bluuebunny/crossref_metadata_2025 huggingface dataset:
Theca cell‐conditioned medium enhances steroidogenesis competence of buffalo (Bubalus bubalis) granulosa cells
Authors: Zhang Jun , Deng Yanfei , Li Jiaojiao , Zi Yonghong , Shi Deshun , Lu Fenghua
Published: August 2020

Theca cells (TCs) play a crucial role in follicular development and atresia. TCs synthesize androgens that act as substrate for granulosa cells (GCs) aromatization to oestrogens needed for follicular growth. However, the effects of TCs in the form of conditioned medium on steroidogenesis in buffalo GCs remain unclear. In the present study, the impacts of TC‐conditioned medium (TCCM) on oestrogen synthesis in buffalo GCs were examined. The results showed that TCs secreted principally testosterone, but almost no androstenedione or oestradiol into TCCM. TCs at passage 3 had a stronger secretion capacity of testosterone in TCCM. Furthermore, TCCM collected at 72 hr improved both the expression levels of oestrogen synthesis‐related genes (CYP11A1, CYP19A1, 3β‐HSD and 17β‐HSD) and the secretion levels of estradiol in GCs. The treatment of 72 hr in TCCM promoted both the expression levels of oestrogen synthesis‐related genes (CYP11A1, CYP19A1 and 3β‐HSD) and the secretion levels of estradiol in GCs. Besides, TCCM that was collected at 72 hr and applied to GCs for 72 hr (72 & 72 hr) improved the sensitivity of buffalo GCs to FSH. This study indicates that TCCM (72 & 72 hr) enhances the steroidogenesis competence of GCs mainly through facilitating the responsiveness of GCs to FSH in buffalo.
Barley beta‐Glucan and Zymosan induce Dectin‐1 and Toll‐like receptor 2 co‐localization and anti‐leishmanial immune response in Leishmania donovani‐infected BALB/c mice
Authors: Patidar Ashok , Mahanty Trishna , Raybarman Chandan , Sarode Aditya Y. , Basak Surajit , Saha Bhaskar , Bhattacharjee Surajit
Published: August 2020

Toll‐like receptors (TLRs), TLR2 in particular, are shown to recognize various glycans and glycolipid ligands resulting in various immune effector functions. As barley β‐glucan and zymosan are the glycans implicated in immunomodulation, we examined whether these ligands interact with Dectin‐1, a lectin‐type receptor for glycans, and TLR2 and induce immune responses that can be used against Leishmania infection in a susceptible host. The binding affinity of barley β‐glucan and zymosan with Dectin‐1 and TLR2 was studied in silico. Barley β‐glucan‐ and zymosan‐induced dectin‐1 and TLR2 co‐localization was studied by confocal microscopy and co‐immunoprecipitation. These ligands‐induced signalling and effector functions were assessed by Western blot analyses and various immunological assays. Finally, the anti‐leishmanial potential of barley β‐glucan and zymosan was tested in Leishmania donovani ‐infected macrophages and in L. donovani‐infected BALB/c mice. Both barley β‐glucan and zymosan interacted with TLR2 and dectin‐1, but with a much stronger binding affinity for the latter, and therefore induced co‐localization of these two receptors on BALB/c‐derived macrophages. Both ligandsactivated MyD88‐ and Syk‐mediated downstream pathways for heightened inflammatory responses in L. donovani‐infected macrophages. These two ligands induced T cell–dependent host protection in L. donovani‐infected BALB/c mice. These results establish a novel modus operandi of β‐glucans through dectin‐1 and TLR2 and suggest an immuno‐modulatory potential against infectious diseases.
The roles of social economic status and undernutrition in regional disparities of the under‐five mortality rate in Vietnam
Authors: Nguyen Chi M. , Nguyen Mai P.
Published: August 2020

Objectives

From 2005 to 2017, the prevalence of mortality in Vietnamese children under five years old showed large regional disparities. In 2017, mortality in the wealthiest region was 12.6‰, whereas the most disadvantaged region it was three times as high, at 36‰. This study aims to identify factors affecting regional disparities of the under‐five mortality rate (U5MR) in Vietnam.

Methods

We applied Structural Equation Modelling to estimate the degree and the pathway through which undernutrition and socio‐economic status (SES) contributed to the under‐five mortality disparities.

Results

SES is estimated as a common latent factor of three socio‐economic measures, that is, education, poverty and income. The direct effect of SES on U5MR is at 2.16 through the underweight pathway, which is 5 times higher than the effect of underweight on U5MR. Through the stunting channel, this direct impact is 1.43, nearly twice as high as the impact of the stunting rate. SES also has an indirect effect on U5MR through these undernutrition pathways. In total, we estimate that an increase in SES index will make the U5MR increase by 2.73‰. Among the three indicators of SES, poverty conveys the strongest signal of a considerable change in SES, thus to a subsequent change in U5MR. Among two types of undernutrition, the effect of stunting on U5MR is dominant, more than 3 times as high as that of underweight.

