bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Changes Associated With the Use of Integrase Strand Transfer Inhibitors Among Virally Controlled Women
Authors: Summers Nathan A. , Lahiri Cecile D. , Angert Christine D. , Aldredge Amalia , Mehta C. Christina , Ofotokun Ighovwerha , Kerchberger Anne M. , Gustafson Deborah , Weiser Sheri D. , Kassaye Seble , Konkle-Parker Deborah , Sharma Anjali , Adimora Adaora A. , Bolivar Hector , Cocohoba Jennifer , French Audrey L. , Golub Elizabeth T. , Sheth Anandi N.
Published: October 2020

Background:

Integrase strand transfer inhibitors (INSTIs) have been associated with weight gain among women living with HIV. We aimed to investigate the association between INSTIs and change in cardiometabolic risk indicators.

Setting:

Retrospective cohort.

Methods:

Data from 2006 to 2017 were analyzed from women living with HIV enrolled in the longitudinal Women's Interagency HIV Study who were virally controlled on antiretroviral therapy (ART) for ≥5 consecutive semiannual visits. Women who switched/added an INSTI to ART (INSTI group) were compared with women who remained on non-INSTI ART (non-INSTI group). Outcomes included changes in fasting lipids and glucose, hemoglobin A1c (HbA1c), blood pressure (BP), and incident diabetes, hypertension, and insulin resistance. Outcomes were measured 6–12 months before and 6–18 months after INSTI switch/add in the INSTI group with comparable visits in the non-INSTI group. Longitudinal linear regression models compared change over time in each outcome by the study group.

Results:

One thousand one hundred eighteen participants (234 INSTI, 884 non-INSTI) were followed for a median 2.0 (Q1 1.9, Q3 2.0) years. Participants were median age 49 years, 61% Black, and 73% overweight or obese (body mass index ≥25 kg/m2). Compared with non-INSTI, the INSTI group experienced greater increases in HbA1c (+0.05 vs. −0.06 mg/dL, P = 0.0318), systolic BP (+3.84 vs. +0.84 mm Hg, P = 0.0191), and diastolic BP (+1.62 vs. −0.14 mm Hg, P = 0.0121), with greatest change in HbA1c among women on INSTIs with ≥5% weight gain.

Conclusions:

INSTI use was associated with unfavorable changes in HbA1c and systolic and diastolic BP during short-term follow-up. Further research is needed to understand long-term cardiometabolic effects of INSTI use.
The current state of immunization against Gram-negative bacteria in children: a review of the literature
Authors: Broad Jonathan , Le Doare Kirsty , Heath Paul T. , Hallchurch Philippa , Whelan Isabelle , Boyd Hannah , Carruthers Elspeth , Sharland Mike , Ladhani Shamez
Published: October 2020

Purpose of review

Gram-negative bacteria (GNB) are a major cause of infection worldwide and multidrug resistance in infants and children. The major pathogens include Klebsiella pneumoniae, Escherichia coli, Enterobacter spp., Pseudomonas aeruginosa and Acinetobacter baumannii. With new antibiotic options limited, immunization is likely to play a critical role in prevention. This review discusses their epidemiology, the current state of vaccine research and potential immunization strategies to protect children. A comprehensive review of the literature, conference abstracts along with web searches was performed to identify current and investigational vaccines against the major GNB in children.

Recent findings

Phase I--III vaccine trials have been undertaken for the major Gram-negative bacteria but not in infants or children. E. coli is a common infection in immune-competent children, including neonatal sepsis. Several vaccines are in late-phase clinical trials, with some already licensed for recurrent urinary tract infections in women. Klebsiella spp. causes community-acquired and hospital-acquired infections, including sepsis in neonates and immunocompromised children although no vaccine trials have extended beyond early phase 2 trials. P. aeruginosa is a common pathogen in patients with cystic fibrosis. Phase 1--3 vaccine and monoclonal antibody trials are in progress, although candidates provide limited coverage against pathogenic strains. Enterobacter spp. and A. baumannii largely cause hospital-acquired infections with experimental vaccines limited to phase 1 research.

The current immunization pipelines for the most prevalent GNB are years away from licensure. Similar to incentives for new antibiotics, global efforts are warranted to expedite the development of effective vaccines.
A Model to Assess the Outcomes Associated With Dementia With Lewy Bodies
Authors: Espinosa Robert , Davis Matthew , Johnson Scott , Cline Stephanie , Weintraub Daniel
Published: October 2020

Background:

Research investigating outcomes associated with dementia with Lewy bodies (DLB) disease progression is scarce. Developing models of DLB disease progression will provide information on the burden of disease and facilitate the evaluation of treatments for DLB from a clinical and cost perspective.

Methods:

Longitudinal, cognitive evaluation data were utilized in order to identify distinct health states for DLB and to estimate transition probabilities across the DLB disease continuum. These probabilities were applied to a health state transition model to evaluate disease progression and associated outcomes for a closed cohort over a fixed time horizon. The effect of a reduction in the risk of disease progression on outcomes was assessed.

Results:

Estimated transition probabilities indicate that a patient >60 years of age with mild DLB has a 54%, 30%, 4%, and 12% chance of remaining mild, progressing to severe DLB, being institutionalized, and dying after 1 year, respectively. Reducing the annual risk of transitioning from mild to severe DLB by 40% decreased time institutionalized and increased time to death.

