bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower probability and shorter duration of infections after Covid-19 vaccine correlate with anti-SARS-CoV-2 circulating IgGs
Authors: Ronchini Chiara , Gandini Sara , Pasqualato Sebastiano , Mazzarella Luca , Facciotti Federica , Mapelli Marina ,   IEO Covid Team, Frige’ Gianmaria , Passerini Rita , Pase Luca , Capizzi Silvio , Mastrilli Fabrizio , Orecchia Roberto , Natoli Gioacchino , Pelicci Pier Giuseppe
Published: September 2021

The correlation between immune responses and protection from SARS-CoV-2 infections and its duration remains unclear. We performed a sanitary surveillance at the European Institute of Oncology (IEO) in Milan over a 17 months period. Pre-vaccination, in 1,493 participants, we scored 266 infections (17.8%) and 8 possible reinfections (3%). Post-vaccination, we identified 30 infections in 2,029 vaccinated individuals (1.5%). We report that the probability of infection post-vaccination is i) significantly lower compared to natural infection, ii) associated with a significantly shorter median duration of infection than that of first infection and reinfection, iii) anticorrelated with circulating antibody levels.
A novel echo-parameter supersedes the Society of Thoracic Surgeons risk score in predicting post transcatheter aortic valve replacement mortality
Authors: Chao Chieh-Ju , Agasthi Pradyumma , Seri Amith R , Barry Timothy , Shanbhag Anusha , Wang Yuxiang , Eleid Mackram , Fortuin David , Sweeney John P. , Pollak Peter , El Sabbagh Abdallah , Lester Steven J. , Freeman William K , Naqvi Tasneem Z. , Holmes David R , Appleton Christopher P. , Arsanjani Reza
Published: September 2021

Objective

To accurately predict post-TAVR mortality, we proposed a family of new echo-parameters (augmented blood pressure) derived from blood pressure and aortic valve gradient measurements and examined them in this study.

Patients and Methods

Patients in the Mayo Clinic National Cardiovascular Diseases Registry-TAVR database who underwent TAVR between January 1, 2012, and June 30, 2017, were identified to retrieve baseline demographics, echocardiographic and mortality data. Augmented blood pressure parameters and valvulo-arterial impedance were evaluated by univariate and multivariate Cox regression. Receiver operating characteristic curve analysis was used to assess the model performance against the Society of Thoracic Surgeons (STS) risk score.

Results

The final cohort contained 974 patients with a mean age of 81.4±8.3 years old, and 56.6% were male. The mean STS risk score was 8.2±5.2. The median follow-up duration was 354 days, and the one-year all-cause mortality rate was 14.2%. Both univariate and multivariate Cox regression showed that augmented systolic blood pressure and augmented mean arterial pressure (AugMAP) parameters were independent predictors for 1-year post-TAVR mortality (all p<0.0001). A univariate model of AugMAP1 supersedes the STS score model in predicting 1-year post-TAVR mortality (area under curve: 0.700 vs. 0.587, p=0.0051).

Conclusion

Augmented mean arterial pressure provides a simple but effective approach for clinicians to quickly estimate the clinical outcome of TAVR patients. It can be incorporated in the assessment of TAVR candidacy.
Oral Pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations
Authors: Murchu Eamon O , Marshall Liam , Hayes Catherine , Harrington Patricia , Moran Patrick , Teljeur Conor , Ryan Máirín
Published: September 2021

Background

The objective of this study was to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral Pre-Exposure Prophylaxis (PrEP) to prevent HIV.

Methods

Databases (PubMed, Embase and the Cochrane Register of Controlled Trials) were searched up to 5/7/2020. RCTs were included that compared oral tenofovir-containing PrEP to placebo, no treatment or alternative medication/dosing schedule. The primary outcome was the rate ratio (RR) of HIV infection using a modified intention-to-treat analysis. All analyses were stratified a priori by population: men who have sex with men (MSM), serodiscordant couples, heterosexuals and people who inject drugs (PWID).

The quality of individual studies was assessed using the Cochrane Risk-of-Bias tool and the certainty of evidence was assessed using GRADE.

Results

Of 2,803 unique records, 15 RCTs met our inclusion criteria. Over 25,000 participants were included, encompassing 38,289 person-years of follow-up data.

PrEP was found to be effective in MSM (Rate Ratio [RR] 0.25, 95% CI: 0.1-0.61; Absolute Rate Difference [ARD] -0.03, 95% CI: -0.01 to -0.05), serodiscordant couples (RR 0.25, 95% CI: 0.14-0.46; ARD -0.01, 95% CI: -0.01 to -0.02) and PWID (RR 0.51, 95% CI: 0.29-0.92; ARD - 0.00, 95% CI: -0.00 to -0.01), but not in heterosexuals (RR 0.77, 95% CI: 0.46-1.29).

Efficacy was strongly associated with adherence (p<0.01). PrEP was found to be safe, however unrecognised HIV at enrolment increased the risk of viral drug mutations. Evidence for risk compensation or an increase in STIs was not found.

Discussion

PrEP is safe and effective in MSM, serodiscordant couples and PWID. Additional research is needed prior to recommending PrEP in heterosexuals. Data were limited by poor adherence in several studies. No RCTs were identified for other high-risk groups, such as trangender women and sex workers.

