bluuebunny/crossref_metadata_2025 huggingface dataset:
Destination Image Recognition And Emotion Analysis: Evidence From User-Generated Content Of Online Travel Communities
Authors: Huang Weidong , Zhu Shuting , Yao Xinkai
Published: June 2020

The tourism destination image is an intangible value that enhances the internal and external spiritual value of the region. To improve tourist experiences and provide reference for relevant departments, we applied the GooSeeker web data crawler tool and Python data mining kit to crawl and analyze the representative online tourism community data. We conduct an empirical analysis through data from the online tourist community ‘mafengwo’. The result, based on the user-generated content data analysis of online travel community, shows that the tourists' perception of the destination image, cognitive theme and emotional experience has different effects on the tourist experience. This research offers insights into destination image cognitive theme and traveler behavior habits, which can provide guidance for platform and destination managers.
Electrophysiology in the time of coronavirus: coping with the great wave
Authors: Li Jia , Mazzone Patrizio , Leung Lisa W M , Lin Weiqian , D’Angelo Giuseppe , Ma Jun , Li Jin , Akhtar Zaki , Li Yuechun , Della Bella Paolo , Lin Jiafeng , Gallagher Mark M
Published: June 2020

Aims 

To chart the effect of the COVID-19 pandemic on the activity of interventional electrophysiology services in affected regions.

Methods and results 

We reviewed the electrophysiology laboratory records in three affected cities: Wenzhou in China, Milan in Italy, and London in the UK. We inspected catheter lab records and interviewed electrophysiologists in each centre to gather information on the impact of the pandemic on working patterns and on the health of staff members and patients. There was a striking decline in interventional electrophysiology activity in each of the centres. The decline occurred within a week of the recognition of widespread community transmission of the virus in each region and shows a striking correlation with the national figures for new diagnoses of COVID-19 in each case. During the period of restriction, workflow dropped to <5% of normal, consisting of emergency cases only. In two of three centres, electrophysiologists were redeployed to perform emergency work outside electrophysiology. Among the centres studied, only Wenzhou has seen a recovery from the restrictions in activity. Following an intense nationwide programme of public health interventions, local transmission of COVID-19 ceased to be detectable after 18 February allowing the electrophysiology service to resume with a strict testing regime for all patients.

Conclusion 

Interventional electrophysiology is vulnerable to closure in times of great social difficulty including the COVID-19 pandemic. Intense public health intervention can permit suppression of local disease transmission allowing resumption of some normal activity with stringent precautions.
The thermo-regulated genetic switch of deep-sea filamentous phage SW1 and its distribution in the Pacific Ocean
Authors: Meng Canxing , Li Site , Fan Qilian , Chen Rouke , Hu Yang , Xiao Xiang , Jian Huahua
Published: June 2020

Viruses, especially bacteriophages, are thought to have important functions in the deep-sea ecosystem, but little is known about the induction mechanism of benthic phages in response to environmental change. Our prior work characterized a cold-active filamentous phage SW1 that infects the deep-sea bacterium Shewanella piezotolerans WP3; however, the underlying mechanism of the putative thermo-regulated genetic switch of SW1 is still unclear. In this study, the DNA copy number and mRNA abundance of the deep-sea phage SW1 were quantified in the whole life cycle of its host S. piezotolerans WP3 at different temperatures. Our results demonstrated that the induction of SW1 is dependent on a threshold temperature (4°C), but this dependency is not proportional to temperature gradient. RNA-Seq analyses revealed two highly transcribed regions at 4°C and verified the presence of a long 3′ untranslated region (UTR) in the SW1 genome. Interestingly, recruitment analysis showed that SW1-like inoviruses prevail in deep sea (depth >1000 m) and photic epipelagic and mesopelagic zones (depth <1000 m), which suggested that the thermo-regulated genetic switch revealed in SW1 may be widely distributed in the ocean.
Centering Human Subjects: The Ethics of “Desk Research” on Political Violence
Authors: Hoover Green Amelia , Cohen Dara Kay
Published: June 2020

Quantitative data about political violence are frequently based on “desk research,” data derived from secondary sources that do not require direct contact between researchers and participants, such as people who witnessed or experienced violence. The research that employs these data is often viewed implicitly as ethically uncomplicated. In contrast, we argue that the production and analysis of political violence data coded from secondary sources require careful ethical deliberation regarding human subjects concerns. We consider two broad classes of quantitative political violence data often gathered through desk research: incident lists and indices. For both types, we identify ethical concerns about how data production and use can affect research participants. We conclude by offering a series of suggestions on how to incorporate ethical considerations about human subjects into the design and evaluation of political violence research based on secondary sources.
High detection rate of azole-resistantAspergillus fumigatusafter treatment with azole antifungal drugs among patients with chronic pulmonary aspergillosis in a single hospital setting with low azole resistance
Authors: Takeda Keita , Suzuki Junko , Watanabe Akira , Arai Teppei , Koiwa Tomohiro , Shinfuku Kyota , Narumoto Osamu , Kawashima Masahiro , Fukami Takeshi , Tamura Atsuhisa , Nagai Hideaki , Matsui Hirotoshi , Kamei Katsuhiko
Published: June 2020

