bluuebunny/crossref_metadata_2025 huggingface dataset:
A dopamine antagonist, domperidone enhances the replication of an oncolytic adenovirus in human tumour cells
Authors: Nishimae Fumitaka , Sakurai Fuminori , Ono Ryosuke , Onishi Rika , Takayama Kosuke , Mizuguchi Hiroyuki
Published: June 2022

Oncolytic adenoviruses (OAds) have attracted much attention as novel anticancer agents. Numerous studies have examined the antitumour effects of combinational use of an OAd and anticancer agents; however, few chemical compounds enhancing OAd infection have been reported. In this study, we screened a food and drug administration (FDA)-approved drug library containing 1134 small chemical compounds to identify chemical compounds that enhance OAd replication in human tumour cells. We found that domperidone, a dopamine D2 receptor antagonist, significantly enhanced the replication of an OAd in human tumour cells, including human pancreatic tumour cells, by two–fivefold, resulting in improvement of OAd-mediated tumour cell killing activities. The E1A mRNA levels were significantly increased in domperidone-pre-treated cells following OAd infection, which contributed to the promotion of OAd replication. However, mRNA levels of the dopamine D2 receptor (DRD2), which is known to be a target molecule of domperidone, were undetectable in most of the tumour cells by real-time reverse transcription (RT)-PCR analysis, indicating that domperidone promoted OAd replication by acting on a molecule other than DRD2. This study provides important clues for the improvement of OAd-mediated cancer therapy.
Phase-specific Deep Brain Stimulation revisited: effects of stimulation on postural and kinetic tremor
Authors: Reis Carolina , He Shenghong , Pogosyan Alek , Haliasos Nikolaos , Low Hu Liang , Misbahuddin Anjum , Aziz Tipu , Fitzgerald James , Green Alexander L. , Denison Timothy , Cagnan Hayriye
Published: June 2022

Background

In Essential tremor (ET), involuntary shaking of the upper limbs during isometric muscle contraction closely reflects the patterns of neural activity measured in the thalamus - a key element of the tremorgenic circuit. Phase-specific deep brain stimulation (DBS) builds upon this observation while using accelerometery of the trembling limb to trigger repetitive electrical perturbations to the thalamus and surrounding areas at a specific time within the tremor cycle. This closed-loop strategy has been shown to induce clinically significant postural tremor relief while delivering less than half the energy of conventional DBS.

Objective

The main aim of the study was to evaluate treatment efficacy across different contexts and movement states.

Methods

We used accelerometery and a digitizing tablet to record the peripheral tremor dynamics of 4 DBS implanted ET patients while alternating stimulation strategies (no stimulation, continuous open-loop and phase-specific) and movement states (intermittent posture holding and spiral drawing).

Results

In addition to observing a suppressive effect of phase-specific DBS on both postural and kinetic tremor, our results reinforce the key role of phase-specificity to achieve tremor control in postural motor states and highlight the difficulty of quantifying phase-dependent effects during continuous movement. Moreover, this study supports the hypothesis that ET patients with more stable tremor characteristics benefit the most from phase-specific DBS.

Conclusions

By creating a better understanding of the dynamic relationship between central and peripheral tremor activity, this study provides important insights for the development of effective patient and context-specific therapeutic approaches for ET.
Vaccination and testing as a means of ending the COVID-19 pandemic: comparative and statistical analysis
Authors: Nesteruk Igor
Published: June 2022

Background

Record numbers of new cases and deaths registered in Japan and European countries in early 2022 once again proved that existing vaccines cannot stop the new infections and deaths caused by SARS-CoV-2 and aroused new questions about methods of overcoming the pandemic.

Aim of the study

to compare the pandemic waves in Japan, Ukraine, USA, Hong Kong, mainland China, European and African countries in 2020, 2021, 2022 and to investigate the influence of testing and vaccination levels.

Methods

The smoothed daily numbers of new cases and deaths per capita, the ratio of these characteristics and the non-linear correlation with the tests per case ratio were used.

Results

As in other countries, the deaths per case ratio in Japan decreases with the increase of the vaccination level. Non-linear correlation revealed, that the daily number of new cases drastically decreases with the increase of the tests per case ratio.

Conclusions

Increasing the level of testing (especially for people who may have contact with infected persons) and adhering to quarantine restrictions for the entire population, including vaccinated people, may be recommended to end the pandemic.
Ethnically Diverse Midlife Women’s Menopausal Transition Symptom Experience and Access to Medical and Integrative Health Care: Informing the Development of an Integrative Medicine Group Visit for the Menopausal Transition
Authors: Taylor-Swanson Lisa , Stoddard Kari , Fritz Julie , Anderson Belinda “Beau” , Cortez Melissa , Conboy Lisa , Sheng Xiaoming , Flake Naomi , Sanchez-Birkhead Ana , Stark Louisa , Woods Nancy Fugate , Gardiner Paula
Published: June 2022

Objective

Individuals in the menopausal transition often seek healthcare in the United States. However, many individuals who seek healthcare do not receive treatments for their symptoms. And, some lack access to providers of both medical care and evidence-based integrative health interventions such as acupuncture, acupressure, or massage. A potential solution to this problem is medical group visits. Medical group visits are when multiple patients are seen by one provider. The present study gathered the opinions of diverse midlife women about interest in and desired design elements of medical group visits for menopause-related symptoms and concerns.

