bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitor of apoptosis proteins antagonist SM164 ameliorates experimental MPO-ANCA-associated vasculitis via enhancing fatty acid oxidation in neutrophils
Authors: Wang Luo-Yi , Wang Rui-Xue , Wang Chen , Chen Su-Fang , Sun Xiao-Jing , Li Zhi-Ying , Chen Min , Little Mark A , Zhao Ming-Hui
Published: October 2022

Objectives

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening autoimmune diseases. Inhibitors of apoptosis proteins (IAPs) are a class of molecules engaged in cell death and inflammation, interventions of which are proven effective in a number of inflammatory diseases. Here we tested whether targeting IAPs could ameliorate AAV and explored the potential mechanism.

Methods

We collected 19 kidney specimens from patients with myeloperoxidase (MPO)-AAV to investigate the expression of IAPs. The IAP pan-inhibitor SM164 was used to treat the experimental autoimmune vasculitis (EAV) rat model of AAV. RNA sequencing of renal cortex and enrichment analysis were developed to interpret gene expression. Functional experiments were performed to investigate the role of SM164 on neutrophils and endothelial cells.

Results

The expression of three IAPs (cIAP1, cIAP2 and XIAP) was upregulated in kidneys of AAV patients compared with normal controls. SM164 dramatically reduced renal injury in EAV rats. Transcriptomic analysis revealed prominent alterations in fatty acid oxidation and respiratory burst following SM164 treatment. Functional studies demonstrated that SM164 inhibited neutrophil activation induced by MPO-ANCA positive IgG or serum from MPO-AAV patients, and such inhibitory effect was abolished by gene silencing or pharmacological inhibition of fatty acid oxidation. SM164 also inhibited the adhesion of neutrophils to endothelial cells with little effect on the endothelial injury induced by serum from MPO-AAV patients.

Conclusion

Inhibition of IAPs with SM164 played a protective role in AAV through enhancing intracellular fatty acid oxidation in neutrophils.
Local networks from different parts of the human cerebral cortex generate and share the same population dynamic
Authors: Willumsen Alex , Midtgaard Jens , Jespersen Bo , Hansen Christoffer K K , Lam Salina N , Hansen Sabine , Kupers Ron , Fabricius Martin E , Litman Minna , Pinborg Lars , Tascón-Vidarte José D , Sabers Anne , Roland Per E
Published: October 2022

A major goal of neuroscience is to reveal mechanisms supporting collaborative actions of neurons in local and larger-scale networks. However, no clear overall principle of operation has emerged despite decades-long experimental efforts. Here, we used an unbiased method to extract and identify the dynamics of local postsynaptic network states contained in the cortical field potential. Field potentials were recorded by depth electrodes targeting a wide selection of cortical regions during spontaneous activities, and sensory, motor, and cognitive experimental tasks. Despite different architectures and different activities, all local cortical networks generated the same type of dynamic confined to one region only of state space. Surprisingly, within this region, state trajectories expanded and contracted continuously during all brain activities and generated a single expansion followed by a contraction in a single trial. This behavior deviates from known attractors and attractor networks. The state-space contractions of particular subsets of brain regions cross-correlated during perceptive, motor, and cognitive tasks. Our results imply that the cortex does not need to change its dynamic to shift between different activities, making task-switching inherent in the dynamic of collective cortical operations. Our results provide a mathematically described general explanation of local and larger scale cortical dynamic.
Usefulness of Cervical Computed Tomography Hounsfield Units to Differentiate Kawasaki Disease From a Deep-neck Abscess
Authors: Ogawa Masato , Matsuki Yuichi , Hoshina Takayuki , Kojiro Masumi , Kusuhara Koichi
Published: October 2022

We measured the Hounsfield units (HUs) value of cervical plain computed tomography images to differentiate between Kawasaki disease (KD) and a deep-neck abscess (DNA). The HUs value was significantly lower in KD than in DNA, making it a useful marker for differentiating between these 2 diseases.
Comparison of Long-Term Microscopic and Endoscopic Audiologic Results After Total Ossicular Replacement Prosthesis Surgery
Authors: Baazil Adrianus H.A. , Ebbens Fenna A. , van Spronsen Erik , De Wolf Maarten J.F. , Dikkers Frederik G.
Published: October 2022

Objective

To compare short-term and long-term outcomes after transcanal endoscope-assisted with microscope-assisted ossiculoplasty using the Fisch titanium total prosthesis (FTTP).

Study Design

Retrospective chart review.

Setting

Tertiary referral center.

Patients

Pediatric (<18 yr of age) and adult patients undergoing ossiculoplasty with the FTTP between January 2016 and December 2019.

Intervention

Transcanal endoscope-assisted (n = 30) or microscope-assisted (n = 76) ossiculoplasty with the FTTP. In the microscopic group, 48 were performed through the ear canal and 28 by retroauricular approach.

Main Outcome Measure

Short-term (3 mo) and long-term (average 20.2 mo) PTA0.5-2kHz air and bone conduction thresholds were evaluated.