The prevalence of azole-resistant Aspergillus fumigatus (ARAF) among chronic pulmonary aspergillosis (CPA) patients treated with azoles in Japan is unknown. The aim of this study was to determine the detection rate of ARAF in isolates from CPA patients who were treated with azoles for varying durations. The potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104) between February 2012 and February 2019, at National Hospital Organization Tokyo National Hospital. The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF among all isolates was 8.3% (n = 10). Of the 10 resistant isolates, eight were ITCZ-resistant and five were VRCZ-resistant. Among 47 isolates obtained from 36 CPA patients who were treated with ITCZ (for an average of 256 days) and/or VRCZ (for an average of 29 days), the resistance rates were 17.0% and 10.6%, respectively. In addition, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients, particularly in those with ongoing long-term azole treatment, at the time of azole antifungal therapy failure.
Relative importance of convective uncertainties in massive stars
Authors: Kaiser Etienne A , Hirschi Raphael , Arnett W David , Georgy Cyril , Scott Laura J A , Cristini Andrea
Published: June 2020

In this work, we investigate the impact of uncertainties due to convective boundary mixing (CBM), commonly called ‘overshoot’, namely the boundary location and the amount of mixing at the convective boundary, on stellar structure and evolution. For this we calculated two grids of stellar evolution models with the MESA code, each with the Ledoux and the Schwarzschild boundary criterion, and vary the amount of CBM. We calculate each grid with the initial masses of 15, 20, and $25\, \rm {M}_\odot$. We present the stellar structure of the models during the hydrogen and helium burning phases. In the latter, we examine the impact on the nucleosynthesis. We find a broadening of the main sequence with more CBM, which is more in agreement with observations. Furthermore, during the core hydrogen burning phase there is a convergence of the convective boundary location due to CBM. The uncertainties of the intermediate convective zone remove this convergence. The behaviour of this convective zone strongly affects the surface evolution of the model, i.e. how fast it evolves redwards. The amount of CBM impacts the size of the convective cores and the nucleosynthesis, e.g. the 12C to 16O ratio and the weak s-process. Lastly, we determine the uncertainty that the range of parameter values investigated introduces and we find differences of up to $70{{\ \rm per\ cent}}$ for the core masses and the total mass of the star.
DC3N observations towards high-mass star-forming regions
Authors: Rivilla V M , Colzi L , Fontani F , Melosso M , Caselli P , Bizzocchi L , Tamassia F , Dore L
Published: June 2020

We present the study of deuteration of cyanoacetylene (HC3N) towards a sample of 28 high-mass star-forming cores divided into different evolutionary stages, from starless to evolved protostellar cores. We report for the first time the detection of DC3N towards 15 high-mass cores. The abundance ratios of DC3N with respect HC3N range in the interval 0.003–0.022, lower than those found in low-mas protostars and dark clouds. No significant trend with the evolutionary stage, or with the kinetic temperature of the region, has been found. We compare the level of deuteration of HC3N with those of other molecules towards the same sample, finding weak correlation with species formed only or predominantly in gas phase (N2H+ and HNC, respectively), and no correlation with species formed only or predominantly on dust grains (CH3OH and NH3, respectively). We also present a single-dish map of DC3N towards the protocluster IRAS 05358+3543, which shows that DC3N traces an extended envelope (∼0.37 pc) and peaks towards two cold condensations separated from the positions of the protostars and the dust continuum. The observations presented in this work suggest that deuteration of HC3N is produced in the gas of the cold outer parts of massive star-forming clumps, giving us an estimate of the deuteration factor prior to the formation of denser gas.
Current usage of tumor treating fields for glioblastoma
Authors: Lassman Andrew B , Joanta-Gomez Adela E , Pan Peter C , Wick Wolfgang
Published: June 2020

Background

Tumor Treating Fields (TTF) have entered clinical practice for newly diagnosed and recurrent glioblastoma (GGM). However, controversies remain unresolved with regard to appropriate usage. We sought to determine TTF usage in major academic neuro-oncology programs in New York City, USA and Heidelberg, Germany and understand current attitudes toward TTF usage among providers.

Methods

We retrospectively determined TTF usage among patients with GGM, before and since the publication of key clinical trial results and regulatory approvals. We also surveyed attendees of an educational session related to TTF during the 2019 American Society of Clinical Oncology annual meeting.

Results

TTF usage remains infrequent (3–12% of patients with newly diagnosed GBM, and 0–16% of patients with recurrent disease) in our practices, although it has increased over time. Among 30 survey respondents (77% of whom self-identified as neuro- or medical oncologists), 60% were convinced that TTF prolongs survival for newly diagnosed GGM despite published phase III data and regulatory approval, and only 30% viewed TTF as definitively part of the standard of care treatment. A majority (87%) opposed mandating TTF incorporation into the design of clinical trials.