Conclusions:

This study used real-world longitudinal data to create a clinically relevant DLB disease progression model. Reducing the rate of disease progression resulted in meaningful benefits with potentially significant public health implications.
Long noncoding RNA nuclear-enriched abundant transcript 1 regulates proliferation and apoptosis of neuroblastoma cells treated by cisplatin by targeting miR-326 through Janus kinase/signal transducer and activator of transcription 3 pathway
Authors: Yang Baoyi , Ye Xiangmei , Wang Jianwei , Xia Shitao
Published: October 2020

Neuroblastoma is a common malignancy and frequently affects children, leading to a low survival rate. Long noncoding RNAs (lncRNAs) are reported to be closely related to cancer progression. The purpose of this study was to explore a novel mechanism of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in neuroblastoma. NEAT1 was upregulated in neuroblastoma cell lines (IMR32 and SK-N-SH). Overexpression of NEAT1 increased proliferation inhibited by cisplatin and decreased apoptosis promoted by cisplatin. MicroRNA-326 (miR-326) was a target of NEAT1 and miR-326 reintroduction abolished the effects of NEAT1 overexpression on cell proliferation and apoptosis. Moreover, NEAT1 overexpression activated Janus kinase/signal transducer and activator of transcription 3 (JAK1/STAT3) signaling pathway through absorbing miR-326. Besides, NEAT1 overexpression promoted tumor growth in vivo through stimulating the expression of p-JAK1 and p-STAT3 but inhibiting miR-326 expression. NEAT1 accelerated proliferation and weakened apoptosis of neuroblastoma cells treated by cisplatin by targeting miR-326 through activating JAK1/STAT3 signaling pathway, suggesting that NEAT1 was a potential biomarker against neuroblastoma.
Cross-cultural applicability of ICD-11 and DSM-5 personality disorder
Authors: Ayinde Olatunde O. , Gureje Oye
Published: October 2020

Purpose of review

This review explores recent literature on the applicability of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and International Classification of Disease, 11th Revision (ICD-11) personality disorder classification systems across countries and cultural contexts.

Recent findings

Several studies examining the cultural validity and utility of DSM-5 and ICD-11 personality disorder have been conducted in a number of language and cultural groups that are different from those in which the tools were originally developed. These studies, using quantitative methods, have largely supported the applicability of the new dimensional and trait approaches to classifying personal disorders. Studies qualitatively exploring the views of service users and clinicians on the development or operationalization of DSM-5 and ICD-11 personality disorder report that a lay summary of diagnostic constructs that

reflect concern about language of diagnostic criteria as well the lived experience of service users would be found useful. Clinicians found the dimensional system of ICD-11 slightly more useful than the categorical system of ICD-10 on several utility scales, but the studies on ICD-11 have been much less in view of its latter appearance.

DSM-5 and ICD-11 personality disorder have shown a preliminary evidence of improved utility across cultures. More studies, including those reflecting the views of service users, are needed to confirm this early observation across many more cultural and linguistic groups.
Political and commercial prospects for inertial fusion energy
Authors: Holland Andrew
Published: October 2020

Fusion energy holds the prospect of an energy source that is clean, safe, affordable and limitless. It will transform the global energy system. Today, around $1.5 billion in private capital has been invested in companies that are working on transformative approaches to fusion. Annually, even more than that is spent on fusion research by governments around the world. However, just achieving a scientific demonstration of fusion power will not be enough on its own to transition the global energy system. It will require innovations in the legal, regulatory, commercial and political spheres to support the massive deployment of fusion power that we know will be necessary to meet the global challenges of climate change and energy scarcity.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 1)'.
Magnetic field generation from composition gradients in inertial confinement fusion fuel
Authors: Sadler James D. , Li Hui , Flippo Kirk A.
Published: October 2020

Experimental asymmetries in fusion implosions can lead to magnetic field generation in the hot plasma core. For typical parameters, previous studies found that the magnetization Hall parameter, given by the product of the electron gyro-frequency and Coulomb collision time, can exceed one. This will affect the hydrodynamics through inhibition and deflection of the electron heat flux. The magnetic field source is the collisionless Biermann term, which arises from the Debye shielding potential in electron pressure gradients. We show that there is an additional source term due to the
Z
dependence of the Coulomb collision operator. If there are ion composition gradients, such as jets of carbon ablator mix entering the hot-spot, this source term can rapidly exceed the Biermann fields. In addition, the Biermann fields are enhanced due to the increased temperature gradients from carbon radiative cooling. With even stronger self-generated fields, heat loss to the carbon regions will be reduced, potentially reducing the negative effect of carbon mix.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 1)’.
An Innovative Non-Pharmaceutical Intervention to Mitigate SARS-CoV02 Spread: Probability Sampling to Identify and Isolate Asymptomatic Cases
Authors: Williams Nathalie E. , Yao Xiaozheng , Pal Ankita , Qian Xiaolu , Rathod Mansi , Xu Chang , Dobra Adrian
Published: October 2020

