivery of high-quality care is a marker of health-care system reliability. Although clinically abstracted outcome databases have revolutionized surgical quality improvement efforts for many high-volume procedures, their utility in aiding the improvement of time-sensitive processes is less clear. The purpose of this study was to determine whether process measures surrounding the delivery of timely surgical care could delineate the variability in the outcome of patients with testicular torsion. Our secondary aim was to use the data to drive quality improvement efforts locally.

Methods:
We performed a retrospective review of encounters for testicular torsion in patients less than 18 years. Characteristics of patients undergoing detorsion/orchiopexy and orchiectomy were compared. We evaluated orchiectomy as a function of age, insurance status, time of presentation, duration of symptoms, time to ultrasound, and time to surgery.

Results:
Over 10 years, we identified 46 patients, of whom 21 met inclusion criteria. Twelve patients (57.1%) underwent detorsion/orchiopexy, whereas 9 patients underwent orchiectomy. After-hours presentation and age were not predictive of orchiectomy, whereas the duration of symptoms was predictive of orchiectomy. Differences in time to surgery for orchiopexy and orchiectomy groups approached but did not reach significance (P = 0.07).

Conclusions:
Significant variability persists in the timely delivery of comprehensive and coordinated care for children suffering from time-sensitive surgical conditions. Pediatric surgical programs would realize significant benefit from a surgical quality improvement program that incorporates validated process metrics, along with outcome measures, to help drive efficiencies and integrate care more effectively.
Soft eSkin: distributed touch sensing with harmonized energy and computing
Authors: Soni Mahesh , Dahiya Ravinder 
Published: December 2019

Inspired by biology, significant advances have been made in the field of electronic skin (eSkin) or tactile skin. Many of these advances have come through mimicking the morphology of human skin and by distributing few touch sensors in an area. However, the complexity of human skin goes beyond mimicking few morphological features or using few sensors. For example, embedded computing (e.g. processing of tactile data at the point of contact) is centric to the human skin as some neuroscience studies show. Likewise, distributed cell or molecular energy is a key feature of human skin. The eSkin with such features, along with distributed and embedded sensors/electronics on soft substrates, is an interesting topic to explore. These features also make eSkin significantly different from conventional computing. For example, unlike conventional centralized computing enabled by miniaturized chips, the eSkin could be seen as a flexible and wearable large area computer with distributed sensors and harmonized energy. This paper discusses these advanced features in eSkin, particularly the distributed sensing harmoniously integrated with energy harvesters, storage devices and distributed computing to read and locally process the tactile sensory data. Rapid advances in neuromorphic hardware, flexible energy generation, energy-conscious electronics, flexible and printed electronics are also discussed.This article is part of the theme issue ‘Harmonizing energy-autonomous computing and intelligence’.
A semi-holographic hyperdimensional representation system for hardware-friendly cognitive computing
Authors: Serb A. , Kobyzev I. , Wang J. , Prodromakis T. 
Published: December 2019

One of the main, long-term objectives of artificial intelligence is the creation of thinking machines. To that end, substantial effort has been placed into designing cognitive systems; i.e. systems that can manipulate semantic-level information. A substantial part of that effort is oriented towards designing the mathematical machinery underlying cognition in a way that is very efficiently implementable in hardware. In this work, we propose a ‘semi-holographic’ representation system that can be implemented in hardware using only multiplexing and addition operations, thus avoiding the need for expensive multiplication. The resulting architecture can be readily constructed by recycling standard microprocessor elements and is capable of performing two key mathematical operations frequently used in cognition, superposition and binding, within a budget of below 6 pJ for 64-bit operands. Our proposed ‘cognitive processing unit’ is intended as just one (albeit crucial) part of much larger cognitive systems where artificial neural networks of all kinds and associative memories work in concord to give rise to intelligence.
This article is part of the theme issue ‘Harmonizing energy-autonomous computing and intelligence’.
Neural network design for energy-autonomous artificial intelligence applications using temporal encoding
Authors: Mileiko Sergey , Bunnam Thanasin , Xia Fei , Shafik Rishad , Yakovlev Alex , Das Shidhartha 
Published: December 2019