PROSPERO ID

CRD42017065937

Article Summary

Strengths and limitations of this study

A systematic review and meta-analysis of RCTs was conducted of the efficacy and safety of oral PrEP to prevent HIV following best practice guidelines (PRISMA guidelines and GRADE framework)

Observational studies were excluded from this review, and as such, PrEP effectiveness may be lower in real-world settings

Change in sexual behaviour, or ‘risk compensation’, is difficult to ascertain based on RCT evidence alone

Due to substantial variation in adherence across studies, findings should be interpreted with caution.
A Novel Penalized Inverse-Variance Weighted Estimator for Mendelian Randomization with Applications to COVID-19 Outcomes
Authors: Xu Siqi , Wang Peng , Fung Wing Kam , Liu Zhonghua
Published: September 2021

Summary

Mendelian randomization (MR) utilizes genetic variants as instrumental variables (IVs) to estimate the causal effect of an exposure variable on an outcome of interest even in the presence of unmeasured confounders. However, the popular inverse-variance weighted (IVW) estimator could be biased in the presence of weak IVs, a common challenge in MR studies. In this article, we develop a novel penalized inverse-variance weighted (pIVW) estimator, which adjusts the original IVW estimator to account for the weak IV issue by using a penalization approach to prevent the denominator of the pIVW estimator from being close to zero. Moreover, we adjust the variance estimation of the pIVW estimator to account for the presence of balanced horizontal pleiotropy. We show that the recently proposed debiased IVW (dIVW) estimator is a special case of our proposed pIVW estimator. We further prove that the pIVW estimator has smaller bias and variance than the dIVW estimator under some regularity conditions. We also conduct extensive simulation studies to demonstrate the performance of the proposed pIVW estimator. Furthermore, we apply the pIVW estimator to estimate the causal effects of five obesity-related exposures on three coronavirus disease 2019 (COVID-19) outcomes. Notably, we find that hypertensive disease is associated with an increased risk of hospitalized COVID-19; and peripheral vascular disease and higher body mass index are associated with increased risks of COVID-19 infection, hospitalized COVID-19 and critically ill COVID-19.
Distinct brainstem to spinal cord noradrenergic pathways differentially regulate spinal neuronal activity
Authors: Kucharczyk Mateusz Wojciech , Di Domenico Francesca , Bannister Kirsty
Published: September 2021

Brainstem to spinal cord pathways modulate spinal neuronal activity. We implemented locus coeruleus (LC) targeting strategies by microinjecting CAV-PRS-ChR2 virus in the spinal cord (LC:SC module) or LC (LC:LC module). While activation of both modules inhibited evoked spinal neuronal firing via α1-adrenoceptor-mediated actions, LC:SC opto-activation abolished diffuse noxious inhibitory controls. The LC as a pain generator is likely mechanistically underpinned by maladaptive communication with discrete descending modulatory pathways.
Electrodeformation of White Blood Cells Enriched with Gold Nanoparticles
Authors: Hallfors N. G. , Teo J. M. , Bertone P. , Joshi C. , Orozaliev A. , Martin M. N. , Isakovic A. F.
Published: September 2021

The elasticity of white blood cells (WBCs) provides valuable insight into the condition of the cells themselves, the presence of some diseases, as well as immune system activity. In this work, we describe a novel process of refined control of WBCs’ elasticity through a combined use of gold nanoparticles (AuNPs) and the microelectrode array device. The capture and controlled deformation of gold nanoparticles enriched white blood cells in vitro are demonstrated and quantified. Gold nanoparticles enhance the effect of electrically induced deformation and make the DEP related processes more controllable.
Computing personalized brain functional networks from fMRI using self-supervised deep learning
Authors: Li Hongming , Dhivya Srinivasan , Cui Zaixu , Zhuo Chuanjun , Gur Raquel E. , Gur Ruben C. , Oathes Desmond J. , Davatzikos Christos , Satterthwaite Theodore D. , Fan Yong
Published: September 2021

A novel self-supervised deep learning (DL) method is developed for computing bias-free, personalized brain functional networks (FNs) that provide unique opportunities to better understand brain function, behavior, and disease. Specifically, convolutional neural networks with an encoder-decoder architecture are employed to compute personalized FNs from resting-state fMRI data without utilizing any external supervision by optimizing functional homogeneity of personalized FNs in a self-supervised setting. We demonstrate that a DL model trained on fMRI scans from the Human Connectome Project can identify canonical FNs and generalizes well across four different datasets. We further demonstrate that the identified personalized FNs are informative for predicting individual differences in behavior, brain development, and schizophrenia status. Taken together, self-supervised DL allows for rapid, generalizable computation of personalized FNs.
Effect of different disease-modifying therapies on humoral response to BNT162b2 vaccine in Sardinian multiple sclerosis patients
Authors: Pitzalis Maristella , Idda Maria Laura , Lodde Valeria , Loizedda Annalisa , Lobina Monia , Zoledzwieska Magdalena , Virdis Francesca , Delogu Giuseppe , Pirinu Federica , Marini Maria Giuseppina , Mingoia Maura , Frau Jessica , Lorefice Lorena , Fronza Maria , Carmagini Daniele , Carta Elisa , Orrù Valeria , Uzzau Sergio , Solla Paolo , Loi Federica , Devoto Marcella , Steri Maristella , Fiorillo Edoardo , Floris Matteo , Zarbo Ignazio Roberto , Cocco Eleonora , Cucca Francesco
Published: September 2021

Objectives

Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients.