Conclusions

Providers continue to view TTF with some level of skepticism, with a lack of additional supportive data and logistical concerns representing continued barriers to uptake.
Coherent quantum transport through ferromagnetic graphene structures: Effects of Rashba spin–orbit coupling
Authors: Hasanirokh Kobra , Naderi Fezzeh
Published: June 2020

In a system consisting of a monolayer ferromagnetic graphene structure, based on the scattering matrix approach, we study the spin-dependent transmission coefficients, group delay time, magnetoresistance and giant magnetoresistance of spin-polarized electron tunneling through the Rashba barrier in single-layer graphene. The results show that Rashba spin–orbit coupling can cause a natural spin filter mechanism; it thus has a significant role in controlling the transmission probabilities. In addition, the quantum transport properties of our system depend critically on the structural parameters. The incidence angle, energy, barrier number, and exchange energies can strongly control the transport properties of multi-layer graphene. It is predicted that controlling spin-dependent transport in single layer graphene results can develop the well-known spintronics.
When Does Spatial Diversification Usefully Maximize the Durability of Crop Disease Resistance?
Authors: Watkinson-Powell Benjamin , Gilligan Christopher A. , Cunniffe Nik J.
Published: June 2020

Maximizing the durability of crop disease resistance genes in the face of pathogen evolution is a major challenge in modern agricultural epidemiology. Spatial diversification in the deployment of resistance genes, where susceptible and resistant fields are more closely intermixed, is predicted to drive lower epidemic intensities over evolutionary timescales. This is due to an increase in the strength of dilution effects, caused by pathogen inoculum challenging host tissue to which it is not well-specialized. The factors that interact with and determine the magnitude of this spatial suppressive effect are not currently well understood, however, leading to uncertainty over the pathosystems where such a strategy is most likely to be cost-effective. We model the effect on landscape scale disease dynamics of spatial heterogeneity in the arrangement of fields planted with either susceptible or resistant cultivars, and the way in which this effect depends on the parameters governing the pathosystem of interest. Our multiseason semidiscrete epidemiological model tracks spatial spread of wild-type and resistance-breaking pathogen strains, and incorporates a localized reservoir of inoculum, as well as the effects of within and between field transmission. The pathogen dispersal characteristics, any fitness cost(s) of the resistance-breaking trait, the efficacy of host resistance, and the length of the timeframe of interest all influence the strength of the spatial diversification effect. A key result is that spatial diversification has the strongest beneficial effect at intermediate fitness costs of the resistance-breaking trait, an effect driven by a complex set of nonlinear interactions. On the other hand, however, if the resistance-breaking strain is not fit enough to invade the landscape, then a partially effective resistance gene can result in spatial diversification actually worsening the epidemic. These results allow us to make general predictions of the types of system for which spatial diversification is most likely to be cost-effective, paving the way for potential economic modeling and pathosystem specific evaluation. These results highlight the importance of studying the effect of genetics on landscape scale spatial dynamics within host−pathogen disease systems.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Inverted Papilloma of the Orbit and Nasolacrimal System
Authors: Wang Jessie , Ford Joshua , Esmaeli Bita , Langer Paul , Esmaili Neda , Griepentrog Gregory J. , Couch Steven M. , Nguyen John , Gold Katherine G. , Duerksen Kathleen , Burkat Cat N. , Hartstein Morris E. , Gandhi Parag , Sobel Rachel K. , Moon Jee-Young , Barmettler Anne
Published: June 2020

Purpose:

Periocular inverted papilloma (IP) is a rare, locally aggressive tumor with a propensity for recurrence and malignant transformation. Historically treated via wide excision, this study examines the characteristics and management of periocular IP, comparing those confined to the nasolacrimal system with those invading the orbit.

Methods:

An Institutional Review Board-approved, Health Insurance Portability and Accountability Act-compliant retrospective, comparative case series was conducted in patients with IP of the orbit or nasolacrimal system across 15 clinical sites.

Results:

Of 25 patients, 22 met inclusion criteria with 9 limited to the nasolacrimal system and 13 invading the orbit. Mean age was 60.4 years, 55% were women, all were unilateral. Mean follow-up was 48 months. Rates of smoking, dust and/or aerosol exposure, human papillomavirus (HPV) status, and inflammatory polyps were elevated compared to rates in the general population (45%, 18%, 18%, and 14%, respectively). Bony erosion on computed tomography scans was statistically significantly associated with orbit-invading IP (p = 0.002). Treatment involved all confined IP undergoing surgery alone while 39% of orbit-invading IP also received radiation therapy and/or chemotherapy (p = 0.054). Orbit-invading IP was more likely to be excised with wide margins than IP confined to the nasolacrimal system (85% vs. 22%, p = 0.007). Overall rates of malignancy, recurrence, and patient mortality from IP were found to be 27%, 23%, and 9%, respectively.

