bluuebunny/crossref_metadata_2025 huggingface dataset:
A Clinical Study of Histopathological and Clinical Image Changes After Sclerotherapy of Lip Venous Malformations
Authors: Maruguchi Hayato , Nomura Tadashi , Takeda Reiko , Sakakibara Shunsuke , Terashi Hiroto
Published: August 2023

Venous malformations (VMs) are histopathologically benign but can greatly impair patients’ quality of life. Screlothprapy is known to be effective in improving symptoms without a scar, but surgical resection of residual lesions is sometimes necessary due to inadequate reduction. However, there is no consensus on what criteria should be used to consider switching to surgical treatment, and individualized decisions must be made for each case. To investigate the factors that contribute to the lack of efficacy of sclerotherapy in reducing lesions and how to predict this, the authors performed a retrospective clinical imaging and histopathological study of 6 cases of labial vein malformations treated with sclerotherapy and 3 cases without sclerotherapy. Clinical image investigations are based on magnetic resonance imaging before and after sclerotherapy. The authors found a significant decrease in the percentage of cystic components in the total lesion of VMs after sclerotherapy. Histopathological investigations are based on resected VMs with or without sclerotherapy. Elastica van Gieson stains suggested a significant increase in fibrotic tissue inside VMs treated with sclerotherapy compared with those without. In conclusion, magnetic resonance imaging signal changes inside the VMs after sclerotherapy was observed, and it may reflect fibrosis of the tissue. These changes in the VMs after sclerotherapy may reduce the effect of sclerotherapy on tissue reduction should be considered.
Moving toward a better understanding of the model bacterial predator Bdellovibrio bacteriovorus
Authors: Caulton Simon G. , Lovering Andrew L.
Published: August 2023

The bacterial predator

Bdellovibrio bacteriovorus

is a model for the wider phenomenon of bacteria:bacteria predation, and the specialization required to achieve a lifestyle dependent on prey consumption.

Bdellovibrio bacteriovorus

is able to recognize, enter and ultimately consume fellow Gram-negative bacteria, killing these prey from within their periplasmic space, and lysing the host at the end of the cycle. The classic phenotype-driven characterization (and observation of predation) has benefitted from an increased focus on molecular mechanisms and fluorescence microscopy and tomography, revealing new features of several of the lifecycle stages. Herein we summarize a selection of these advances and describe likely areas for exploration that will push the field toward a more complete understanding of this fascinating ‘two-cell’ system.
Predicting polycystic ovary syndrome (PCOS) with machine learning algorithms from electronic health records
Authors: Zad Zahra , Jiang Victoria S. , Wolf Amber T. , Wang Taiyao , Cheng J. Jojo , Paschalidis Ioannis Ch. , Mahalingaiah Shruthi
Published: August 2023

Introduction

Predictive models have been used to aid early diagnosis of PCOS, though existing models are based on small sample sizes and limited to fertility clinic populations. We built a predictive model using machine learning algorithms based on an outpatient population at risk for PCOS to predict risk and facilitate earlier diagnosis, particularly among those who meet diagnostic criteria but have not received a diagnosis.

Methods

This is a retrospective cohort study from a SafetyNet hospital’s electronic health records (EHR) from 2003-2016. The study population included 30,601 women aged 18-45 years without concurrent endocrinopathy who had any visit to Boston Medical Center for primary care, obstetrics and gynecology, endocrinology, family medicine, or general internal medicine. Four prediction outcomes were assessed for PCOS. The first outcome was PCOS ICD-9 diagnosis with additional model outcomes of algorithm-defined PCOS. The latter was based on Rotterdam criteria and merging laboratory values, radiographic imaging, and ICD data from the EHR to define irregular menstruation, hyperandrogenism, and polycystic ovarian morphology on ultrasound.

Results

We developed predictive models using four machine learning methods: logistic regression, supported vector machine, gradient boosted trees, and random forests. Hormone values (follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone binding globulin) were combined to create a multilayer perceptron score using a neural network classifier. Prediction of PCOS prior to clinical diagnosis in an out-of-sample test set of patients achieved AUC of 85%, 81%, 80%, and 82%, respectively in Models I, II, III and IV. Significant positive predictors of PCOS diagnosis across models included hormone levels and obesity; negative predictors included gravidity and positive bHCG.

Conclusions

Machine learning algorithms were used to predict PCOS based on a large at-risk population. This approach may guide early detection of PCOS within EHR-interfaced populations to facilitate counseling and interventions that may reduce long-term health consequences. Our model illustrates the potential benefits of an artificial intelligence-enabled provider assistance tool that can be integrated into the EHR to reduce delays in diagnosis. However, model validation in other hospital-based populations is necessary.
Immunoregulatory macrophages modify local pulmonary immunity and ameliorate hypoxic-pulmonary hypertension
Authors: Fernandez-Gonzalez Angeles , Mukhia Amit , Nadkarni Janhavi , Willis Gareth R. , Reis Monica , Zhumka Kristjan , Vitali Sally , Liu Xianlan , Galls Alexandra , Mitsialis S. Alex , Kourembanas Stella
Published: August 2023

Rationale

Macrophages play a central role in the onset and progression of vascular disease in pulmonary hypertension (PH) and cell-based immunotherapies aimed at treating vascular remodeling are lacking.