Conclusion

These findings have important implications for socio‐economic and health interventions: those that strongly focus on the reduction of regional poverty and stunting rates would be effective in bridging the regional gap in the U5MR in Vietnam.
Multiple insertions of COIN, a novel maize Foldback transposable element, in the Conring gene cause a spontaneous progressive cell death phenotype
Authors: Kim Saet‐Byul , Karre Shailesh , Wu Qingyu , Park Minkyu , Meyers Emily , Claeys Hannes , Wisser Randall , Jackson David , Balint‐Kurti Peter
Published: August 2020

Similar progressive leaf lesion phenotypes, named conring for “concentric ring,” were identified in 10 independently derived maize lines. Complementation and mapping experiments indicated that the phenotype had the same genetic basis in each line – a single recessive gene located in a 1.1‐Mb region on chromosome 2. Among the 15 predicted genes in this interval, Zm00001d003866 (subsequently renamed Conring or Cnr) had insertions of four related 138 bp transposable element (TE) sequences at precisely the same site in exon 4 in nine of the 10 cnr alleles. The 10th cnr allele had a distinct insertion of 226 bp of in exon 3. Genetic evidence suggested that the 10 cnr alleles were independently derived, and arose during the derivation of each line. The four TEs, named COINa (for COnring INsertion) through COINd, have not been previously characterized and consist entirely of imperfect 69‐bp terminal inverted repeats characteristic of the Foldback class of TEs. They belong to three clades of a family of maize TEs comprising hundreds of sequences in the genome of the B73 maize line. COIN elements preferentially insert at TNA sequences with a preference for C and G nucleotides in the immediately flanking 5′ and 3′ regions, respectively. They produce a three‐base target site duplication and do not have homology to other characterized TEs. We propose that Cnr is an unstable gene that is mutated insertionally at high frequency, most commonly due to COIN element insertions at a specific site in the gene.
Analytical and Numerical Solutions of the Riccati Equation Using the Method of Variation of Parameters. Application to Population Dynamics
Authors: Tumbarell Aranda Orestes , Oliveira Fernando A.
Published: August 2020

This work presents new approximate analytical solutions for the Riccati equation (RE) resulting from the application of the method of variation of parameters. The original equation is solved using another RE explicitly dependent on the independent variable. The solutions obtained are easy to implement and highly applicable, which is confirmed by solving several examples corresponding to REs whose solution is known, as well as optimizing the method to determine the density of the members that make up a population. In this way, new perspectives are open in the study of the phenomenon of pattern formation.
Using Virtual Reality in Biomedical Engineering Education
Authors: Singh Anita , Ferry Dawn , Ramakrishnan Arun , Balasubramanian Sriram
Published: August 2020

This study explored virtual reality (VR) as an educational tool to offer immersive and experiential learning environments to biomedical engineering (BME) students. VR and traditional two-dimensional (2D) videos were created and used to teach required communication skills to BME students' while working with clinical partners in healthcare settings. The videos of interdisciplinary teams (engineering and nursing students) tackling medical device-related problems, similar to those commonly observed in healthcare settings, were shown to BME students. Student surveys indicated that, through VR videos, they felt more immersed in real-world clinical scenarios while learning about the clinical problems, each team-member's areas of expertise, their roles and responsibilities, and how an interdisciplinary team operated collectively to solve a problem in the presented settings. Students with a prior in-person immersion experience, in the presented settings, reported VR videos to serve as a possible alternative to in-person immersion and a useful tool for their preparedness for real-world clinical immersion. We concluded that VR holds promise as an educational tool to offer simulated clinical scenarios that are effective in training BME students for interprofessional collaborations.
Additional length model for the impedance end correction of microperforated panels
Authors: Jiang Congshuang , Li Xianhui , Xing Tuo , Zhang Bin
Published: August 2020

An additional length model is usually used to describe the reactive part of the impedance end correction of microperforated panels, which is extended to describe the resistive part. The cross-sectional impedance is computed along the axis of one perforation cell with a circular hole. Except for the obvious jumps in the narrow regions at the inlet and outlet of the perforation, the impedance varies linearly along the axis following exactly that of the viscous wave in the circular hole. The additional length for the impedance end correction is obtained by extrapolating the linearly varying impedance inside the hole. Empirical models for the resistive and reactive additional lengths are obtained based on the thermoviscous acoustic simulation with 96 test cases. Within an error of about 10%, a unified additional length model is presented for both the resistive and reactive parts of the impedance end correction. Comparison with other existing models shows the accuracy of the proposed model.
Lack of reproducibility of temporary hearing threshold shifts in a harbor porpoise after exposure to repeated airgun sounds
Authors: Kastelein Ronald A. , Helder-Hoek Lean , Cornelisse Suzanne A. , von Benda-Beckmann Alexander M. , Lam Frans-Peter A. , de Jong Christ A. F. , Ketten Darlene R.
Published: August 2020

Noise-induced temporary hearing threshold shift (TTS) was studied in a harbor porpoise exposed to impulsive sounds of scaled-down airguns while both stationary and free-swimming for up to 90 min. In a previous study, ∼4 dB TTS was elicited in this porpoise, but despite 8 dB higher single-shot and cumulative exposure levels (up to 199 dB re 1 μPa2s) in the present study, the porpoise showed no significant TTS at hearing frequencies 2, 4, or 8 kHz. There were no changes in the study animal's audiogram between the studies or significant differences in the fatiguing sound that could explain the difference, but audible and visual cues in the present study may have allowed the porpoise to predict when the fatiguing sounds would be produced. The discrepancy between the studies may have resulted from self-mitigation by the porpoise. Self-mitigation, resulting in reduced hearing sensitivity, can be achieved via changes in the orientation of the head, or via alteration of the hearing threshold by processes in the ear or central nervous system.
The Lombard effect in singing humpback whales: Source levels increase as ambient ocean noise levels increase
Authors: Guazzo Regina A. , Helble Tyler A. , Alongi Gabriela C. , Durbach Ian N. , Martin Cameron R. , Martin Stephen W. , Henderson E. Elizabeth
Published: August 2020