Conclusions:

IP invading the orbit typically requires aggressive therapy, while IP confined to the nasolacrimal system may be treated more conservatively. Using risk factors, characteristics, and outcomes, a treatment algorithm was created to guide management.
Implications of COVID-19 for the busy gastroenterologist
Authors: Ferreira-Silva Joel , Peixoto Armando , Rodrigues-Pinto Eduardo , Macedo Guilherme
Published: June 2020

Coronavirus disease 2019 (COVID-19) is an infection caused by a novel coronavirus (SARS-CoV-2) originated in China in December 2020 and declared pandemic by WHO. This coronavirus mainly spreads through the respiratory tract and enters cells through angiotensin-converting enzyme 2 (ACE2). The clinical symptoms of COVID-19 patients include fever, cough, and fatigue. Gastrointestinal symptoms (diarrhea, anorexia, and vomiting) may be present in 50% of patients and may be associated with worst prognosis. Other risk factors are older age, male gender, and underlying chronic diseases. Mitigation measures are essential to reduce the number of people infected. Hospitals are a place of increased SARS-CoV-2 exposure. This has implications in the organization of healthcare services and specifically endoscopy departments. Patients and healthcare workers safety must be optimized in this new reality. Comprehension of COVID-19 gastrointestinal manifestations and implications of SARS-CoV-2 in the management of patients with gastrointestinal diseases, under or not immunosuppressant therapies, is essential. In this review, we summarized the latest research progress and major societies recommendations regarding the implications of COVID-19 in gastroenterology, namely the adaptations that gastroenterology/endoscopy departments and professionals must do in order to optimize the provided assistance, as well as the implications that this infection will have, in particularly vulnerable patients such as those with chronic liver disease and inflammatory bowel disease under or not immunosuppressant therapies.
Age- and Sex-Related Development of the Normal Human Ear in a Child Population
Authors: Chunyang Xu , Lei Liu
Published: June 2020

Background:

A large number of researches related to auricle development have been conducted in different countries, but there were few similar studies in China, especially in Chinese children. This study was designed to investigate the auricular development by measuring normal age- and sex-related dimensions of auricles in Chinese children.

Methods:

A total of 900 participants were evaluated according to their age and gender. From the landmarks, the dimensions of the and tragus including length and width, the relevant indices, inclination angles were measured. The average score of each item was calculated according to age and gender.

Results:

The dimensions of the and tragus including width and length showed certain developmental patterns respectively. No significantly difference was found for the inclination angles and relative indices between different age groups and different sides.

Conclusions:

The data indicated that there was a certain pattern of auricular development. There were also gender difference in the development of auricle. There were certain proportional relationships between different subunits of the auricle. These results may be useful for designing the plan of auricular reconstruction.
Three-Dimensional Evaluation on Cortical Bone During Orthodontic Surgical Treatment
Authors: Crimi Salvatore , Defila Luca , Nanni Martina , Cicciù Marco , Fiorillo Luca , Cervino Gabriele , Marchetti Claudio , Bianchi Alberto
Published: June 2020

Adult patients’ severe malocclusions, especially the skeletal ones, cannot be exclusively solved by the orthodontic treatment and therefore a combined orthodontic-surgical treatment is necessary. Today, numerous software allows to plane and to visualize the final treatment results simulating the best therapeutic option. This is a retrospective experimental study that aims to analyze the changes in the buccal cortical bone in patients undergoing orthodontics surgeries and to evaluate the correlation between the dental movement and the changes in the relative bone cortex. The study sample consists of 32 subjects. By applying the CBCT radiographic examinations, the measurements were made in well-defined points of reference. The 3D study of the dental changes of position and the cortical buccal bone related variation, suggests how the determined orthodontic movement of the dental element does not achieve an easily predictable bone variation. Therefore, it also suggests that there is no direct proportionality relationship between the extent of bone apposition/reabsorption and dental movement.
Fenestrated Falx Cerebri and Additional Sinuses in the Tentorium Cerebelli
Authors: Nayak Satheesha B. , Vasudeva Soumya K.
Published: June 2020

Morphological variations of falx cerebri and tentorium cerebelli are extremely rare. The authors report an extremely rare type of combined variation of falx cerebri and dural venous sinuses in the tentorium cerebelli. During the removal of the brain from cranial cavity, it was noted that the anterior part of the falx cerebri had fenestrations and it looked like a mesh. There was no associated variations of medial surface of cerebrum. Further, there were unusual sinuses within the tentorium cerebelli. Two of them were present in the right half of the tentorium cerebelli and one in the left half of the tentorium cerebelli. There variations could be of importance to radiologists and neurosurgeons. The fenestrations of falx cerebri might lead to misinterpretations in cases of head injuries and the additional sinuses in the tentorium cerebelli might cause unexpected bleeding during surgeries of posterior cranial fossa.
Insights into the complete genomes of carbapenem-resistant Acinetobacter baumannii harbouring bla
OXA-23,
bla
OXA-420 and bla
NDM-1 genes using a hybrid-assembly approach
Authors: Vijayakumar Saranya , Wattal Chand , J.K. Oberoi , Bhattacharya Sanjay , Vasudevan Karthick , Anandan Shalini , Walia Kamini , Veeraraghavan Balaji
Published: June 2020

Carbapenem resistance in

Acinetobacter baumannii

is due to bla
OXA-23, which is endemic in India. Recently, the sporadic presence of bla
OXA-58 as well as the occurrence of dual carbapenemases were observed. The mobility as well as the dissemination of these resistance genes were mainly mediated by various mobile genetic elements. The present study was aimed at characterizing the genetic arrangement of bla
OXA-23,
bla
NDM-1 and bla
OXA-58 identified in two complete genomes of carbapenem-resistant