Objective

To evaluate the effect of pulmonary administration of macrophages modified to have an anti-inflammatory/pro-resolving phenotype in attenuating early pulmonary inflammation and progression of experimentally induced PH.

Methods

Mouse bone marrow derived macrophages (BMDMs) were polarizedin vitroto a regulatory (M2reg) phenotype. M2regprofile and anti-inflammatory capacity were assessedin vitroupon lipopolysaccharide (LPS)/interferon-γ (IFNγ) restimulation, before their administration to 8- to 12-week-old mice. M2regprotective effect was tested at early (2 to 4 days) and late (4 weeks) time points during hypoxia (8.5% O2) exposure. Levels of inflammatory markers were quantified in alveolar macrophages and whole lung, while PH development was ascertained by right ventricular systolic pressure (RSVP) and right ventricular hypertrophy (RVH) measurements. Bronchoalveolar lavage (BAL) from M2reg-transplanted hypoxic mice was collected, and its inflammatory potential tested on naïve BMDMs.

Results

M2regmacrophages demonstrated a stable anti-inflammatory phenotype upon a subsequent pro-inflammatory stimulus by maintaining the expression of specific anti-inflammatory markers (Tgfß, Il10 and Cd206) and downregulating the induction of proinflammatory cytokines and surface molecules (Cd86, Il6 and Tnfα). A single dose of M2regsattenuated the hypoxic monocytic recruitment and perivascular inflammation. Early hypoxic lung and alveolar macrophage inflammation leading to PH development was significantly reduced and, importantly, M2regsattenuated RVH, RVSP and vascular remodeling at 4 weeks post treatment.

Conclusions

Adoptive transfer of M2regshalts the recruitment of monocytes and modifies the hypoxic lung microenvironment, potentially changing the immunoreactivity of recruited macrophages and restoring normal immune functionality of the lung. These findings provide new mechanistic insights on the diverse role of macrophage phenotype on lung vascular homeostasis that can be explored as novel therapeutic targets.
Prediction of Multiple Individual Primary Cardiovascular Events Using Pooled Cohorts
Authors: Sussman Jeremy B. , Whitney Rachael T. , Burke James F. , Hayward Rodney A. , Galecki Andrzej , Sidney Stephen , Allen Norrina Bai , Gottesman Rebecca F. , Heckbert Susan R. , Longstreth William T. , Psaty Bruce M , Elkind Mitchell S.V. , Levine Deborah A.
Published: August 2023

Introduction

Most current clinical risk prediction scores for cardiovascular disease prevention use a composite outcome. Risk prediction scores for specific cardiovascular events could identify people who are at higher risk for some events than others informing personalized care and trial recruitment. We sought to predict risk for multiple different events, describe how those risks differ, and examine if these differences could improve treatment priorities.

Methods

We used participant-level data from five cohort studies. We included participants between 40 and 79 years old who had no history of myocardial infarction (MI), stroke, or heart failure (HF). We made separate models to predict 10-year rates of first atherosclerotic cardiovascular disease (ASCVD), first fatal or nonfatal MI, first fatal or nonfatal stroke, new-onset HF, fatal ASCVD, fatal MI, fatal stroke, and all-cause mortality using established ASCVD risk factors. To limit overfitting, we used elastic net regularization with alpha = 0.75. We assessed the models for calibration, discrimination, and for correlations between predicted risks for different events. We also estimated the potential impact of varying treatment based on patients who are high risk for some ASCVD events, but not others.

Results

Our study included 24,505 people; 55.6% were women, and 20.7% were non-Hispanic Black. Our models had C-statistics between 0.75 for MI and 0.85 for HF, good calibration, and minimal overfitting. The models were least similar for fatal stroke and all MI (0.58). In 1,840 participants whose risk of MI but not stroke or all-cause mortality was in the top quartile, we estimate one blood pressure-lowering medication would have a 2.4% chance of preventing any ASCVD event per 10 years. A moderate-strength statin would have a 2.1% chance. In 1,039 participants who had top quartile risk of stroke but not MI or mortality, a blood pressure-lowering medication would have a 2.5% chance of preventing an event, but a moderate-strength statin, 1.6%.

Conclusion

We developed risk scores for eight key clinical events and found that cardiovascular risk varies somewhat for different clinical events. Future work could determine if tailoring decisions by risk of separate events can improve care.
Trends in cardiac arrest mortality in the US, 1999-2020
Authors: Gonuguntla Karthik , Chobufo Muchi Ditah , Shaik Ayesha , Patel Neel , Penmetsa Mouna , Thyagaturu Harshith , Taha Amro , Alharbi Anas , Sattar Yasar , Balla Sudarshan
Published: August 2023

Importance

Cardiac arrest affects over 600,000 in the US. Despite large-scale public health and educational initiatives, survival rates are lower in certain racial and socioeconomic groups.

Objective

To examine the trends in annual rates of cardiac arrests mortality among adults stratified by age, race, and gender in the U.S.

Design

A county-level cross-sectional longitudinal study using death data from the Centres for Disease Control and Prevention’s (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database from 1999 to 2020.

Setting

Using the multiple causes of death dataset from the CDC’s WONDER database, cardiac arrests were identified using the International Classification of Diseases (ICD), tenth revision, clinical modification codes.

Participants

Individuals aged 15 years or more whose death was attributed to cardiac arrest.