Methods

We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine.

Results

MS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male, sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients.

Conclusion

Humoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.
Descriptive characteristics of continuous oximetry measurement in moderate to severe COVID-19 patients
Authors: Sobel Jonathan A. , Levy Jeremy , Almog Ronit , Reiner-Benaim Anat , Miller Asaf , Eytan Danny , Behar Joachim A.
Published: September 2021

Non-invasive oxygen saturation (SpO2) is a central vital sign that supports the management of COVID-19 patients. However, reports on SpO2 characteristics are scarce and none has analysed high resolution continuous SpO2 in COVID-19. We provide the first analysis of high resolution SpO2 across the spectrum of COVID-19 disease severity and respiratory support. A total of 367 COVID-19 patients’ recordings, comprising 27K hours of continuous SpO2 data, could be retrieved from patients hospitalized at the Rambam Health Care Campus. Using oximetry digital biomarkers (OBM), we quantified SpO2 characteristics and showed that the percentage of time under 93% oxygen saturation threshold is the best single OBM discriminating between critical and non-critical patients. OBMs traditionally used in the field of sleep medicine research, were informative for assessing the patient’s response to respiratory support. In addition, periodicity and hypoxic burden biomarkers were affected up to several hours before the initiation of the mechanical ventilation. Characteristics from high resolution SpO2 signal may enable to anticipate clinically relevant events, monitoring of treatment response and may be indicative of future deterioration.x
Metacommunity framework and its core terms entanglement
Authors: Kolasa Jurek , Hammond Matthew P. , Yan Joyce
Published: September 2021

The metacommunity framework links space and ecological processes but is vulnerable to complex entanglement among its integral components. Most ecological processes are context-dependent. However, when ecological theories show it, they may be seriously crippled unless they explicitly tackle it. Otherwise, findings emerging from accumulated cases will be of limited value and likely remain ambiguous or misleading. Specifically, interactions among the core terms of metacommunity theory interact in complex ways that we identify as entanglement. We employ four core dimensions to alleviate this issue and create a space where various studies converse and effectively complement each other irrespective of the case specifics. The dimensions encompass the metacommunity empirical domain: (1) inter-habitat differences, (2) species habitat specialization, (3) effective dispersal, and (4) species interactions (negative to positive). Then, we assess the entanglement effects by testing that (a)changing values in one dimension, with others constant, alters study conclusions, and (b)these effects increase and dominate when integral dimensions interact reciprocally. As a metric, we analyzed species diversity in a stochastic, agent-based, unified metacommunity model, UMM, where species move, select habitats, reproduce, and interact. In the simulations, each dimension has four or five levels spanning a broad spectrum of conditions. The exercise strongly supports both hypotheses. It also suggests that positive interactions, in contrast to the popular emphasis, promote biodiversity more than negative ones like competition or predation. The proposed integrated conceptual system can expand to include meta-ecosystems, habitat gradients, and other processes. Thus, it can offer a unified approach to spatial processes in ecology. Finally, by combining the four dimensions into one interactive system, we identify a rich array of lower-level hypotheses that inevitably emerge from this system. The hypotheses’ shared origin anchors individual studies in coherent structure to advance sound generalizations.
Backward masking in mice requires visual cortex
Authors: Gale Samuel D , Strawder Chelsea , Bennett Corbett , Mihalas Stefan , Koch Christof , Olsen Shawn R
Published: September 2021

Visual masking is used to infer the timescale of conscious perception in humans; yet the underlying circuit mechanisms are not understood. Here we describe a two-alternative choice backward masking task in mice and humans, in which the location of a briefly presented grating is effectively masked within a 50 ms window after stimulus onset. Importantly, human subjects reported reduced perceptual visibility during masking that closely corresponded with behavior deficits. In mice, optogenetic silencing of visual cortex reduces performance over a similar time course as masking. However, response rates and accuracy do not match masking, demonstrating that cortical silencing and masking are distinct phenomena. Spiking responses recorded in primary visual cortex (V1) are consistent with masked behavior when quantified over long, but not short, time windows, indicating masking involves further downstream processing. Behavioral performance can be quantitatively recapitulated by a dual accumulator model constrained by V1 activity. The model and the animal’s performance for the earliest decisions imply that the initial spike arriving from the periphery can trigger a correct response, but subsequent V1 spikes, evoked by the mask, degrade performance for longer decisions. To test the necessity of visual cortex for backward masking, we optogenetically silenced mask-evoked cortical activity which fully restored discrimination of target location. Together, these results demonstrate that mice, like humans, are susceptible to backward visual masking and that visual cortex has a crucial role in this process.
Innate immune signaling drives late cardiac toxicity following DNA damaging cancer therapies
Authors: Shamseddine Achraf , Patel Suchit H. , Chavez Valery , Adnan Mutayyaba , Bona Melody Di , Li Jun , Dang Chau T. , Ramanathan Lakshmi V. , Oeffinger Kevin C. , Liu Jennifer E. , Steingart Richard M. , Piersigilli Alessandra , Socci Nicholas D. , Chan Angel T. , Yu Anthony F. , Bakhoum Samuel F. , Schmitt Adam M.
Published: September 2021

