bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Characteristics and Stage at Presentation of Glaucoma Patients in Sub-Saharan Africa
Authors: Olawoye Olusola , Kizor-Akaraiwe Nkiru , Pons Jonathan , Sarimiye Tarela , Washaya Jennifer , Hughes Sowunmi , Ashaye Adeyinka , Garba Farouk , Gessesse Girum W. , Chitedze Richard , Ibanga Affiong , Saka Vincent , Agre Jeremie , Mahdi Abdull , Ogunro Adunola , Budengeri Patrick , Ajibode Haroun A. , Tamrat Lemlem , Onakoya Adeola , Okeke Suhanya , Hulley Jo-Anne , Giorgis Abeba , Onyekachi Ireka W. , Okosa Chimdi Chuka , Ogbonnaya Chimdia , Abdulsalam Shuaib , Fowobaje Kayode , Cook Stephen , Lawrence Scott , Macheka Boniface , Chan Ving Fai , Blanco Augusto Azuara , Congdon Nathan , Realini Tony ,   the STAGE Research Group
Published: June 2022

Précis:

The initial presentation of glaucoma varies meaningfully across SSA. A comprehensive strategy with regional customization based on local differences is needed to reduce glaucoma blindness in SSA.

Purpose:

To explore regional variations in the presentation of newly diagnosed glaucoma in Sub Saharan Africa (SSA).

Methodology:

This was a multicenter, cross-sectional study in which newly diagnosed, consecutive, glaucoma patients aged older than or equal to 18 years were recruited from 27 eye clinics in 10 countries throughout SSA. Demographic and ophthalmic examination data were collected. Glaucoma severity was based on optic nerve head and visual field assessment. Statistical analyses were performed using STATA version 14.0.

Results:

Among 1214 enrolled patients with newly diagnosed glaucoma from Western, Eastern, and Southern Africa, the overall mean (SD) age was 59.9 (17.1) years. More than half of all patients (716/1178; 60.8%) presented with severe glaucoma in the worse eye, and one-third (36.9%) had severe glaucoma in both eyes. Primary open angle glaucoma was the commonest form of glaucoma in all regions (77.4%). A family history of blindness (260/1204, 21.6%) was common. Patients from Western Africa had lower mean presenting intraocular pressure (26.4 [11.1] mm Hg, P<0.001), but had worse glaucoma in the better eye based on mean cup-disc ratio (0.8; P<0.001) and mean visual field mean deviation [10.4 (8.4)] dB, P=0.016) compared with other regions. Exfoliation glaucoma was more common in Eastern Africa (30/170=17.7%, P<0.001) compared with other regions.

Conclusion:

The initial presentation of glaucoma varies meaningfully across SSA. A comprehensive strategy with regional customization based on local differences is needed to reduce glaucoma blindness in SSA.
ABCDE and ABCDEF care bundles
Authors: Moraes Fabio da Silva , Marengo Lívia Luize , Moura Mariana Del Grossi , Bergamaschi Cristiane de Cássia , de Sá Del Fiol Fernando , Lopes Luciane Cruz , Silva Marcus Tolentino , Barberato-Filho Silvio
Published: June 2022

Background:

The ABCDE (Awakening and Breathing Coordination of daily sedation and ventilator removal trials, Delirium monitoring and management, and Early mobility and exercise) and ABCDEF (Assessment, prevent and manage pain, Both spontaneous awakening and spontaneous breathing trials, Choice of analgesia and sedation, assess, prevent and manage Delirium, Early mobility and exercise, Family engagement) care bundles consist of small sets of evidence-based interventions and are part of the science behind Intensive Care Unit (ICU) liberation. This review sought to analyse the process of implementation of ABCDE and ABCDEF care bundles in ICUs, identifying barriers, facilitators and changes in perception and attitudes of healthcare professionals; and to estimate care bundle effectiveness and safety.

Methods:

We selected qualitative and quantitative studies addressing the implementation of ABCDE and ABCDEF bundles in the ICU, identified on MEDLINE, Embase, CINAHL, The Cochrane Library, Web of Science, Epistemonikos, PsycINFO, Virtual Health Library and Open Grey, without restriction on language or date of publication, up to June 2018. The outcomes measured were ICU and hospital length of stay; mechanical ventilation time; incidence and prevalence of delirium or coma; level of agitation and sedation; early mobilization; mortality in ICU and hospital; change in perception, attitude or behaviour of the stakeholders; and change in knowledge of health professionals. Two reviewers independently selected the studies, performed data extraction, and assessed risk of bias and methodological quality. A meta-analysis of random effects was performed.

Results:

Twenty studies were included, 13 of which had a predominantly qualitative and 7 a quantitative design (31,604 participants). The implementation strategies were categorized according to the taxonomy developed by the Cochrane Effective Practice and Organization of Care Group and eighty strategies were identified. The meta-analysis results showed that implementation of the bundles may reduce length of ICU stay, mechanical ventilation time, delirium, ICU and hospital mortality, and promoted early mobilization in critically-ill patients.

Conclusions

: This study can contribute to the planning and execution of the implementation process of ABCDE and ABCDEF care bundles in ICUs. However, the effectiveness and safety of these bundles need to be corroborated by further studies with greater methodological rigor.