A. baumannii

(CRAB). Complete genomes obtained using a hybrid-assembly approach revealed the accurate arrangement of Tn2006 with bla
OXA-23, ISAba125 with bla
NDM and ISAba3 with bla
OXA-58. In addition, the association of IntI1 integrase with the bla
CARB-2 gene and several virulence factors required for type-IV pili assembly, motility and biofilm formation have been identified. The current study provided deeper insight into the complete characterization of insertion sequences and transposons associated with the carbapenem-resistant genes using short reads of IonTorrent PGM and long reads of MinIon in

A. baumannii

.
Tocilizumab for patients with COVID-19 pneumonia. The TOCIVID-19 prospective phase 2 trial
Authors: Perrone Francesco , Piccirillo Maria Carmela , Ascierto Paolo Antonio , Salvarani Carlo , Parrella Roberto , Marata Anna Maria , Popoli Patrizia , Ferraris Laurenzia , Marrocco-Trischitta Massimiliano M. , Ripamonti Diego , Binda Francesca , Bonfanti Paolo , Squillace Nicola , Castelli Francesco , Muiesan Maria Lorenza , Lichtner Miriam , Calzetti Carlo , Salerno Nicola Duccio , Atripaldi Luigi , Cascella Marco , Costantini Massimo , Dolci Giovanni , Facciolongo Nicola Cosimo , Fraganza Fiorentino , Massari Marco , Montesarchio Vincenzo , Mussini Cristina , Negri Emanuele Alberto , Botti Gerardo , Cardone Claudia , Gargiulo Piera , Gravina Adriano , Schettino Clorinda , Arenare Laura , Chiodini Paolo , Gallo Ciro
Published: June 2020

Background

Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.

Methods

A multicentre, single-arm, hypothesis-driven phase 2 trial was planned to study the effect of Tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints). A cohort of patients consecutively enrolled after phase 2 was used as a validation dataset. A multivariable logistic regression was performed to generate hypotheses, while controlling for possible confounders.

Results

out of 301 patients in phase 2 intention-to-treat (ITT) analysis, 180 (59.8%) received tocilizumab. With 67 death events, lethality rates were 18.4% (97.5%CI: 13.6-24.0, P=0.52) and 22.4% (97.5%CI: 17.2-28.3, P<0.001) at 14 and 30 days. Lethality rates were lower in the validation dataset, including 920 patients. No signal of specific drug toxicity was reported. The multivariable logistic regression suggests tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Also, it supports a positive effect on lethality rate of the use of corticosteroids.

Conclusions

Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Such result support the use of tocilizumab while waiting for ongoing phase 3 trials.

Registration

EudraCT (2020-001110-38);clinicaltrials.gov(NCT04317092)
SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication
Authors: Alexandersen Soren , Chamings Anthony , Bhatta Tarka Raj
Published: June 2020

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in late December 2019 and has spread worldwide. Coronaviruses are enveloped, positive sense, single-stranded RNA viruses and employ a complicated pattern of virus genome length RNA replication as well as transcription of genome length and leader containing subgenomic RNAs. Although not fully understood, both replication and transcription are thought to take place in so-called double-membrane vesicles in the cytoplasm of infected cells. We here describe detection of SARS-CoV-2 subgenomic RNAs in diagnostic samples up to 17 days after initial detection of infection, provide evidence for their nuclease resistance and likely protection by cellular membranes consistent with being part of virus-induced replication organelles. Furthermore, we show that the ratios of genomic to subgenomic RNA as well as the ratios of plus to negative strand RNA of genomic and subgenomic RNA are consistent with what have been detected for other coronaviruses in cell culture; albeit with the caveat that in vivo diagnostic samples, even in relatively early infection, the ratios of these RNAs are most reminiscent of late culture, semi-purified virus preparations shown to have a relatively constant ratio of genomic to subgenomic RNAs of around 5-10 or higher, while the ratios of positive to negative strands are more than 100 for the genomic RNA and around 20 for the subgenomic RNAs. Overall, our results may help explain the extended PCR positivity of some samples, and may also, at least in part, help explain discrepancies in results of different diagnostic PCR methods described by others; in particular for samples with a low virus load or of poor quality. Overall, we present evidence that subgenomic RNAs may not be an indicator of active coronavirus replication/infection, but that these RNAs, similar to the virus genome RNA, may be rather stable, and thus detectable for an extended period, most likely due to their close association with cellular membranes.
Simultaneous classification of bilateral hand gestures using bilateral microelectrode recordings in a tetraplegic patient
Authors: Thomas Tessy M. , Nickl Robert W. , Thompson Margaret C. , Candrea Daniel N. , Fifer Matthew S. , McMullen David P. , Osborn Luke E. , Pohlmeyer Eric A. , Anaya Manuel , Anderson William S. , Wester Brock A. , Tenore Francesco V. , Cantarero Gabriela L. , Celnik Pablo A. , Crone Nathan E.
Published: June 2020