Results

In total, 106 patients were included. Nine of 30 (30.0%) of endoscopic and 15 of 76 (19.7%) of microscopic patients were pediatric. Endoscopic preoperative air conduction PTA0.5-2kHz was 52.1 ± 15.8 dB and 52.2 ± 17.9 dB for the microscopic group (p > 0.05). Three months postoperative endoscopic air conduction PTA0.5-2kHz was 37.6 ± 17.4 dB (14.5 dB improvement) and 44.6 ± 19.9 dB (7.6 dB improvement) in the microscopic group (p > 0.05). Three months postoperative endoscopic PTA0.5-2kHz ABG was 26.8 ± 16.6 dB and 28.4 ± 14.7 dB in the microscopic group (p > 0.05). Latest follow-up endoscopic air conduction PTA0.5-2kHz audiogram (mean follow-up, 20.6 ± 10.4 mo) was 36.1 ± 18.2 dB (16.0 dB improvement) and 40.1 ± 16.8 dB (12.1 dB improvement) in the microscopic group (mean follow-up, 19.9 ± 10.3 mo)(p > 0.05). For endoscopic air conduction PTA0.5-2kHz, between the 3 months and latest follow-up audiogram, 25.0% showed improvement, 50.0% remained stable, and 25.0% deteriorated. In the microscopic group, 26.7% improved, 46.6% remained stable, and 26.7% deteriorated (p > 0.05).

Conclusion

Our study shows that hearing results with the Fisch titanium total prosthesis are in line with literature. Endoscope-assisted total ossiculoplasty proves to be a suitable technique with comparable results to the microscopic approach.
Improving child care through healthy eating and physical activity
Authors: Payes Roshelle M. , Chong Caliste , Botsko Christopher
Published: October 2022

Purpose of review

Most young children in the United States spend a significant portion of their time in early care and education (ECE) settings, commonly known as child care. This review highlights recent literature to support a continued focus and increased investment in embedding nutrition and physical activity standards within ECE settings and systems as a critical strategy for child obesity prevention. Pediatricians can support the promotion of these standards by understanding their local child care settings and sharing information with families about the importance of healthy eating and physical activity in early childhood.

Recent findings

The child care sector is fragile and complex, but quality improvement efforts have been successful in improving healthy eating and physical activity. Diverse child care providers, including family child care homes, can effectively embed nutrition and physical activity standards in their environments to promote healthy eating and active play, limit screen time, and support breastfeeding families. A small but growing body of evidence also demonstrates how these standards can be embedded in broader state systems to stimulate change across a state.

The literature demonstrates progress supporting diverse child care settings to embed high-impact standards into their environments. There is a small but growing body of evidence around systems-change efforts as well. Greater attention is needed on embedding physical activity standards in facilities, especially family child care homes, and state systems.
Nutritional Management of Infants With a Giant Ruptured Omphalocele
Authors: Burke Shannon , Laverde Ruth , Klarich Mary Kate , Vu Lan Tuyet
Published: October 2022

The nutritional requirements of neonates with congenital abdominal wall defects (AWDs) remain poorly described. In particular, there is a lack of literature on the calorie, protein, and micronutrient needs of those with AWD. Nutritional therapy is a cornerstone of care in patients with burns due to the metabolic consequences of injury to the epithelial layer. Similarly, children with AWD may require specialized nutritional plans to support their growth and wound healing. This case series supports the theory that patients with ruptured omphaloceles may require higher calorie, protein, and micronutrient provisions in comparison to patients with intact omphaloceles, due to increased metabolic demand to support wound healing and skin epithelialization.
Early Surgical Intervention of Congenital Syngnathia
Authors: Kang Dong Ohk , Ahn Jaemyung , Paeng Jun-Young
Published: October 2022

Congenital syngnathia is a rarely reported malformation when there is a fusion between the maxilla and the mandible. It is necessary to modify it in childhood because congenital syngnathia causes incongruity in pronunciation, diet, and esthetics during the growth process. In this case report, 1 case of syngnathia, a rare craniofacial anomaly, is presented with a review of reports. Prompt diagnosis and surgery were performed right after birth for the present case. A partial limitation point was resolved for further growth. Herein, the authors present the case of a female infant (7 d after birth) diagnosed with congenital syngnathia and treated by early surgical intervention.
Rapid fluoroquinolone resistance detection in Pseudomonas aeruginosa using mismatch amplification mutation assay-based real-time PCR
Authors: Madden Danielle E. , McCarthy Kate L. , Bell Scott C. , Olagoke Olusola , Baird Timothy , Neill Jane , Ramsay Kay A. , Kidd Timothy J. , Stewart Adam G. , Subedi Shradha , Choong Keat , Fraser Tamieka A. , Sarovich Derek S. , Price Erin P.
Published: October 2022

Background. Antimicrobial resistance (AMR) is an ever-increasing global health concern. One crucial facet in tackling the AMR epidemic is earlier and more accurate AMR diagnosis, particularly in the dangerous and highly multi-drug-resistant ESKAPE pathogen,

Pseudomonas aeruginosa

.

Objectives. We aimed to develop two SYBR Green-based mismatch amplification mutation assays (SYBR-MAMAs) targeting GyrA T83I (gyrA248) and GyrA D87N, D87Y and D87H (gyrA259). Together, these variants cause the majority of fluoroquinolone (FQ) AMR in

P. aeruginosa

.

Methods. Following assay validation, the gyrA248 and gyrA259 SYBR-MAMAs were tested on 84 Australian clinical

P. aeruginosa

isolates, 46 of which demonstrated intermediate/full ciprofloxacin resistance according to antimicrobial susceptibility testing.

Results. Our two SYBR-MAMAs correctly predicted an AMR phenotype in the majority (83%) of isolates with intermediate/full FQ resistance. All FQ-sensitive strains were predicted to have a sensitive phenotype. Whole-genome sequencing confirmed 100 % concordance with SYBR-MAMA genotypes.