Protocol registration:

PROSPERO CRD42019121307.
A review on the evolution of simulation-based training to help build a safer future
Authors: Bienstock Jared , Heuer Albert
Published: June 2022

Throughout history, simulation has been used to demonstrate various techniques, acquire skills, and maintain best practices in healthcare. Simulation has evolved significantly, primarily because of the extent to which it can enhance both clinical proficiency and patient care. Although simulation-based training (SBT) in healthcare has grown exponentially in the 21st century, it has been around for centuries. This paper aims to reflect on the history and evolution of simulation in healthcare and review its current applications in order to provide a foundation for developing new applications for future expanded use.
Challenges associated with diagnostic exome sequencing in liver diseases
Authors: Kong Xiao-Fei , Bogyo Kelsie , Kapoor Sheena , Groopman Emily E. , Thomas-Wilson Amanda , Cocchi Enrico , Rasouly Hila Milo , Zheng Beishi , Sun Siming , Zhang Junying , Martinez Mercedes , Vittorio Jennifer M , Dove Lorna M. , Marasa Maddalena , Wang Timothy C. , Verna Elizabeth C. , Worman Howard J. , Gharavi Ali G. , Goldstein David B. , Wattacheril Julia
Published: June 2022

Exome sequencing (ES) has been used in a variety of clinical settings but there are limited data on its utility for diagnosis and/or prediction of monogenic liver diseases. We analyzed ES data in 758 patients with liver diseases., We developed a curated list of 502 genes for monogenic disorders associated with liver phenotypes and analyzed ES data for these genes in 758 patients with chronic liver diseases (CLD). For comparison, we examined ES data in 7,856 self-declared healthy controls (HC), and 2,187 patients with chronic kidney disease (CKD). Candidate pathogenic (P) or likely pathogenic (LP) variants were initially identified in 19.9% of participants, most of which were attributable to previously reported pathogenic variants with implausibly high allele frequencies. After variant annotation and stringent filtering based on population minor allele frequency, we detected a significant enrichment of P/LP variants in the CLD cohort compared to the HC cohort (X2test OR: 5.00, 95% CI:3.06-8.18,, p-value=4.5 e-12). A second-level manual annotation was necessary to capture true pathogenic variants that were removed by stringent allele frequency filters. After these sequential steps, the diagnostic rate of monogenic disorders was 5.7% in the CLD cohort, attributable to P/LP variants in 25 genes. We also identified concordant liver disease phenotypes for 15/22 kidney disease patients with P/LP variants in liver genes, mostly associated with cystic liver disease phenotypes. Clinically confirmed sequencing results had many implications for clinical management, including familial testing for early diagnosis and management, preventative screening for associated comorbidities, and in some cases for therapy. Exome sequencing provided a 5.7% diagnostic rate in CLD patients and required multiple rounds of review to reduce both false positive and false negative findings. The identification of concordant phenotypes in many patients with P/LP variants and no known liver disease also indicates a potential for predictive testing for selected monogenic liver disorders.
Over the hills and far away: linking landscape factors with cavity excavation on living forest trees by the Black Woodpecker (Dryocopus martius, L. 1758)
Authors: Cabrera Cedric , Monnet Jean-Matthieu , Boutteaux Jean-Jacques , Doutau Baptiste , Denis Pascal , Paillet Yoan
Published: June 2022

The Black Woodpecker (Dryocopus martius, L. 1758) is the largest primary cavity excavator in Western Europe. Its cavities represent an essential microhabitat for many other forest species and the landscape factors linked with cavity excavation by the Black Woodpecker are needed to support the conservation of this species. Such relationships should thus be quantified at the scale of the home range in Western Europe.

We used cavity maps by foresters and naturalists to build a large (2689 cavity bearing trees) database distributed over 11 sites in France. Based on this and on a set of background points, we analysed the effects of stand composition and landscape features (forest cover, landscape connectivity and fragmentation) at three different scales around each plot corresponding to a forest management unit (10ha), the core (100ha) and extended (250ha) home range scales.

We showed that landscape shape index and forest composition (especially the presence of mixed forests) had significant effects but that the magnitude varied across the three scales. We notably observed the strongest effects at the core home range scale (100ha), indicating that Black Woodpecker requirements for cavity excavation are more pronounced at this scale. The Black Woodpecker tend to avoid conifer-dominated stands to excavate cavities, but benefits from mixed forests, that couple favourable foraging and cavity excavation sites. The bird also prefers continuous forest landscapes with low edge densities. We also showed that effects of landscape were stronger in wetter climates and higher slopes, indicating context-dependence.

Forest planning rarely integrates the landscape patterns in western temperate Europe, a better understanding of the features linked with cavity excavation by the Black Woodpecker may hence help to better integrate their conservation in forest management planning. Our results also show the importance to maintain mixed broadleaf-conifer forests as well as continuous and well-connected forest landscapes to favour features that benefit secondary cavity nesters at the large scale.
Binge alcohol drinking alters the differential control of cholinergic interneurons over nucleus accumbens D1 and D2 medium spiny neurons
Authors: Kolpakova Jenya , van der Vinne Vincent , Gimenez-Gomez Pablo , Le Timmy , Martin Gilles E.
Published: June 2022

Background

Ventral striatal cholinergic interneurons (ChIs) play a central role in basal ganglia function by regulating associative learning and reward processing. In the nucleus accumbens (NAc), ChIs regulate glutamatergic, dopaminergic, and GABAergic neurotransmission. However, it is unclear how ChIs orchestrate the control of these neurotransmitters to determine the excitability of medium spiny neurons (MSNs) expressing either dopamine D1 or D2 receptors. Additionally, the effects of binge alcohol drinking on ChIs-mediated modulation of glutamatergic synaptic transmission in NAc MSNs are also undefined.