Many animals increase the intensity of their vocalizations in increased noise. This response is known as the Lombard effect. While some previous studies about cetaceans report a 1 dB increase in the source level (SL) for every dB increase in the background noise level (NL), more recent data have not supported this compensation ability. The purpose of this study was to calculate the SLs of humpback whale song units recorded off Hawaii and test for a relationship between these SLs and background NLs. Opportunistic recordings during 2012–2017 were used to detect and track 524 humpback whale encounters comprised of 83 974 units on the U.S. Navy's Pacific Missile Range Facility hydrophones. Received levels were added to their estimated transmission losses to calculate SLs. Humpback whale song units had a median SL of 173 dB re 1 μPa at 1 m, and SLs increased by 0.53 dB/1 dB increase in background NLs. These changes occurred in real time on hourly and daily time scales. Increases in ambient noise could reduce male humpback whale communication space in the important breeding area off Hawaii. Since these vocalization changes may be dependent on location or behavioral state, more work is needed at other locations and with other species.
An interspecies translation model implicates integrin signaling in infliximab-resistant inflammatory bowel disease
Authors: Brubaker Douglas K. , Kumar Manu P. , Chiswick Evan L. , Gregg Cecil , Starchenko Alina , Vega Paige N. , Southard-Smith Austin N. , Simmons Alan J. , Scoville Elizabeth A. , Coburn Lori A. , Wilson Keith T. , Lau Ken S. , Lauffenburger Douglas A.
Published: August 2020

A platform for comparing trans-omics datasets between IBD mouse models and human patients reveals therapeutically relevant targets.
Colonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing System
Authors: Gogos Artemis , Federle Michael J.
Published: August 2020

Streptococcus pyogenes
is a human-restricted pathogen most often found in the human nasopharynx. Multiple bacterial factors are known to contribute to persistent colonization of this niche, and many are important in mucosal immunity and vaccine development. In this work, mice were infected intranasally with transcriptional regulator mutants of the Rgg2/3 quorum sensing (QS) system—a peptide-based signaling system conserved in sequenced isolates of
S. pyogenes
.
Overproduction of the AlgT Sigma Factor Is Lethal to Mucoid Pseudomonas aeruginosa
Authors: Cross Ashley R. , Raghuram Vishnu , Wang Zihuan , Dey Debayan , Goldberg Joanna B.
Published: August 2020

Pseudomonas aeruginosa
is an opportunistic bacterial pathogen capable of causing chronic lung infections. Phenotypes important for the long-term persistence and adaption to this unique lung ecosystem are largely regulated by the AlgT sigma factor. Chronic infection isolates often contain mutations in the anti-sigma factor
mucA
, resulting in uncontrolled AlgT and continuous production of alginate in addition to the expression of ∼300 additional genes. Here, we report that in the absence of wild-type MucA, AlgT overproduction is lethal and that suppressors of toxic AlgT production have mutations in the MucA protease, MucP. Since AlgT contributes to the establishment of chronic infections, understanding how AlgT is regulated will provide vital information on how
P. aeruginosa
is capable of causing long-term infections.
QuantiFERON-TB Gold Plus with Chemiluminescence Immunoassay: Do We Need a Higher Cutoff?
Authors: Bisognin Francesco , Lombardi Giulia , Re Maria Carla , Dal Monte Paola
Published: August 2020

QuantiFERON-TB Gold Plus (QFT-Plus) is the most widely used interferon gamma release assay (IGRA) for the diagnosis of latent tuberculosis infection (LTBI). The aim of this study was to compare QFT-Plus results by enzyme-linked immunosorbent assay (ELISA) on the SkyLab system with those obtained with chemiluminescence immunoassay (CLIA) on the Liaison XL analyzer. Agreement between the two assays was evaluated on 419 QFT-Plus blood samples and was found to be substantial (75.4%); higher agreement was found for positive (95.
Development and Validation of the Elecsys Anti-SARS-CoV-2 Immunoassay as a Highly Specific Tool for Determining Past Exposure to SARS-CoV-2
Authors: Muench Peter , Jochum Simon , Wenderoth Verena , Ofenloch-Haehnle Beatus , Hombach Michael , Strobl Matthias , Sadlowski Henrik , Sachse Christopher , Torriani Giulia , Eckerle Isabella , Riedel Alexander
Published: August 2020

The Elecsys Anti-SARS-CoV-2 immunoassay (Roche Diagnostics) was developed to provide accurate, reliable detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, cross-reactivity, and agreement with a vesicular stomatitis virus-based pseudoneutralization assay for the Elecsys Anti-SARS-CoV-2 immunoassay. Sensitivity and agreement between Elecsys Anti-SARS-CoV-2 immunoassay and pseudoneutralization assay measurements were evaluated using samples from patients with PCR-confirmed SARS-CoV-2 infection, a majority of whom were hospitalized.
Human Cytomegalovirus miR-US5-2 Downregulation of GAB1 Regulates Cellular Proliferation and
UL138
Expression through Modulation of Epidermal Growth Factor Receptor Signaling Pathways
Authors: Hancock Meaghan H. , Mitchell Jennifer , Goodrum Felicia D. , Nelson Jay A.
Published: August 2020