Late cardiac toxicity is a potentially lethal complication of cancer therapy, yet the pathogenic mechanism remains largely unknown, and few treatment options exist. Here we report DNA damaging agents such as radiation and anthracycline chemotherapies induce delayed cardiac inflammation following therapy due to activation of cGAS and STING-dependent type I interferon signaling. Genetic ablation of cGAS-STING-signaling in mice inhibits DNA damage induced cardiac inflammation, rescues late cardiac functional decline, and prevents death from cardiac events. Treatment with a STING antagonist suppresses cardiac interferon signaling following DNA damaging therapies and effectively mitigates cardiotoxicity. These results identify a therapeutically targetable, pathogenic mechanism for one of the most vexing treatment-related toxicities in cancer survivors.
A structural biology community assessment of AlphaFold 2 applications
Authors: Akdel Mehmet , Pires Douglas E V , Porta Pardo Eduard , Jänes Jürgen , Zalevsky Arthur O , Mészáros Bálint , Bryant Patrick , Good Lydia L. , Laskowski Roman A , Pozzati Gabriele , Shenoy Aditi , Zhu Wensi , Kundrotas Petras , Ruiz Serra Victoria , Rodrigues Carlos H M , Dunham Alistair S , Burke David , Borkakoti Neera , Velankar Sameer , Frost Adam , Lindorff-Larsen Kresten , Valencia Alfonso , Ovchinnikov Sergey , Durairaj Janani , Ascher David B , Thornton Janet M , Davey Norman E , Stein Amelie , Elofsson Arne , Croll Tristan I , Beltrao Pedro
Published: September 2021

Most proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods have led to protein structure predictions that have reached the accuracy of experimentally determined models. While this has been independently verified, the implementation of these methods across structural biology applications remains to be tested. Here, we evaluate the use of AlphaFold 2 (AF2) predictions in the study of characteristic structural elements; the impact of missense variants; function and ligand binding site predictions; modelling of interactions; and modelling of experimental structural data. For 11 proteomes, an average of 25% additional residues can be confidently modelled when compared to homology modelling, identifying structural features rarely seen in the PDB. AF2-based predictions of protein disorder and protein complexes surpass state-of-the-art tools and AF2 models can be used across diverse applications equally well compared to experimentally determined structures, when the confidence metrics are critically considered. In summary, we find that these advances are likely to have a transformative impact in structural biology and broader life science research.
The Impact of Body Mass Index on Physical Activity and Cardiac Workload
Authors: Bloom Myra Jane , Brown Lakin Mckenzie , Jost Scarlet Rae , Lang Andrew Stuart Ian Donald , Mankin Nancy Viola , Mast Zachary William , McMahan Ericka Rachel , Merheb Jonathan Abdou , Nelson Philip Paul , Nnaji Joshua Chinweoke , Valderrama Enrique Francisco
Published: September 2021

Background

Having an abnormal body mass index (BMI) adversely affects cardiac workload and level of physical activity.

Objective

To examine the relationship between cardiac workload, physical activity, Sex, and BMI.

Methods

The number of steps taken per day (Steps) and minutes per week spent in targeted heart rate zones were collected from primarily first and second year university students (n = 1,801; 62% female) over a standard, 15-week long semester. Other data collected included BMI, Sex, Age, and Class Standing. Sex differences in BMI, Steps, and training heart rate zone (heart rates above 50% of max) minutes (THR) were evaluated, correlations between the study parameters were analyzed, and one-way ANOVA was used to test between competing models. The values p < .05 were considered statistically significant.

Results

Statistically significant (p < .05) differences between males and females were found for Steps, THR, and BMI. Males were more physically active but spent 18% less time with heart rates above 50% of max. Students who had abnormal BMI values, both low and high, experienced greater cardiac workload (p < .05), even though they were found to be less physically active (p < .05).

Conclusion

Our study revealed that university students with abnormal BMI values experienced greater cardiac workload, even though they are less physically active. Thus, physical fitness and healthy lifestyle interventions should also include underweight students in addition to students who are overweight or obese.
Using causality and correlation analysis to decipher microbial interactions in activated sludge
Authors: Cai Weiwei , Han Xiangyu , Yao Hong
Published: September 2021