Methods

We optogenetically stimulated ChIs while recording evoked and spontaneous excitatory postsynaptic currents (sEPSCs) in D1- and D2-MSN of ChAT.ChR2.eYFPxDrd1.tdtomato mice. To determine the effect of ChIs on mouse behavior and alcohol consumption, we implanted ChAT.ChR2.eYFP mice with fiber optic cannulas and stimulated ChIs while mice were allowed to drink 20% alcohol using the binge alcohol drinking- in-the-dark (DID) paradigm.

Results

We demonstrated that NAc ChIs decrease the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in both D1- and D2-MSNs,. While inhibition of D1-MSNs glutamate release by ChIs depends on dopamine release, that of D2-MSNs results from a direct interactions between ChIs and glutamatergic terminals. Interestingly, after two weeks of binge alcohol drinking, the effect of ChIs stimulation on glutamate release was reversed in D1-MSNs, while its effect on D2-MSNs remained unchanged. Finally, in vivo optogenetic stimulation of NAc ChIs significantly increased alcohol consumption.

Conclusions

These results identify ChIs as a key target for the regulation of NAc circuitry and as a potential treatment of alcohol addiction.
T-cell potential for CD19-expressing malignancies revealed by multi-dimensional single-cell profiling
Authors: Rezvan Ali , Romain Gabrielle , Fathi Mohsen , Heeke Darren , Martinez-Paniagua Melisa , An Xingyue , Bandey Irfan N , Saeedi Arash , Sadeghi Fatemeh , Fousek Kristen , Puebla-Osorio Nahum , Cooper Laurence J.N. , Bernatchez Chantale , Singh Harjeet , Ahmed Nabil , Mattie Mike , Bot Adrian , Neelapu Sattva , Varadarajan Navin
Published: June 2022

Adoptive immunotherapy with T cells expressing chimeric antigen receptors (CARs) for B-cell malignancies serves as a model for identifying subsets with superior clinical activity. We profiled the infusion products (IP) of 16 patients with large B-cell lymphoma (LBCL) using an integrated suite of single-cell assays to reveal the therapeutic potential of CD19-specific CAR+ T cells. Timelapse imaging microscopy in nanowell grids (TIMING) profiling revealed that T cells from responders showed migration (persistent motion for at least one body length), and migration was associated with serial killing capacity. In addition, confocal microscopy revealed that migration is linearly correlated with both mitochondrial volume and lysosomal volume; and scRNA-seq demonstrated that T cells from responders were enriched in pathways related to T-cell killing, migration and actin cytoskeleton, and TCR clustering. A marker-free sorting strategy enriched T cells with migratory capacity and validated serial killing, bioenergetics, and in vivo efficacy. In aggregate, we demonstrate that migration is a cell-intrinsic biomarker independent of CAR design or biomanufacturing, desired in the bioactivity of CAR+ T cells associated with clinical antitumor efficacy.
CNVscore calculates pathogenicity scores for copy number variants together with uncertainty estimates accounting for learning biases in reference Mendelian disorder datasets
Authors: Requena Francisco , Salgado David , Malan Valérie , Sanlaville Damien , Bilan Frédéric , Béroud Christophe , Rausell Antonio
Published: June 2022

Copy number variants (CNVs) are a major cause of rare pediatric diseases with a broad spectrum of phenotypes. Genetic diagnosis based on comparative genomic hybridization tests typically identifies ∼8-10% of patients as having CNVs of unknown significance, revealing the current limits of clinical interpretation. The adoption of whole-genome sequencing (WGS) as a first-line genetic test has significantly increased the load of CNVs identified in single genomes. Alongside short- and long-read sequencing technologies, a number of pathogenicity scores have been developed for filtering and prioritizing large sets of candidate CNVs in clinical settings. However, current approaches are often based, either explicitly or implicitly, on clinically annotated reference sets, which are likely to bias their predictions. In this study we developed CNVscore, a supervised-learning approach combining tree ensembles and a Bayesian classifier trained on pathogenic and non-pathogenic CNVs from reference databases. Unlike previous approaches, CNVscore couples pathogenicity estimates with uncertainty scores, making it possible to evaluate the suitability of a model for the query CNVs. Comprehensive comparative benchmark tests across independent sets and against alternative methods showed that CNVscore effectively distinguishes between pathogenic and benign CNVs. We also found that CNVs associated with CNVscores of low uncertainty were predicted with significantly higher accuracy than those of high uncertainty. However, the performance of current scoring approaches, including CNVscore, was compromised on CNV sets enriched in highly uncertain variants and presenting unconventional features, such as functionally relevant non-coding elements or the presence of disease genes irrelevant for the clinical phenotypes investigated. Finally, we used the CNVscore framework to guide CNV scoring model selection for the French National Database of Constitutional CNVs (BANCCO), which includes clinical diagnosis annotations. The CNVscore framework provides an objective strategy for leveraging the uncertainty on bioinformatic predictions to enhance the assessment of CNV pathogenicity in rare-disease cohorts. CNVscore is available as open-source software from https://github.com/RausellLab/CNVscore and is integrated into the CNVxplorer webserver http://cnvxplorer.com.
Protection against Omicron BA.2 reinfection conferred by primary Omicron or pre-Omicron infection with and without mRNA vaccination
Authors: Carazo Sara , Skowronski Danuta M. , Brisson Marc , Barkati Sapha , Sauvageau Chantal , Brousseau Nicholas , Gilca Rodica , Fafard Judith , Talbot Denis , Ouakki Manale , Gilca Vladimir , Carignan Alex , Deceuninck Geneviève , De Wals Philippe , De Serres Gaston
Published: June 2022

Background

We estimated the protection against the Omicron BA.2 variant associated with prior primary infection (PI) due to pre-Omicron or Omicron BA.1 virus, with and without mRNA vaccination.