Human cytomegalovirus (HCMV) causes significant disease in immunocompromised individuals, including transplant patients. HCMV establishes latency in hematopoietic stem cells in the bone marrow. The mechanisms governing latency and reactivation of viral replication are complex and not fully understood. HCMV-encoded miRNAs are small regulatory RNAs that reduce protein expression. In this study, we found that the HCMV miRNA miR-US5-2 targets the epidermal growth factor receptor (EGFR) adaptor protein GAB1 which directly affects downstream cellular signaling pathways activated by EGF. Consequently, miR-US5-2 blocks the EGF-mediated proliferation of human fibroblasts. Early growth response gene 1 (EGR1) is a transcription factor activated by EGFR signaling that regulates expression of HCMV UL138. We show that miR-US5-2 regulates UL138 expression through GAB1-mediated downregulation of the signaling pathways that lead to EGR1 expression. These data suggest that miR-US5-2, through downregulation of GAB1, could play a critical role during reactivation from latency by reducing proliferation and UL138 expression.
Molecular Elucidation of Riboflavin Production and Regulation in Candida albicans, toward a Novel Antifungal Drug Target
Authors: Demuyser Liesbeth , Palmans Ilse , Vandecruys Paul , Van Dijck Patrick
Published: August 2020

Candida albicans
is an important fungal pathogen causing common superficial infections as well as invasive diseases with an extremely high morbidity and mortality. Antifungal therapies are limited in efficiency and availability. In this research, we describe the regulation of riboflavin production in
C. albicans
. Since riboflavin biosynthesis is essential to this organism, we can appreciate that targeting it would be a promising new strategy to combat these fungal infections. We provide evidence that one particular enzyme in the production process,
Ca
Rib1, would be most promising as an antifungal drug target, as it plays a central role in regulation and proves to be essential in a mouse model of systemic infection.
Use of awake proning to avoid invasive ventilation in a patient with severe COVID-19 pneumonitis
Authors: Whittemore Paul , Macfarlane Laura , Herbert Anna , Farrant John
Published: August 2020

A 60-year-old man with swab-positive COVID-19 and extensive ground-glass change seen on CT imaging was successfully managed on our COVID-19 high-dependency unit with only low-flow oxygen and strict awake proning instructions. He was successfully weaned off oxygen entirely without any requirement for non-invasive or invasive ventilation and made a recovery to be discharged home after an 18-day hospital stay.
Exploring the factors that affect new graduates’ transition from students to health professionals: a systematic integrative review protocol
Authors: Opoku Eric Nkansah , Van Niekerk Lana , Jacobs-Nzuzi Khuabi Lee-Ann
Published: August 2020

Introduction

To become a competent health professional, the nature of new graduates’ transition plays a fundamental role. The systematic integrative review will aim to identify the existing literature pertaining to the barriers during transition, the facilitators and the evidence-based coping strategies that assist new graduate health professionals to successfully transition from students to health professionals.

Methods and analysis

The integrative review will be conducted using Whittemore and Knafl’s integrative review methodology. Boolean search terms have been developed in consultation with an experienced librarian, using Medical Subject Heading terms on Medline. The following electronic databases have been chosen to ensure that all relevant literature are captured for this review: PubMed, EBSCOhost (including Cumulative Index of Nursing and Allied Health Literature (CINAHL), Medline, Academic Search Premier, Health Science: Nursing and Academic Edition), Scopus and Web of Science. A follow-up on the reference list of selected articles will be done to ensure that all relevant literature is included. The Covidence platform will be used to facilitate the process.

Ethics and dissemination

Ethical approval is not required for this integrative review since the existing literature will be synthesised. The integrative review will be published in a peer-reviewed journal once all the steps have been completed. The findings will also be presented at international and national conferences to ensure maximum dissemination.
Hospital referrals of patients with acute poisoning by the Belgian Poison Centre: analysis of characteristics, associated factors, compliance and costs
Authors: Descamps Anne-Marie Katrien , Vandijck Dominique , Buylaert Walter , Mostin Martine , De Paepe Peter
Published: August 2020

Objective

Aims were (1) to assess the characteristics, associated factors and compliance of patients with acute poisoning advised by the Belgian Poison Centre (BPC) to go (conditionally) to the hospital, (2) to assess the compliance and potential health-economic impact.

Methods

Three types of referrals to the hospital of patients who called the BPC between 1 January and 30 June 2018 were analysed: referrals in case of deterioration in the patient’s condition (Hosp-watchful-wait), referrals (Hosp-referral) or urgent referrals (Hosp-urgent-referral). Factors associated with type of recommendation were registered. A survey was conducted on a second dataset of patients who called the BPC between 1 March and 15 May 2019 and referred (conditionally) to the hospital.