Conclusions. Our GyrA SYBR-MAMAs provide a rapid and cost-effective method for same-day identification of FQ AMR in

P. aeruginosa

. An additional SYBR-MAMA targeting the GyrB S466Y/S466F variants would increase FQ AMR prediction to 91 %. Clinical implementation of our assays will permit more timely treatment alterations in cases where decreased FQ susceptibility is identified, leading to improved patient outcomes and antimicrobial stewardship.
Regulation of DNA replication initiation by ParA is independent of parS location in Bacillus subtilis
Authors: Koh Alan , Strahl Henrik , Murray Heath
Published: October 2022

Replication and segregation of the genetic information is necessary for a cell to proliferate. In

Bacillus subtilis

, the Par system (ParA/Soj, ParB/Spo0J and parS) is required for segregation of the chromosome origin (oriC) region and for proper control of DNA replication initiation. ParB binds parS sites clustered near the origin of replication and assembles into sliding clamps that interact with ParA to drive origin segregation through a diffusion-ratchet mechanism. As part of this dynamic process, ParB stimulates ParA ATPase activity to trigger its switch from an ATP-bound dimer to an ADP-bound monomer. In addition to its conserved role in DNA segregation, ParA is also a regulator of the master DNA replication initiation protein DnaA. We hypothesized that in

B. subtilis

the location of the Par system proximal to oriC would be necessary for ParA to properly regulate DnaA. To test this model, we constructed a range of genetically modified strains with altered numbers and locations of parS sites, many of which perturbed chromosome origin segregation as expected. Contrary to our hypothesis, the results show that regulation of DNA replication initiation by ParA is maintained when a parS site is separated from oriC. Because a single parS site is sufficient for proper control of ParA, the results are consistent with a model where ParA is efficiently regulated by ParB sliding clamps following loading at parS.
Digital Health Tools for the Passive Monitoring of Depression: A Systematic Review of Methods
Authors: de Angel Valeria , Lewis Serena , White Katie , Oetzmann Carolin , Leightley Daniel , Oprea Emanuela , Lavelle Grace , Matcham Faith , Pace Alice , Mohr David C , Dobson Richard , Hotopf Matthew
Published: October 2022

Background: The use of digital tools to measure physiological and behavioural variables of potential relevance to mental health is a growing field sitting at the intersection between computer science, engineering and clinical science. We aim to summarise the literature on remote measuring technologies, mapping methodological challenges and threats to reproducibility, and to identify leading digital signals for depression. Methods: Medical and computer science databases were searched between January 2007 to November 2019. Published studies linking depression and objective behavioural data obtained from smartphone and wearable device sensors in adults with unipolar depression and healthy subjects were included (PROSPERO registration: 2019 CRD42019159929). A descriptive approach was taken to synthesise study methodologies. Results We included 52 studies and found threats to reproducibility and transparency arising from failure to provide comprehensive descriptions of recruitment strategies, sample information, feature construction and the determination and handling of missing data. The literature is characterised by small sample sizes, short follow-up duration and great variability in quality of reporting, limiting the interpretability of pooled results. Bivariate analyses show some consistency in statistically significant associations between depression and digital features from sleep, physical activity, location, and phone use data. Regression and classification machine learning models found predictive value of aggregated features. Interpretation: Recommendations are put forward to improve aspects of generalisability and reproducibility, such as wider diversity of samples, thorough reporting methodology and the potential for reporting bias in studies with numerous features. Funding: National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.
Secondary Analyses for Genome-wide Association Studies using Expression Quantitative Trait Loci
Authors: Ngwa Julius S , Yanek Lisa R , Kammers Kai , Kanchan Kanika , Taub Margaret A , Scharpf Robert B , Faraday Nauder , Becker Lewis C , Mathias Rasika A , Ruczinski Ingo
Published: October 2022

Genome-wide association studies (GWAS) have successfully identified thousands of single nucleotide polymorphisms (SNPs) associated with complex traits; however, the identified SNPs account for a fraction of trait heritability, and identifying the functional elements through which genetic variants exert their effects remains a challenge. Recent evidence suggests that SNPs associated with complex traits are more likely to be expression quantitative trait loci (eQTL). Thus, incorporating eQTL information can potentially improve power to detect causal variants missed by traditional GWAS approaches. Using genomic, transcriptomic, and platelet phenotype data from the Genetic Study of Atherosclerosis Risk family-based study, we investigated the potential to detect novel genomic risk loci by incorporating information from eQTL in the relevant target tissues (i.e. platelets and megakaryocytes). Permutation analyses were performed to obtain family-wise error rates for eQTL associations, substantially lowering the genome-wide significance threshold for SNP-phenotype associations. In addition to confirming the well known association between PEAR1 and platelet aggregation, our eQTL focused approach identified a novel locus (rs1354034) and gene (ARHGEF3) not previously identified in a GWAS of platelet aggregation phenotypes. A colocalization analysis showed strong evidence for a functional role of this eQTL.
Talin1 dysfunction is genetically linked to systemic capillary leak syndrome
Authors: Elefant Naama , Nikolopoulou Pinelopi A , Vassiliki Papadaki V , Oz-Levi Danit , Rouni Georgia , Sion-Sarid Racheli , Edwards William JS , Arapatzi Christina , Yanovsky-Dagan Shira , Cowell Alana R , Meiner Vardiella , Vainstein Vladimir , Grammenoudi Sofia , Lancet Doron , Goult Benjamin T , Harel Tamar , Kostourou Vassiliki
Published: October 2022