Studies estimate that a substantial proportion of SARS-CoV-2 transmission occurs through individuals who do not exhibit symptoms. Mitigation strategies test only those who are moderately to severely symptomatic, excluding the substantial portion of cases that are asymptomatic yet still infectious and likely responsible for a large proportion of the virus’ spread (1-8). While isolating asymptomatic cases will be necessary to effectively control viral spread, these cases are functionally invisible and there is no current method to identify them for isolation. To address this major omission in COVID-19 control, we develop a strategy, Sampling-Testing-Quarantine (STQ), for identifying and isolating individuals with asymptomatic SARS-CoV-2 in order to mitigate the epidemic. STQ uses probability sampling in the general population, regardless of symptoms, then isolates the individuals who test positive along with their household members who are high probability for asymptomatic infections. To test the potential efficacy of STQ, we use an agent-based model, designed to computationally simulate the epidemic in the Seattle with infection parameters, like R0 and asymptomatic fraction, derived from population data. Our results suggest that STQ can substantially slow and decrease the spread of COVID-19, even in the absence of school and work shutdowns. Results also recommend which sampling techniques, frequency of implementation, and population subject to isolation are most efficient in reducing spread with limited numbers of tests.

Significance Statement

A substantial portion of SARS-CoV-2 infections are spread through asymptomatic carriers. Until a vaccine is developed, research indicates an urgent need to identify these asymptomatic infections to control COVID-19, but there is currently no effective strategy to do so. In this study, we develop such a strategy, a procedure called Sampling-Testing-Quarantine (STQ), that combines techniques from survey methods for sampling from the general population and testing and isolation techniques from epidemiology. With computational simulations, we demonstrate that STQ procedures can dramatically decrease and slow COVID-19 spread, even in the absence of widespread work, school, and community lockdowns. We also find particular implementation strategies (including sampling techniques, frequencies of implementation, and people who are subject to isolation) are most efficient in mitigating spread.
One size fits all?: Modeling face-mask fit on population-based faces
Authors: Solano Tomas , Mittal Rajat , Shoele Kourosh
Published: October 2020

The use of face masks by the general population during viral outbreaks such as the COVID-19 pandemic, although at times controversial, has been effective in slowing down the spread of the virus. The fit of simple cloth masks on the face as well as the resulting perimeter leakage and face mask efficacy are expected to be highly dependent on the type of mask and facial topology. However, this effect has to date, not been examined and quantified. Here, we study the leakage of a rectangular cloth mask on a large virtual population of subjects with diverse facial features, using computational mechanics modeling. The effect of weight, age, gender, and height on the leakage is studied. The Centers for Disease Control and Prevention (CDC) recommended mask size was used as a basis for comparison and was found not to be the most effective design for all subjects. Thin, feminine, and young faces benefit from mask sizes smaller than that recommended by the CDC. The results show that side-edge tuck-in of the masks could lead to a larger localized gap opening in many face categories, and is therefore not recommended for all. The perimeter leakage from the face mask worn by thin/feminine faces is mostly from the leakage area along the bottom edge of the mask and therefore, a tuck-in of the bottom edge of the mask or a mask smaller than the CDC recommended mask size are proposed as a more effective design. The leakage from the top edge of the mask is determined to be largely unaffected by mask size and tuck-in ratio, meaning that other mechanical alterations such as a nose wire strip are necessary to reduce the leakage at this site.
Bangla Technique of Laparoscopic Cholecystectomy: a Novel, Safe and Cost-effective modification of American and French Techniques
Authors: Hannan Md Jafrul , Parveen Mosammat Kohinoor , Nandy Alak Kumar
Published: October 2020

Abstract and Keywords

Background

Laparoscopic cholecystectomy (LC) can be performed by following either of the two approaches proposed by the American and the French school. The two approaches have comparable operative times, but use different arrangements for the patient’s and operators’ positions, and sites for port insertions.

The aim of the present paper is to describe an alternative to the American and the French approaches, referred to as the Bangla technique, which uses a standard four port approach but requires the presence of only one assistant along with the surgeon. It is hoped that the Bangla technique will improve surgery outcomes for gallbladder disease patients and encourage healthcare professionals in resource-poor settings to adopt minimally invasive/laparoscopic approaches to surgical problems.

Methods

The sample consisted of a total of 280 gallbladder disease retrospective observational cases (of which 21 were children between 6 and 16 of age) who were treated with the Bangla technique at the South Point Hospital Chittagong, Bangladesh, between January 2018 and February 2020.

Results

Surgery data showed that using the Bangla technique, the average operating time and average operation theater time were36.25 and 45.9 minutes, respectively. Of the patients, 86% left the hospital on the same day of operation, while the remaining left the following day. In 91.7% of the cases, there were no complications, while content leakage and bleeding occurred in 6.7% and 1.4% cases, respectively.

Conclusion

The proposed LC technique will benefit infection prevention and control by reducing the number of personnel in the operation theatre (one assistant and the surgeon) and, as such, reducing surgery-related expenses, which can be further decreased by using only one monitor. More so, the Bangla technique can be combined with the cystic artery sparing technique to reduce the risk of injury to the common bile duct and bleeding.