Most daily tasks require simultaneous control of both hands. Here we demonstrate simultaneous classification of gestures in both hands using multi-unit activity recorded from bilateral motor and somatosensory cortices of a tetraplegic participant. Attempted gestures were classified using hierarchical linear discriminant models trained separately for each hand. In an online experiment, gestures were continuously classified and used to control two robotic arms in a center-out movement task. Bimanual trials that required keeping one hand still resulted in the best performance (70.6%), followed by symmetric movement trials (50%) and asymmetric movement trials (22.7%). Our results indicate that gestures can be simultaneously decoded in both hands using two independently trained hand models concurrently, but online control using this approach becomes more difficult with increased complexity of bimanual gesture combinations. This study demonstrates the potential for restoring simultaneous control of both hands using a bilateral intracortical brain-machine interface.
Analysis of the outbreak of COVID-19 in Japan on the basis of an SIQR model
Authors: Odagaki Takashi
Published: June 2020

The SIR model is modified, which may be called an SIQR model, so as to be appropriate for COVID-19 which has the following characteristics: [1] a long incubation period, [2] transmission of the virus by asymptomatic patients and [3] quarantine of patients identified through PCR testing. It is assumed that the society consists of four compartments; susceptibles (S), infecteds at large (simply called infecteds) (I), quarantined patients (Q) and recovered individuals (R), and the time evolution of the pandemic is described by a set of ordinary differential equations. It is shown that the quarantine rate can be determined from the time dependence of the daily confirmed new cases, from which the number of the infecteds at large can be estimated. The number of daily confirmed new cases is shown to be proportional to the number of infecteds a characteristic time earlier, and the infection rate and quarantine rate are determined for the period from mid-February to mid-April in Japan, and transmission characteristics of the initial stages of the outbreak in Japan are analyzed. The effectiveness of different measures is discussed for controlling the outbreak and it is shown that identifying patients through PCR testing and isolating them in a quarantine is more effective than lockdown measures aimed at inhibiting social interactions of the general population. An effective reproduction number for infecteds at large is introduced which is appropriate to epidemics controlled by quarantine measures.
Reconfiguration of Amplitude Driven Dominant Coupling Modes (DoCM) mediated by α-band in Adolescents with Schizophrenia Spectrum Disorders
Authors: Dimitriadis Stavros I.
Published: June 2020

Electroencephalography (EEG) based biomarkers have been shown to correlated with the presence of psychotic disorders. Increased delta and decreased alpha power in psychosis indicate an abnormal arousal state. We investigated brain activity across the basic EEG frequencies and also dynamic functional connectivity of both intra and cross-frequency coupling that could reveal a neurophysiological biomarker linked to an aberrant modulating role of alpha frequency in adolescents with schizophrenia spectrum disorders (SSDs).

A dynamic functional connectivity graph (DFCG) has been estimated using the imaginary part of phase lag value (iPLV) and correlation of the envelope (corrEnv). We analyzed DFCG profiles of electroencephalographic resting state (eyes closed) recordings of healthy controls (HC) (n=39) and SSDs subjects (n=45) in basic frequency bands {δ,θ,α1,α2,β1,β2,γ}. In our analysis, we incorporated both intra and cross-frequency coupling modes. Adopting our recent Dominant Coupling Mode (DoCM) model leads to the construction of an integrated DFCG (iDFCG) that encapsulates the functional strength and the DoCM of every pair of brain areas.

We revealed significantly higher ratios of delta/alpha1,2 power spectrum in SSDs subjects versus HC. The probability distribution (PD) of amplitude driven DoCM mediated by alpha frequency differentiated SSDs from HC with absolute accuracy (100%). The network Flexibility Index (FI) was significantly lower for subjects with SSDs compared to the HC group.

Our analysis supports a central role of alpha frequency alterations in the neurophysiological mechanisms of SSDs. Currents findings open up new diagnostic pathways to clinical detection of SSDs and supports the design of rational neurofeedback training.

Highlights

Ratios of delta/alpha1,2 relative power spectrum were significant higher in SSDs subjects compared to HC

Probability distribution (PD) of amplitude driven DoCM mediated by alpha frequency differentiated SSDs from HC with 100%

Network Flexibility index (FI) was significant lower for subjects with SSDs compared to HC group.
Varenicline rescues nicotine-induced decrease in motivation for sucrose reinforcement
Authors: Hart Erin , Hertia Daniel , Barrett Scott T , Charntikov Sergios
Published: June 2020

Varenicline is one of the top medications used for smoking cessation and is often prescribed before termination of nicotine use. The effect of this combined nicotine and varenicline use on the reward system and motivation for primary reinforcement is underexplored. The goal of this study was to assess the effects of nicotine and varenicline on the consumption of sucrose. In Experiment 1, we first assessed the responding for sucrose after pretreatment with nicotine (0, 0.1, or 0.4 mg/kg) and varenicline (0.0, 0.1, 1.0 mg/kg) using a behavioral economics approach. The responding for sucrose was then assessed using a progressive ratio schedule of reinforcement after pretreatment with all possible combinations of nicotine and varenicline doses. In Experiment 2, rats were assessed for the consumption of sucrose in home cages after pretreatment with nicotine and varenicline. We found that a) nicotine decreased economic demand for sucrose, b) varenicline rescued nicotine-induced reduction in economic demand for sucrose, and c) history of varenicline treatment predicted responding for sucrose on a progressive ratio schedule of reinforcement where rats with a history of varenicline treatment responded significantly lower for sucrose across nicotine doses than rats that have not being exposed to varenicline. The results of Experiment 2 largely confirmed that nicotine decreases motivation for sucrose using a passive consumption protocol and that varenicline rescues this effect. Overall, these findings suggest that varenicline interacts with the effects of nicotine by restoring nicotine-induced reduction in motivation for appetitive rewards.
NMDA receptors control cortical axonal projections via EPHRIN-B/EPHB signaling
Authors: Zhou Jing , Lin Yong , Huynh Trung , Noguchi Hirofumi , Bush Jeffrey O. , Pleasure Samuel J.
Published: June 2020