Network theory is widely used to understand microbial interactions in activated sludge and numerous other artificial and natural environments. However, when using correlation-based methods, it is not possible to identify the directionality of interactions within microbiota. Based on the classic Granger test of sequencing-based time-series data, a new Microbial Causal Correlation Network (MCCN) was constructed with distributed ecological interaction on the directed, associated links. As a result of applying MCCN to a time series of activated sludge data, we found that the hub species OTU56, classified as belonging the genus Nitrospira, was responsible for completing nitrification in activated sludge, and mainly interacted with Proteobacteria and Bacteroidetes in the form of amensal and commensal relationships, respectively. Phylogenetic tree suggested a mutualistic relationship between Nitrospira and denitrifiers. Zoogloea displayed the highest ncf value within the classified OTUs of the MCCN, indicating that it could be a foundation for activated sludge through forming the characteristic cell aggregate matrices into which other organisms embed during floc formation. Overall, the introduction of causality analysis greatly expands the ability of a network to shed a light on understanding the interactions between members of a microbial community.
The longevity response to warm temperature is neurally controlled via the regulation of collagen genes
Authors: Palani Sankara Naynar , Sellegounder Durai , Liu Yiyong
Published: September 2021

Studies in diverse species have associated higher temperatures with shorter lifespan and lower temperatures with longer lifespan. However, the mechanisms behind these inverse effects of temperature on longevity are not well understood. Here, we demonstrate that in Caenorhabditis elegans, functional loss of NPR-8, a G protein-coupled receptor related to mammalian neuropeptide Y receptors, increases worm lifespan at 25°C but not at 20°C or 15°C, and that the lifespan increase at 25°C is regulated by the NPR-8-expressing AWB and AWC chemosensory neurons as well as AFD thermosensory neurons. RNA sequencing revealed that both warm temperature and old age profoundly alter gene expression. Further investigation uncovered that the NPR-8-dependent longevity response to warm temperature is achieved by regulating the expression of a subset of collagen genes. As elevated collagen expression is a common feature of many lifespan-extending interventions and enhanced stress resistance, collagen expression could be critical for healthy aging.
Tuft cell-produced cysteinyl leukotrienes and IL-25 synergistically initiate lung type 2 inflammation
Authors: Ualiyeva Saltanat , Lemire Evan , Aviles Evelyn C. , Boyd Amelia A. , Wong Caitlin , Lai Juying , Liu Tao , Matsumoto Ichiro , Barrett Nora A. , Boyce Joshua A. , Haber Adam L. , Bankova Lora G.
Published: September 2021

Aeroallergen sensing by airway epithelial cells can trigger pathogenic immune responses leading to chronic type 2 inflammation, the hallmark of airway diseases such as asthma. Airway tuft cells are specialized chemosensory epithelial cells and the dominant source of the epithelial cytokine IL-25 in the trachea and of cysteinyl leukotrienes (CysLTs) in the naïve murine nasal mucosa. The interaction of IL-25 and CysLTs and the contribution of tuft cell-derived CysLTs to the development of allergen-triggered inflammation in the airways has not been clarified. Here we show that inhalation of LTC4 in combination with a subthreshold dose of IL-25 leads to dramatic synergistic induction of type 2 inflammation throughout the lungs, causing rapid eosinophilia, dendritic cell (DC) and inflammatory type 2 innate lymphoid cell (ILC2) expansion, and goblet cell metaplasia. While lung eosinophilia is dominantly mediated through the classical CysLT receptor CysLT1R, type 2 cytokines and activation of innate immune cells require signaling through both CysLT1R and CysLT2R. Tuft cell-specific deletion of the terminal enzyme requisite for CysLT production, Ltc4s, was sufficient to reduce both the innate immune response in the lung – eosinophilia, KLRG1+ ILC2 activation and DC recruitment – and the systemic immune response in the draining lymph nodes after inhalation of the mold aeroallergen Alternaria. Our findings identify surprisingly potent synergy of CysLTs and IL-25 downstream of aeroallergen-trigged activation of airway tuft cells leading to a highly polarized type 2 immune response and further implicate airway tuft cells as powerful modulators of type 2 immunity in the lungs.

One Sentence Summary

Tuft cells produce two highly synergistic mediators: LTC4 and IL-25 to cooperatively induce allergen-driven airway inflammation.
Remotely-sensed slowing down in spatially patterned dryland ecosystems
Authors: Veldhuis Michiel P. , Martinez-Garcia Ricardo , Deblauwe Vincent , Dakos Vasilis
Published: September 2021

Regular vegetation patterns have been predicted to indicate a system slowing down and possibly desertification of drylands. However, these predictions have not yet been observed in dryland vegetation due to the inherent logistic difficulty to gather longer-term in situ data. Here, we use recently developed methods using remote-sensing EVI time-series in combination with classified regular vegetation patterns along a rainfall gradient in Sudan to test these predictions. Overall, three temporal indicators (responsiveness, temporal autocorrelation, variance) show slowing down as vegetation patterns change from gaps to labyrinths to spots towards more arid conditions, confirming predictions. However, this transition exhibits non-linearities, specifically when patterns change configuration. Model simulations reveal that the transition between patterns temporarily slows down the system affecting the temporal indicators. These transient states when vegetation patterns reorganize thus affect the systems resilience indicators in a non-linear way. Our findings suggest that spatial self-organization of dryland vegetation is associated with critical slowing down, but this transition towards reduced resilience happens in a non-linear way. Future work should aim to better understand transient dynamics in regular vegetation patterns in dryland ecosystems, because long transients make regular vegetation patterns of limited use for management in anticipating critical transitions.
Drought Stress Induces Morpho-physiological and Proteome Changes ofPandanus amaryllifolius
Authors: Mohd Amnan Muhammad Asyraf , Aizat Wan Mohd , Khaidizar Fiqri Dizar , Tan Boon Chin
Published: September 2021