Mini Abstract

Laparoscopic cholecystectomy can be performed following the American or the French approach. The present paper proposes an alternative to the American and the French approaches referred to as the Bangla technique, which uses a standard four port approach but requires the presence of only one assistant along with the surgeon.
Social Distancing with Movement Restrictions and the Effective Replication Number of COVID-19: Multi-Country Analysis Based on Phone Mobility Data
Authors: Setti Mounir Ould , Voutilainen Ari
Published: October 2020

Linking phone mobility data to the effective replication number (Rt) could help evaluation of the impact of social distancing on the coronavirus disease 2019 (COVID-19) spread and estimate the time lag (TL) needed for the effect of movement restrictions to appear. We used a time-series analysis to discover how patterns of five indicators of mobility data relate to changes in Rt of 125 countries distributed over three groups based on Rt-mobility correlation. Group 1 included 71 countries in which Rt correlates negatively with residential and positively with other mobility indicators. Group 2 included 25 countries showing an opposite correlation pattern to Group 1. Group 3 included the 29 remaining countries. We chose the best-fit TL based on forecast and linear regression models. We used linear mixed models to evaluate how mobility indicators and the stringency index (SI) relate with Rt. SI reflects the strictness of governmental responses to COVID-19. With a median of 14 days, TLs varied across countries as well as across groups of countries. There was a strong negative correlation between SI and Rt in most countries belonging to Group 1 as opposed to Group 2. SI (units of 10%) associated with decreasing Rt in Group 1 [β −0.15, 95% CI −0.15 – (−0.14)] and Group 3 [-0.05, −0.07 – (−0.03)], whereas, in Group 2, SI associated with increasing Rt (0.13, 0.11 – 0.16). Mobile phone mobility data could contribute evaluations of the impact of social distancing with movement restrictions on the spread of the COVID-19.
Physical health complaints among healthcare workers engaged in the care of critically ill COVID-19 patients: A single tertiary-care center prospective study from Japan
Authors: Namikawa Hiroki , Tochino Yoshihiro , Okada Akiko , Ota Keiko , Okada Yasuyo , Fujioka Kazuya , Yamada Koichi , Watanabe Tetsuya , Nakagama Yu , Kido Yasutoshi , Takemoto Yasuhiko , Mizobata Yasumitsu , Kakeya Hiroshi , Kuwatsuru Yumiko , Shibata Toshihiko , Shuto Taichi
Published: October 2020

Background

Healthcare workers (HCWs) who care for patients with the novel coronavirus infectious disease (COVID-19) are at an increased risk and fear contracting the infection themselves. HCWs are chronically exposed to very intense stress, both and physically and mentally. Hospitals must reduce both the physical and mental burden of HCWs on the front lines and ensure their safety. No prospective study has focused on the physical health complaints among HCWs engaged in the care of critically ill COVID-19 patients. This study aimed to investigate the occupational risk among HCWs of experiencing physical symptoms during the current COVID-19 pandemic.

Methods

A twice-weekly questionnaire targeting HCWs who care for COVID-19 patients was performed at Osaka City University Hospital from April 30 to May 31, 2020 using a shareable Research Electronic Data Capture tool. The demographic characteristics of the participants, frequency of exposure to at-risk care, and physical complaints were evaluated.

Results

A total of 35 doctors, 88 nurses, and 35 technicians were engaged in the care of these critically ill COVID-19 patients. 76 HCWs participated in this study, of whom 24 (31.6%) were doctors, 43 (56.6%) were nurses, and 9 (11.8%) were technicians. The frequency of experiencing any physical symptom was 25.0% among HCWs. Exposure to at-risk care was significantly higher among nurses than among doctors (p < 0.001); likewise, the frequency of experiencing physical symptoms was higher among nurses than among doctors (p < 0.01). The multivariate analysis revealed that nurses (odds ratio 8.29; p = 0.01) might be independently at risk of experiencing physical symptoms.

Conclusions

Our results indicate that occupational health care at hospitals must be allocated to HCWs who are highly exposed to at-risk care, particularly nurses engaged in the care of COVID-19 patients.
Understanding the phase separation characteristics of nucleocapsid protein provides a new therapeutic opportunity against SARS-CoV-2
Authors: Zhao Dan , Xu Weifan , Zhang Xiaofan , Wang Xiaoting , Yuan Enming , Xiong Yuanpeng , Wu Shenyang , Li Shuya , Wu Nian , Tian Tingzhong , Feng Xiaolong , Shu Hantao , Lang Peng , Shen Xiaokun , Li Haitao , Li Pilong , Zeng Jianyang
Published: October 2020

The ongoing coronavirus disease 2019 (COVID-19) pandemic has raised an urgent need to develop effective therapeutics against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As a potential antiviral drug target, the nucleocapsid (N) protein of SARS-CoV-2 functions as a viral RNA chaperone and plays vital and multifunctional roles during the life cycle of coronavirus1-3. In this study, we discovered that the N protein of SARS-CoV-2 undergoes liquid-liquid phase separation (LLPS) bothin vitroandin vivo, which is further modulated by viral RNA. In addition, we found that, the core component of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, nsp12, preferentially partitions into the N protein condensates. Moreover, we revealed that, two small molecules, i.e., CVL218 and PJ34, can be used to intervene the N protein driven phase separation and loosen the compact structures of the condensates of the N-RNA-nsp12 complex of SARS-CoV-2. The discovery of the LLPS-mediated interplay between N protein and nsp12 and the corresponding modulating compounds illuminates a feasible way to improve the accessibility of antiviral drugs (e.g., remdesivir) to their targets (e.g., nsp12/RdRp), and thus may provide useful hints for further development of effective therapeutic strategies against SARS-CoV-2.
Clarifying predictions for COVID-19 from testing data: the example of New-York State
Authors: Griette Quentin , Magal Pierre
Published: October 2020