Systemic capillary leak syndrome (SCLS) is a rare life-threatening disorder due to profound vascular leak. The trigger and the cause of the disease is currently unknown and there is no specific treatment. Here, we identified a rare heterozygous splice-site variant in theTLN1gene in a familial SCLS case, suggestive of autosomal dominant inheritance with incomplete penetrance. Talin1 has a key role in cell adhesions by activating and linking integrins to the actin cytoskeleton. This variant causes in-frame skipping of exon 54 and is predicted to affect talin’s c-terminal actin binding site (ABS3). Modelling the SCLS-TLN1variant by mimicking the actin-binding disruption inTLN1heterozygous endothelial cells resulted in disorganized endothelial adherens junctions. Mechanistically, we established that disruption of talin’s ABS3 sequestrates talin’s interacting partner, vinculin, at cell-extracellular matrix adhesions, leading to destabilization of the endothelial barrier. We propose that pathogenic variant inTLN1underlie SCLS, providing insight into the molecular mechanism of the disease which can be explored for future therapeutic interventions.

Systemic capillary leak syndrome (SCLS) is a rare potentially lethal disease with unknown etiology and non-specific treatment. Here, we established a heterozygous splice variant of talin1, a key cell adhesion protein, as a genetic link to a familial SCLS case.
CD4+T cell subset imbalances in rheumatoid arthritis
Authors: Mulhearn B , Marshall L , Sutcliffe M , Hannes SK , Fonseka C , Hussell T , Raychaudhuri S , Barton A , Viatte S
Published: October 2022

Background

Despite the report of an imbalance between CD4+T helper (Th) cell subsets in rheumatoid arthritis (RA), patient stratification for precision medicine has been hindered by the discovery of ever more Th cell subsets, as well as contradictory association results.

Objectives

To capture previously reported Th imbalance in RA with deep immunophenotyping techniques; to compare hypothesis-free unsupervised automated clustering with hypothesis-driven conventional biaxial gating and explore if Th cell heterogeneity accounts for conflicting association results.

Methods

Unstimulated and stimulated peripheral blood mononuclear cells from RA patients and controls were immunophenotyped with a 37-marker panel by mass cytometry (chemokine receptors, intra-cellular cytokines, intra-nuclear transcription factors). First, conventional biaxial gating and standard definitions of Th cell subsets were applied to compare subset frequencies between cases and controls. Second, unsupervised clustering was performed with FlowSOM and analysed using mixed-effects modelling of Associations of Single Cells (MASC).

Results

Conventional analytical techniques fail to identify classical Th subset imbalance, while unsupervised automated clustering, by allowing for unusual marker combinations, identified an imbalance between pro- and anti-inflammatory subsets. For example, a pro-inflammatory Th1-like (IL-2+T-bet+) subset and an unconventional but pro-inflammatory IL-17+T-bet+subset were significantly enriched in RA (odds ratio=5.7, p=2.2 × 10−3; odds ratio=9.7, p=1.5×10−3, respectively). In contrast, a FoxP3+IL-2+HLA-DR+Treg subset was reduced in RA (odds ratio=0.1, p=7.7×10−7).

Conclusions

Innovative approaches capture known CD4+T cell subset imbalances in RA blood.
Investigating inequalities in HIV testing in sub-Saharan Africa: insights from a spatial analysis of 25 countries
Authors: Ante-Testard Pearl Anne , Carrasco-Escobar Gabriel , Benmarhnia Tarik , Temime Laura , Jean Kévin
Published: October 2022

Introduction

We aim to explore spatial variations in socioeconomic inequalities in self-reported recent HIV testing uptake in sub-Saharan Africa (SSA) at different geographical scales, in order to identify potential geographical hotspots of inequalities. Additionally, to evaluate the potential benefits of HIV testing programs, we assess whether local levels of HIV testing match the local levels of HIV prevalence.

Methods

We analyzed data from 25 countries in SSA with Demographic and Health Surveys between 2011 and 2019. We quantified socioeconomic inequalities in self-reported HIV testing in the last 12 months with both the Slope Index of Inequality (SII) and Relative Index of Inequality (RII) in different geographical scales to capture sex-specific within-country spatial variations. We also conducted sampling cluster-level analyses based on the Local Indicator of Spatial Association to consider the autocorrelation in SII and RII across SSA countries. To assess the spatial efficiency of HIV testing programs, we measured the correlation between recent HIV testing uptake and HIV prevalence through Pearson correlation across geographical scales.

Results

We observed pro-rich inequalities on both absolute and relative scales in recent HIV testing in the majority of SSA countries in female and male participants at the national level. We also identified inequalities at subnational levels. Within- and between-country heterogeneities in sex-specific inequalities on both inequality scales and their respective spatial distributions varied depending on the scale used. Clustering of high absolute and relative inequalities were mostly observed in Western and Central Africa with a few regions in Eastern and Southern Africa. Despite significant sex-specific correlations between HIV testing and HIV prevalence in all countries when assessed at the national level, we report an absence of such a correlation at fine scale in 39 of 50 sex-country combinations.