Neural networks (NNs) are steering a new generation of artificial intelligence (AI) applications at the micro-edge. Examples include wireless sensors, wearables and cybernetic systems that collect data and process them to support real-world decisions and controls. For energy autonomy, these applications are typically powered by energy harvesters. As harvesters and other power sources which provide energy autonomy inevitably have power variations, the circuits need to robustly operate over a dynamic power envelope. In other words, the NN hardware needs to be able to function correctly under unpredictable and variable supply voltages. In this paper, we propose a novel NN design approach using the principle of pulse width modulation (PWM). PWM signals represent information with their duty cycle values which may be made independent of the voltages and frequencies of the carrier signals. We design a PWM-based perceptron which can serve as the fundamental building block for NNs, by using an entirely new method of realizing arithmetic in the PWM domain. We analyse the proposed approach building from a 3 × 3 perceptron circuit to a complex multi-layer NN. Using handwritten character recognition as an exemplar of AI applications, we demonstrate the power elasticity, resilience and efficiency of the proposed NN design in the presence of functional and parametric variations including large voltage variations in the power supply.This article is part of the theme issue ‘Harmonizing energy-autonomous computing and intelligence’.
Understanding extraction principles underpinning historical antimicrobial drug discovery for improving rediscovery and reproducibility
Authors: Keulen Geertje van , Luft Diana , Jenkins Rowena E. 
Published: December 2019

Area of expertise: Microbiology, biochemistry, antimicrobials, medieval Welsh texts exploration.

Future goals: Medieval and other historical Welsh texts are newly being translated into English, which include the Red Book of Hergest used by the Physicians of Myddfai, the famous Welsh medical practitioners of the 12th century. The previous translations have so far only been studied for Welsh Language (esp. poetry) and cultural aspects, while these books also contain a wealth of information on historical approaches to societal, environmental and medical problems. We aimed to explore the translated texts for the recovery of (bio)chemical, public health and environmental knowledge of the ancient Welsh environment and society.
The newly translated medieval Welsh antimicrobial recipes were reviewed for plant names/parts and other sources, medical indication of application, and materials or processes related to extraction and formulation of the remedy in order to better understand principal components and their activities, and to be able to redesign recipes using modern chemical extraction protocols. Statistical analysis showed that a wide range of materials could potentially function for selective extraction or for precipitation of (non-)active components. Clear descriptions of processes and protocols were usually missing. It therefore requires considerable human and material resources to truly assess the merits of medieval recipes.
It would therefore be worthwhile to discuss the merit of a systematic review of historical extraction and purification principles, to be able to suggest common principles aiding effective rediscovery and redesign of antimicrobials from historical texts. Did medieval societies employ “Standard Operating Procedures”? How can modern scientists accurately and efficiently assess the merits of historical treatment alternatives to infection in the age of increasing antimicrobial resistance?
Chikungunya virus recruits the ESCRT trafficking machinery at multiple steps during the intracellular life cycle
Authors: Torii Shiho , Orba Yasuko , Sasaki Michihito , Wada Yuji , Hobson-Peters Jody , Hall Roy , Sawa Hirofumi 
Published: December 2019

Chikungunya virus (CHIKV) causes a re-emerging zoonotic disease characterized by fever and joint pain. Since there are no available vaccines nor medicine for CHIKV infection, better understanding of molecular mechanisms underlying CHIKV infection is demanded to develop new treatments. To date, few studies exist describing host factors necessary for intracellular trafficking of CHIKV; thus, the aim of this study is to identify trafficking genes regulating CHIKV infection and to investigate their roles.
We conducted imaging-based siRNA screen targeting 73 trafficking genes, examined the interaction with CHIKV proteins by co-immunoprecipitation and confocal analyses, and then investigated which infection steps of CHIKV were affected by the identified gene(s).
The siRNA screen showed that endosomal sorting complexes required for transport (ESCRT) proteins were involved in CHIKV infection. Co-immunoprecipitation analyses between ESCRT proteins and CHIKV proteins revealed that both structural and non-structural proteins of CHIKV interacted with HGS, a component of ESCRT-0 complex. Confocal analyses demonstrated colocalization of HGS with CHIKV E2 and dsRNA, a marker for the replicated CHIKV genome. Gene knockdown analyses using CHIKV replicon and CHIKV-like particle system demonstrated that HGS facilitated both genome replication and post-translational steps of CHIKV infection, as well as other ESCRT factors.
Here, we propose for the first time that CHIKV requires ESCRT factors at multiple steps during its intracellular life cycle.
The piRNA pathway in host-pathogen interaction: Aedes albopictus and arboviruses
Authors: Marconcini Michele , Houé Vincent , Valerio Federica , Palatini Umberto , Pischedda Elisa , Ometto Lino , Forneris Federico , Failloux Anna-Bella , Bonizzoni Mariangela , Chávez Alejandro Nabor Lozada 
Published: December 2019