Drought is one of the significant threats to the agricultural sector. However, there is limited knowledge on the plant response to drought stress and post-drought recovery.Pandanus amaryllifolius, a moderate drought-tolerant plant, is well known for its ability to survive in low-level soil moisture conditions. Understanding the molecular regulation of drought stress signaling in this plant could help guide the rational design of crop plants to counter this environmental challenge. This study aimed to determine the morpho-physiological, biochemical and protein changes ofP. amaryllifoliusin response to drought stress and during recovery. Drought significantly reduced leaf relative water content ofP. amaryllifolius. In contrast, relative electrolyte leakage, proline and malondialdehyde contents, and the activities of antioxidant enzymes in the drought-treated and recovered samples were relatively higher than the well-watered sample. The protein changes between drought-stressed, well-watered, and recovered plants were evaluated using tandem mass tags (TMT)-based quantitative proteomics. Of the 1,415 differentially abundant proteins, 74 were significantly altered. The majority of proteins differing between them were related to carbon metabolism, photosynthesis, stress response, and antioxidant activity. This is the first study that reports the protein changes in response to drought stress inPandanus. The data generated provide an insight into the drought-responsive mechanisms inP. amaryllifolius.
Inhibition of Kallikrein-related peptidases 7 restrains pancreatic tumor growth through induction of ferroptosis
Authors: Wang Yueqing , Xiang Fengyi , Deng Hao , Leng Shuang , Zhao Dengze , Chen Yue , Xie Donghui , Li Qingyun , Cao Chunyu , Zheng Weihong , Liu Wei , Liu Xiaowen , Zheng Jun , Tan Xiao
Published: September 2021

Pancreatic cancer is one of the most aggressive and lethal malignancies with extremely poor prognosis, and KLK7 was considered as a potential therapeutic target. In this study, we analyzed the expression of KLK7 in TCGA and GTEx databases and found that KLK7 had a negative correlation to long-term survival rate (>1.5 years) of pancreatic cancer patients. Compound 42 is a coumarinic derivative, a suicide substrate inhibitor of KLK7, which has been proved to inhibit the proliferation of PANC-1 cells in vitro effectively in our previous study. In this study, we further investigated the inhibition ability of Compound 42 in tumor formation and development in CDX and PDX tumor models of pancreatic cancer subsequently. Besides, we studied the inhibitory mechanism of Compound 42 and the result showed that Compound 42 arrested the pancreatic cancer cell cycle in G0/G1 phase and induced ferroptosis through down-regulation of GPX4 protein level and accumulation of iron ion. Thus, these experiments demonstrate that Compound 42, suppressing pancreatic cancer in vivo, is expected to become a novel drug for pancreatic cancer treatment.
Prospective isolation of mouse and human hematopoietic stem cells using Plexin domain containing 2
Authors: Tanaka Yosuke , Kubota Yasushi , Lieberam Ivo , Barlow Jillian L. , Bramley Josh W. , Sakuma Chiaki , Shibata Takashi , Nakagawa Masataka , Kurosawa Yasunori , Maruyama Toshiaki , Okumura C.J. , Akuta Teruo , Kent David G. , Jessell Thomas M , Goyama Susumu , Kimura Shinya , Kitamura Toshio
Published: September 2021

Numerous strategies exist to isolate hematopoietic stem cells (HSCs) using complex combinations of markers and flow cytometry. However, robust identification of HSCs using imaging techniques is substantially more challenging which has prompted the recent development of HSC reporter mice. To date, none of the molecules used in these reporters have been useful for human HSC identification. Here we report that PLXDC2 is a useful marker for both mouse and human HSCs. Using a green fluorescent protein (GFP) knock-in at the Plxdc2 locus in mice (hereafter denoted as Plxdc2-GFP), we showed that Plxdc2-GFP is highly expressed in HSCs with 1 in 2.8 Plxdc2-GFP+CD150+ cells giving long-term multi-lineage reconstitution in transplantation. Moreover, we developed a novel human PLXDC2 antibody and showed that human PLXDC2+ HSCs have stronger long-term multilineage reconstitution ability compared with PLXDC2- HSCs in a xenograft model. Thus, our study identifies PLXDC2 as a highly relevant molecule in HSC identification, potentially allowing greater purity and live in vivo tracking of these cells.