Results

5476 referrals were included: 72.4% accidental poisoning, 25.3% intentional self-harm, 1.2% substance abuse and 1.1% unclear intentionality. There were 2368 (43.2%) Hosp-watchful-wait cases, 2677 (48.9%) Hosp-referrals and 431 (7.9%) Hosp-urgent-referrals. In Hosp-watchful-wait cases, soaps and detergents were represented most (20.5%). In Hosp-referrals and Hosp-urgent-referrals, benzodiazepines (12.7% and 15.1%, respectively) predominated. Factors associated with hospitalisation type were number of symptoms, intentionality, type of agent(s) involved and advising antidotes. The survey showed that 7.8% of Hosp-watchful-wait patients went to the hospital versus 57.3% of Hosp-referrals and 59.6% of Hosp-urgent-referrals. The mean cost for Hosp-watchful-wait patients, Hosp-referrals and Hosp-urgent-referrals was estimated at €127, €767 and €796, respectively.

Conclusion

Only a small proportion of patients followed the advice of the BPC to go (conditionally) to the hospital. A systematic follow-up of cases is warranted to examine the appropriateness of referrals and the compliance of patients.
Does the physician in triage strategy improve door-to-balloon time for patients with STEMI?
Authors: Schwarzfuchs Dan , Shashar Sagi , Sagy Iftach , Novack Victor , Zeldetz Vladimir
Published: August 2020

Background

The physician in triage (PIT) strategy was implemented in the emergency department (ED) of the Soroka University Medical Center (SUMC) to improve overcrowding and waiting time. Our objective in the current study was to assess the impact of the PIT strategy on door-to-balloon time for the treatment of acute ST-elevation myocardial infarction (STEMI).

Methods

The PIT programme began on January 2016, working weekdays between 8:00 and 23:00 hours. We included patients who visited the ED and were diagnosed with STEMI, from November 2014 to February 2018. The primary outcome was improvement in door-to-balloon (D2B) time<90 min between the preintervention and postintervention period. The analysis included a comparison between the two time periods using univariate tests, a time trend analysis illustrated by the locally weighted scatterplot smoothing curves and a regression analysis using generalised estimating equation models. To determine the impact of the PIT, as opposed to other changes in the department, we stratified the population arriving after January 2016 to patients arriving during PIT hours versus patients arriving on weekends and at nights (23:00–8:00 hours).

Results

In all, 415 patients met all the inclusion criteria of which 237 (57.1%) visited on weekdays 8:00–23:00 hours. The per cent of patients with D2B<90 min was 13.9% higher for postintervention versus preintervention visits (p=0.006). D2B time was significantly shorter by 9 min for postintervention visits (p=0.001). In the postintervention period, patients arriving between 8:00 and 23:00 hours on weekdays were more likely to have D2B <90 min than those arriving nights and weekends; 90/146 (61.6%) vs 47.2% (51/108), respectively, p=0.02. ORs for D2B<90 min was 2.04 (95% CI 1.06 to 3.91) for weekday visits, and 1.90 (0.88 to 4.12) for weekend and night visits.

Conclusion

The PIT model in SUMC is associated with D2B reduction for patients with STEMI. To achieve further reduction, both targeted interventions should be performed and PIT strategy should be applied for full time, including nights and weekends.
Relaxin-expressing oncolytic adenovirus induces remodeling of physical and immunological aspects of cold tumor to potentiate PD-1 blockade
Authors: Jung Bo-Kyeong , Ko Hae Young , Kang Hyunji , Hong JinWoo , Ahn Hyo Min , Na Youjin , Kim Hyeongi , Kim Jin Su , Yun Chae-Ok
Published: August 2020

Background

Currently, several antibody (Ab)-based therapies have shown excellent therapeutic effects in the clinic. Nonetheless, Ab penetration into tumor tissues is limited due to abnormal vasculature, tumor interstitial pressure, and excessive extracellular matrix (ECM) accumulation, thus demanding novel strategies to overcome these barriers.

Methods

The intratumoral distribution of therapeutic Abs were detected by fluorescence microscopy or positron emission tomography in both human gastric xenograft and syngeneic pancreatic hamster tumor models. The antitumor efficacy by combination of oncolytic adenovirus (Ad), which coexpresses relaxin (RLX), interleukin (IL)-12, and granulocyte macrophage colony-stimulating factor (GM-CSF) (oAd/IL12/GM-RLX) and antibody against the programmed cell death protein 1 (αPD-1) was examined in hamster subcutaneous and orthotopic pancreatic tumor models. The immunological aspects of these combination therapy regimen were assessed by flow cytometry or immunohistochemistry in subcutaneous hamster tumor models.

Results

Relaxin-expressing oncolytic Ad effectively degraded tumor ECM and enhanced the tumor penetration of trastuzumab in comparison with trastuzumab monotherapy. Based on these results, an oAd/IL12/GM-RLX was used to enhance the potency of immune checkpoint blockade. The combination of the oAd/IL12/GM-RLX and αPD-1 promoted a concomitant degradation of the tumor ECM and amelioration of the immunosuppressive tumor niches, ultimately enhanced intratumoral infiltration of both αPD-1 and activated T cells. Of note, the combination therapy was able to elicit a potent and durable antitumor immune response against cold tumors that were refractory to immune checkpoint inhibitor monotherapy.