In this article, we use testing data as an input of a new epidemic model. We get nice a concordance between the best fit the model to the reported cases data for New-York state. We also get a good concordance of the testing dynamic and the epidemic’s dynamic in the cumulative cases. Finally, we can investigate the effect of multiplying the number of tests by 2, 5, 10, and 100 to investigate the consequences on the reduction of the number of reported cases.
Severe COVID-19 patients display a back boost of seasonal coronavirus-specific antibodies
Authors: Westerhuis Brenda M. , Aguilar-Bretones Muriel , Raadsen Matthijs P. , de Bruin Erwin , Okba Nisreen M.A. , Haagmans Bart L. , Langerak Thomas , Endeman Henrik , van den Akker Johannes P.C. , Gommers Diederik A.M.P.J. , van Gorp Eric C.M. , Rockx Barry H.G. , Koopmans Marion P.G. , van Nierop Gijsbert P.
Published: October 2020

Severe acquired respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19). In severe COVID-19 cases, higher antibody titers against seasonal coronaviruses have been observed than in mild cases. To investigate antibody cross-reactivity as potential explanation for severe disease, we determined the kinetics, breadth, magnitude and level of cross-reactivity of IgG against SARS-CoV-2 and seasonal CoV nucleocapsid and spike from 17 severe COVID-19 cases at the clonal level. Although patients mounted a mostly type-specific SARS-CoV-2 response, B-cell clones directed against seasonal CoV dominated and strongly increased over time. Seasonal CoV IgG responses that did not neutralize SARS-CoV-2 were boosted well beyond detectable cross-reactivity, particularly for HCoV-OC43 spike. These findings support a back-boost of poorly protective coronavirus-specific antibodies in severe COVID-19 patients that may negatively impact de novo SARS-CoV-2 immunity, reminiscent of original antigenic sin.
Diversity and prevalence of ANTAR RNAs across actinobacteria
Authors: Mehta Dolly , Ramesh Arati
Published: October 2020

Computational approaches are often used to predict regulatory RNAs in bacteria, but their success is limited to RNAs that are highly conserved across phyla, in sequence and structure. The ANTAR regulatory system consists of a family of RNAs (the ANTAR-target RNAs) that selectively recruit ANTAR proteins. This protein-RNA complex together regulates genes at the level of translation or transcriptional elongation. Despite the widespread distribution of ANTAR proteins in bacteria, their targets RNAs haven’t been identified in certain bacterial phyla such as actinobacteria. Here, by using a computational search model that is tuned to actinobacterial genomes, we comprehensively identify ANTAR-target RNAs in actinobacteria. These RNA motifs lie in select transcripts, often overlapping with the ribosome binding site or start codon, to regulate translation. Transcripts harboring ANTAR-target RNAs majorly encode proteins involved in the transport and metabolism of cellular metabolites like sugars, amino acids and ions; or encode transcription factors that in turn regulate diverse genes. In this report, we substantially diversify and expand the family of ANTAR RNAs across bacteria.
Modulation of Recombinant Human T-type calcium Channels by Δ9-tetrahydrocannabinolic acid in vitro
Authors: Mirlohi Somayeh , Bladen Chris , Santiago Marina , Connor Mark
Published: October 2020

Introduction

Low voltage-activated T-type calcium channels (T-type ICa), CaV3.1, CaV3.2, and CaV3.3 are opened by small depolarizations from the resting membrane potential in many cells and have been associated with neurological disorders including absence epilepsy and pain. Δ9-tetrahydrocannabinol (THC) is the principal psychoactive compound in Cannabis and also directly modulates T-type ICa, however, there is no information about functional activity of most phytocannabinoids on T-type calcium channels, including Δ9-tetrahydrocannabinol acid (THCA), the natural non-psychoactive precursor of THC. The aim of this work was to characterize THCA effects on T-type calcium channels.

Materials and Methods

We used HEK293 Flp-In-TREx cells stably expressing CaV3.1, 3.2 or 3.3. Whole-cell patch clamp recordings were made to investigate cannabinoid modulation of ICa.

Results

THCA and THC inhibited the peak current amplitude CaV3.1 with a pEC50s of 6.0 ± 0.7 and 5.6 ± 0.4, respectively. 1μM THCA or THC produced a significant negative shift in half activation and inactivation of CaV3.1 and both drugs prolonged CaV3.1 deactivation kinetics. THCA (10 μM) inhibited CaV3.2 by 53% ± 4 and both THCA and THC produced a substantial negative shift in the voltage for half inactivation and modest negative shift in half activation of CaV3.2. THC prolonged the deactivation time of CaV3.2 while THCA did not. THCA inhibited the peak current of CaV3.3 by 43% ± 2 (10μM) but did not notably affect CaV3.3 channel activation or inactivation, however, THC caused significant hyperpolarizing shift in CaV3.3 steady state inactivation.