Methods

A test-negative case-control study was conducted among healthcare workers (HCWs) tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 predominated and was presumptively diagnosed. Logistic regression models compared the likelihood of BA.2 reinfection (second positive test ≥30 days after PI) among HCWs with history of PI and none to three doses of mRNA vaccine versus infection-naïve, unvaccinated HCWs.

Findings

Among 37,732 presumed BA.2 cases, 2,521 (6.7%) and 659 (1.7%) were reinfections following pre-Omicron or BA.1 PI, respectively. Among 73,507 controls, 7,360 (10.0%) and 12,315 (16.8%) had a pre-Omicron or BA.1 PI, respectively. Pre-Omicron PI was associated with 38% (95%CI:19-53) reduction in BA.2 infection risk, with higher BA.2 protection among those also vaccinated with one (56%), two (69%) or three (70%) vaccine doses. Omicron BA.1 PI was associated with greater protection against BA.2 (72%; 95%CI:65-78), higher among two-dose vaccinated at 96% (95%CI:95-96) but not improved with a third dose (96%; 95%CI:95-97). Hybrid Omicron BA.1 PI plus two or three dose vaccine-induced protection persisted for five months post-infection.

Interpretation

Twice-vaccinated individuals who experienced BA.1 infection were subsequently well-protected for a prolonged period against BA.2 reinfection and derived no meaningful added benefit against BA.2 from a third dose of mRNA vaccine.
HIV and SARS-CoV-2 infection in postpartum Kenyan women and their infants
Authors: Begnel Emily R. , Chohan Bhavna H. , Ojee Ednah , Adhiambo Judith , Owiti Prestone , Ogweno Vincent , Holland LaRinda A. , Fish Carolyn S. , Richardson Barbra A. , Khan Adam K. , Maqsood Rabia , Lim Efrem S. , Lehman Dara A. , Slyker Jennifer , Kinuthia John , Wamalwa Dalton , Gantt Soren
Published: June 2022

Background

HIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya.

Methods

We conducted a nested study of 53 HIV-uninfected and 51 healthy women living with HIV, as well as their HIV-exposed uninfected (N=41) and HIV-unexposed (N=48) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between 1 May-31 December 2020 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on stool samples from seropositive participants.

Results

SARS-CoV-2 seropositivity was found in 38% of the 104 mothers and in 17% of the 89 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR]=1.51, 95% CI: 0.780-2.94) or infant HIV exposure (HR=1.48, 95% CI: 0.537-4.09). Maternal SARS-CoV-2 was associated with a >10-fold increased risk of infant infection (HR=10.3, 95% CI: 2.89-36.8). Twenty percent of participants had symptoms, but no participant experienced severe COVID-19 or death. Seroreversion occurred in ∼30% of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants.

Conclusions

These data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection in 2020, and that antibody responses waned rapidly. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19.
Mechanoregulatory role of TRPV4 in prenatal skeletal development
Authors: Khatib Nidal , Monsen James , Ahmed Saima , Huang Yuming , Hoey David A. , Nowlan Niamh C.
Published: June 2022

Biophysical cues are essential for guiding skeletal development, but the mechanisms underlying the physical regulation of cartilage and bone formation are unknown. TRPV4 is a cell membrane ion channel responsible for transducing mechanical stimuli as a means of regulating skeletal cell homeostatic processes. Dysregulation of TRPV4 is associated with several skeletal developmental pathologies, indicating its involvement in cartilage and bone development, potentially in a mechanosensing capacity. In this study, we test the hypothesis that mechanically mediated prenatal skeletogenesis depends on TRPV4 activity. We first validate a novel model where we establish that dynamically loading embryonic mouse hindlimb explants cultured ex vivo promotes joint cartilage growth and morphogenesis, but not diaphyseal mineralization. We next reveal that TRPV4 protein expression is mechanically regulated and spatially localized to patterns of high biophysical stimuli in the femoral condyles of cultured limbs. Finally, we demonstrate that TRPV4 activity is crucial for the mechanical regulation of joint cartilage growth and shape, mediated via the control of cell proliferation and matrix biosynthesis, indicating a mechanism by which mechanical loading could direct morphogenesis during joint formation. We conclude that the regulatory pathways initiated by TRPV4 mechanotransduction are essential for the for the cartilage response to physical stimuli during skeletal development. Therefore, TRPV4 may be a valuable target for the development of therapeutic skeletal disease modifying drugs and developmentally-inspired tissue engineering strategies for skeletal repair.
Genetic landscape of Human neutrophil antigen variants in India from population-scale genomes
Authors: Rophina Mercy , Bhoyar Rahul C , Imran Mohamed , Senthivel Vigneshwar , Divakar Mohit Kumar , Mishra Anushree , Jolly Bani , Sivasubbu Sridhar , Scaria Vinod
Published: June 2022

Background

Antibodies against human neutrophil antigens (HNAs) play a significant role in various clinical conditions such as neonatal alloimmune neutropenia (NAIN). Transfusion-related acute lung injury (TRALI) and other non-hemolytic transfusion reactions. This study aims to identify the genotype and allele frequencies of HNAs in the healthy Indian population.