Exposures

Calendar year.

Main outcomes and measures

National trends in annual mortality from cardiac arrest in select demographic groups and at the state level.

Results

Between 1999 and 2020, the annual cardiac arrest related AAMR (CA-MR) declined through 2019 (132.9 to 89.7 per 100,000 residents, followed by an increase in 2020 (104.5 per 100,000). White patients constituted 82% of all deaths and 51% were female. The overall CA-MR during the study period was 104.48 per 100,000 persons. The CA-MR was higher for men as compared with women (123.5 vs. 89.7 per 100,000) and higher for Black as compared with White adults (154.4 vs. 99.1 per 100,000).

Conclusion and relevance

CA-MR in the overall population has declined, followed by an increase in 2020, which is likely the impact of COVID-19 pandemic. There were also significant racial and sex differences in mortality rates.

Visual Abstract

Visual representation of cardiac arrest-related mortality and the impact of social vulnerability index on mortality rates42

Key Points

Question

What are the temporal trends on cardiac arrest-related deaths in the United States (U.S.)?

Findings

In this national cross-sectional study spanning 22 years, there was an overall declining trend in cardiac arrest mortality across all age groups, gender, race, and regions. However, in 2020 there was an increase in the rates of cardiac arrest mortality, likely due to the COVID-19 pandemic. There was also a state-level variation in cardiac arrest mortality, with certain states showing an increase in mortality rates.

Meaning

There was an overall reduction in the age-adjusted mortality rates due to cardiac arrest. This decrease in mortality rate was consistent across all genders, races, and US regions. There was also significant racial and sex differences in mortality rates.
Probing efficient microbial CO2utilization through metabolic and process modeling
Authors: de Vries Philip J. Gorter , Mol Viviënne , Sonnenschein Nikolaus , Jensen Torbjørn Ølshøj , Nielsen Alex Toftgaard
Published: August 2023

Microbial gas fermentation is proving to be a promising technology to upcycle carbon-rich waste gasses into value-added biochemicals, though production yields of varied products are currently limited. Through the holistic pairing of process modeling with host agnostic black box metabolic modeling, here we investigate an efficient thermophilic CO2upcycling process, based on acetogenic carbon utilization. From a process engineering perspective, higher temperatures were found to favor overall gas transfer rates, even with lower gas solubility, particularly for the more expensive and often limiting H2gas. Metabolically, for growth coupled products, thermophilic production favors higher product yields as a result of a higher maintenance energy input. A process simulation for acetate production in a large-scale bubble column reactor predicts an optimal feed gas composition of approximately 9:1 mol H2to mol CO2and a process with higher production yields and rates at higher temperatures. To assess the expansion of the product portfolio beyond acetate, both a product volatility analysis and a metabolic pathway model were implemented.In-siturecovery of volatile products is shown to be within range for acetone but challenging due to the extensive evaporation of water, while the production of more valuable compounds is energetically unfavorable compared to acetate. We discuss alternative approaches to overcome these challenges to utilize acetogenic CO2fixation for the production of a wider range of carbon negative chemicals.
Activation of cannabinoid CB2 receptors by (−)-cannabichromene but not (+)-cannabichromene
Authors: Udoh Michael , Santiago Marina , Haneef Syed , Rodger Alison , Marlowe Charles K. , Barr Philip J. , Connor Mark
Published: August 2023

Introduction

Cannabichromene (CBC) is a minor constituent of Cannabis that is a selective cannabinoid CB2 receptor agonist and activator of TRPA1. To date, it has not been shown whether (−)-CBC, (+)-CBC (or both) can mediate these effects. In this study we investigate the activity of the CBC enantiomers at CB1, CB2 and TRPA1in vitro.

Materials and Methods

CBC enantiomers were purified from synthetic CBC by chiral chromatography, and their optical activity was confirmed by spectroscopy. Human CB1 and CB2 receptor activity was measured using a fluorescent assay of membrane potential in stably transfected AtT20 cells. TRPA1 activation was measured using a fluorescent assay of intracellular calcium in stably transfected HEK293 cells.

Results

(−)-CBC activated CB2 with an EC50of 1.5 µM, to a maximum of 60 % of CP55940. (+)-CBC did not activate CB2 at concentrations up to 30 µM. Only 30 µM (−)– CBC produced detectable activation of CB1, (+)-CBC was inactive. Both (−)-CBC and (+)– CBC activated TRPA1; at 30 µM (−)-CBC produced an activation 50% of that of the reference agonist cinnamaldehyde (300 µM), 30 µM (+)-CBC activated TRPA1 to 38% of the cinnamaldehyde maximum.