Aedes albopictus is an aggressive invasive species and a competent vector for over 20 arboviruses, including Chikungunya, Dengue and Zika viruses. Understanding the molecular and cellular interactions between viruses and vectors is key to implement transmission-blocking strategies to prevent viral outbreaks. However, the mechanisms that shape vector competence are poorly understood. Recent evidence reveals that the genomes of Aedes spp. harbour fragmented viral sequences which produce PIWI-interacting RNAs (piRNAs), suggesting a role in vector competence. Current knowledge of the piRNA pathway in Ae. albopictus is limited, and its possible role in the establishment of persistent infections widely unknown.
We combined cutting-edge bioinformatic analyses based on next-generation sequencing data with molecular biology and virology techniques to characterise the main genes of the piRNA pathway in this mosquito species, assess their polymorphisms and analyse their expression throughout mosquito development and following infection with the Chikungunya and Dengue-1 viruses.
We identified seven piwi genes which displayed high levels of polymorphism across populations and signs of adaptive evolution. Superposition of protein homology models indicate high structure similarity among all Piwi proteins, with high levels of amino acid conservation in the inner regions devoted to RNA binding. On the contrary, solvent-exposed surfaces showed low conservation, with sites under positive selection. Infection experiments indicated specific responses depending on viral species, time of infection and mosquito tissue, highlighting distinct roles for specific Piwi proteins.
In conclusion, this work helps define the role of the piRNA pathway in persistent arboviral infections and understand the evolutionary divergence among piwi proteins.
National Collection of Pathogenic Viruses: A Repository for Well Characterised and Authenticated Viruses
Authors: Onianwa Okechukwu , Russell Julie , Alexander Sarah 
Published: December 2019

The National Collection of Pathogenic Viruses (NCPV) is one of four repositories making up Public Health England Culture Collections. It was established two decades ago to offer safe and secure facilities for storage of patents and deposits as well as to supply standardised virus products to the wider scientific community. Within the collection are strains of both medical and veterinary importance, with representation from a wide variety of virus families, classified as Hazard Groups 2, 3 and 4 by the Advisory Committee for Dangerous Pathogens (ACDP). These include arboviruses such as Dengue, Yellow-fever, Oropouche and Sandfly fever Naples.
Throughout the year, the collection receives virus deposits. The depositing process is free and simple. The quality of every virus material received in the collection is assessed through a series of tests to confirm viability and absence of microbial contamination (including mycoplasmas). Virus identity is confirmed by nucleic acid profiling. Once standards are met, the virus products are made available to the wider scientific community. In addition to facilitating access to viruses and their associated products as well as secure storage for patents, NCPV also undertakes collaborative projects and contract research/developmental work with academic and commercial partners, by providing expertise in the handling of viral pathogens.
A repository for well-characterised, authenticated viruses is a useful resource for the scientific community, aiding in the understanding of circulating viral pathogens and providing access to quality-assured reference reagents for the identification and development of vaccines and therapeutics in the event of global viral outbreaks.
Chikungunya virus resistant to the antiviral favipiravir is severely attenuated in mosquitoes
Authors: Langendries Lana , Jacobs Sofie , Abdelnabi Rana , Neyts Johan , Delang Leen 
Published: December 2019

It is currently unclear whether antiviral drug-resistant arboviruses can be transmitted by their mosquito vectors. We showed previously that the dissemination and the transmission of a chikungunya virus (CHIKV) resistant to the antiviral favipiravir was markedly decreased as compared to WT (Delang et al, mSphere 2018). The attenuated phenotype of this resistant virus was confirmed in Aag2 and C6/36 mosquito cells. Here, we aimed to study the mechanism of the attenuated phenotype in more detail.
First, replication kinetics studies at 32°C for both Vero and mosquito cells confirmed that the attenuated fitness in mosquito cells is associated with the cell line and not with temperature. A passaging experiment of WT CHIKV on Vero cells in the absence of favipiravir showed that the observed attenuation of the resistant CHIKV was not due to passaging on Vero cells during the resistance selection. To identify the molecular mechanism of the attenuated phenotype, the genes encoding for the non-structural proteins (nsP) of the favipiravirres CHIKV were swapped into a WT CHIKV backbone. The replication fitness of these nsP2, nsP3 or nsP4 single swap variants did not differ significantly from the fitness of WT CHIKV in Vero and C6/36 cells, indicating that a combination of mutations in multiple non-structural proteins is responsible for the attenuated phenotype. Double nsP swap variants are therefore constructed and these will provide additional information on the molecular mechanism of the attenuation. Together, our results may provide interesting insights in the mosquito tropism of CHIKV.
Karyotype changes in cultivated tick cell lines
Authors: Kotsarenko Kateryna , Vechtova Pavlina , Sterba Jan 
Published: December 2019

Background. Tick cell lines are an easy-to-handle system for the study of viral and bacterial infections and different aspects of tick physiology. However, long-term cultivation of tick cells can influence genome stability. The aim of our work was to analyze and compare the karyotypes of Ixodes scapularis, I. ricinus, and Ornithodoros moubata tick cell lines after long-term been in culture.