Methods

Genetic variants from whole genomes of 1029 healthy Indian individuals were retrieved to accurately perform frequency estimation of HNA-1, HNA-3, HNA-4 and HNA-5 alleles using in-house computational pipeline.

Results

In HNA class I, the genotype frequencies of FCGR3B*01 (HNA1a/a), FCGR3B*02 (HNA1b/b) and FCGR3B*03 (HNA1c/c) were 0.29%, 27.31% and 1.75% respectively. In HNA-3 the frequencies of HNA3a/a (SLC44A2*01), HNA3a/b and HNA3b/b (SLC44A2*02) were found to be 62.0%, 31.7% and 5.8% respectively. Frequency of ITGAM*01 encoding HNA4a/a was 90.1% and that of ITGAM*02 encoding HNA4b/b was 0.3%. Furthermore, HNA5a/a (ITGAL*01) and HNA5b/b (ITGAL*02) were found to have 12.9% and 48.6% genotype frequencies in the Indian population respectively. It was also found that the allele frequency HNA-5 variant, rs2230433 (ITGAL_chr16:30506720G>C) encoding 5b allele was highly prevalent (78.2%) in the Indian population which was comparable to South Asians (65.6%) but differed greatly from East Asians (14.3%), Latino Americans (25.7%), African-Americans (42.2%), European-Finnish (25.4%), European-non-Finnish (29.4%), Greater Middle Easterners (34.5%), Amish (30.2%) and Ashkenazi Jewish (31.4%).

Conclusion

This study presents the first comprehensive report of HNA variant and genotype frequencies using large scale representative whole genome sequencing data of the Indian population. Significant difference was observed in the prevalence of HNA5a and HNA5b in India in comparison to other global populations.
A 10-year retrospective analysis ofToxoplasma gondiiqPCR screening in allogeneic hematopoietic stem cell transplantation recipients
Authors: Xhaard Alienor , Villate Alban , Hamane Samia , Michonneau David , Menotti Jean , Robin Marie , Sicre de Fontbrune Flore , Dhédin Nathalie , Peffault de la Tour Régis , Socié Gérard , Bretagne Stéphane
Published: June 2022

Weekly bloodToxoplasma gondiiDNA screening using real-time quantitative polymerase chain reaction (qPCR) has been implemented in all allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients at our hospital. We retrospectively analyzed the consequences of a positive blood qPCR in the management ofToxoplasmainfection (TI) and disease (TD).

From 2011 to 2020, 52 (4.13%) of 1 257 alloHSCT recipients had at least one positive qPCR, 45 (3.5%) with TI and seven (0.56%) with TD (central nervous system involvement). Forty-four patients were qPCR-positive before day 100, 30 without and 14 with anti-Toxoplasmaprophylaxis. Twenty-five of them (56.8%) started or continued prophylactic dosage treatment: all became qPCR-negative, including 20 (80%) receiving only prophylactic dosage treatment. Twenty-four of them (54.5%) received non-prophylactic dosage treatment: qPCR became negative in 22/24 (91.7%), while TI contributed to death in two cases. Six of the eight patients diagnosed after D100 were breakthrough TI or TD. No death was attributable to TI or TD.qPCRkinetics available for 24 patients increased until anti-Toxoplasmatreatment began, then decreased with all treatment regimens.

Clinical follow-up and qPCR monitoring with quantification of the parasitic load appears a reasonable strategy to avoid TD and to use minimal effective dosage of anti-Toxoplasmatreatments.
Inflammasome activation and pulmonary viral loads define two distinct clinical outcomes in COVID-19
Authors: de Sá Keyla S.G. , Amaral Luana A. , Caetano Camila C.S. , Becerra Amanda , Batah Sabrina S. , de Oliveira Isadora M. , Lopes Letícia S. , Almeida Leticia , Oliveira Samuel , Wada Danilo Tadao , Koenigkam-Santos Marcel , Martins Ronaldo B. , Rosales Roberta R. C. , Arruda Eurico , Fabro Alexandre T , Zamboni Dario S.
Published: June 2022

COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation. Additionally, we correlated these factors with the patient’s clinical and histopathological conditions. Robust inflammasome activation, mediated by macrophages and endothelial cells, was detected in the lungs of lethal cases of SARS-CoV-2. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2. Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, viral loads and inflammasome activation significantly differed between the two clusters. Our data demonstrated two distinct profiles in lethal cases of COVID-19, thus indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation led to different clinical outcomes. We provide important information to understand clinical variations in severe COVID-19, a process that is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.
The most common human ADAR1p150 Zα domain mutation P193A is well tolerated in mice and does not activate the integrated stress response pathway
Authors: Liang Zhen , Taylor Scott , Goradia Ankita , Heraud-Farlow Jacki , Walkley Carl R
Published: June 2022