Discussion

THCA modulated T-type ICa currents in vitro, with significant modulation of kinetics and voltage dependence at low μM concentrations. This study suggests that THCA may have potential for therapeutic use in pain and epilepsy via T-type channel modulation without the unwanted psychoactive effects associated with THC.
TWIST1controls cellular senescence and energy metabolism in mesenchymal stem cells
Authors: Voskamp Chantal , Anderson Laura A. , Koevoet Wendy J. L. M. , Barnhoorn Sander , Mastroberardino Pier G. , van Osch Gerjo J.V.M. , Narcisi Roberto
Published: October 2020

Mesenchymal stem cells (MSC) are promising cells for regenerative medicine therapies, because they can differentiate towards multiple cell lineages. However, heterogeneity in differentiation capacity is one of the main drawbacks that limit their use clinically. Differences in the occurrence of cellular senescence and in the expression of the senescence associated secretory phenotype (SASP) in MSC populations contribute to their heterogeneity. Here, we show the involvement ofTWIST1expression in the regulation of MSC senescence, demonstrating that silencing ofTWIST1in MSCs increased the occurrence of senescence. These senescent MSCs had a SASP that was different from irradiation-induced senescent MSCs. In addition, metabolic evaluation performed by the Seahorse XF apparatus showed that bothTWIST1silencing-induced and irradiation-induced senescent MSCs had a higher oxygen consumption compared to control MSCs, whileTWIST1silencing-induced senescent MSCs had a low extracellular acidification rate compared to the irradiation-induced senescent MSCs. Overall, our data indicate howTWIST1regulation influences senescence in human MSCs and thatTWIST1silencing-induced senescence is characterized by a specific expression of the SASP and the metabolic state.
Human Cytomegalovirus antagonizes activation of Fcγ receptors II and III by distinct and synergizing modes of IgG manipulation
Authors: Kolb Philipp , Hoffmann Katja , Sievert Annika , Reinhard Henrike , Mercé-Maldonado Eva , Le-Trilling Vu Thuy Khanh , Gütle Dominique , Hengel Hartmut
Published: October 2020

Human Cytomegalovirus (HCMV) is endowed with multiple highly sophisticated immune evasion strategies. This includes the evasion from antibody mediated immune control by counteracting host Fc-gamma receptor (FcγR) mediated immune control mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC). We have previously shown that HCMV avoids FcγR activation by concomitant expression of the viral Fc-gamma binding glycoproteins (vFcγRs) gp34 and gp68. We now show that gp34 and gp68 bind IgG simultaneously at topologically different Fcγ sites and achieve efficient antagonization of host FcγR activation by distinct but synergizing mechanisms. While gp34 enhances immune complex internalization, gp68 acts as inhibitor of host FcγR binding to immune complexes. In doing so, gp68 induces Fcγ accessibility to gp34 and simultaneously limits host FcγR recognition. The synergy of gp34 and gp68 is compelled by the interfering influence of excessive non-immune IgG ligands and highlights conformational changes within the IgG globular chains critical for antibody effector function.

Graphical Abstract

NK cells elicit a powerful antibody-mediated antiviral response through ADCC. gp68 (ochroid) binds IgG in a 2:1 ratio reducing, but not abolishing accessibility of immune complexes to FcγRIII+(dark blue) immune effector cells such as NK cells. gp34 (red, natively forming a dimer (Sprague et al., 2008)) effectively internalizes immune complexes making them unavailable to surveilling FcγRIII+effector cells but cannot compete with FcγRIII for a similar binding region on IgG. Supported by functional evaluation, we propose a model in which g34 and gp68 work in cooperation to achieve efficient antagonization of antibody-mediated effector mechanisms.
HowEuglena gracilisswims: flow field reconstruction and analysis
Authors: Giuliani Nicola , Rossi Massimiliano , Noselli Giovanni , DeSimone Antonio
Published: October 2020

Euglena gracilisis a unicellular organism that swims by beating a single anterior flagellum. We study the nonplanar waveforms spanned by the flagellum during a swimming stroke, and the three-dimensional flows that they generate in the surrounding fluid.

Starting from a small set of time-indexed images obtained by optical microscopy on a swimmingEuglenacell, we construct a numerical interpolation of the stroke. We define an optimal interpolation (which we call synthetic stroke) by minimizing the discrepancy between experimentally measured velocities (of the swimmer) and those computed by solving numerically the equations of motion of the swimmer driven by the trial interpolated stroke. The good match we obtain between experimentally measured and numerically computed trajectories provides a first validation of our synthetic stroke.

We further validate the procedure by studying the flow velocities induced in the surrounding fluid. We compare the experimentally measured flow fields with the corresponding quantities computed by solving numerically the Stokes equations for the fluid flow, in which the forcing is provided by the synthetic stroke, and find good matching.