Methods. Mitotic spreads were prepared to count the number of chromosomes in ISE6, ISE18, IRE11, IRE/CTVM19, IRE/CTVM20, and OME/CTVM22 cell lines. The genome size of tick cell cultures was estimated by flow cytometry using propidium iodide staining.

Results. The modal chromosome numbers around 22 and around 48 were typical for both I. ricinus and I. scapularis cell lines and differed from the diploid chromosome number in Ixodesticks – 28. In the OME/CTVM22cell line, the modal chromosome number was 33, instead of 20 in Ornithodoros ticks. All tick cell lines had a larger genome size in compare to genomes of parental ticks.

Conclusions.Tick cell lines can be used for research purposes, however, differences in the internal processes between different cell populations should be taken into account.
Acknowledgments: We thank Lesley Bell-Sakyi and the Tick Cell Biobank for provision of the tick cell lines.
Targeting functional RNA structures in CHIKV and ZIKV
Authors: Prosser Oliver , Merits Andres , Stonehouse Nicola J , Tuplin Andrew 
Published: December 2019

Emerging arboviruses such as Zika virus (ZIKV) and Chikungunya virus (CHIKV) represent a significant threat to human health and have a high potential to cause outbreaks in the near future. At present, there are no specific antivirals available for either of these important pathogens, despite the wide global prevalence of their vector, Aedes spp. mosquitos.
The positive-strand genomes of ZIKV and CHIKV, members of the flavivirus and alphavirus genera respectively, contain functional, structured cis-acting RNA elements which are essential for virus replication. By specifically targeting such RNA elements using antisense locked nucleic acid oligonucleotides (antisense-LNA), we aim to disrupt their function, and analyse the effect this has on virus replication at different life cycle stages.
Obtaining high quality, single-nucleotide-resolution structural data is essential prior to targeting RNA structures. Consequently, we mapped RNA structural elements within the ZIKV 5’ genome region using a combination of biochemical SHAPE probing, thermodynamic models and phylogenetic analysis. We are currently validating our structural data by analysis of mutant phenotypes in a reverse genetic system.
We demonstrate that functional RNA elements in CHIKV can be specifically targeted - inhibiting replication in both sub-genomic replicon and infectious virus systems. Surface plasmon resonance confirmed that an antisense-LNA binds to a specific stem-loop target with a Kd of 310nM and has an IC50 of 35nM in a sub-genomic replicon system. In future work, we aim to investigate selection of RNA-aptamers against CHIKV and target ZIKV genomic stem-loops using antisense-LNAs.
Transcriptomic analysis of human neurons and astrocytes infected with TBEV strains of different virulence
Authors: Selinger Martin , Vechtova Pavlina , Tykalova Hana , Sterba Jan , Grubhoffer Libor 
Published: December 2019

Tick-borne encephalitis virus (TBEV; Flaviviridae) can cause serious infections in humans which may result in encephalitis/meningoencephalitis. It has been previously reported that TBEV infects both, neurons and astrocytes, however, with a different outcome. So far, the principle of this cell type-specific response to TBEV is not fully understood.
In order to gain more insight into this phenomenon, we described new in vitro infection model utilizing human neural stem cells (hNSCs) and two strains of Western European TBEV subtype varying in the pathogenicity - mild Neudoerfl and severe Hypr. In detail, neurons and astrocytes were artificially differentiated from hNSCs and presence of CNS markers was checked. TBEV infection in both cell types was characterised afterwards. As expected, both cell types proved to be susceptible to TBEV infection. Viability was negatively affected only in infected neurons. In order to identify possible effectors responsible for different susceptibility of neurons and astrocytes, the analyses of changes in poly-(A) and small RNA transcriptome upon TBEV infection were performed. Preliminary results from poly-(A) RNA transcriptome revealed that in both cell types mainly interferon-stimulated genes (ISGs) were up-regulated. However, the expression kinetics of particular ISGs varied. In addition, the vast spectrum of long non-coding RNAs was described to be differentially expressed upon infection. Surprisingly, U1 snRNA was found to be the most down-regulated RNA species among almost all infected samples.
Further analyses are in progress in order to get a complete description of virus-induced changes on the transcriptomic level.