Conclusions

These findings highlight the importance of investigating the spatial variability of various HIV indicators and related inequalities. Results may help local, national and international policymakers to prioritize areas and socioeconomic subgroups in need of HIV testing services. Our results also show the need to monitor efficiency of HIV testing programs in relation to HIV risk at subnational levels as a complementary to national estimates.
Genomic epidemiology of the rotavirus G2P[4] strains in coastal Kenya pre- and post-rotavirus vaccine introduction, 2012 – 2018
Authors: Makori Timothy O. , Bargul Joel L. , Lambisia Arnold W. , Mwanga Mike J. , Murunga Nickson , de Laurent Zaydah R. , Lewa Clement S. , Mutunga Martin , Kellam Paul , Cotten Matthew , Nokes D. James , Phan My , Agoti Charles N.
Published: October 2022

The introduction of rotavirus vaccines into the national immunization programme in many countries has led to a decline of childhood diarrhoea disease burden. Coincidentally, the incidence of some rotavirus group A (RVA) genotypes, has increased, which may result from non-vaccine-type replacement. Here we investigate the evolutionary genomics of rotavirus G2P[4] which has shown an increase in countries that introduced the monovalent Rotarix® vaccine. We examined the 63 RVA G2P[4] strains sampled from children (aged below 13 years) admitted to Kilifi County Hospital, Coastal Kenya, pre- (2012 to June 2014) and post- (July 2014-2018) rotavirus vaccine introduction. All the 63 genome sequences showed a typical DS-1 like genome constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. G2 sub-lineage IVa-3 strains predominated in the pre-vaccine era co-circulating with low numbers of G2 sub-lineage IVa-1 strains, whereas sub-lineage IVa-3 strains dominated the post-vaccine period. In addition, in the pre-vaccine period, P[4] sub-lineage IVa strains co-circulated with low numbers of P[4] lineage II strains, but P[4] sub-lineage IVa strains predominated in the post-vaccine period. On the global phylogeny, the Kenyan pre- and post-vaccine G2P[4] strains clustered separately, suggesting that different virus populations circulated in the two periods. However, the strains from both periods exhibited conserved amino acid changes in the known antigenic epitopes, suggesting that replacement of the predominant G2P[4] cluster was unlikely a result of immune escape. Our findings demonstrate that the pre- and post-vaccine G2P[4] strains circulating in Kilifi, coastal Kenya, differed genetically, but likely were antigenically similar. This information informs the discussion on the consequences of rotavirus vaccination on rotavirus diversity.
COVID-19 vaccine equity and the right to health for displaced Venezuelans in Latin America
Authors: Hill David C. , Andrade-Romo Zafiro , Solari Karla , Adams Ellithia , Forman Lisa , Grace Daniel , Silva-Santisteban Alfonso , Perez-Brumer Amaya
Published: October 2022

Given the magnitude of Venezuelan displacement in Latin America, there is a need to assess how migrants were, and will continue to be, addressed in COVID-19 vaccination policies. To explore migration status as a dimension of vaccine equity in Latin America and in relation to international human rights, we assessed national vaccination plans, peer-reviewed, and gray literature published between January 2020 and June 2021. Three key rights-related concerns were found to restrict the health rights of migrants in the region: 1) lack of prioritization of migrants in vaccine distribution; 2) onerous documentation requirements to be eligible for COVID-19 vaccination; and (3) how pervasive anti-migrant discrimination limited equitable health care access. While international human rights law prohibits against discrimination based on migration status, few countries analyzed realized their obligations to provide equal access to COVID-19 vaccines to non-citizens, including displaced Venezuelans. Especially for migrants and displaced people, effective and sustainable vaccination strategies for COVID-19 and future pandemics in Latin America must be guided not only by epidemiological risk but also seek to align with human rights obligations. To achieve this, States must also take special measures to facilitate vaccine access for communities facing systemic discrimination, exclusion, and marginalization.
A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic datasets
Authors: Vlasschaert Caitlyn , Mack Taralynn , Heimlich J. Brett , Niroula Abhishek , Uddin Mesbah , Weinstock Joshua , Sharber Brian , Silver Alexander J. , Xu Yaomin , Savona Michael , Gibson Christopher , Lanktree Matthew B. , Rauh Michael J. , Ebert Benjamin L. , Natarajan Pradeep , Jaiswal Siddhartha , Bick Alexander G.
Published: October 2022

Clonal hematopoiesis of indeterminate potential (CHIP) is a common form of age-related somatic mosaicism that is associated with significant morbidity and mortality. CHIP mutations can be identified in peripheral blood samples sequenced using approaches that cover the whole genome, whole exome or targeted genetic regions; however, differentiating true CHIP mutations from sequencing artifacts and germline variants is a considerable bioinformatic challenge. We present a stepwise method that combines filtering based on sequencing metrics, variant annotation, and novel population-based associations to increase the accuracy of CHIP calls. We apply this approach to ascertain CHIP in ∼550,000 individuals in the UK Biobank complete whole exome cohort and the All of Us Research Program initial whole genome release cohort. CHIP ascertainment on this scale unmasks recurrent artifactual variants and highlights the importance of specialized filtering approaches for several genes includingTET2andASXL1. We show how small changes in filtering parameters can considerably increase CHIP misclassification and reduce the effect size of epidemiological associations. Our high-fidelity call set refines prior population-based associations of CHIP with incident outcomes. For example, the annualized incidence of myeloid malignancy in individuals with small CHIP clones is 0.03%/year, which increases to 0.5%/year amongst individuals with very large CHIP clones. We also find a significantly lower prevalence of CHIP in individuals of self-reported Latino or Hispanic ethnicity in All of Us, highlighting the importance of including diverse populations. The standardization of CHIP calling will increase the fidelity of CHIP epidemiological work and is required for clinical CHIP diagnostic assays.
Spatial interactions between parrotfishes and implications for species coexistence
Authors: Manning J.C. , McCoy S.J. , Benhamou S.
Published: October 2022