Callosal projections from primary somatosensory cortex (S1) are key for processing somatosensory inputs and integrating sensory-motor information. How the callosal innervation pattern in S1 is formed during early postnatal development is not clear. We found that the normal termination pattern of these callosal projections is disrupted in cortex specific NMDAR mutants. Rather than projecting selectively to the primary/secondary somatosensory cortex (S1/S2) border, axons were uniformly distributed throughout S1. In addition, the density of this projection increased over postnatal life until the mice died by P30. By combining genetic and antibody-mediated loss of function, we demonstrated that it is NR2B-containing NMDA receptors in target S1 that mediate this guidance phenotype, thus playing a central role in interhemispheric connectivity. Furthermore, we found that this function of NMDA receptors in callosal circuit formation is independent of ion channel function and instead depends on interactions with EPHRIN-B/EPHB. Thus, NMDAR cooperates with EPHRIN-B/EPHB in target S1 to control the formation callosal circuits by acting as an accessory axon guidance receptor modulating EPH-dependent repulsion.
Evolutionary genetics ofDrosophila melanogasterimmunity: role of the X chromosome and sex-specific dominance
Authors: Arun Manas Geeta , Agarwala Amisha , Jigisha  , Kashyap Mayank , Venkatesan Saudamini , Chechi Tejinder Singh , Syed Zeeshan Ali , Gupta Vanika , Prasad Nagaraj Guru
Published: June 2020

Intralocus Sexual Conflict (IaSC) ensues when males and females of the same species experience divergent selection on shared traits. A large number of traits have been implicated in IaSC and there is growing evidence for sexual antagonism associated with immunity. X chromosomes are thought to be hotspots of sexually antagonistic genetic variation and have been shown to harbour substantial immunity-related genetic variation.

Here, using interpopulation crosses and cytogenetic cloning, we investigated the role of the X chromosome in improved immune response of laboratory populations of the fruit-flyDrosophila melanogasterselected against systemic infection byPseudomonas entomophila.

We could not detect any contribution of the X chromosome in the evolved immune response of our selected populations. However, we found strong evidence of sex-specific dominance related to immunity in our populations. Our results indicate that alleles that confer a superior immune response to the selected populations are, on average, partially dominant in females but partially recessive in males.

We argue that sex-specific dominance over immunity evolved as a by-product of sexually antagonistic selection in the wild ancestors of our populations. We also highlight sex-specific dominance as a potential mechanism of sex differences in immunity, with population-level sex differences primarily driven by sex differences in heterozygotes.
Typical lipreading and audiovisual speech perception without motor simulation
Authors: Vannuscorps Gilles , Andres Michael , Carneiro Sarah , Rombaux Elise , Caramazza Alfonso
Published: June 2020

All it takes is a face to face conversation in a noisy environment to realize that viewing a speaker’s lip movements contributes to speech comprehension. Following the finding that brain areas that control speech production are also recruited during lip reading, the received explanation is that lipreading operates through a covert unconscious imitation of the observed speech movements in the observer’s own speech motor system – a motor simulation. However, motor effects during lipreading do not necessarily imply simulation or a causal role in perception. In line with this alternative, we report here that some individuals born with lip paralysis, who are therefore unable to covertly imitate observed lip movements, have typical lipreading abilities and audiovisual speech perception. This constitutes existence proof that typically efficient lipreading abilities can be achieved without motor simulation. Although it remains an open question whether this conclusion generalizes to typically developed participants, these findings demonstrate that alternatives to motor simulation theories are plausible and invite the conclusion that lip-reading does not involve motor simulation. Beyond its theoretical significance in the field of speech perception, this finding also calls for a re-examination of the more general hypothesis that motor simulation underlies action perception and interpretation developed in the frameworks of the motor simulation and mirror neuron hypotheses.
UBR-Box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target
Authors: Saurabh Kumar , Shah Parag P. , Doll Mark A. , Siskind Leah J. , Beverly Levi J.
Published: June 2020

Background

N-end rule ubiquitination pathway is known to be disrupted in many diseases, including cancer. UBR5, an E3 ubiquitin ligase, is mutated and/or overexpressed in human lung cancer cells suggesting its pathological role in cancer.

Methods

We determined expression of UBR5 protein in multiple lung cancer cell lines and human patient samples. Using immunoprecipitation followed by mass spectrometry we determined the UBR5 interacting proteins. The impact of loss of UBR5 for lung adenocarcinoma cell lines was analyzed using cell viability, clonogenic assays andin vivoxenograft models in nude mice. Additional Western blot analysis was performed to assess the loss of UBR5 on downstream signaling. Statistical analysis was done by one-way ANOVA forin vitrostudies and Wilcoxon paired t-test for tumor volumesin vivo.