Discussion

It is unclear whether (−)-CBC is the sole or even the predominant enantiomer of CBC enzymatically synthesized inCannabis. This study shows that (−)-CBC is the active isomer at CB2 receptors, while both isomers activate TRPA1. The results suggest that medicinal preparations of CBC that target cannabinoid receptors would be most effective when (−)-CBC is the dominant isomer.
Lysosomal release of amino acids at ER three-way junctions regulates transmembrane and secretory protein mRNA translation
Authors: Choi Heejun , Liao Ya-Cheng , Yoon Young J. , Grimm Jonathan , Lavis Luke D. , Singer Robert H. , Lippincott-Schwartz Jennifer
Published: August 2023

One-third of the mammalian proteome is comprised of transmembrane and secretory proteins that are synthesized on endoplasmic reticulum (ER). Here, we investigate the spatial distribution and regulation of mRNAs encoding these membrane and secretory proteins (termed “secretome” mRNAs) through live cell, single molecule tracking to directly monitor the position and translation states of secretome mRNAs on ER and their relationship to other organelles. Notably, translation of secretome mRNAs occurred preferentially near lysosomes on ER marked by the ER junction-associated protein, Lunapark. Knockdown of Lunapark reduced the extent of secretome mRNA translation without affecting translation of other mRNAs. Less secretome mRNA translation also occurred when lysosome function was perturbed by raising lysosomal pH or inhibiting lysosomal proteases. Secretome mRNA translation near lysosomes was enhanced during amino acid deprivation. Addition of the integrated stress response inhibitor, ISRIB, reversed the translation inhibition seen in Lunapark knockdown cells, implying an eIF2 dependency. Altogether, these findings uncover a novel coordination between ER and lysosomes, in which local release of amino acids and other factors from ER-associated lysosomes patterns and regulates translation of mRNAs encoding secretory and membrane proteins.
Elucidating the activation mechanism for GBP1 oligomerization
Authors: Weismehl Marius , Chu Xiaofeng , Kutsch Miriam , Lauterjung Paul , Herrmann Christian , Kudryashev Misha , Daumke Oliver
Published: August 2023

The dynamin-related human guanylate-binding protein 1 (GBP1) mediates host defense against microbial pathogens. Upon GTP binding and hydrolysis, auto-inhibited GBP1 monomers dimerize and assemble into soluble and membrane-bound oligomers, which are crucial for innate immune responses. How higher-order GBP1 oligomers are built from dimers and how assembly is coordinated with nucleotide-dependent conformational changes has remained elusive. Here, we present cryo-electron microscopy-based structural data of the soluble and membrane-bound GBP1 oligomers demonstrating that GBP1 assembles in an outstretched dimeric conformation. We identify a surface-exposed helix in the large GTPase domain, which contributes to the oligomerization interface, and probe its nucleotide- and dimerization-dependent movements facilitating the formation of an antimicrobial protein coat on a Gram-negative bacterial pathogen. Our results reveal a sophisticated activation mechanism for GBP1 in which nucleotide-dependent structural changes coordinate dimerization, oligomerization, and membrane binding to allow encapsulation of pathogens with an antimicrobial protein coat.
Adaptation of theSpalax galilitranscriptome to life under hypoxia may hold a key to a complex phenotype including longevity and cancer resistance
Authors: Poetzsch G. , Jelacic L. , Bicker A. , Balling M. , Hellmann L. , Dammer L. , Andrade-Navarro M.A. , Shams I. , Avivi A. , Hankeln T.
Published: August 2023

The muroid rodentNannospalax galili(syn.Spalax) is adapted to life in underground burrows and tolerates acute exposure to severe hypoxia. Adaptation to hypoxia is correlated with delayed onset of ageing and resistance against tumour formation.Spalaxbecomes five to seven times older than its relatives, the mouse and rat, without displaying signs of ageing or developing ageing-related disorders like cancer. Investigating and understanding adapted genes and gene regulatory networks ofSpalaxmight pinpoint novel strategies to maintain an extended healthy phenotype in humans. Here we analysed and compared RNA-Seq data of liver, kidney and spleen ofSpalaxand rat subjected to 6% O2or normoxia. We identified differentially expressed genes and pathways common to multiple organs inSpalaxand rat. Body-wide differences betweenSpalaxand rat affected biological processes like cell death, defence against reactive oxygen species (ROS), DNA repair, energy metabolism, immune response and angiogenesis, which altogether might play a crucial role inSpalax’s adaptation to life under oxygen deprivation. In all organs, mRNA expression of genes associated with genome stability maintenance and DNA repair was elevated inSpalaxcompared to rat, accompanied by a lower gene expression of genes associated with aerobic energy metabolism and proinflammatory processes. These transcriptomic changes might be accountable for the extraordinary lifespan ofSpalaxand its cancer resistance. Our results reveal gene regulatory networks that become candidates for the investigation of the molecular bases that underlie the complex phenotype ofSpalax.
Hierarchical Assembly of Single-Stranded RNA
Authors: Pietrek Lisa M. , Stelzl Lukas S. , Hummer Gerhard
Published: August 2023

Single-stranded RNA (ssRNA) plays a major role in the flow of genetic information– most notably in the form of messenger RNA (mRNA)–and in the regulation of biological processes. The highly dynamic nature of chains of unpaired nucleobases challenges structural characterizations of ssRNA by experiments or molecular dynamics (MD) simulations alike. Here we use hierarchical chain growth (HCG) to construct ensembles of ssRNA chains. HCG assembles the structures of protein and nucleic acid chains from fragment libraries created by MD simulations. Applied to homo- and heteropolymeric ssRNAs of different lengths, we find that HCG produces structural ensembles that overall are in good agreement with diverse experiments including nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and single-molecule Förster resonance energy transfer (FRET). The agreement can be further improved by ensemble refinement using Bayesian inference of ensembles (BioEn). HCG can also be used to assemble RNA structures that combine base-paired and unpaired regions, as illustrated for the 51untranslated region (UTR) of SARS-CoV-2 mRNA.
Diagnostic accuracy of MRI compared to CTPA for pulmonary Embolism : A meta analysis
Authors: Desai Dev H. , Shah Abhijay , Shah Hetvi , Naik Aarya A. , Sadat Sharif Mohammed , Raval Dwija
Published: August 2023