To date, few molecules are available for isolation of HSCs across species. The present study shows that PLXDC2 is a highly useful molecule for isolation of HSCs, which works across mouse and human.
GABAB receptor/HCN channel complexes in VTA dopamine neurons limit synaptic inhibition and prevent anxiety-like behavior
Authors: Pérez-Garci Enrique , Rizzi Giorgio , Fritzius Thorsten , Porcu Alessandra , Besseyrias Valerie , Gassmann Martin , Tan Kelly R. , Bettler Bernhard
Published: September 2021

Aversive stimuli inhibiting dopamine neurons in the ventral tegmental area (DAVTA neurons) induce anxiety-like behaviors. The inhibition of DAVTA neurons is prolonged by GABAB receptor (GBR)-activated K+-currents, which exhibit a rapid desensitization of unknown physiological relevance. We now report that GBRs associate via auxiliary KCTD16 subunits with HCN channels, which facilitates activation of hyperpolarization- activated currents (Ih) by GBR-activated K+ currents. Activation of Ih underlies rapid K+ current desensitization in DAVTA neurons and limits GBR-mediated inhibition. Disruption of the GBR/HCN complex in KCTD16-/- mice or blockade of Ih prolongs optogenetically driven inhibition of DAVTA neuron firing. KCTD16-/- mice exhibit an increased anxiety-like behavior in response to stressful stimuli, which is reproduced by in vivo CRISPR/Cas9-mediated KCTD16 ablation in DAVTA neurons or intra-VTA infusion of HCN antagonist to wild-type mice. Our data reveal that GBR-induced Ih protect DAVTA neurons from prolonged GBR- mediated inhibition in response to stressors, which moderates anxiety-like behaviors.
Effects of temperature on acceleration and simulation of indoor corrosion test of Q235 carbon steel
Authors: Huang Changxu , Su Xuhong , Song Qingqing , Wang Xudong
Published: September 2021

Purpose

The purpose of this paper is to study the influence of temperature on the acceleration and simulation of indoor corrosion tests and the corrosion behavior of Q235 carbon steel.

Design/methodology/approach

The indoor corrosion test was carried out by continuous salt spray in a salt spray chamber. Weight loss analysis, X-ray diffraction, cannon 1500 D, scanning electron microscopy and electrochemical techniques are used to analyze the results.

Findings

It was found that thickness loss of Q235 carbon steel increases with higher temperature and it can reach 0.095 mm at 50°C. Compared with the Xisha exposure test, the acceleration rate can achieve 230 times. This phenomenon indicates that decreasing the experimental temperature is beneficial to the anti-corrosion of the Q235 carbon steel. It is fascinating to find that acceleration and simulation increase with temperature simultaneously, which shows that β-FeOOH promotes the corrosion rate and α-FeOOH provides high simulation. Meanwhile, electrochemical impedance spectroscopy indicates that the resistance of the rust layer improves with temperature.

Practical implications

Through the study, the authors found that with the increase of temperature, the acceleration and simulation of indoor corrosion test improved, corrosion products and kinetics are the same as those in outdoor exposure test, and which means that the laboratory can achieve the long-term corrosion degree of outdoor exposure in a short time, and the similarity with outdoor exposure is high. This helps to the study of marine atmospheric corrosion, and indoor accelerated corrosion tests can largely eliminate regional differences by adjusting some environmental factors, and lay a foundation for marine atmospheric corrosion.

Originality/value

The effects of temperature on the acceleration and simulation of indoor corrosion tests are discussed. Through laboratory experiments, the long-term service life of Q235 carbon in the Xisha marine atmosphere can be predicted effectively.
The public-private partnership valuation paradox
Authors: Gray Stephen , Hall Jason , Pollard Grant , Cannavan Damien
Published: September 2021

Purpose

In the context of public-private partnerships (PPPs), it has been argued that the standard valuation framework produces a paradox whereby government appears to be made better off by taking on more systematic risk. This has led to a range of approaches being applied in practice, none of which are consistent with the standard valuation approach. The purpose of this paper is to demonstrate that these approaches are flawed and unnecessary.

Design/methodology/approach

The authors step through the proposed alternative valuation approaches and demonstrate their inconsistencies and illogical outcomes, using theory, logic and mathematical proof.

Findings

In this paper, the authors demonstrate that the proposed (alternative) approaches suffer from internal inconsistencies and produce illogical outcomes in some cases. The authors also show that there is no problem with the current accepted theory and that the apparent paradox is not the result of a deficiency in the current theory but is rather caused by its misapplication in practice. In particular, the authors show that the systematic risk of cash flows is frequently mis-estimated, and the correction of this error solves the apparent paradox.

Practical implications

Over the past 20 years, PPP activity around the globe amounts to many billions of dollars. Decisions on major infrastructure funding are of enormous social and economic importance.

Originality/value

To the best of the authors’ knowledge, this study is the first to demonstrate the flaws and internal inconsistencies with proposed valuation framework alternatives for the purposes of evaluating PPPs.
Systematic review of application of artificial intelligence tools in architectural, engineering and construction
Authors: Momade Mohammed Hamza , Durdyev Serdar , Estrella Dave , Ismail Syuhaida
Published: September 2021

Purpose

This study reviews the extent of application of artificial intelligence (AI) tools in the construction industry.

Design/methodology/approach

A thorough literature review (based on 165 articles) was conducted using Elsevier's Scopus due to its simplicity and as it encapsulates an extensive variety of databases to identify the literature related to the scope of the present study.

Findings

The following items were extracted: type of AI tools used, the major purpose of application, the geographical location where the study was conducted and the distribution of studies in terms of the journals they are published by. Based on the review results, the disciplines the AI tools have been used for were classified into eight major areas, such as geotechnical engineering, project management, energy, hydrology, environment and transportation, while construction materials and structural engineering. ANN has been a widely used tool, while the researchers have also used other AI tools, which shows efforts of exploring other tools for better modelling abilities. There is also clear evidence of that studies are now growing from applying a single AI tool to applying hybrid ones to create a comparison and showcase which tool provides a better result in an apple-to-apple scenario.