Finally, we use the synthetic stroke to derive a coarse-grained model of the flow field resolved in terms of a few dominant singularities. The far field is well approximated by a time-varying Stresslet, and we show that the average behavior ofEuglenaduring one stroke is that of an off-axis puller. The reconstruction of the flow field closer to the swimmer body requires a more complex system of singularities. A system of two Stokeslets and one Rotlet, that can be loosely associated with the force exerted by the flagellum, the drag of the body, and a torque to guarantee rotational equilibrium, provides a good approximation.
Migrating lung monocytes internalize and inhibit growth ofAspergillus fumigatusconidia
Authors: Schiefermeier-Mach Natalia , Haller Thomas , Geley Stephan , Perkhofer Susanne
Published: October 2020

Monocytes are important players to combat ubiquitously present fungusAspergillus fumigatus. Recruitment of monocytes to sites of fungal infection was shownin vivo, and purified murine and human blood monocytes are able to induce inflammatory and fungicidal mediators as well as the host cell and the fungal transcriptional responses upon exposure toA.fumigatus. Mononuclear tissue phagocytes are phenotypically and functionally different from those circulating in the blood and their role in antifungal defences is much less understood.

In this study, we identified a population of migratingCD43+ monocytes in cells isolated from rat distal lungs. These cells phenotypically different from alveolar macrophages, showed clearly distinct locomotory behaviour on the surface of primary alveolar cells resembling previously described endothelial patrolling. TheCD43+ monocytes internalized liveA.fumigatusconidia resulting in inhibition of conidial germination and hyphal growth. Thus, migrating lung monocytes might play an important role in local defence against pulmonary pathogens.
An analysis of globalisation in international business research 1993–2018: rise of the sceptics
Authors: Dabic Marina , Maley Jane , Novak Ivan
Published: October 2020

Purpose

The rise of the global economy has been an essential element in the international business (IB) agenda since the 1980s, and the topic of globalisation has not failed to captivate the attention of IB researchers and practitioners alike. Globalisation has impacted on such diverse issues as trade relations, geopolitical boundaries, social class, human rights, environmental commitments, religion, ethnicity, sovereignty and conservation of culture. The purpose of this paper is to provide an analysis of the current state of IB research on the topic of globalisation and to guide researchers who are new to IB research as to which journals and authors to consult when studying this phenomenon.

Design/methodology/approach

The paper presents a bibliometric analysis using the Web of Science database. A multiple correspondence analysis provides a map of keywords and authors, as well as a framework to track the globalisation literature over the 26-year period, 1993–2018.

Findings

The findings identify several fundamental themes and significant gaps in the extant literature; the most alarming gap centres around the effect of globalisation on social issues and, consequently, the rise of the anti-globalisation crusaders.

Research limitations/implications

The literature review produced 529 articles listed only in the Web of Science Core Collection in the period 1993–2018.

Practical implications

A distinctive contribution of this study is that it investigates the intersection between globalisation and IB. This paper seeks to expose the intellectual structure of globalisation research, identify existing and emerging themes of globalisation research and discuss future research streams.

Social implications

The findings show the rise of the globalisation sceptic and reveal the mounting concerns regarding the unequal benefits of globalisation.

Originality/value

There are two key benefits of this review. First, the theory extends by identifying a swing from an alignment with the transformationalist theory to sceptical theory. Second, the review has the potential to guide scholars on precisely what needs to be explored in IB globalisation research.
Plasma generation optimization: a new physically-based metaheuristic algorithm for solving constrained optimization problems
Authors: Kaveh Ali , Akbari Hossein , Hosseini Seyed Milad
Published: October 2020

Purpose

This paper aims to present a new physically inspired meta-heuristic algorithm, which is called Plasma Generation Optimization (PGO). To evaluate the performance and capability of the proposed method in comparison to other optimization methods, two sets of test problems consisting of 13 constrained benchmark functions and 6 benchmark trusses are investigated numerically. The results indicate that the performance of the proposed method is competitive with other considered state-of-the-art optimization methods.

Design/methodology/approach

In this paper, a new physically-based metaheuristic algorithm called plasma generation optimization (PGO) algorithm is developed for solving constrained optimization problems. PGO is a population-based optimizer inspired by the process of plasma generation. In the proposed algorithm, each agent is considered as an electron. Movement of electrons and changing their energy levels are based on simulating excitation, de-excitation and ionization processes occurring through the plasma generation. In the proposed PGO, the global optimum is obtained when plasma is generated with the highest degree of ionization.

Findings

A new physically-based metaheuristic algorithm called the PGO algorithm is developed that is inspired from the process of plasma generation.

Originality/value

The results indicate that the performance of the proposed method is competitive with other state-of-the-art methods.
A model of intention to use official COVID-19 websites
Authors: Sumaedi Sik , Bakti I. Gede Mahatma Yuda , Rakhmawati Tri , Astrini Nidya J. , Widianti Tri , Damayanti Sih , Massijaya M. Azwar , Jati Rahmi K.
Published: October 2020

Purpose

This research aims to test the effects of attitude, perceived behavioral control (PBC), subjective norm and perceived quality of official coronavirus disease 2019 (COVID-19) websites on intention to use official COVID-19 websites.

Design/methodology/approach

This study collected data using an online questionnaire. It involved 120 Indonesians who used official COVID-19 websites. The data were analyzed using the multiple regression analysis.

Findings

This research found that intention to use official COVID-19 websites is significantly and positively affected by the quality of the website, attitude and subjective norm. PBC does not influence intention to use official COVID-19 websites.

Research limitations/implications

This research was only conducted in the context of Indonesians. Furthermore, a convenience sampling technique was applied. Future research should be done in a different context with larger samples to test the generalization of this research's findings.