Home range behavior mediates species interactions and distributions, and spatiotemporal segregation may facilitate coexistence of competing species. We investigated home range behavior and spatial interactions in four common parrotfishes on coral reefs in Bonaire, Caribbean Netherlands, to determine how spatial interactions mediate species interactions and contribute to their coexistence. We first computed home ranges for males and females of each species. We then quantified spatial overlap (i.e., static interaction) between the home ranges of neighboring male parrotfishes and their activity in shared areas to estimate interaction potential for pairs of individuals. Finally, we analyzed dynamic interactions in simultaneously tracked, spatially co-occurring interspecific pairs of parrotfishes to investigate how they interact in shared space. Generally, spatial overlap of home ranges was much lower for intraspecific pairs than for interspecific pairs, but the probability of finding males in areas shared with males of other species was species-dependent. Males in interspecific pairs moved mostly independently of each other in shared areas, but we did find some evidence of avoidance in interspecific pairs sharing the most space. We discuss our findings within the context of parrotfish social and foraging ecology to further elucidate the spatial ecology of these functionally important reef fishes.
Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy
Authors: Rothman Jason Seth , Borges-Merjane Carolina , Holderith Noemi , Jonas Peter , Silver R. Angus
Published: October 2022

Abstract

Stereological methods for estimating the 3D particle size and density from 2D projections are essential to many research fields. These methods are, however, prone to errors arising from undetected particle profiles due to sectioning and limited resolution, known as ‘lost caps’. A potential solution by Keiding et al. (1972) accounts for lost caps by quantifying the smallest detectable profiles in terms of their limiting section angle (ϕ). However, this simple solution has not been widely adopted nor validated. Rather, model-independent design-based stereological methods, which do not explicitly account for lost caps, have come to the fore. Here, we provide the first experimental validation of the Keiding model by quantifying ϕ of synaptic vesicles using electron-tomography 3D reconstructions. This analysis reveals a Gaussian distribution for ϕ rather than a single value. Nevertheless, curve fits of the Keiding model to the 2D diameter distribution accurately estimate the mean ϕ and 3D diameter distribution. While systematic testing using Monte Carlo simulations revealed an upper limit to determining ϕ, our analysis shows that mean ϕ can be used to estimate the 3D particle density from the 2D density under a wide range of conditions, and this method is potentially more accurate than minimum-size-based lost-cap corrections and disector methods. We applied the Keiding model to estimate the size and density of somata, nuclei and vesicles in rodent cerebella, where high packing density can be problematic for design-based methods.
Quality indicators on medicines packaging as guide to routine quality assurance for procured generic medicines: A community pharmacy survey in Nigeria
Authors: Orubu Ebiowei S.F , Ukuta Elamene C.O. , Robert Faith O.
Published: October 2022

Introduction

While medicines quality assurance is best performed by a Stringent Regulatory Authority (SRA), many countries still lack this capacity. In these contexts, brand manufacturers take additional steps to signal authenticity to their consumers through the use of overt authentication technologies on medicines packaging. The aim of this study was to use quality indicators on the secondary packaging of medicines to identify, and, thus, risk rank, therapeutic groups most prone to being substandard or falsified.

Method

This study profiled medicines in the inventory of a conveniently selected pharmacy in Nigeria by three common packaging quality indicators: (i) National Agency for Food and Drug Administration, NAFDAC, registration number, (ii) a mobile authentication service, MAS, number, and (iii) a hologram.

Results

The inventory contained 66 medicines available as 380 oral, parenteral, or topical products. Of these, 92% had a NAFDAC number, 20% had a MAS number, and 10% bore a hologram – either exclusively, or simultaneously. Antimicrobials – mostly antibiotics and antimalarials – were the most common therapeutic group containing one or all three quality indications. Antibiotic medicines for children formulated as suspensions and drops had the most quality assurance indicators on their packaging.

Conclusion

This result suggests that antimicrobials, especially those formulated for use in children, may be the medicine group at the greatest risk of being substandard or falsified (SF) in Nigeria.The implication of this finding is the need for healthcare facilities to implement strict medicines quality assurance procurement practices especially for antimicrobials. Continued vigilance by the public would also be necessary.
Mushrooms arising from the mole latrine reveal the life of talpid moles: proposals of ‘myco-talpology’ and ‘habitat-cleaning symbiosis’
Authors: Sagara Naohiko , Tuno Nobuko , Fukasawa Yu , Kawada Shin-ichiro , Kasuya Taiga
Published: October 2022

