bluuebunny/crossref_metadata_2025 huggingface dataset:
Agreement Between Measured Weight and Fluid Balance in Mechanically Ventilated Children in Intensive Care
Authors: Gelbart Ben , Marchesini Vanessa , Kapalavai Sudeep Kumar , Veysey Andrea , Serratore Alyssa , Appleyard Jessica , Bellomo Rinaldo , Butt Warwick , Duke Trevor
Published: April 2023

OBJECTIVES:

To investigate the agreement between change in body weight (BW) and fluid balance (FB), and the precision and safety of BW measurement in mechanically ventilated infants in intensive care.

DESIGN:

Prospective observational study.

SETTING:

Tertiary PICU.

PATIENTS:

Infants following cardiac surgery, at baseline, 24 hours, and 48 hours.

INTERVENTIONS:

BW and FB measurement at three time points.

MEASUREMENTS AND MAIN RESULTS:

Between May 2021 and September 2022, we studied 61 children. The median age was 8 days (interquartile range [IQR], 1.0–14.0 d). The median BW at baseline was 3,518 g (IQR, 3,134–3,928 g). Change in BW was –36 g (IQR, –145 to 105 g) and –97 g (IQR, –240 to –28 g) between baseline and 24 hours, and between 24 and 48 hours, respectively. Change in FB was –82 mL (IQR, –173 to 12 mL) and –107 mL (IQR, –226 to 103) between baseline and 24 hours, and between 24 and 48 hours, respectively. In Bland-Altman analyses, the mean bias between BW and FB at 24 and 48 hours was 54 g (95% CI, 12–97) and –43 g (95% CI, –108 to 23), respectively. This exceeded 1% of the median BW, and limits of agreement ranged from 7.6% to 15% of baseline BW. The precision of paired weight measurements, performed sequentially at each time interval, was high (median difference of ≤1% of BW at each time point). The median weight of connected devices ranged from 2.7% to 3% of BW. There were no episodes of tube or device dislodgments and no change in vasoactive therapies during weight measurements.

CONCLUSIONS:

There is moderate agreement between the changes in FB and BW, albeit greater than 1% of baseline BW, and the limits of this agreement are wide. Weighing mechanically ventilated infants in intensive care is a relatively safe and precise method for estimating change in fluid status. Device weight represents a relatively large proportion of BW.
Availability of Pediatric Emergency Care Coordinators in US Emergency Departments in 2018
Authors: Boggs Krislyn M. , Espinola Janice A. , Sullivan Ashley F. , Li Joyce , Auerbach Marc , Hasegawa Kohei , Samuels-Kalow Margaret E. , Camargo Carlos A.
Published: April 2023

Objectives

In 2007, the US Institute of Medicine recommended that every emergency department (ED) appoint pediatric emergency care coordinators (PECCs). Despite this recommendation, our national surveys showed that few (17%) US EDs reported at least 1 PECC in 2015. This number increased slightly to 19% in 2016 and 20% in 2017. The current study objectives were to determine the following: percent of US EDs with at least 1 PECC in 2018, factors associated with availability of at least 1 PECC in 2018, and factors associated with addition of at least 1 PECC between 2015 and 2018.

Methods

In 2019, we conducted a survey of all US EDs to characterize emergency care in 2018. Using the National ED Inventory-USA database, we identified 5514 EDs open in 2018. This survey collected availability of at least 1 PECC in 2018. A similar survey was administered in 2016 and identified availability of at least 1 PECC in 2015.

Results

Overall, 4781 (87%) EDs responded to the 2018 survey. Among 4764 EDs with PECC data, 1037 (22%) reported having at least 1 PECC. Three states (Connecticut, Massachusetts, and Rhode Island) had PECCs in 100% of EDs. The EDs in the Northeast and with higher visit volumes were more likely to have at least 1 PECC in 2018 (all P < 0.001). Similarly, EDs in the Northeast and with higher visit volumes were more likely to add a PECC between 2015 and 2018 (all P < 0.05).