Background

This meta-analysis presents a comparison between Computed Tomography Pulmonary Angiography (CTPA) and Magnetic Resonance Angiography (MRA), to diagnose a pulmonary embolism. Computed tomography presents the advantage of imaging the entire thorax, facilitating the diagnosis of conditions that are commonly mistaken for pulmonary embolism, such as pneumonia, aortic dissection, and malignancy. UK and US guidelines have established CT amongst the basic investigations for pulmonary embolism. MRA does not require the use of ionizing radiation or iodinated contrast, thus making it possible for routine use of multiphasic acquisitions as well as for repeated contrast injections

Methodology

For the collection of the data, a search was done by two individuals using PubMed, Google Scholar, and Cochrane Library databases for all relevant literature. Full - Text Articles written only in English were considered. Each qualifying paper was independently evaluated by two reviewers. Each article was analyzed for the number of patients, their age, procedure modality, and incidence of the pre decided complications.

Results

The results also showed a high positive predictive value of 0.947 or 94.7% for MRA in the diagnosis of Pulmonary embolism, as compared with CTPA. Some analyses have marked MRA to have low specificity. These results establish MRA as a respectable alternative for diagnosis of APE, especially in cases when reducing radiation exposure is desired. However, the gold standard of diagnosis remains Computed Tomography Pulmonary Angiography.

Conclusion

As the results show, though MRA has high statistical value for the diagnosis of pulmonary embolism, it also has its drawbacks. MRA cannot be used in severely ill patients as it continues to be challenging, with the longer scan times and multiple breath holds that are required in different MR protocols are difficult to follow in these patients. CTPA remains the gold standard for diagnosis of Pulmonary embolism, with MRA as a secondary test used when CTPA is contraindicated.
Diagnostic performance of urinary 5-Hydroxyindoleacetic Acid in acute appendicitis: a systematic review and diagnostic test accuracy meta-analysis
Authors: Arredondo Montero Javier , Bueso Asfura Oscar Emilio , Pérez Riveros Blanca Paola , Rico Jiménez María
Published: August 2023

Background

This study aimed to analyze the diagnostic performance of urinary 5-Hydroxyindoleacetic Acid (5-HIAA) in acute appendicitis (AA).

Methods

We conducted a systematic review of the literature in the main databases of medical bibliography. Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics, and a random-effect meta-analysis were performed. Additionally, a diagnostic test accuracy meta-analysis (DTA) was performed.

Results

Twelve studies with data from 1467 participants (724 patients with a confirmed diagnosis of AA and 743 controls) were included in this review. The random-effect meta-analysis of urinary 5-HIAA (AA vs controls) included 7 articles (352 AA and 258 controls) and resulted in a significant mean difference [95% CI] of 23.30 [15.82-30.77] μmol/L (p<0.001). The DTA meta-analysis of urinary 5-HIAA included 8 articles and resulted in a pooled sensitivity [95% CI] of 68.6 [44.1-85.9]% and a pooled specificity [95% CI] of 82 [54.7-94.5]%.

Conclusions

Although the evidence is heterogeneous and limited, urinary 5-HIAA emerges as a potential non-invasive diagnostic tool for AA. Urinary 5-HIAA does not seem to be a useful biomarker to distinguish between NCAA and CAA. Future prospective studies with a large sample size and a rigorous design are necessary to validate these findings.
Plant TIR domains physically interact with EDS1 family proteins to propagate immune signalling
Authors: Chen Jian , Zhang Xiaoxiao , Bernoux Maud , Rathjen John P. , Dodds Peter N.
Published: August 2023

Plant Toll/interleukin-1 receptor/resistance protein (TIR) type nucleotide-binding and leucine-rich repeat immune receptors (NLRs) require Enhanced Disease Susceptibility 1 (EDS1) family proteins and the helper NLRs NRG1 and ADR1 for immune activation. TIR signalling domains possess NADase activity, producing NAM and v-cADPR from NAD+in vitro. However, after TIR activation different small non-cyclic signalling molecules have been detected bound to EDS1/SAG101 and EDS1/PAD4 heterodimers. These molecules have not been detected inin vitroassays or as free moleculesin plantaand it is not clear how they are delivered to the EDS1 complexes. Here we investigate physical and functional interactions between TIR signalling domains, EDS1 family proteins and helper NLRs to clarify these signalling transduction pathways. We show that theNbEDS1-NbSAG101b-NbNRG1 signalling pathway inN. benthamianais necessary and sufficient for cell death signalling induced by six different TIR-containing NLRs from a range of plant species, suggesting this module is likely a universal requirement for TIR-NLR mediated cell death inN. benthamiana. We also find that TIR domains physically interact withNbEDS1,NbPAD4 andNbSAG101in planta, independently of each other. We also find evidence for direct interaction ofNbNRG1 withNbSAG101b via its C-terminal EP domain, but not with other EDS1 family members. These data suggest a model in which physical interaction between activated TIRs and EDS1 signalling complexes facilitates efficient transfer of low abundance products of TIR catalytic activity directly to EDS1 heterocomplexes. The interaction could also alter TIR catalytic activity to favor production of the ligands recognised by EDS1/SAG101 and EDS1/PAD4.
Differences Between Human and Non-Human Primate Theory of Mind: Evidence from Computational Modeling
Authors: Horschler Daniel J. , Berke Marlene D. , Santos Laurie R. , Jara-Ettinger Julian
Published: August 2023