Methods

We conducted one focus group with ethnically diverse midlife women to learn about their experiences in the menopausal transition, specifically their symptom experience, barriers, and facilitators to accessing medical and integrative health providers, and their interest in and suggestions for the design of an integrative medical group visit. Qualitative research methods were used to summarize session results.

Results

Nine women participated and were diverse in terms of race/ethnicity and religious affiliation, and were highly educated. Themes included: an interest in participating in this conversation; that medical terms were mostly unfamiliar, and that terminology was less important than having a conversation; many symptoms were experienced; social factors affected participants, stressing the need for communication on this topic; receiving both unhelpful and helpful healthcare, a desire for whole person care; a need for information about what conditions Integrative Health interventions can treat, barriers to accessing both conventional and integrative care providers and facilitators include knowledge about insurance coverage and word of mouth. The group expressed great interest in the proposed integrative medical group visit (IMGV) model but expressed barriers such as a lack of time available, and needing childcare. Women indicated that an online format may help to overcome barriers.

Conclusions

These findings highlight the importance of engagement with stakeholders before the design and implementation of IMGV and the great need among midlife women for education about the menopausal transition and relevant interventions and self-care.
Responses to COVID-19 Threats: An Evolutionary Psychological Analysis
Authors: Colarelli Stephen M. , Mirando Tyler J. , Han Kyunghee , Li Norman P. , Vespi Carter , Klein Katherine A. , Fales Charles P.
Published: June 2022

Responses to COVID-19 public health interventions have been lukewarm. For example, only 64% of the US population has received at least two vaccinations. Because most public health interventions require people to behave in ways that are evolutionarily novel and mismatched with evolved human perceptual and decision-making mechanisms, it is imperative that we gain a better understanding of how people respond to public health information, including how they respond under different pandemic conditions and how specific groups may differ in their responses. We conducted two studies, using data from primarily public sources. We found that state-level COVID-19 threats (e.g., infection and mortality rates) had no relationships with mental health symptoms, suggesting that people were not attending to threat information. This result is consistent with the evolutionary psychological explanation that COVID-19 threat information is insufficient to activate the human behavioral immune system. Furthermore, individual differences affected how people responded to COVID-19 threats, supporting a niche picking explanation. Finally, aggregate state IQ levels correlated positively with aggregate vaccination rates, suggesting that intelligence can partially counteract the evolutionary novelty of abstract threat information, supporting the savanna-IQ interaction hypothesis. We conclude with policy implications for improving interventions and promoting greater compliance.
INDICATIONS, CONTRAINDICATIONS, AND SOME SIDE EFFECTS OF HYPERBARIC OXYGEN THERAPY (HBOT) IN CHILDREN WITH SPECIAL NEEDS: A Cross-sectional Study
Authors: Zayed Khalid Mahmoud El Sayed
Published: June 2022

Disclaimer

The author has withdrawn their manuscript because, upon further review of the results, the pertinent patients’ data were found to be erratic in some of the performed examinations and medical tests. In addition, some aspects of the data analysis tests were found to be in error and need to be revised and corrected. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author at drzayed@outlook.com.
Vascular differences between glioblastoma IDH-wildtype and astrocytoma IDH-mutant grade 4 at imaging and transcriptomic level
Authors: Álvarez-Torres María del Mar , López-Cerdán Adolfo , de la Iglesia Vayá Maria , Fuster-Garcia Elies , García-García Francisco , García-Gómez Juan M
Published: June 2022

A global agreement in Central Nervous System (CNS) tumors classification is essential in order to decide treatment correctly, predict prognosis, evaluate treatment response, compare outcomes, and select adequate patients for clinical trials at international level.

The last update of the World Health Organization (WHO) of CNS tumor classification and grading 2021 considered for the first time glioblastoma IDH-wildtype and astrocytoma IDH-mutant grade 4 as different tumors. IDH mutation produces a metabolic reprogramming of tumor cells, thus affecting the processes of hypoxia and vascularity. The differences in the aggressiveness of these gliomas, which affect patient survival, are evident, with a clear advantage for those patients who present IDH mutated tumors.

Despite the clinical relevance of IDH mutation, current protocols do not include full sequencing for every patient. Alternative biomarkers could be useful and complementary to get a more reliable classification. In this sense, MRI-perfusion biomarkers, such as relative cerebral blood and flow (rCBV and rCBF), could be key because they are non-invasive, can be used from the presurgical moment, and do not suppose additional economical or effort costs.