ADAR1 mediated A-to-I RNA editing is a self/non-self discrimination mechanism for cellular double stranded RNAs. ADAR mutations are one cause of Aicardi-Goutières Syndrome, an inherited paediatric encephalopathy, broadly classed as a “Type I interferonopathy”. The most common ADAR1 mutation is a proline 193 alanine (p.P193A) mutation, mapping to the ADAR1p150 isoform specific Zα domain. We report the development of an independent murine P195A knock-in mouse, homologous to the human P193A mutation. The Adar1P195A/P195A mice are largely normal and the mutation is well tolerated. Contrasting with previous reports when the P195A mutation was compounded with an ADAR1 null allele, the majority of mice have only a modest reduction in weaning weight and survived long-term. Severe runting and shortened survival of Adar1P195A/-animals are dependent on the parental genotype. The P195A mutation is well tolerated in vivo and the loss of MDA5 is sufficient to completely rescue the Adar1P195A/- mice.
Codistribution as an indicator of whole metacommunity response to environmental change
Authors: Terry J. Christopher D. , Langdon William , Rossberg Axel G.
Published: June 2022

Metacommunity structure can be summarised by fitting joint species distribution models and partitioning the variance explained into environmental, spatial and codistribution components. Here we identify how these components respond through time with directed environmental change and propose this as an indicator of sustained directional pressure. Through simulations, we identify how declines in the codistribution component can diagnose ecological breakdown, while rises in environmental and spatial components may indicate losses in peripheral areas and dispersal limitations. We test the method in two well-studied systems. Butterflies are known to be strongly responding to climate change, and we show that over 21 years the codistribution component declines for butterfly communities in southern England. By contrast, birds in the same region are under less climate pressure and, despite high occupancy turnover, show minimal change in metacommunity structure. The approach has high potential to summarise and compare the impact of external drivers on whole communities.
Single-shot Volumetric Chemical Imaging by Mid-Infrared Photothermal Fourier Light Field Microscopy
Authors: Zhang Yi , Jia Danchen , Yang Qianwan , Xue Yujia , Tan Yuying , Guo Zhongyue , Zhang Meng , Tian Lei , Cheng Ji-Xin
Published: June 2022

Three-dimensional molecular imaging of living organisms and cells plays a significant role in modern biology. Yet, current volumetric imaging modalities are largely fluorescence-based and thus lack chemical content information. Mid-infrared photothermal microscopy as a new chemical imaging technology provides infrared spectroscopic information at sub-micrometer spatial resolution. Here, by harnessing thermosensitive fluorescent dyes to sense the mid-infrared photothermal effect, we demonstrate mid-infrared photothermal Fourier light field (MIP-FLF) microscopy for single-shot volumetric infrared spectroscopic imaging at the speed of 8 volumes per second and sub-micron spatial resolution. Protein contents in bacteria and lipid droplets in living pancreatic cancer cells are visualized. Altered lipid metabolism in drug-resistant pancreatic cancer cells is observed with the MIP-FLF microscope.
Arabidopsis AAR2, a conserved splicing factor in eukaryotes, acts in microRNA biogenesis
Authors: Fan Lusheng , Gao Bin , Xu Ye , Flynn Nora , Le Brandon , You Chenjiang , Li Shaofang , Achkar Natalia , Manavella Pablo A. , Yang Zhenbiao , Chen Xuemei
Published: June 2022

MicroRNAs (miRNAs) play an essential role in plant growth and development, and as such, their biogenesis is fine-tuned via regulation of the core microprocessor components. Here, we report thatArabidopsisAAR2, a homolog of a U5 snRNP assembly factor in yeast and humans, not only acts in splicing but also promotes miRNA biogenesis. AAR2 interacts with the microprocessor component HYPONASTIC LEAVES1 (HYL1) in the cytoplasm, nucleus and dicing bodies. Inaar2mutants, abundance of nonphosphorylated HYL1, the active form of HYL1, and the number of HYL1-labeled dicing bodies are reduced. Primary miRNA (pri-miRNA) accumulation is compromised despite normal promoter activities ofMIRgenes inaar2mutants. RNA decay assays show that theaar2-1mutation leads to faster degradation of pri-miRNAs in a HYL1-dependent manner, which reveals a previously unknown and negative role of HYL1 in miRNA biogenesis. Taken together, our findings reveal a dual role of AAR2 in miRNA biogenesis and pre-mRNA splicing.

Significance

In yeast and humans, AAR2 is involved in pre-mRNA splicing through regulating U5 snRNP assembly. This study shows thatArabidopsisAAR2 promotes microRNA (miRNA) accumulation in addition to its conserved role in pre-mRNA splicing. AAR2 is associated with the microprocessor component HYL1 and promotes its dephosphorylation to produce the active form in miRNA biogenesis. The study also reveals a previously unknown role of HYL1 in causing the degradation of the primary precursors to miRNAs (pri-miRNAs) and a role of AAR2 in protecting pri-miRNAs from HYL1-depedent degradation. Taken together, our findings provide new insights into the role of a conserved splicing factor in miRNA biogenesis in plants.
Antiviral T-cell Biofactory platform for SARS-CoV-2
Authors: Ssemadaali Marvin A. , Newmyer Sherri , Radhakrishnan Harikrishnan , Arredondo Juan , Javitz Harold S. , Dandekar Satya , Bhatnagar Parijat
Published: June 2022