Conclusions

Our findings are the first to demonstrate that expression of four genes (IL-12p35, IL-12p40, GM-CSF, and RLX) mediated by a single oncolytic Ad vector can promote remodeling of both physical and immunological aspects of the tumor niches to overcome the major limitations of Ab-based therapies that have emerged in recent clinical trials.
Quality of life among ischemic stroke patients eligible for endovascular treatment: analysis of the DEFUSE 3 trial
Authors: Asaithambi Ganesh , Tipps Megan E
Published: August 2020

Background

The endovascular treatment (ET) for acute ischemic stroke is increasing among eligible patients. Assessing patients’ perspectives on quality of life (QOL) can supplement the use of formal outcome scales and enable the assessment of outcomes across multiple domains affected by stroke.

Methods

We analyzed publicly available data from the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke (DEFUSE 3) trial. We evaluated patients who survived beyond the time of discharge from their acute hospitalizations and completed all Neuro-QOL short forms at 90-day follow-up.

Results

Our final analysis included 128 patients (median age 67 [range 23–90] years, 50.8% men). As modified Rankin Scale (mRS) scores increased, there was a consistent increase in the severity of Neuro-QOL measures. T-scores for mobility, cognitive function, and the ability to participate in social roles declined significantly while depression T-scores increased significantly. We found that QOL T-scores for patients with mRS 3 did not differ significantly from T-scores for patients with mRS 2 in any domain.

Conclusions

Among ischemic stroke patients eligible for ET, QOL scores help validate and supplement quantitatively measured outcomes.
Vessel diameter and catheter-to-vessel ratio affect the success rate of clot aspiration
Authors: Kyselyova Anna Andriana , Fiehler Jens , Leischner Hannes , Flottmann Fabian , Buhk Jan Hendrik , Frölich Andreas Maximilian
Published: August 2020

Background

A direct aspiration first pass technique (ADAPT) is an efficient, safe, cost-effective, and fast thrombectomy technique.

Objective

To evaluate anatomical and clot characteristics associated with success of the aspiration component as part of ADAPT.

Methods

106 cases of acute carotid-T, basilar, and middle cerebral artery occlusion undergoing endovascular treatment with ADAPT were retrospectively assessed for successful catheter-clot contact and successful primary aspiration, defined as a Thrombolysis in Cerebral Infarction score ≥2b after primary aspiration with 5F or 6F aspiration catheters. Patient age, National Institutes of Health Stroke Scale (NIHSS) score, time from symptom onset to groin puncture, time from groin puncture to revascularization, aortic arch type, access vessel tortuosity, vessel diameter at the proximal end of the thrombus, catheter-to-vessel ratio (CVR), clot density, length, and perviousness were determined.

Results

Successful clot contact with the aspiration catheter was achieved in 76 cases (72%); these patients were younger (67.7±15.2 vs 73.7±11.4 years; p=0.05) and had less tortuous access vessels (1 vs 2 reverse curves; p=0.004) than those in whom clot contact failed. Successful primary aspiration occurred in 36 of these cases (47%) and was associated with significantly smaller vessel diameter at the proximal thrombus end (2.5±0.7 mm vs 3.1±1.3 mm; p=0.01) and higher CVR (CVR outer diameter: 0.85±0.2 vs 0.68±0.2; p=0.01 and CVR inner diameter: 0.72±0.2 vs 0.58±0.2; p<0.001). No significant differences were seen in aortic arch type, radiographic clot features, and NIHSS score.

Conclusion

With ADAPT, patient age and vessel tortuosity affect the ability to deliver the aspiration catheter and achieve clot contact, whereas vessel diameter and CVR at the aspiration site seem to affect the effectiveness of clot aspiration. Strategies aimed at improving catheter deliverability and increasing CVR may increase the efficacy of ADAPT.
Simulating lattice gauge theories within quantum technologies
Authors: Bañuls Mari Carmen , Blatt Rainer , Catani Jacopo , Celi Alessio , Cirac Juan Ignacio , Dalmonte Marcello , Fallani Leonardo , Jansen Karl , Lewenstein Maciej , Montangero Simone , Muschik Christine A. , Reznik Benni , Rico Enrique , Tagliacozzo Luca , Van Acoleyen Karel , Verstraete Frank , Wiese Uwe-Jens , Wingate Matthew , Zakrzewski Jakub , Zoller Peter
Published: August 2020

Lattice gauge theories, which originated from particle physics in the context of Quantum Chromodynamics (QCD), provide an important intellectual stimulus to further develop quantum information technologies. While one long-term goal is the reliable quantum simulation of currently intractable aspects of QCD itself, lattice gauge theories also play an important role in condensed matter physics and in quantum information science. In this way, lattice gauge theories provide both motivation and a framework for interdisciplinary research towards the development of special purpose digital and analog quantum simulators, and ultimately of scalable universal quantum computers. In this manuscript, recent results and new tools from a quantum science approach to study lattice gauge theories are reviewed. Two new complementary approaches are discussed: first, tensor network methods are presented – a classical simulation approach – applied to the study of lattice gauge theories together with some results on Abelian and non-Abelian lattice gauge theories. Then, recent proposals for the implementation of lattice gauge theory quantum simulators in different quantum hardware are reported, e.g., trapped ions, Rydberg atoms, and superconducting circuits. Finally, the first proof-of-principle trapped ions experimental quantum simulations of the Schwinger model are reviewed.