The main purpose of this work is to evaluate and validate the association between MRI-DSC biomarkers and IDH mutation status in high-grade astrocytomas. In addition, to get a deeper understanding of the vascular differences, we aim to study the transcriptomic bases of these vascular differences between these two high-grade astrocytomas.
Gut microbial metabolites lower 24-hour systolic blood pressure in untreated essential hypertensive patients
Authors: Jama Hamdi A. , Rhys-Jones Dakota , Nakai Michael , Yao Chu K , Climie Rachel E. , Sata Yusuke , Anderson Dovile , Creek Darren J. , Head Geoffrey A. , Kaye David M. , Mackay Charles R. , Muir Jane , Marques Francine Z.
Published: June 2022

Background

Fibres remain undigested until they reach the colon, where some are fermented by gut microbiota, producing metabolites called short-chain fatty acids (SCFAs). SCFAs lower blood pressure (BP) of experimental models, but their translational potential is unknown. We aimed to determine whether SCFAs lower 24-hour systolic BP (SBP) in untreated participants with essential hypertension.

Methods

We performed a phase II randomized placebo-controlled double-blind cross-over trial using SCFA-supplementation, delivered as acetylated and butyrylated high amylose maize starch (HAMSAB). Twenty treatment-naïve hypertensive participants were recruited from the community and randomised to 40g/day of HAMSAB or placebo. Participants completed each arm for three-weeks, with a three-week washout period between them. The primary endpoint was a 24-hour SBP decrease.

Results

Participants were on average 55.8±11.2-years old (mean±SD), had a body mass index (BMI) of 25.7±2.5km2/m, 30% were female, baseline 24-hour SBP 136±6mmHg. No adverse effects were reported. After the intervention, the placebo-subtracted reduction in 24-hour SBP was 6.1±9.9mmHg (P= 0.027). This was independent of age, sex, BMI and study arm. There was no statistical significance in the placebo arm. Day and night SBP were reduced by 6.5±12.3mmHg (P=0.01) and 5.7±9.8mmHg (P=0.02), respectively, and 24-h central SBP by 7.2±14.7 mmHg (P=0.005). HAMSAB increased levels of acetate and butyrate by 7.8-fold (P=0.016), shifted the microbial ecosystem, and expanded the prevalence of SCFA-producers.

Conclusions

We observed a clinically relevant reduction in 24-hour SBP in participants with essential hypertension treated with the gut microbial-derived metabolites acetate and butyrate. These metabolites may represent a novel option for lowering BP.
Overall and sex-specific effect of berberine for dyslipidemia: systematic review and meta-analysis of placebo-controlled trials
Authors: Blais Joseph E , Huang Xin , Zhao Jie V
Published: June 2022

Background

Berberine is a nutraceutical that may improve lipid profiles. Berberine may also affect sex hormones and exert sex-specific effects, which has been overlooked.

Objectives

To comprehensively review the efficacy and safety of lipid-lowering effect of berberine with consideration of potential sex disparity.

Methods

Eligible studies were randomized controlled trials in adults that compared berberine versus placebo and measured blood lipids or lipoproteins. Studies were identified from Medline, Embase, Wanfang, CNKI, two clinical trial registries and previous systematic reviews. Mean differences (MD) were estimated using inverse variance weighting with random effects models. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials.

Results

16 studies were included with treatment of 4 to 24 weeks. Berberine reduced low-density lipoprotein (LDL) cholesterol (−0.45 mmol/L, 95% CI -0.60 to -0.31, 12 studies, n=1,224), total cholesterol (−0.47 mmol/L, 95% CI -0.61 to -0.33, 15 studies, n=1,397), triglycerides (−0.32 mmol/L, 95% CI -0.44 to -0.19, 16 studies, n=1,421) and apolipoprotein B (−0.25 mg/dL, 95% CI -0.40 to -0.11, 2 studies, n=127). Berberine increased high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.12, 13 studies, n=1,248). Notably, the effect on HDL cholesterol was different in women (0.11 mmol/L, 95% CI 0.09 to 0.13) from that in men (−0.07 mmol/L, 95% CI -0.16 to 0.02). Gastrointestinal adverse events were the most frequently reported adverse events.

Conclusions

Berberine decreased LDL cholesterol, triglycerides, and apolipoprotein B, with a potential sex-specific effect on HDL cholesterol. Large-scale trials considering sex disparity are required.
Autophagy activity is inhibited by hnRNP R
Authors: Ji Changhe
Published: June 2022

Autophagy is a self-eating intracellular degradation process in eukaryotic cell. Muti-pathways have been found can regulate autophagy activity through different mechanisms. In this study, we found that a nuclear abundant RNA binding protein, hnRNP R is involved in autophagy process by binding with ATG3, p62, Lamp1, LC3 and ATG9. On the other hand, hnRNP R also can regulate autophagy, we found depletion hnRNP R can activate the autophagy flux and activity. Furthermore, we also checked that autophagy has not connection with stress granules. This finding highlights some novel and nuclear located RNA binding proteins play important role in the regulation of autophagy activity.
Cluster analysis of angiotensin biomarkers to identify antihypertensive drug treatment in population studies
Authors: Woldeyes Arisido M , Luisa Foco , Robin Shoemaker , Roberto Melotti , Christian Delles , Martin Gögele , Stefano Barolo , Stephanie Baron , Michel Azizi , Anna Dominiczak , Christina Zennaro M , Peter Pramstaller P , Marko Poglitsch , Cristian Pattaro
Published: June 2022

Background

Hypertension is a leading cause of death worldwide. Population-based studies offer an opportunity to assess the effectiveness of anti-hypertensive drugs (AHD) in real-world scenarios. However, lack of quality AHD documentation, especially when electronic health record linkage is unavailable, leads to reporting and classification bias. Here we assessed to which extent Renin-Angiotensin-Aldosterone System (RAAS) biomarkers can identify AHD treatments in the general population.