Practical implications

To improve intention to use official COVID-19 websites, people must be directed to have a positive attitude toward the website. The developer must ensure the quality of the website. It is also essential to involve leaders and public figures whose opinions might be able to sway citizens to use official COVID-19 websites consistently.

Originality/value

This research is the first one of its kind that studied citizens' intention to use official COVID-19 websites.
Research on grassland ecosystem service value in China under climate change based on meta-analysis: a case study of Qinghai province
Authors: Kang Binyue , Shao Qiuyu , Xu Hengkang , Jiang Fengyan , Wei Xiaoting , Shao Xinqing
Published: October 2020

Purpose

Grassland in Qinghai as the main type of ecosystem in this region is located in arid and semi-arid areas. The ecosystem is fragile and sensitive to climate change. Grassland ecosystem not only provides essential ecological and life functions for human society but also plays a vital role in mitigating and adapting to climate change. The empirical literature on grassland ecosystem services value (ESV) does not consider the impact of climate change and regional economic development level factors, which prevents policymakers from making appropriate decisions. This paper aims to analyze the influencing factors of grassland ESV assessment, and, based on the meta-prediction model, account the grassland ESV in Qinghai province.

Design/methodology/approach

To understand the value of grassland ecosystem services in China under climate change, this paper used 61 research literature on the evaluation of grassland ESV in China, including a total of 564 value observations to establish a value transfer database. Based on the meta-analysis method, this study has constructed a value transfer model, to evaluate the grassland ESV in Qinghai province, and an interpretation model, which can analyze if the independent variables affect the grassland ESV significantly.

Findings

The study finds that the evaluation methods, types of ecosystem service functions, climate change and grassland types can affect the grassland ESV significantly. Based on the meta-regression prediction model to evaluate the grassland ESV in Qinghai is US$1,542.67/ha/year. It indicates several targeted approaches to increase the grassland ESV, and climate change also has a specific impact on the value of grassland ecosystem services.

Research limitations/implications

This study provides a scientific basis for grassland management related to the development of grasslands and ecological compensation, as well as promote the sustainable development of grassland ecosystems.

Originality/value

This paper contributes to the field of grassland ESV assessment in at least three aspects; first, it innovatively introduces the meta-analysis to carry out an integrated analysis of previous research results; second, it includes a broader set of influence variables in the analysis, including meteorological and economic factors; and third, it establishes a methodological basis for the field of grassland ESV accounting.
VAT on foreign digital services in Mauritius; a comparative study with South Africa
Authors: Beebeejaun Ambareen
Published: October 2020

Purpose

Value added tax (VAT) is an indirect tax that is payable upon the consumption of goods and services. Recently, the Government of Mauritius has introduced a new set of rules to extend the VAT system to non-resident providers of electronic services to consumers based in Mauritius. The purpose of this research paper is therefore to assess the adequacy and efficiency of the recent VAT amendments in terms of compliance requirements and collection measures and to identify loopholes in the present legal provisions.

Design/methodology/approach

The methodologies for the research are in essence comprised of the black letter approach which will analyse the legal provisions relating to VAT in Mauritius. A comparative analysis will also be conducted to find out the corresponding legal provisions relating to VAT on digital services in South Africa.

Findings

This research paper has highlighted some recommendations inspired by the laws of South Africa and the Organisation for Economic Cooperation and Development Based Erosion Profiting Shifting action plan which may be of use to Mauritius stakeholders when devising regulations on the imposition of VAT on foreign suppliers of digital services under Section 14B of the VAT Act.

Originality/value

To the author's best knowledge, this research paper is the first study conducted in the field of indirect taxation of foreign suppliers of digital services to residents of Mauritius.
The Covid-19 pandemic and the struggle to tackle gender-based violence
Authors: Ince Yenilmez Meltem
Published: October 2020

Purpose

The purpose of this study is to look at the policies for the protection of women during pandemics while taking gender and feminist interests into crucial consideration. In perilous times like this, where many humans are living in fear and struggling to survive a world filled with diverse traumatizing events such as wars, universal pandemic, man-induced tragedies, natural destruction, overwhelming stress and stress-related illnesses abound. Currently, Covid-19 pandemic is rampaging in different areas of the world.

Design/methodology/approach

Studies are reviewed the major reasons of the violence against women during lockdown. A qualitative review of the literature is performed and analyzed. As there have been compulsory lockdowns in different parts of the world, Turkey included, the lockdown is ideal for preventing the spread of Covid-19.

Findings

There are issues this Covid-19 pandemic has caused, and one major issue is the stigma and trauma women face around the world, even in their homes. Domestic violence is a serious concern. It is, therefore, paramount for the government to intervene on this issue by declaring domestic violence as “essential services” and must set modalities in place for instant reliefs to women in such distress. It is even further envisaged that the term lockdowns have a diverse number of interpretations. One such prevailing argument is that humans are enslaved to their general imaginations, may continue in the pathways set aside by gender stereotypes or the same lockdowns, can be used as a means to set aside patriarchal notions and pursue a violence-free existence.

Originality/value

This research will increase the awareness in terms of preventing gender-based violence and try to address how this pandemic makes it worse for women. In addition, there are many studies focused on family violence and Covid-19 while few focus on gender.