Myco-talpology is the science of moles and mushrooms based on our discovery in 1976 that underground nests of talpid moles can be located by the aboveground fruiting of the agaricsHebeloma danicumorHebeloma sagarae, a Japanese sibling species of EuropeanHebeloma radicosum. Hyphae of these mushrooms specifically colonise mole latrines near nests, forming ectomycorrhizas with the roots of their host trees. By this process, the hyphae and roots absorb, transform, and translocate the nutrients from mole excretions, cleaning the mole’s habitat. The mushrooms fruit on the ground with thick root-like tissue stretching up from the ectomycorrhizas. The presence of the fruit bodies serves as the only indicator for underground mole nests, enabling us to provide novel insights into mole ecology. We excavated 74H. sagaraeorH. danicumsites in Japan and 13H. radicosumsites in Europe and identified the nesting species. These investigations provided new perspectives on latrine making, nest structure, breeding and nestlings, the neighbouring presence of different Talpini species, and long-term nesting at the same site with inhabitant changes. Moreover, they suggested that a tripartite habitat-cleaning symbiosis among moles, mushrooms, and mushroom-host trees in the latrine must have existed for a long time in Japanese and European forests. While moles are traditionally considered inhabitants of open areas, their special relationship with mushrooms and trees suggests they may originally be forest inhabitants.
KBeagle: An Adaptive Strategy and Tool for Improvement of Imputation Accuracy and Computing Efficiency
Authors: Qin Jie , Liu Xinrui , Liu Yaxin , Peng Wei , Kangzhu Yixi , Zhong Jincheng , Wang Jiabo
Published: October 2022

With the development of molecular biology and genetics, deep sequencing technology has become the main way to discover genetic variation and reveal the molecular structure of genome. Due to the complexity of the whole genome segment structure, a large number of missing genotypes have appeared after sequencing, and these missing genotypes can be imputed by genotype imputation method. With the in-depth study of genotype imputation methods, computational intensive and computationally efficient imputation software come into being. Beagle software, as an efficient imputation software, is widely used because of its advantages of low memory consumption, fast running speed and relatively high imputation accuracy. K-Means clustering can divide individuals with similar population structure into a class, so that individuals in the same class can share longer haplotype fragments. Therefore, combining K-Means clustering algorithm with Beagle software can improve the interpolation accuracy. The Beagle and KBeagle method was used to compare the imputation efficiency. The KBeagle method presents a higher imputation matching rate and a shorter computing time. In the genome selection and heritability estimated section, the genotype dataset after imputed, unimputed, and with real genotype show similar prediction accuracy. However the estimated heritability using genotype dataset after imputed is closer to the estimation by the dataset with real genotype. We generated a compounds and efficient imputation method, which presents valuable resource for improvement of imputation accuracy and computing time. We envisage the application of KBeagle will be focus on the livestock sequencing study under strong genetic structure.
Genotypic Characterization of Urinary Tract Infections causing bacteria isolates among Adults at Kiambu Level 5 Hospital, Kenya: Selected Extended Spectrum β-Lactamase genes and Biofilm Formation
Authors: Wanja Fredrick Kimunya , Omwenga Eric Omori , Ngugi Caroline Wangare , Maina John Ndemi , Kiiru John Ndemi
Published: October 2022

The menace of antimicrobial resistance to public health is constantly arising globally. Many pathogenic bacteria use mechanisms such as mutations and biofilm formation, which significantly reduces efficacy of antimicrobial agents. In this cross-sectional study, we aimed at determining the prevalence of selected extended spectrum β-lactamase (ESβLs) genes and analyse the possible biofilm formation abilities of the isolated bacteria causing urinary tract infection among adult patients seeking medicare at Kiambu Level 5 hospital, Kenya. The double-disk synergy test was used for phenotypic identification of ESβLs producing isolates, while microtiter plate assays with some modifications were used to test biofilm formation analysis. A total of 10 isolates were bioassayed for ESβL genes presence out of 57 bacteria isolates obtained from urine samples. From this study, theblaTEMgenes were found to be the most prevalent ESβLs genes (100%), followed byblaOXAandblaSHVgenes at 40% and 30% respectively. In addition, the co-carriage ofblaTEMandblaSHVwas revealed at 50% lower than that ofblaTEM+ blaOXAgenes at 66.7% among the studyE. coliisolates. Biofilm formation finding disclosed that most of the isolates form biofilms 36 (63.2%), with Gram-negatives being the most biofilm formers 25 (69.4%) compared to the Gram-positive 11 (30.6%).E. coli15(41.7 %),Klebsiella sp. 7(19.4%) andS. aureus7(19.4%) were the most common biofilm formers. Further analysis showed no significant difference in biofilm formation among all tested isolates with a p-value of more than 0.05. However, overall Gram-positive isolates had a significant P-value of 0.056. Although biofilm formation’s impact on urinary tract infections is not fully recognized, the carriage of ESβLs resistance genes and the biofilm formation ability negatively impact effectiveness of UTI treatment. Therefore, we advocate for surveillance studies to map ESβLs distribution and biofilm formation genes among UTI etiological agents to halt UTI treatment failure.
A Systematic Review on Medical Oxygen Ecosystem: Current State and Recent Advancements
Authors: Haque Ehtashamul , Tarek Saber Al , Sarker Farhana , Haque Md. Atiqul , Mamun Khondaker A.
Published: October 2022

Background

Medical oxygen is an essential component of modern healthcare, with a wide variety of applications ranging from supplemental use in surgery and trauma patients to the primary medication in oxygen therapy. This is the most effective treatment for any respiratory illness. Despite the importance of oxygen for public health and its demand as a life-saving drug, research on the subject is limited, with the majority of studies conducted following the outbreak of the COVID-19 pandemic. Due to the lack of empirical studies, we aimed to compile the recent research efforts with the current state of the field through a systematic review.