Graphical abstract
Why Black-Scholes Equations Are Effective Beyond Their Usual Assumptions: Symmetry-Based Explanation
Authors: Chinnakum Warattaya , Aguilar Sean
Published: August 2020

Nobel-Prize-winning Black-Scholes equations are actively used to estimate the price of options and other financial instruments. In practice, they provide a good estimate for the price, but the problem is that their original derivation is based on many simplifying statistical assumptions which are, in general, not valid for financial time series. The fact that these equations are effective way beyond their usual assumptions leads to a natural conclusion that there must be an alternative derivation for these equations, a derivation that does not use the usual too-strong assumptions. In this paper, we provide such a derivation in which the only substantial assumption is a natural symmetry: namely, scale-invariance of the corresponding processes. Scale-invariance also allows us to describe possible generalizations of Black-Scholes equations, generalizations that we hope will lead to even more accurate estimates for the corresponding prices.
Ruin Probabilities of Continuous-Time Risk Model with Dependent Claim Sizes and Interarrival Times
Authors: Hoang Nguyen Huy , Ta Bao Quoc
Published: August 2020

In this paper we investigate an insurance continuous-time risk model when the claim sizes and inter-arrival times are m-dependent random variables. We provide an upper exponential bound for the ruin probability.
Why the Use of Convex Combinations Works Well for Interval Data: A Theoretical Explanation
Authors: Phadkantha Rungrapee , Yamaka Woraphon
Published: August 2020

One of the main objectives of econometrics is to predict future values of important economics-related quantities, such as unemployment level, stock prices, currency exchange rates, etc. — and especially to predict how different possible economy-boosting measures will affect these quantities. To perform this prediction, we design a model of such effect and train it on the available data. Usually, the daily (or weekly) data are used for this training. However, economics-related quantities fluctuate all the time. So, for each moment of time (e.g., for each day) instead of a single value of the corresponding quantity, we have smallest and largest daily values — i.e., the interval range of daily values. At first glance, it may seem that using both endpoints of this interval for training will lead to more accurate predictions, but in reality, predictions become less accurate. Predictions become more accurate if we only use midpoints of the corresponding intervals. Several recent papers showed that even more accurate predictions are possible if we allow general convex combinations of the intervals’ endpoints — and select the corresponding coefficients so as to best fit the data. In this paper, we provide a theoretical explanation for these results.
The Black-Litterman Model for Portfolio Optimization on Vietnam Stock Market
Authors: Ta Bao Quoc , Vuong Thao
Published: August 2020

The Black-Litterman asset allocation model is an extended portfolio management model to construct optimal portfolios by combining the market equilibrium with investor views into asset allocation decisions. In this paper we apply Black-Litterman model for portfolio optimization on Vietnames stock market. We chose ARIMA methodology utilized in financial econonometrics to predict the views of investor which are used as inputs of the Black-Litterman asset allocation process to find optimal portfolio and weights.
A Mixed Copula-Based Vector Autoregressive Model for Econometric Analysis
Authors: Yamaka Woraphon , Thongkairat Sukrit
Published: August 2020

In many practical applications, the dynamics of different quantities is reasonably well described by linear equations. In economics, such linear dynamical models are known as vector autoregressive (VAR) models. These linear models are, however, only approximate. The deviations of the actual value of each quantity from the predictions of the linear model are usually well described by normal or Student-t distributions. To complete the description of the joint distribution of all these deviations, we need to supplement these marginal distributions with the information about the corresponding copula. To describe this dependence, in the past, researchers followed the usual idea of trying copulas from several standard families: Gaussian, Student, Clayton, Frank, Gumbel, and Joe families. To get a better description, we propose to also use convex combinations of copulas from different families; such convex combinations are known as mixed copulas. On the example of the dynamics of US macroeconomic data, including GDP, unemployment, consumer price index, and the real effective exchange rate, we show that mixed copulas indeed lead to a better description of the actual data. Specifically, it turns out that the best description is obtained if we use a convex combination of Student and Frank copulas.
Continuous weaving fusion frames in Hilbert spaces
Authors: Sadri Vahid , Ahmadi Reza , Rahimlou Gholamreza
Published: August 2020

In this paper, we first introduce the notation of weaving continuous fusion frames in separable Hilbert spaces. After reviewing the conditions for maintaining the weaving [Formula: see text]-fusion frames under the bounded linear operator and also, removing vectors from these frames, we will present a necessarily and sufficient condition about [Formula: see text]-woven and [Formula: see text]-fusion woven. Finally, perturbation of these frames will be introduced.
Ecological Interactions and Macroevolution: A New Field with Old Roots
Authors: Hembry David H. , Weber Marjorie G.
Published: August 2020

Linking interspecific interactions (e.g., mutualism, competition, predation, parasitism) to macroevolution (evolutionary change on deep timescales) is a key goal in biology. The role of species interactions in shaping macroevolutionary trajectories has been studied for centuries and remains a cutting-edge topic of current research. However, despite its deep historical roots, classic and current approaches to this topic are highly diverse. Here, we combine historical and contemporary perspectives on the study of ecological interactions in macroevolution, synthesizing ideas across eras to build a zoomed-out picture of the big questions at the nexus of ecology and macroevolution. We discuss the trajectory of this important and challenging field, dividing research into work done before the 1970s, research between 1970 and 2005, and work done since 2005. We argue that in response to long-standing questions in paleobiology, evidence accumulated to date has demonstrated that biotic interactions (including mutualism) can influence lineage diversification and trait evolution over macroevolutionary timescales, and we outline major open questions for future research in the field.
New Microbial Biodiversity in Marine Sediments
Authors: Baker Brett J. , Appler Kathryn E. , Gong Xianzhe
Published: August 2020