Results

We show variability of UBR5 expression levels in lung adenocarcinoma cell lines and in primary human patient samples. To gain better insight into the role that UBR5 may play in lung cancer progression we performed unbiased interactome analyses for UBR5. Data indicate that UBR5 has a wide range of interacting protein partners that are known to be involved in critical cellular processes such as DNA damage, proliferation and cell cycle regulation. We have demonstrated that shRNA-mediated loss of UBR5 decreases cell viability and clonogenic potential of lung adenocarcinoma cell lines. In addition, we found decreased levels of activated AKT signaling after the loss of UBR5 in lung adenocarcinoma cell lines using multiple means of UBR5 knockdown/knockout. Furthermore, we demonstrated that loss of UBR5 in lung adenocarcinoma cells results in significant reduction of tumor volume in nude mice.

Conclusions

These findings demonstrate that deregulation of the N-end rule ubiquitination pathway plays a crucial role in the etiology of some human cancers, and blocking this pathway via UBR5-specific inhibitors, may represent a unique therapeutic target for human cancers.
Interspecific introgression reveals a role of male genital morphology during the evolution of reproductive isolation inDrosophila
Authors: Frazee Stephen R. , Harper Angelica R. , Afkhami Mehrnaz , Wood Michelle L. , McCrory John C. , Masly John P.
Published: June 2020

Rapid divergence in genital structures among nascent species has been posited to be an early-evolving cause of reproductive isolation, although evidence supporting this idea as a widespread phenomenon remains mixed. Using a collection of interspecific introgression lines between twoDrosophilaspecies that diverged ∼240,000 years ago, we tested the hypothesis that even modest divergence in genital morphology can result in substantial fitness losses. We studied the reproductive consequences of variation in the male epandrial posterior lobes betweenDrosophila mauritianaandD. sechelliaand found that divergence in posterior lobe morphology has significant fitness costs on several pre-fertilization and post-copulatory reproductive measures. Males with divergent posterior lobe morphology also significantly reduced the life span of their mates. Interestingly, one of the consequences of genital divergence was decreased oviposition and fertilization, which suggests that a sensory bias for posterior lobe morphology could exist in females, and thus posterior lobe morphology may be the target of cryptic female choice in these species. Our results provide evidence that divergence in genitalia can in fact give rise to substantial reproductive isolation early during species divergence, and they also reveal novel reproductive functions of the external male genitalia inDrosophila.
Ultrasensitive single-cell proteomics workflow identifies >1000 protein groups per mammalian cell
Authors: Cong Yongzheng , Motamedchaboki Khatereh , Misal Santosh A. , Liang Yiran , Guise Amanda J. , Truong Thy , Huguet Romain , Plowey Edward D. , Zhu Ying , Lopez-Ferrer Daniel , Kelly Ryan T.
Published: June 2020

We report on the combination of nanodroplet sample preparation, ultra-low-flow nanoLC, high-field asymmetric ion mobility spectrometry (FAIMS), and the latest-generation Orbitrap Eclipse Tribrid mass spectrometer for greatly improved single-cell proteome profiling. FAIMS effectively filtered out singly charged ions for more effective MS analysis of multiply charged peptides, resulting in an average of 1056 protein groups identified from single HeLa cells without MS1-level feature matching. This is 2.3 times more identifications than without FAIMS and a far greater level of proteome coverage for single mammalian cells than has been previously reported for a label-free study. Differential analysis of single microdissected motor neurons and interneurons from human spinal tissue indicated a similar level of proteome coverage, and the two subpopulations of cells were readily differentiated based on single-cell label-free quantification.
Precision combination therapies based on recurrent oncogenic co-alterations
Authors: Li Xubin , Dowling Elisabeth K. , Yan Gonghong , Bozorgui Behnaz , Imarinad Parisa , Elnaggar Jacob H. , Luna Augustin , Menter David G. , Kopetz Scott , Sander Chris , Korkut Anil
Published: June 2020

Cancer cells depend on multiple driver alterations whose oncogenic effects can be suppressed by drug combinations. Discovery of effective combination therapies is challenging due to the complexity of the biomolecular landscape of drug responses. Here, we developed the method REFLECT (REcurrent Features Leveraged for Combination Therapies), which integrates machine learning and cancer informatics algorithms. The method maps recurrent co-alteration signatures from multi-omic data across patient cohorts to combination therapies. Using the REFLECT framework, we generated a precision therapy resource matching 2,201 drug combinations to co-alteration signatures across 201 cohorts stratified from 10,392 patients and 33 cancer types. We validated that REFLECT-predicted combinations introduce significantly higher therapeutic benefit through analysis of independent data from comprehensive drug screens. In patient cohorts with immunotherapy response markers, HER2 activation and DNA repair aberrations, we identified therapeutically actionable co-alteration signatures shared across patient sub-cohorts. REFLECT provides a framework to design combination therapies tailored to patient cohorts in data-driven clinical trials.