Can non-human primates (NHPs) represent other minds? Answering this question has been historically difficult because primates can fail experimental tasks due to a lack of motivation, or succeed through simpler mechanisms. Here we introduce a computational approach for comparative cognition that enables us to quantitatively test the explanatory power of competing accounts. We formalized a collection of theories of NHP social cognition with varying representational complexity and compared them against data from classical NHP studies, focusing on the ability to determine what others know based on what they see. Our results uncovered that, while the most human-like models of NHP social cognition make perfect qualitative predictions, they predict effect sizes that are too strong to be plausible. Instead, theories of intermediate representational complexity best explained the data. At the same time, we show that it is possible for human-like models to capture non-human primate behavior (NHP), as long as we assume that NHPs rely on these representations only about one third of the time. These results show that, in visual perspective taking tasks, NHPs likely draw upon simpler social representations than humans, either in terms of representational complexity, or in terms of use.
Antibiotic potentiation and inhibition of cross-resistance in pathogens associated with cystic fibrosis
Authors: Kadeřábková Nikol , Furniss R. Christopher D. , Maslova Evgenia , Eisaiankhongi Lara , Bernal Patricia , Filloux Alain , Landeta Cristina , Gonzalez Diego , McCarthy Ronan R. , Mavridou Despoina A.I.
Published: August 2023

Critical Gram-negative pathogens, likePseudomonas,StenotrophomonasandBurkholderia, have become resistant to most antibiotics. Complex resistance profiles together with synergistic interactions between these organisms increase the likelihood of treatment failure in distinct infection settings, for example in the lungs of cystic fibrosis patients. Here, we discover that cell envelope protein homeostasis pathways underpin both antibiotic resistance and cross-protection in CF-associated bacteria. We find that inhibition of oxidative protein folding inactivates multiple species-specific resistance proteins. Using this strategy, we sensitize multi-drug resistantPseudomonas aeruginosato β-lactam antibiotics and demonstrate promise of new treatment avenues for the recalcitrant pathogenStenotrophomonas maltophilia. The same approach also inhibits cross-protection between resistantS. maltophiliaand susceptibleP. aeruginosa, allowing eradication of both commonly co-occurring CF-associated organisms. Our results provide the basis for the development of next-generation strategies that target antibiotic resistance, while also impairing specific interbacterial interactions that enhance the severity of polymicrobial infections.
Multifunctionality of V-type ATPase during asexual growth and development ofPlasmodium falciparum
Authors: Shadija Neeta , Dass Swati , Xu Wei , Ke Hangjun
Published: August 2023

V-type ATPases are highly conserved hetero-multi-subunit proton pumping machineries found in all eukaryotic organisms. They use ATP hydrolysis to pump protons, acidifying intracellular or extracellular compartments, and are thus crucial for various biological processes. Despite being evolutionarily conserved in malaria parasites, this proton pump remains understudied. To understand the localization and biological function of V-type ATPase in the deadliest human malaria parasitePlasmodium falciparum, we utilized CRISPR/Cas9 to endogenously tag the subunit A of the V1domain at the C-terminus. V1A (PF3D7_1311900) was tagged with a triple hemagglutinin (3HA) epitope and TetR-DOZI-aptamers for conditional expression under the regulation of anhydrotetracycline. Through immunofluorescence assays, we identified that V-type ATPase was expressed throughout the intraerythrocytic developmental cycle and was mainly localized on the digestive vacuole and plasma membrane. Immuno-electron microscopy further revealed that V-type ATPase was also localized on secretory organelles, such as rhoptries in merozoites. Knockdown of V1A led to cytosolic pH imbalance and blockage of hemoglobin digestion in the digestive vacuole, resulting in an arrest of parasite development in the trophozoite stage and, ultimately, parasite demise. Using BN-PAGE/Western blot, we detected a large molecular weight complex (∼ 1.0 MDa) corresponding to the total molecular weights of V1and Vodomains. The complex was readily disrupted by the V-type ATPase specific inhibitor Bafilomycin A1, but not by low glucose conditions or treatment with chloroquine. Together, our data suggest that V-type ATPase is localized on several subcellular compartments inP. falciparumand plays critical roles to support malaria parasites to grow and replicate inside red blood cells.
Experience-dependent information routing through the basolateral amygdala
Authors: Antonoudiou Pantelis , Stone Bradly , Colmers Phillip L.W. , Evans-Strong Aidan , Walton Najah , Weiss Grant , Maguire Jamie
Published: August 2023