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Abstract

Vaccines help reduce new infections, but interventions that can prevent the disease from transitioning to a severe stage are rather limited. Dysregulated IFN kinetics are mostly exploited by pathogenic viruses, including SARS-CoV-2. The clinical benefits of systemically infused IFN are, unfortunately, mired by undesired side effects. To address this situation, we engineered a T cell to synthesize interferons (IFNs) as antiviral proteins upon recognizing the virus envelop protein of SARS-CoV-2, i.e.,anti-SARS T-cell Biofactory. The T-cell Biofactory, capable of regulating the IFN expression with spatiotemporal resolution within the infected tissues, can mitigate these concerns. In this work, we determined the prophylactic and therapeutic effects of the type-I and type-III IFNs produced from the T-cell Biofactory against SARS-CoV-2 infection in host cells and investigated the expression profiles of ensuing IFN-stimulated genes (ISGs). To enable the translation of T-cell Biofactory as an effective antiviral countermeasure, we also investigated an irradiation dose that renders the T-cell Biofactory non-proliferative and thus non-oncogenic. The ongoing public health crisis motivated us to direct the T-cell Biofactory technology to target SARS-CoV-2. The T-cell Biofactory, based on T cells engineered with chimeric antigen receptors (CAR T cells), is a platform technology that can be rapidly re-engineered and become available for targeting any new pathogen.
Effect of educational intervention based on theory of planned behavior on aggression preventive behaviors in students
Authors: Khaleghi Ali Asghar , Jafarzadeh Saeedeh , Afzali Harsini Pooyan , Kashfi Seyyed Hannan , Mohammadkhah Fatemeh , Khani Jeihooni Ali
Published: June 2022

Purpose

Aggressive behaviors are common among students. Given the importance of education in reducing aggressive behavior, this study aims to examine the influence of a theory of planned behavior (TPB)-based educational intervention on aggression-preventive behaviors in fifth-grade male students in Fasa city, Iran.

Design/methodology/approach

A total of 120 male students were randomly picked from several public schools in Fasa city, Iran, between 2018 and 2019. Assessments were completed before and three months after the intervention. Intervention consisted of eight 55–60-min training sessions based on the TPB’s processes and constructs.

Findings

Prior to the educational intervention, there was no significant difference between the two groups in terms of attitude, subjective norms, perceived behavioral control, intention to stop aggressiveness or to engage in aggression-preventive activities. However, three months following the intervention, the experimental group demonstrated a considerable rise in the aforementioned constructs (p > 0.001 in all cases).

Originality/value

The study’s findings demonstrated the efficacy of a TPB-based educational intervention on constructs of the TPB theory. Results suggest application of a TPB-based educational intervention can have a pro-social impact on the attitudes and behavior of elementary age boys.
Carbon emission reduction and green marketing decisions in a two-echelon low-carbon supply chain considering fairness concern
Authors: Sun Hongxia , Zhong Yang
Published: June 2022

Purpose

The purpose of this paper is to investigate the impact of fairness concern on the optimal pricing, carbon emission reduction (CER), green marketing efforts (GME) and utility of supply chain members in a two-echelon low-carbon supply chain composed of one manufacturer and one retailer. First, three basic models that consider the manufacturer’s different attitudes toward the retailer’s fairness concern are constructed. The optimal decisions of these models are obtained. Second, these optimal solutions are compared, and the effects of some key parameters including fairness concern on the optimal decisions and utility are examined for the three models. Furthermore, the manufacturer may misestimate the retailer’s fairness concern; therefore, an extended model is proposed.

Design/methodology/approach

The authors adopt the manufacturer-led Stackelberg game theoretic framework, where the manufacturer decides the wholesale price and CER level and, then, the retailer determines the retail price and GME.

Findings

The results show that fairness concern has a negative impact on the wholesale price, the level of CER and GME, and fairness concern are not always beneficial for maximizing utility, although it is related to whether the manufacturer pays attention to the retailer’s fairness concern. The manufacturer will gain more utility when considering the fairness concern of retailers than non-consideration. Overestimating or underestimating the fairness concern of the retailers does not lead to benefits for the manufacturer.

Research limitations/implications

This study has the following two limitations that need to be addressed in future research. First, the authors only consider the fairness concern of a single retailer but not peer-induced fairness among multiple competing retailers, which can be taken into account in future studies. Second, the demand function is linearly related to price, CER and GME. Because of the uncertainty of market information, the uncertainty demand function can be further considered.

Originality/value

This paper simultaneously considers the factors CER, GME and fairness concern. The utility function of the retailer is established according to taking the Nash bargaining solution as a fairness reference point, and four different models are constructed and compared.
Efficiency of temporal sensor data compression methods to reduce LoRa-based sensor node energy consumption
Authors: Väänänen Olli , Hämäläinen Timo
Published: June 2022

Purpose

Minimizing the energy consumption in a wireless sensor node is important for lengthening the lifetime of a battery. Radio transmission is the most energy-consuming task in a wireless sensor node, and by compressing the sensor data in the online mode, it is possible to reduce the number of transmission periods. This study aims to demonstrate that temporal compression methods present an effective method for lengthening the lifetime of a battery-powered wireless sensor node.

Design/methodology/approach

In this study, the energy consumption of LoRa-based sensor node was evaluated and measured. The experiments were conducted with different LoRaWAN data rate parameters, with and without compression algorithms implemented to compress sensor data in the online mode. The effect of temporal compression algorithms on the overall energy consumption was measured.