Microbes in marine sediments represent a large portion of the biosphere, and resolving their ecology is crucial for understanding global ocean processes. Single-gene diversity surveys have revealed several uncultured lineages that are widespread in ocean sediments and whose ecological roles are unknown, and advancements in the computational analysis of increasingly large genomic data sets have made it possible to reconstruct individual genomes from complex microbial communities. Using these metagenomic approaches to characterize sediments is transforming our view of microbial communities on the ocean floor and the biodiversity of the planet. In recent years, marine sediments have been a prominent source of new lineages in the tree of life. The incorporation of these lineages into existing phylogenies has revealed that many belong to distinct phyla, including archaeal phyla that are advancing our understanding of the origins of cellular complexity and eukaryotes. Detailed comparisons of the metabolic potentials of these new lineages have made it clear that uncultured bacteria and archaea are capable of mediating key previously undescribed steps in carbon and nutrient cycling.
Physiological Responses of Fish to Oil Spills
Authors: Grosell Martin , Pasparakis Christina
Published: August 2020

Millions of tons of oil are spilled in aquatic environments every decade, and this oil has the potential to greatly impact fish populations. Here, we review available information on the physiological effects of oil and polycyclic aromatic hydrocarbons on fish. Oil toxicity affects multiple biological systems, including cardiac function, cholesterol biosynthesis, peripheral and central nervous system function, the stress response, and osmoregulatory and acid–base balance processes. We propose that cholesterol depletion may be a significant contributor to impacts on cardiac, neuronal, and synaptic function as well as reduced cortisol production and release. Furthermore, it is possible that intracellular calcium homeostasis—a part of cardiotoxic and neuronal function that is affected by oil exposure—may be related to cholesterol depletion. A detailed understanding of oil impacts and affected physiological processes is emerging, but knowledge of their combined effects on fish in natural habitats is largely lacking. We identify key areas deserving attention in future research.
High Oxygen Exchange Activity of Pristine La0.6Sr0.4FeO3–δ Films and Its Degradation
Authors: Schmid Alexander , Nenning Andreas , Opitz Alexander , Kubicek Markus , Fleig Jürgen
Published: August 2020

The polarization resistance of La0.6Sr0.4FeO3–δ
(LSF) thin film electrodes was investigated by electrochemical impedance spectroscopy. Different states were considered, ranging from pristine films right after deposition to films degraded under various conditions. Impedance measurements performed inside the pulsed laser deposition chamber (in-situ) revealed the existence of a very facile, low resistive state of as-deposited thin films with up to two orders of magnitude lower resistances compared to conventional ex-situ measurements and literature data. Ex-situ and in-situ measurements show different

p

O

2

dependencies of polarization resistances, suggesting a different oxygen exchange reaction mechanism on the as-deposited films. The time dependence of the polarization resistance indicates that two degradation mechanisms with different timescales are responsible for the much higher resistances found in ex-situ measurements. Degradation mechanisms are discussed and conclusions with respect to the rate determining step of oxygen exchange on different surfaces are drawn.
Inhibition of the ROS-EGFR Pathway Mediates the Protective Action of Nox1/4 Inhibitor GKT137831 against Hypertensive Cardiac Hypertrophy via Suppressing Cardiac Inflammation and Activation of Akt and ERK1/2
Authors: Zeng Si-yu , Yan Qiu-jiang , Yang Li , Mei Qing-hua , Lu Hui-qin
Published: August 2020

Oxidative stress, inflammation, and hypertension constitute a self-perpetuating vicious circle to exacerbate hypertension and subsequent hypertensive cardiac hypertrophy. NADPH oxidase (Nox) 1/4 inhibitor GKT137831 alleviates hypertensive cardiac hypertrophy in models of secondary hypertension; however, it remains unclear about its effect on hypertensive cardiac hypertrophy in models of essential hypertension. This study is aimed at determining the beneficial role of GKT137831 in hypertensive cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and its mechanisms of action. Treating with GKT137831 prevented cardiac hypertrophy in SHRs. Likewise, decreasing production of reactive oxygen species (ROS) with GKT137831 reduced epidermal growth factor receptor (EGFR) activity in the left ventricle of SHRs. Additionally, EGFR inhibition also reduced ROS production in the left ventricle and blunted hypertensive cardiac hypertrophy in SHRs. Moreover, inhibition of the ROS-EGFR pathway with Nox1/4 inhibitor GKT137831 or selective EGFR inhibitor AG1478 reduced protein and mRNA levels of proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β), as well as the activities of Akt and extracellular signal-regulated kinase (ERK) 1/2 in the left ventricle of SHRs. In summary, GKT137831 prevents hypertensive cardiac hypertrophy in SHRs, Nox-deprived ROS regulated EGFR activation through positive feedback in the hypertrophic myocardium, and inhibition of the ROS-EGFR pathway mediates the protective role of GKT137831 in hypertensive cardiac hypertrophy via repressing cardiac inflammation and activation of Akt and ERK1/2. This research will provide additional details for GKT137831 to prevent hypertensive cardiac hypertrophy.