Methods

We have performed a systematic review targeting the medical oxygen ecosystem, following the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P). For the study, we have limited our scope to healthcare facilities and domiciliary applications of medical oxygen. We considered the articles published in the last twenty years, starting from the SARS outbreak in November 2002 to 15thMay 2022.

Results

Our systematic search resulted in forty-one preliminary articles, with three more articles appended for a complete outlook on the topic. Based on the selected articles, the current state of the topic was presented through detailed discussion and analysis.

Conclusion

We have presented an in-depth discussion of the research works found through the systematic search while extrapolating to provide insights on the current subject scenario. We have highlighted the areas with inadequate contemporary studies and presented some research gaps in the field.
Impact of vaccination on the presence and severity of symptoms of hospitalised patients with an infection by the Omicron variant (B.1.1.529) of the SARS-CoV-2 (subvariant BA.1)
Authors: Beraud Guillaume , Bouetard Laura , Civljak Rok , Michon Jocelyn , Tulek Necla , Lejeune Sophie , Millot Romain , Garchet-Beaudron Aurélie , Lefebvre Maeva , Velikov Petar , Festou Benjamin , Abgrall Sophie , Lizatovic Ivan Kresimir , Baldolli Aurélie , Esmer Huseyin , Blanchi Sophie , Froidevaux Gabrielle , Kapincheva Nikol , Faucher Jean-François , Duvnjak Mario , Afşar Elçin , Švitek Luka , Yarimoglu Saliha , Yarimoglu Rafet , Janssen Cécile , Epaulard Olivier
Published: October 2022

Objectives

The emergence of SARS-CoV-2 variants raised questions over the extent to which vaccines designed in 2020 have remained effective. We aimed to assess whether vaccine status was associated with the severity of Omicron SARS-CoV-2 infection in hospitalised patients.

Methods

We conducted an international, multicentric, retrospective study in 14 centres (Bulgaria, Croatia, France, Turkey). We collected data on patients hospitalised ≥24 hours between 01/12/2021 and 03/03/2022, with PCR-confirmed infection at a time of exclusive Omicron circulation, with hospitalisation related or not to the infection. Patients who had received prophylaxis by monoclonal antibodies were excluded. Patients were considered fully vaccinated if they had received at least 2 injections of either mRNA and/or ChAdOx1-S, or 1 injection of Ad26.CoV2-S vaccines.

Results

Among the 1215 patients (median [IQR] age 73.0 [57.0; 84.0]; 51.3% males), 746 (61.4%) were fully vaccinated. In multivariate analysis, being vaccinated was associated with lower 28-day mortality (RR=0.50 [0.32-0.77]), ICU admission (R=0.40 [0.26-0.62], and oxygen requirement (RR=0.34 [0.25-0.46]), independently of age and comorbidities. When co-analysing these Omicron patients with 948 Delta patients from a study we recently conducted, Omicron infection was associated with lower 28-day mortality (RR=0.53 [0.37-0.76]), ICU admission (R=0.19 [0.12-0.28], and oxygen requirements (RR=0.50 [0.38-0.67]), independently of age, comorbidities and vaccination status.

Conclusions

mRNA- and adenovirus-based vaccines have remained effective on severity of Omicron SARS-CoV-2 infection. Omicron is associated with a lower risk of severe forms, independently of vaccination and patient characteristics.
Faecal cytokine levels of preterm infants coupled with microbiome profiles represent a potential non-invasive method to predict severity of necrotizing enterocolitis
Authors: Zenner Christian , Chalklen Lisa , Adjei Helena , Dalby Matthew J. , Mitra Suparna , Cornwell Emma , Shaw Alex , Sim Kathleen , Kroll J. Simon , Hall Lindsay J.
Published: October 2022

Objectives

Necrotizing enterocolitis (NEC) is a life-threatening disease, and the most common gastrointestinal emergency in premature infants. Accurate early diagnosis is challenging. Modified Bell’s staging is routinely used to guide diagnosis, but early diagnostic signs are non-specific, potentially leading to unobserved disease progression, which is problematic given the often rapid deterioration observed in NEC infants. New techniques, using biomarkers as diagnostic tool to improve diagnosis of NEC, are emerging. Here we investigated faecal cytokine levels, coupled with gut microbiota profiles, as a non-invasive method to discover specific NEC-associated signatures that can be applied as potential diagnostic markers.

Study design

Premature babies born below 32 weeks of gestation were admitted to the 2-site neonatal intensive care unit (NICU) of Imperial College hospitals (St. Mary’s or Queen Charlotte’s & Chelsea) between January 2011 and December 2012. All but two babies received a first course of antibiotics from birth onwards. Faecal samples from diapers were collected consecutively during the NICU stay.

Results

Evaluation of microbiota profiles between the study groups revealed only minor differences. However, at later time points, significant changes in microbiota structure were observed for Firmicutes, withEnterococcusbeing the least abundant in Bell stage 2/3 NEC. Faecal cytokine levels were similar to those found in previous studies evaluating systemic cytokine concentrations in NEC settings, but measurement in faeces represents a non-invasive method to evaluate the early onset of the disease. For IL-1α, IL-5 and IL-10, a significantly rising gradient of levels were observed from healthy to NEC1 to NEC2/3.

Conclusions

Differences in certain faecal cytokine profiles in patients with NEC indicate their potential use as diagnostic biomarkers to facilitate earlier diagnosis. Additionally, associations between microbial and cytokine profiles, contribute to improving knowledge about NEC pathogenesis.