The basolateral amygdala (BLA) is an emotional processing hub and is well-established to influence both positive and negative valence processing. Selective engagement of a heterogeneous cell population in the BLA is thought to contribute to this flexibility in valence processing. However, how this process is impacted by previous experiences which influence valence processing is unknown. Here we demonstrate that previous positive (EE) or negative (chronic unpredictable stress) experiences differentially influence the activity of specific populations of BLA principal neurons projecting to either the nucleus accumbens core or bed nucleus of the stria terminalis. Using chemogenetic manipulation of these projection-specific neurons we can mimic or occlude the effects of chronic unpredictable stress or enriched environment on valence processing to bidirectionally control avoidance behaviors and stress-induced helplessness. These data demonstrate that previous experiences influence the responsiveness of projection-specific BLA principal neurons, biasing information routing through the BLA, to govern valence processing.
Comparative single-nucleus RNA-seq analysis captures shared and distinct responses to beneficial and pathogenic microbes in roots
Authors: Yang Qiuhua , Li Zhuowen , Guan Kaixiang , Liu Zhijian , Huang Ancheng , Zhai Jixian , Long Yanping , Song Yi
Published: August 2023

Distinguishing and differentially responding to beneficial and pathogenic microbes are fundamental for plants to maintain microbiome homeostasis and promoting plant fitness. Using a recently developed protoplast-free single-nucleus RNA-seq approach, we generated single-cellular atlas of root responses to beneficial and pathogenic microbes. Notably, we identified triterpene biosynthesis as a novel cell type specific response to root pathogens and genetically confirmed the role of triterpene biosynthesis in regulating beneficial/pathogenic microbe ratios in a two-strain mixed community. Our results provide novel insights and vital resources for further elucidating novel regulators of beneficial and pathogenic microbe colonization and microbiome homeostasis.
RUNX1 is required in granulocyte–monocyte progenitors to attenuate inflammatory cytokine production by neutrophils
Authors: Zezulin Alexandra U. , Yen Daniel , Ye Darwin , Howell Elizabeth D. , Bresciani Erica , Diemer Jamie , Ren Jian-gang , Ahmad Mohd Hafiz , Castilla Lucio H. , Touw Ivo P. , Minn Andy J. , Tong Wei , Liu P. Paul , Tan Kai , Yu Wenbao , Speck Nancy A.
Published: August 2023

The transcription factor RUNX1 is mutated in familial platelet disorder with associated myeloid malignancy (FPDMM) and in sporadic myelodysplastic syndrome and leukemia. RUNX1 was shown to regulate inflammation in multiple cell types. Here we show that RUNX1 is required in granulocyte–monocyte progenitors (GMPs) to epigenetically repress two inflammatory signaling pathways in neutrophils: Toll-like receptor 4 (TLR4) and type I interferon (IFN) signaling. RUNX1 loss in GMPs augments neutrophils’ inflammatory response to the TLR4 ligand lipopolysaccharide through increased expression of the TLR4 coreceptor CD14. RUNX1 bindsCd14and other genes encoding proteins in the TLR4 and type I IFN signaling pathways whose chromatin accessibility increases when RUNX1 is deleted. Transcription factor footprints for the effectors of type I IFN signaling—the signal transducer and activator of transcription (STAT1::STAT2) and interferon regulatory factors (IRFs)—were enriched in chromatin that gained accessibility in both GMPs and neutrophils when RUNX1 was lost. STAT1::STAT2 and IRF motifs were also enriched in the chromatin of retrotransposons that were derepressed in RUNX1-deficient GMPs and neutrophils. We conclude that a major direct effect of RUNX1 loss in GMPs is the derepression of type I IFN and TLR4 signaling, resulting in a state of fixed maladaptive innate immunity.
Digital marketing adoption by small travel agencies: a comprehensive PLS-SEM model using reflective and higher-order formative constructs
Authors: Sharma Ankita , Sharma Swati
Published: August 2023

Purpose

This study examines the vital factors that influence digital marketing adoption among small travel agencies (brick-and-mortar) and the impact of digital marketing adoption on organizational performance modeled as a formative-formative HOC.

Design/methodology/approach

This empirical study builds on diffusion of innovation (DOI) theory and technology-organization-environment (TOE) framework to identify the factors of digital marketing adoption by small travel agencies. Data were collected from 226 small travel agents in India using purposive and snowball sampling. Partial least square-structural equation modelling (PLS-SEM) is used to analyze the reflectively and formatively measured constructs.

Findings

The findings reveal significant constructs of digital marketing adoption by small travel agencies. The study also establishes the positive impact of digital marketing adoption on organizational performance. Trust partially mediates the impact of technological factors (relative advantage, security concerns) and organizational factor (knowledge) on digital marketing adoption.

Research limitations/implications

The study provides methodological contribution to the literature by applying confirmatory composite analysis (CCA) approach in PLS-SEM. The study contributes to the literature by integrating DOI theory and TOE framework. The study enriches the literature on trust as it recognizes the crucial role of trust as a mediating construct.

Practical implications

The study provides useful implications to marketing practitioners of small travel agencies. The study shows strong predictive capacity and can be generalized throughout diverse samples.

Originality/value

The study adds value to the literature as it explores the digital marketing adoption among the under researched small travel agencies by integrating DOI-TOE theory. The study uniquely proposes and validates organizational performance as a formative-formative higher-order construct.
The role of artificial intelligence in improving the omnichannel customer experience
Authors: Calvo Ana Valeria , Franco Ana Dolores , Frasquet Marta
Published: August 2023

Purpose

This study aims to explore the role that artificial intelligence (AI) systems could play in configuring and enhancing the omnichannel customer experience (OCE).This paper aims to pave the way to better understand the intersection between these two novel topics through perspectives and associated interpretations from managers', consultants' and consumers' beliefs, experiences and thoughts.