Method

Angiotensin I, angiotensin II and aldosterone levels were simultaneously determined through mass-spectrometry analysis in 800 participants of the Cooperative Health Research In South Tyrol (CHRIS) study with documented AHD treatment. We conducted unsupervised cluster analysis, assessing agreement, sensitivity and specificity of the resulting clusters against known AHD treatment. Through lasso penalized regression we identified clinical characteristics associated with RAAS biomarkers, accounting for the effects of cluster and treatment classifications.

Results

We identified three well-separated clusters: cluster 1 (n=444) preferentially including individuals not receiving RAAS-targeting AHD; cluster 2 (n=235) identifying angiotensin type 1 receptor blockers (ARB) users (weighted kappa κw=74%; sensitivity=73%; specificity=83%); and cluster 3 (n=121) well discriminating angiotensin-converting enzyme inhibitors (ACEi) users (κw=81%; sensitivity=55%; specificity=90%). Individuals in clusters 2 and 3 had higher frequency of diabetes as well as higher fasting glucose and BMI levels. Age, sex and kidney function were strong predictors of the RAAS biomarkers independently of the cluster structure.

Conclusions

Unsupervised clustering of angiotensin I, angiotensin II and aldosterone is a viable technique to identify individuals on ACEi and ARB AHD treatment outside of a controlled clinical setting.
Prevalence of untreated HIV and HIV incidence among occupational groups in Rakai, Uganda: a population-based longitudinal study, 1999-2016
Authors: Popoola Victor O. , Kagaayi Joseph , Ssekasanvu Joseph , Ssekubugu Robert , Kigozi Grace , Ndyanabo Anthony , Nalugoda Fred , Chang Larry W. , Lutalo Tom , Tobian Aaron A.R. , Kabatesi Donna , Alamo Stella , Mills Lisa A. , Kigozi Godfrey , Wawer Maria J. , Santelli John , Gray Ronald H. , Reynolds Steven J , Serwadda David , Lessler Justin , Grabowski M. K.
Published: June 2022

Abstract

Introduction

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including bar work and transportation. However, data on changes in prevalence of untreated HIV infection and HIV incidence within occupations following rollout of antiretroviral therapy and voluntary medical male circumcision programs in 2004 are limited.

Methods

We evaluated 12 rounds of survey data collected between 1999-2016, from the Rakai Community Cohort Study, a population-based study of adolescents and adults 15-49 years in Uganda, to assess changes in the prevalence of untreated HIV infection and incidence by self-reported primary occupation. Adjusted prevalence risk ratios (adjPRR) for untreated HIV and incidence rate ratios for HIV incidence with 95% confidence intervals (CIs) were estimated using Poisson regression. Primary outcomes were stratified by gender and HIV incidence compared over three time periods (1999-2004; 2005-2011; 2011-2016) representing, respectively, the period prior to scale up of combined HIV prevention and treatment, the scale up period, and full implementation.

Results

33,866 individuals, including 19,113 (56%) women participated. Of these participants, 17,840 women and 14,244 men who were HIV-negative at their first study visit contributed 57,912 and 49,403 person-years of follow-up, respectively. Agriculture was the most common occupation at all study visits, though its prevalence declined from 39 to 29% among men and from 61 to 40% among women between 1999 and 2016. Untreated HIV infection substantially declined between 1999 and 2016 across most occupational subgroups, including by 70% among men (12 to 4.2%; adjPRR=0.30; 95%CI:0.23-0.41) and by 78% among women working in agriculture (14.7 to 4.0%; adjPRR=0.22; 95%CI:0.18-0.27), along with increasing antiretroviral therapy coverage. Exceptions included men working in transportation and women working in tailoring/laundry services. HIV incidence declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers or men working in transportation.