Conclusions

The availability of PECCs in EDs remains low (22%), with a small increase in national prevalence between 2015 and 2018. Northeast states report a high PECC prevalence, but more work is needed to appoint PECCs in all other regions.
Overlapping Intravelar Veloplasty Improves the Speech Outcomes in Submucous Cleft Palate
Authors: Lee Seo Koo , Nam Seung Min , Cha Han Gyu , Jung Se A. , Choi Chang Yong , Park Eun Soo
Published: April 2023

Background

Submucous cleft palate (SMCP) is a subgroup of cleft palate that can present as velopharyngeal insufficiency due to muscle displacement. The pharyngeal flap and Furlow palatoplasty have been introduced to correct SMCP patient with velopharyngeal insufficiency. However, pharyngeal flap and Furlow palatoplasty can occur various complications. We consider the overlapping intravelar veloplasty (IVVP) can overcome these complications. Therefore, we present the speech outcomes of overlapping IVVP for the treatment of patients with SMCP.

Methods

We retrospectively reviewed 12 patients with SMCP underwent overlapping IVVP between April 2016 and October 2018. The patients who underwent speech evaluation, nasometry, and nasoendoscopy before and after surgery and who were followed up for >18 months were enrolled in this study

Results

The average age of the patients was 5 years (range, 3–11 years) and the postoperative follow-up period ranged from 18 to 24 months (mean, 20 months). The preoperative perceptual speech evaluation was moderate and the postoperative evaluation was normal (P < 0.01). The preoperative and postoperative nasalance scores obtained using a nasometer were 37.00 and 12.50, respectively, (P < 0.01). Preoperative and postoperative velopharyngeal movements were grades 3 and 0, respectively, (P < 0.01).

Conclusions

Our study showed that overlapping IVVP could provide successful correction of velopharyngeal insufficiency in patients with SMCP, including relatively old patients.
High-intensity interval training improves cognitive impairment of vascular dementia rats by up-regulating expression of brain-derived neurotrophic factor in the hippocampus
Authors: Guo Chengcheng , Yao Yang , Ma Chunchao , Wang Zhiyun
Published: April 2023

The present study aims to investigate the effect and its potential mechanism of high-intensity intermittent training (HIIT) on cognitive function in vascular dementia (VD) rats. The VD rats with the cognitive impairment were induced by bilateral common carotid artery occlusion (BCCAO), and the ones in the moderate-intensity continuous training (MICT) group and HIIT group received MICT or HIIT for 5 consecutive weeks, respectively. The swimming speed, endurance, and grip strength of rats were all measured after training. The effect and mechanisms of HIIT on ameliorating the cognitive dysfunction were further evaluated by the Morris water maze test, histomorphological analysis, and Western blot analysis. As a result, no significant difference in motor function between VD rats and sham rats was observed. After 5-week HIIT, the motor function of VD rats was significantly enhanced. The results of the Morris water maze test revealed that HIIT significantly reduced escape latency as well as distance to find the platform compared with the sedentary control group (SED group), indicating the improvement in cognitive function. In addition, the hippocampal tissue damage of VD rats measured by H&E staining was markedly ameliorated after 5-week HIIT. Moreover, brain-derived neurotrophic factor (BDNF) expression level in the cerebral cortex and hippocampus tissue detected by Western blot were significantly up-regulated in HIIT group compared to SED group and MICT group. In conclusion, HIIT can improve BCCAO-induced cognitive impairment via up-regulating BDNF expression in VD rats.
Ergosterol extraction: a comparison of methodologies
Authors: Wilkes Thomas I.
Published: April 2023

Ergosterol is a component of the cell membrane of mycorrhizal fungi and is frequently used to quantify their biomass. Arbuscular mycorrhizal (AM) fungi and ectomycorrhizal (ECM) fungi establish a symbiotic relationship with a respective host plant. Several methods are currently employed for quantification of ergosterol; however, these utilise a series of potentially hazardous chemicals with varying exposure times to the user. The present comparative study aims to ascertain the most reliable method to extract ergosterol whilst limiting hazard exposure to the user. Chloroform, cyclohexane, methanol and methanol hydroxide extraction protocols were applied to a total of 300 samples of root samples and a further 300 growth substrate samples across all protocols. Extracts were analysed via HPLC methodologies. Chromagraphic analysis showed chloroform-based extraction procedures produced a consistently higher concentration of ergosterol in both root and growth substrate samples. Methanol hydroxide, without the addition of cyclohexane, produced a very low concentration of ergosterol, with a reduction of quantified ergosterol of between 80 and 92 % compared to chloroform extractions. Hazard exposure was greatly reduced following the chloroform extraction protocol when compared with other extraction procedures.
The possible impact of novel mutations in human papillomavirus 52 on the infection characteristics
Authors: Gong Yingxin , Wang Yan , Zhou Qi , Qu Wenjie , Chen Fang , Wang Yaping , Mo Jiayin , Zhang Hongwei , Lin Lin , Bi Tianyi , Wang Xujie , Gu Jiashi , Sui Long , Li Yanyun
Published: April 2023