Design/methodology/approach

The study adopts an explorative inductive design. Data from 41 in-depth interviews with high-level retail managers (12), AI consultants (3) and omnichannel consumers (26) was analyzed using grounded theory methodology.

Findings

The study's results revealed that, when AI systems are implemented in the omnichannel experience, some dimensions of the OCE change in relevance. The findings show that some OCE dimensions are easier to relate with experiential elements of the omnichannel experience, such as personalization, consistency and flexibility. In contrast, integration and connectivity are perceived as internal retailer capabilities that enable the omnichannel strategy. Consumers' data also show differences in the omnichannel customer journeys for the product categories of clothes, electronics and furniture.

Originality/value

This study presents insights on the impact of AI on OCE from top-retail managers', consultants' and consumers' perspectives. This choice allowed researchers to explore and uncover interesting intersecting points and examine issues related to omnichannel experience and AI systems implementation, providing guidance for future research.
Impact of COVID-19 stress on employee performance and well-being: role of trust in management and psychological capital
Authors: Pradhan Rabindra Kumar , Panda Madhusmita , Hati Lopamudra , Jandu Kailash , Mallick Manolina
Published: August 2023

Purpose

The COVID-19 pandemic presents an unprecedented case of organisation–environment interaction in the occupational settings. Using Palmer and colleagues (2003) model of work stress, this study aims to examine the influence of COVID-19 stress on employee performance and psychological well-being. Furthermore, drawing on conservation of resources theory (Hobfoll, 1989), the role of trust in management and psychological capital as moderators has also been explored.

Design/methodology/approach

Data were collected from the service sector employees (N = 507) using purposive sampling technique.

Findings

Structural equation modelling analysis revealed the negative impact of COVID-19 stress on employee performance and psychological well-being; moderated by trust in management and psychological capital, respectively.

Research limitations/implications

The proposed conceptual model contributes to the stress management literature by providing an understanding of how COVID-19-related stress impacts employee behaviour in organisational context. The present study considers the COVID-19 stress as bio-psycho-socioeconomic challenge that impacts and determines nearly all the activities of the individuals, groups and organisations at a global scale.

Practical implications

The findings of the studies offer several managerial implications pertaining to performance and well-being at workplace especially during such crisis characterised by the elements of uncertainty and ambiguity. Identification of the personal resources would prove beneficial for the management in devising and implementing customised interventions for employees and the organisation. Since the pandemic has impacted each individual differently, human resource managers should remind their employees to be vigilant about self-care and take advantage of their health care benefits, particularly with regards to mental health.

Originality/value

The proposed conceptual model contributes to the workplace stress management literature by providing an understanding of how COVID-19-related stress impacts employee outcomes in the organisational context. Furthermore, identifying personal resources would prove beneficial for the management in devising and implementing customised interventions at the workplace.
Exploring overnight social care for older adults: a scoping review
Authors: Boyle Naomi , Seddon Diane , Toms Gill
Published: August 2023

Purpose

Demand for care at home is growing because of the increase in life expectancy, an ageing population and the chronic conditions that often accompany longevity. Daytime care at home services have been widely reported on, but less is known about overnight care at home. This paper aims to gather evidence about overnight social care for older adults in their homes.

Design/methodology/approach

Recent studies were identified through searches in three electronic databases. Studies published in English between January 2016 and June 2022 exploring overnight care at home for older adults were eligible for inclusion. An additional Google search identified home care services within the UK currently providing overnight support.

Findings

The review retrieved five relevant papers, highlighting the paucity of research in this area. A narrative review of the literature identified common themes that suggested domiciliary night care staff play an integral role in meeting the overnight care and support needs of older adults who wish to be cared for at home. Despite the limited evidence base in this area, the Google search for UK domiciliary services who provide overnight support identified several active programmes.

Originality/value

To the best of our knowledge, this is the first scoping review exploring the provision of overnight social care to older adults in their own homes. The review highlights the need for further research to inform commissioning and practice development.
Permeability evolution in fine‐grained Aji granite during triaxial compression experiments
Authors: Sueyoshi Kazumasa , Katayama Ikuo , Sawayama Kazuki
Published: August 2023

Triaxial compression experiments were carried out on samples of fine‐grained Aji granite to measure the evolution of permeability during deformation prior to failure under confining pressures of 20 and 40 MPa. During the initial stages of deformation, a small decrease in permeability was observed, due to the closure of pre‐existing microcracks; permeability then increased with increasing differential stress. During deformation, permeability varied by up to two orders of magnitude, and we observed a small pressure dependence, with a larger variation observed at 20 MPa than at 40 MPa. This suggests that more cracks developed during brittle deformation under the lower confining pressure. The observed increase in permeability during our experiments was approximately proportional to inelastic volumetric strain, which corresponded to the volume of dilatant cracks. On the other hand, prior to brittle failure, we observed a further increase in permeability that was greater than the inelastic volumetric strain, suggesting crack aperture opening accelerated at this stress level (>∼80%). The permeability enhancement resulting from the crack dilation affects the gas‐sealing capacity of the fluid‐saturated caprock. Our experimental findings would be beneficial for the safety assessment in applications such as the long‐term storage of various gaseous wastes.