Conclusion

Untreated HIV infection and HIV incidence have declined in most occupational sub-groups in Rakai, Uganda. However, women working in bars and restaurants and men working in transportation continue to have relatively high burden of untreated HIV and HIV incidence, and as such should be considered key priority populations for targeted HIV programming.
Maladaptive laterality in cortical networks related to social communication in autism spectrum disorder
Authors: Persichetti Andrew S. , Shao Jiayu , Gotts Stephen J. , Martin Alex
Published: June 2022

Neuroimaging studies of individuals with autism spectrum disorders (ASD) consistently find an aberrant pattern of “reduced” laterality in brain networks that support functions related to social communication and language. However, it is unclear how the underlying functional organization of these brain networks is altered in ASD individuals. We tested four models of “reduced” laterality in a social-communication network in seventy ASD individuals (14 females) and a control group of the same number of tightly matched typically developing (TD) individuals (19 females) using high quality resting-state fMRI data and a method of measuring patterns of functional laterality across the brain. We found that a functionally defined social-communication network exhibited the typical pattern of left laterality in both groups, while there was a significant increase in laterality of homotopic regions in the right hemisphere in ASD individuals. Furthermore, left laterality was positively correlated with a measure of verbal ability in both groups, while right laterality in ASD, but not TD, individuals was negatively correlated with the same verbal measure. Crucially, these differences in patterns of laterality were not found in two other functional networks and were specifically correlated to a measure of verbal, but not visuospatial, ability. These results suggest that previous reports of “reduced” laterality in social-communication regions in ASD is due to a shift towards functional decoupling of the two hemispheres, which may cause them to act as independent systems with the atypical right-lateralized network being maladaptive.
Targeted delivery of interferon-gamma by synNotch T cells sensitizes neuroblastoma cells to T cell-mediated killing
Authors: Iglesias Fiorella , Weston Siani , Avila Stephanie V. , Zhou Holly , Yousef Sara , Fluchel Mark , Morales Erin , Olsen Michael L. , Radhakrishnan Sabarinath V. , Luetkens Tim
Published: June 2022

Downregulation of HLA is one of the most common tumor escape mechanisms by enabling tumors to persist in the presence of tumor-reactive T cells. HLA loss is particularly common in children with high-risk neuroblastoma, who have a 50% long-term survival despite dose-intensive regimens. We have now developed an approach for the targeted induction of HLA to restore sensitivity of neuroblastoma cells to T cell-mediated killing. Using synNotch technology, we have generated T cells that, upon binding of the neuroblastoma surface antigen GD2, secrete IFN-γ without conferring direct cytotoxic activity (snGD2i). Treatment with snGD2i cells induces high and durable expression of HLA on neuroblastoma cells in vitro and in vivo and restores sensitivity to TCR-transgenic T cells targeting neuroblastoma-specific antigens. In contrast, treatment does not lead to upregulation of immune checkpoints or systemically increased levels of IFN-γ. Targeted delivery of IFN-γ using snGD2i cells is a promising new strategy to address immune escape in neuroblastoma.

STATEMENT OF SIGNIFICANCE

HLA loss remains one of the most common and unsolved immune escape mechanisms in cancer cells. We have now developed a cell-based approach for the targeted upregulation of HLA on tumor cells, which efficiently sensitizes the malignant cells to killing by tumor-reactive T cells.
The coordination of innate and adaptive immunity in bacteria
Authors: Arias Clemente F. , Acosta Francisco J. , Bertocchini Federica , Herrero Miguel A. , Fernández-Arias Cristina
Published: June 2022

Bacteria have evolved a variety of innate and adaptive immune strategies to fight bacteriophage (phage) infections. Innate defenses (unspecific mechanisms directed against any phage infecting the cell) range from the identification and cleavage of the viral DNA by restriction nucleases to the suicidal death of infected host cells, an extreme solution that prevents the spread of the infection throughout the population. Adaptive immunity, on the other hand, involves the creation of an immune memory that targets specific phages in case of reinfection. It is obvious that not every infection leads to the suicide of the host cell or to the formation of immune memory against the infecting phage, so what determines the outcome of an anti-phage response? In this work, we suggest that the dynamic aspects of phage infections are key to addressing this question. We show that the rates of viral DNA replication and cleavage define functional categories of phages that differ in their susceptibility to the immune strategies evolved by bacteria. From this viewpoint, the combined action of diverse bacterial defenses would be necessary to reduce the chances of phage immune evasion. This perspective allows us to formulate simple molecular mechanisms that could account for the decision of infected cells to undergo suicidal cell death or to incorporate new phages into the immune memory. This work highlights the importance of dynamics to understand bacterial immunity and formulates explicit hypotheses that could inspire a new and original empirical approach to the study of phage/bacteria interactions.
Understanding Supramolecular Assembly of Supercharged Proteins
Authors: Jacobs Michael I. , Bansal Prateek , Shukla Diwakar , Schroeder Charles M.
Published: June 2022