Findings

Energy consumption was measured with different LoRaWAN spreading factors. The LoRaWAN transmission energy consumption significantly depends on the spreading factor used. The other significant factors affecting the LoRa-based sensor node energy consumption are the measurement interval and sleep mode current consumption. The results show that temporal compression algorithms are an effective method for reducing the energy consumption of a LoRa sensor node by reducing the number of LoRa transmission periods.

Originality/value

This paper presents with a practical case that it is possible to reduce the overall energy consumption of a wireless sensor node by compressing sensor data in online mode with simple temporal compression algorithms.
Carbon Isotope Stratigraphy of the Cambrian System in the Eastern Tarim Basin, China
Authors: WANG Huajian , SU Jin , WANG Xiaomei , YE Yuntao , WANG Yu , FANG Yu , ZHANG Shuichang
Published: June 2022

The ultra‐deep Cambrian System in the Tarim Basin is an important field for petroleum exploration, while fine division of the Cambrian strata remains controversial. In recent years, carbon isotope stratigraphy of the Cambrian System has been established and widely used. Here, we report an integrated profile of carbonate and organic carbon isotopic values (δ13Ccarb and δ13Corg) from cuttings of the Tadong2 Well in the eastern Tarim Basin. Three carbon isotope anomalies of BACE, ROECE and SPICE were recognized on the δ13Ccarb profile. Three apogees and a nadir on the δ13Corg profile and the onset of ROECE on the δ13Ccarb profile were suggested as boundaries of the present four series of the Cambrian System. Suggested boundaries are easily identifiable on the gamma logging profile and is consistent with the previous division scheme, based on biostratigraphic evidence in outcrop sections. Abnormal carbon cycle perturbations and organic carbon burials during the BACE and SPICE events might be related to the reduction and expansion of a huge dissolved organic carbon reservoir in the deep ocean of the ancient Tarim Basin.
Prevalence of early childhood obesity in Ireland: Differences over time, between sexes and across child growth criteria
Authors: Jabakhanji Samira Barbara , Boland Fiona , Ward Mark , Biesma Regien
Published: June 2022

Background

Various child growth criteria exist for monitoring overweight and obesity prevalence in young children.

Objectives

To estimate early overweight and obesity prevalence in Ireland and compare the differences in prevalence across ages, growth criteria and sexes.

Methods

Longitudinal body mass index data from the nationally representative Growing Up in Ireland infant cohort (n = 11 134) were categorized (‘under‐/normal weight’, ‘risk of overweight’, ‘overweight’, ‘obesity’) using the sex‐ and age‐specific International Obesity Task Force growth reference, World Health Organization growth standard and World Health Organization growth reference criteria. Differences in prevalences between criteria and sexes, and changes in each weight category and criterion across ages (9 months, 3 years, 5 years), were investigated.

Results

Across criteria, 11%–40% of children had overweight or obesity at 9 months, 14%–46% at 3 years and 8%–32% at 5 years of age. Prevalence estimates were highest using the World Health Organization growth reference, followed by International Obesity Task Force estimates. Within each criterion, prevalence decreased significantly over time (p < 0.05). However, when combining both World Health Organization criteria, as recommended for population studies, prevalence increased, due to differences in definitions between them. Significantly more boys than girls had overweight/obesity using either World Health Organization criterion, which was reversed using the International Obesity Task Force growth reference.

Conclusions

To increase transparency and comparability, studies of childhood obesity need to consider differences in prevalence estimates across growth criteria. Effective prevention, intervention and policy‐making are needed to control Ireland's high overweight and obesity prevalence.
What are the odds of burnt‐out risk and leaving the job? Turnover intent consequences of worker burnout using a two sample New Zealand study
Authors: Haar Jarrod
Published: June 2022

Job burnout is a pressing issue for organizations, and this study explores the new Burnout Assessment Tool (BAT), which provides a robust calculation of burnt‐out risk. Next, the odds of high turnover intentions from burnt‐out risk are calculated using two samples: (1) N = 709 employees and (2) N = 313 managers. Analysis shows the odds of burnt‐out risk are higher for managers (17%) than employees (8%). High burnt‐out risk in employees shows a 47% likelihood of high turnover intent versus 13% for employees with nonburnt‐out risk. High burnt‐out risk in managers shows a 51% likelihood of high turnover intent versus 12% for managers with nonburnt‐out risk. Furthermore, moderating effects of supervisor organizational embodiment were found to interact with burnt‐out risk for employees only, showing the highest turnover intent when embodiment is high, reflecting the potential backlash against the organization.
Perspectivas históricas de la Revista Internacional del Trabajo 1921‐2021: un siglo de investigación sobre el mundo del trabajo1
Authors: HOEHTKER Dorothea
Published: June 2022

En este artículo se analiza la historia de la Revista Internacional del Trabajo (RIT), una importante publicación periódica de la Organización Internacional del Trabajo (OIT) creada en 1921 conforme a lo dispuesto en el artículo 396 del Tratado de Versalles de 1919. Se estudia, desde diversas perspectivas, la transformación del antiguo boletín institucional polivalente en la moderna revista académica que es hoy, atendiendo a su trayectoria institucional, la función de los editores y los perfiles profesionales y académicos de los autores. Se investiga la contribución de la RIT a los debates académicos y de política y su importancia para la OIT, examinando desde una perspectiva histórica los contenidos, temas y ámbitos geográficos de los casi 3 000 artículos publicados hasta la fecha.