Practical implications

The findings can be used, not only by the researchers interested in the application of AI tools in construction, but also by the industry practitioners, who are keen to further understand and explore the applications of AI tools in the field.

Originality/value

There are no studies to date which serves as the center point to learn about the different AI tools available and their level of application in different fields of AEC. The study sheds light on various studies, which have used AI in hybrid/evolutionary systems to develop effective and accurate predictive models, to offer researchers and model developers more tools to choose from.
Agriculture value chain sustainability during COVID-19: an emerging economy perspective
Authors: Kumari Sneha , Venkatesh V.G. , Deakins Eric , Mani Venkatesh , Kamble Sachin
Published: September 2021

Purpose

Agriculture value chains (AVCs) have experienced unprecedented disruption during the COVID-19 pandemic, with lockdowns and stringent social distancing restrictions making buying and selling behaviours complex and uncertain. This study aims provide a theoretical framework describing the stakeholder behaviours that arise in severely disrupted value chains, which give rise to inter-organisational initiatives that impact industry sustainability.

Design/methodology/approach

A mixed-methods approach is adopted, in which uncertainty theory and relational governance theory and structured interviews with 15 AVC stakeholders underpin the initial conceptual model. The framework is empirically validated via partial least squares structural equation modelling using data from an online survey of 185 AVC stakeholders based in India.

Findings

The findings reveal that buyer and supplier uncertainty created by the COVID-19 lockdowns gives rise to behaviours that encourage stakeholders to engage in relational governance initiatives. Progressive farmers and other AVC stakeholders welcome this improved information sharing, which encourages self-reliance that positively impacts agricultural productivity and sustainability.

Practical implications

The new framework offers farmers and other stakeholders in developing nations possibilities to sustain their AVCs even in dire circumstances. In India, this also requires an enabling ecosystem to enhance smallholders' marketing power and help them take advantage of recent agricultural reforms.

Originality/value

Research is scarce into the impact of buyer and seller behaviour during extreme supply chain disruptions. This study applies relational governance and uncertainty theories, leading to a proposed risk aversion theory.
The evolving passage of consumer ethics research: a systematic literature review
Authors: Hassan Syed Masroor , Rahman Zillur
Published: September 2021

Purpose

As a crucial counter-equivalent to business ethics, consumer ethics has emerged as a promising research domain for practitioners and academicians alike. Despite its pertinence for both industry and academia, little is known about the existing state of consumer ethics research. To address this limitation, a systematic literature review was conducted to identify key research themes, gaps in the extant literature and set the agenda for future research.

Design/methodology/approach

This literature review is based on a sample of 81 research articles drawn from Scopus and EBSCO host databases and analysed on different classification bases, covering a period from 2004 to 2019.

Findings

The results reveal that pro-social behaviour has gained recent attention in consumer ethics research. Moreover, there has been a renewed focus to understand and mitigate the attitude–behaviour gap in ethical consumption. The authors also found that majority of the studies have been conducted in Europe and North America, in a single country context.

Research limitations/implications

Consumer ethics has significant economic and social consequences worldwide. Consumer ethics insights can help marketers and practitioners to devise strategies that minimize business losses due to unethical consumer behaviour, incentivize ethical consumption and align corporate social responsibility initiatives that draw consumer support.

Originality/value

To the best of our knowledge, this is the first major (systematic) review on consumer ethics after Vitell’s review of 2003. This review provides valuable directions for future research to carry this domain forward.
Is the global reporting initiative suitable to account for university social responsibility? Evidence from European institutions
Authors: Amiano Bonatxea Iratxe , Gutiérrez-Goiria Jorge , Vazquez-De Francisco Maria Jose , Sianes Antonio
Published: September 2021

Purpose

Recognising the importance of universities in the achievement of social and global objectives, this paper aims to study the relevance of the global reporting initiative (GRI) methodology for reporting University Social Responsibility (USR) activities, taking into account the specificity of higher education institutions (HEI).

Design/methodology/approach

After a review of the literature and background, the European HEI reports prepared according to the latest version of GRI standards are selected and a comparative study is carried out. The analysis focusses on comparing to what extent the standards are responding to the information needs generated in the field of higher education.

Findings

General issues, common to all types of organisations, are adequately reported by HEIs, but difficulties are encountered in integrating a vision that incorporates the role of their missions in standards related to economic, social and environmental aspects.

Research limitations/implications

There are few GRI reports with this format and further research is encouraged as the number of reports increase. So far, major limitations have been found by HEIs to account for their societal missions when using the GRI.

Practical implications

The debates on USR are promoting an increase in the number of reports on sustainability. This paper provides some examples of the use of disclosures that can be adapted in this context, to move towards the systematisation of these practices.

Originality/value

This is, to the authors’ knowledge, the first comparative study on the application of GRI to sustainability reports at a European level, focussing on the adequacy between disclosures and missions.