Ordered supramolecular assemblies of supercharged synthetic proteins have recently been created using electrostatic interactions between oppositely charged proteins. Despite recent progress, the fundamental mechanisms governing the assembly process between oppositely supercharged proteins are not fully understood. In this work, we use a combination of experiments and computational modeling to systematically study the supramolecular assembly process for a series of oppositely supercharged green fluorescent protein (GFP) variants. Our results show that the assembled structures of oppositely supercharged proteins critically depend on surface charge distributions. In addition, net charge is a sufficient molecular descriptor to predict the interaction fate of oppositely charged proteins under a given set of solution conditions (e.g., ionic strength). Interestingly, our results show that a large excess of charge is necessary to nucleate assembly and that charged residues that are not directly involved in interprotein interactions contribute to a substantial fraction (∼30%) of the interaction energy between oppositely charged proteins via long-range electrostatic interactions. Dynamic subunit exchange experiments enabled by Förster resonance energy transfer (FRET) further show that relatively small, 16-subunit assemblies of oppositely charged proteins have kinetic lifetimes on the order of ∼10-40 minutes, which is governed by protein composition and solution conditions. Overall, our work shows that a balance between kinetic stability and electrostatic charge ultimately determine the fate of supramolecular assemblies of supercharged proteins. Broadly, our results inform how protein supercharging can be used to generate different ordered supramolecular assemblies from a single parent protein building block.
Bacterial lipoxygenases are associated with host-microbe interactions and may provide cross-kingdom host jumps
Authors: Kurakin Georgy
Published: June 2022

In this bioinformatic research, we studied the association of bacterial lipoxygenases (LOXs) with pathogenic and symbiotic traits by text networks analysis, phylogenetic analysis, and statistical analysis of molecular structure. We found that bacterial lipoxygenases are associated with a broad host range — from coral to plants and humans. In humans, bacterial LOXs are associated with opportunistic and nosocomial infections as well as with affecting specific patient populations like cystic fibrosis patients. Moreover, bacterial LOXs are associated with plant-human (or human-plant) host jumps in emerging pathogens. We also inferred a possible mechanism of such host jumps workingviaa host’s oxylipin signalling “spoofing”.

Graphical abstract
Evaluating the differential expression of TAM family receptors and efferocytosis activities in differentiated and polarized THP-1 macrophage
Authors: Chamberland Megan , Farrell Brian , Yeh Johannes
Published: June 2022

Tissue homeostasis is tightly balanced between cell death and renewal. Each day, as many as 1011 cells die in the human body that need to be removed and replaced. The clearance of apoptotic cells, termed efferocytosis, is crucial to tissue homeostasis. Central to this process is macrophage-mediated efferocytosis. Apart from general phagocytosis, efferocytosis is apoptotic cell-specific, which aids in clearing dead cells and preventing the accumulation of self-antigens released by the apoptotic cells. The TAM family receptor kinases (TYRO3, AXL, MERTK) and ligands (GAS6 and PROS) play important roles in engaging the apoptotic cells to initiate efferocytic engulfment and the downstream cellular responses. Dysregulated efferocytic function in macrophages is associated with human diseases such as atherosclerosis, lupus, lung fibrosis, and cancer. Conversely, understanding the regulation and molecular mechanisms of macrophage efferocytosis can potentially lead to beneficial treatments for the above diseases. Despite numerous efferocytosis studies that use primary and cell line-derived macrophages, there has not been a thorough characterization of a cell line system that can be reliably used for efferocytosis assays. Consequently, many macrophage efferocytosis assays reported do not clearly distinguish efferocytosis from phagocytosis. Here we evaluated the THP-1 cell line as a potential human macrophage cell line system for efferocytosis studies. Consequently, many macrophage efferocytosis assays reported do not clearly distinguish efferocytosis from phagocytosis. Through the study we examined the differential expression of the TAM family receptors and their ligands in the various THP-1 macrophage differentiation and polarization states. We also characterized the THP-1 cell line as a reliable system for performing in vitro efferocytosis studies.
A Descriptive Analysis of Calls to the NSW Teratogen Information Service regarding use of anti-infectives during pregnancy
Authors: Ritchie Helen , Hegedus Elizabeth , Ma Joanne , Kennedy Debra
Published: June 2022

Background

MotherSafe is a free telephone-based counseling service for Australian consumers and health-care providers concerned about drug exposures during pregnancy and breastfeeding. Anti-infectives are the most commonly prescribed drugs for pregnant women. This study aims to provide a retrospective, descriptive analysis of prospectively collected calls received by MotherSafe regarding anti-infective exposures during pregnancy between 2000 and 2020. Aggregate data were examined by type of caller, reason for call, pregnancy category and exposure type. Inductive thematic analysis of the comments recorded by MotherSafe counsellors at the time of call was undertaken.

Results

Over the study period, 25,890 calls related to exposure to anti-infectives during pregnancy (antibiotic, antiviral, and antifungal medications). Calls from patients were dominated by low-risk exposures (pregnancy category A) to drugs while calls from health care professionals related to drugs with limited human information (pregnancy category B3). Analysis of MotherSafe counsellor comments revealed over 200 instances of concerns relating to health care professional advice to the patient. Three themes emerged: incorrect or conflicting advice, poor counselling, and refusal to treat, prescribe or dispense. It is likely that these comments are biased to the negative as patients would not call MotherSafe if they were happy with HCP advice. However, the findings are concerning as they reveal an underlying lack of knowledge in some health care professionals which may have led to undertreatment of patients. This study reinforced the importance of Teratogen Information Services such as MotherSafe in providing counselling and clear communication of evidence-based information to guide decision-making, reducing potential emotional distress in pregnant women, and optimizing maternal, pregnancy and infant outcomes.
Expanding the phenotype of ATP6AP1 deficiency
Authors: Barua Subit , Berger Sara , Pereira Elaine M. , Jobanputra Vaidehi
Published: June 2022

Vacuolar ATPases (V-ATPases) are large multisubunit proton pumps conserved among all eukaryotic cells that are involved in diverse functions including acidification of membrane-bound intracellular compartments. The ATP6AP1 gene encodes an accessory subunit of the vacuolar (V)-ATPase protein pump. Pathogenic variants in ATP6AP1 have been described in association with a congenital disorder of glycosylation (CDG), which are highly variable, but often characterized by immunodeficiency, hepatopathy, and neurologic manifestations. Although the most striking and common clinical feature is hepatopathy, the phenotypic and genotypic spectrum of ATP6AP1-CDG continues to expand. Here, we report identical twins who presented with acute liver failure and jaundice. Prenatal features included cystic hygroma, atrial septal defect, and ventriculomegaly. Postnatal features included pectus carinatum, connective tissue abnormalities, and hypospadias. Whole-exome sequencing (WES) revealed a novel de novo in-frame deletion in the ATP6AP1 gene (c.230_232delACT;p.Tyr77del). Although both twins have the commonly reported clinical feature of hepatopathy seen in other individuals with ATP6AP1-CDG-related disorder, they do not have neurological sequelae. This report expands the phenotypic spectrum of ATP6AP1-CDG-related disorder with both probands exhibiting unique prenatal and postnatal features, including fetal ventriculomegaly, umbilical hernia, pectus carinatum, micropenis, and hypospadias. Furthermore, this case affirms that neurological features described in the initial case series on ATP6AP1-CDG do not appear to be central, whereas the prenatal and connective tissue manifestations may be more common than previously thought. This emphasizes the importance of long-term clinical follow-up and variant interpretation using current updated recommendations.
Brand betrayal and moral judgment: consumers’ responses to M&A of local foodservice brands
Authors: Yu Heyao , Legendre Tiffany S. , Jung InHaeng
Published: June 2022

Purpose

Mergers and acquisitions (M&As) are typical corporate strategies that provide hospitality business competitiveness. However, some recent evidence shows that when the merged and acquired (M&Aed) restaurants have strong local characteristics, consumers feel betrayed and perceive the M&As, legitimate business activities, as immoral actions. Building upon expectancy violation theory and moral foundation theory, this study aims to examine the moderating role of locavorism on the indirect effects of preexisting relationship quality on desire for avoidance and psychological loss through brand betrayal and moral judgment.

Design/methodology/approach

This study used the M&A of Whataburger chain restaurant as the scenario and recruited 399 Texas Whataburger consumers. A moderated mediation model was developed to examine the mechanisms through which preexisting relationship quality on negative responses to M&A of local restaurants.

Findings

The results showed preexisting relationship quality influences desire for avoidance and psychological loss negatively through brand betrayal and moral judgment. The indirect effects of relationship quality on the desire for avoidance and psychological loss become more accentuated among locavores.

Practical implications

The results implied that merging and acquiring (M&Aing) companies should closely monitor consumer dialogues to promptly respond to post-M&A uncertainties when M&Aed company has a strong local identity.

Originality/value

The unique contribution of this study is showing why consumers have extreme negative emotions and judgment of immorality when M&A decisions are made for local hospitality brands through the lens of brand betrayal and moral foundation theory. The results can help M&Aing companies mitigate consumers’ negative responses to M&A of local restaurants.
COVID-19 crisis overshadowing the health workforces’ rights and resilience: a systematic review
Authors: Khosravizadeh Omid , Ahadinezhad Bahman , Rafiei Sima , Kalhor Rohollah , Maleki Aisa
Published: June 2022

Purpose

In the time of the COVID-19 crisis, many physical, psychological and spiritual difficulties are imposed on the front line staff and overshadow their rights, resilience and retention. In addition, the loss of this important organizational resource imposes huge costs on the system. The purpose of this study is systemic review of the influential factors, policies and strategies applied to defend the rights of health-care staff and improve the resilience and retention of health system human resources in the COVID-19 crisis.

Design/methodology/approach

This systematic review was conducted in 2021. Data were collected by keyword search in Google Scholar, PubMed, Scopus, Web of Science, Science Direct, Magiran, SID and Irandoc databases until December 2021. In addition, the quality of the studies was evaluated by three experts using the Strobe checklist. The analysis used in this study to categorize the results was thematic analysis.

Findings

Factors that cause tension and injustice to employees and also strategies to overcome it and increase their resilience were classified into general categories according to their nature. Factors included factors related to safety, economic and financial, staff characteristics, crisis management characteristics, organizational climate and working conditions. Existing strategies also fall into four categories of physical, psychological and spiritual health promotion strategies; organizational climate and work environment; education and empowerment and economic and financial.

Originality/value

This study is a systematic review of the factors that affect the health workforce rights and resilience of health-care personnel during the COVID-19 crisis. On the other hand, the policies and strategies used in different countries to overcome the difficulties and increase the resilience and retention of health workers have been summarized and can be used in other crises.
Who is Homo Islamicus? A Qurʾānic perspective on the economic agent in Islamic economics
Authors: Furqani Hafas , Echchabi Abdelghani
Published: June 2022

Purpose

This paper aims to explain the nature of the economic agent in Islamic economics. He is commonly referred to as Homo Islamicus.

Design/methodology/approach

This is done by deriving the concept from the Qurʾān as the primary epistemological source in Islamic economics. The paper, thus, attempts to explore the message of the Qurʾān and internalize its concepts and values in their totality into the conception of the economic agent from an Islamic perspective.

Findings

The paper brings an insight regarding the nature of the economic agent in Islamic perspective. The concept of the economic agent that is developed from the Qurʾānic teachings will be useful in developing assumptions and theories in Islamic economics.

Research limitations/implications

This paper explores the normative behavioral framework of man from the Qurʾānic perspective (i.e. what is expected of man) in order to serve as the basis on which assumptions, concepts and theories could be produced and applied in real life. Further studies could extend the discussion by examining the application of the concepts in practice.

Practical implications

This paper promotes a normative behavioral framework that could be the basis in developing the body of knowledge of Islamic economics.

Originality/value

This paper promotes a concept of the economic agent in Islamic perspective, termed as Homo Islamicus, who is going to portray Islamic ethical teachings in economic actions. The paper brought insights from the Qurʾānic teachings and principles in developing the concept of Homo Islamicus who will be the representative agent in theorizing Islamic economics.
Jacinda Ardern's compassionate leadership: a case of social change leadership in action
Authors: Van Wart Montgomery , Macaulay Michael , Haberstroh Katie
Published: June 2022

Purpose

This article investigates the leadership style of Jacinda Ardern, Prime Minister of Aotearoa New Zealand. It uses the model of Social Change Leadership (SCL) to evaluate her approach to leadership as well as some notable successes and failures of her premiership.

Design/methodology/approach

The article adopts a grounded theory approach in which five increasingly refined research iterations were conducted to detect and articulate patterns of significance (Strauss and Corbin, 1997). Ultimately, the team selected 19 leadership examples to be cross referenced with the SCL model.

Findings

The article finds that in terms of leadership style Ardern corresponds closely to the SCL framework. The 19 examples show clusters of behavior that clearly denote a SCL constellation in terms of her approach. It also finds, however, that in terms of performance goals there is a less clear picture with less coherence to the framework. These findings in turn point to an interesting potential tension in the SCL model that has hitherto not been acknowledged.

Originality/value

The article is the first of its kind to apply SCL to a major global political leader. It is the first structured, academic assessment of Ardern's leadership. It adds a theoretical contribution to ongoing discussions on the efficacy and utility of the SCL framework.
The bright and dark sides of hotel kiosks: an empirical study
Authors: Kim Jungsun (Sunny) , Joe SungJun , Erdem Mehmet
Published: June 2022

Purpose

This study examined the antecedents of technostressors as well as how customers' perceived convenience and technostressors of using a check-in/out kiosk influence their behavioral intention in a full-service hotel setting.

Design/methodology/approach

Using survey data collected from 630 hotel customers, hypotheses were tested via structural equation modeling and multi-group analysis.

Findings

The results showed that perceived usefulness of a check-in/out kiosk had direct effects on both technostressors (i.e. work overload and role ambiguity), and that perceived ease-of-use had indirect effects on the technostressors, via perceived usefulness. The findings showed that both role ambiguity and perceived convenience significantly influenced intention to use a check-in/out kiosk. Intention to use was positively associated with intention to revisit a hotel providing the kiosk. These findings were equivalent across the younger and older groups.

Practical implications

Based on the findings, hotels can implement effective strategies to reduce technostressors associated with a check-in/out kiosk and focus on enhancing the factors that influence customer acceptance of the system. This is especially important given the increased emphasis on self-service technology since the onset of the COVID-19 pandemic.

Originality/value

This research contributed to the relevant literature by developing a check-in/out kiosk acceptance model using a multi-theoretical approach, and empirically testing it within the full-service hotel domain. It fills the knowledge gap regarding the antecedents and outcomes of technostressors in the hospitality research literature by providing empirical evidence.
What can we learn from Star Wars about the future of tourism? Absolutely everything!
Authors: Ivanov Stanislav
Published: June 2022

Purpose

This viewpoint is a response to Yeoman's (2022) editorial on Sunderland AFC and the future of tourism. This viewpoint aims to outline the lessons one can learn from Star Wars about the future of tourism.

Design/methodology/approach

The paper reviews the live-action movies and series of the Star Wars franchise.

Findings

The paper derives specific conclusions in the following directions: the future technology in travel, tourism and hospitality; the tourists' motivation and behaviour; the management of travel, tourism and hospitality companies; destination management; economy and society and lessons from the franchise.

Originality/value

This is one of the first papers to elaborate on the lessons one can learn about the future of tourism from the Star Wars live-action movies and series.