Human papillomavirus 52 (HPV52) infection is prevalent in the Chinese population, and variations in HPV52 show correlations with oncogenicity. However, no specific variation in HPV52 was reported to show relevancy to infection characteristics. In this study, we retrieved 222 isolates of E6 and L1 full-length genes from 197 Chinese women with HPV52 infection. After sequence alignment and phylogenetic tree construction, we found that 98.39 % of the collected variants belonged to the sublineage B2 and two variants displayed incongruence between the phylogenetic tree of E6 and L1. The analysis of the infection pattern showed that the presence of C6480A/T mutation in the L1 gene was associated with single infection (P=0.01) and persistent infection (P=0.047) of HPV52, while the A6516G nucleotide change was relevant to transient infection (P=0.018). Our data also indicated that variations T309C in the E6 gene and C6480T, C6600A in L1 were more commonly presented in patients with high-grade cytology (P<0.05). One HPV52 breakthrough infection after vaccination was identified, which hinted at the immune escape post-vaccination. Young coitarche age and non-condom usage were correlated to multiple infections. This study provided insight into the polymorphism of HPV52 and revealed the impact of variations in HPV52 on its infection characteristics.
Extracellular release of damaged mitochondria induced by pre-hematopoietic stem cell transplant conditioning exacerbates graft-versus-host disease
Authors: Vijayan Vijith , Yan Hao , Lohmeyer Juliane K. , Prentiss Kaylin A. , Patil Rachna V. , Barbarito Giulia , Lopez Ivan , Elezaby Aly , Peterson Kolten , Baker Jeanette , Ostberg Nicolai P. , Bertaina Alice , Negrin Robert S. , Mochly-Rosen Daria , Weinberg Kenneth , Haileselassie Bereketeab
Published: April 2023

Despite therapeutic advancements, GVHD is a major complication of HSCT. In current models of GVHD, tissue injury induced by cytotoxic conditioning regimens, along with translocation of microbes expressing Pathogen Associated Molecular Patterns (PAMPs), result in activation of host antigen-presenting cells (APC) to stimulate alloreactive donor T lymphocytes. Recent studies have demonstrated that in many pathologic states, tissue injury results in the release of mitochondria from the cytoplasm to the extracellular space. We hypothesized that extracellular mitochondria, which are related to archaebacteria, could also trigger GVHD by stimulation of host APC. We found that clinically relevant doses of radiation or busulfan induced extracellular release of mitochondria by various cell types, including cultured intestinal epithelial cells. Conditioning-mediated mitochondrial release was associated with mitochondrial damage and impaired quality control but did not affect the viability of the cells. Extracellular mitochondria directly stimulated host APCs to express higher levels of MHC-II, co-stimulatory CD86, and pro-inflammatory cytokines, resulting in increased donor T cell activation, and proliferation in mixed lymphocyte reactions. Analyses of plasma from both experimental mice and a cohort of children undergoing HSCT demonstrated that conditioning induced extracellular mitochondrial releasein vivo. In mice undergoing MHC mismatched HSCT, administration of purified syngeneic extracellular mitochondria increased host APC activation and exacerbated GVHD. Our data suggests that pre-HSCT conditioning results in extracellular release of damaged mitochondria which increase alloreactivity and exacerbate GVHD. Therefore, decreasing the extracellular release of damaged mitochondria following conditioning could serve as a novel strategy for GVHD prevention.
Aspiration thrombectomy for patients with stroke and late onset to treatment: a subset analysis of the COMPLETE registry
Authors: Hassan Ameer E. , Fifi Johanna T. , Zaidat Osama O. ,   COMPLETE Study Investigators
Published: April 2023

Background

The purpose of this study was to report the safety and performance of aspiration thrombectomy for patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO) and late onset to treatment.

Methods

This is a retrospective subset analysis of a global prospective multicenter registry (COMPLETE) that enrolled adults with AIS due to LVO and a pre-stroke modified Rankin Scale score (mRS) of 0 or 1 who were treated with aspiration thrombectomy with the Penumbra System. This subset analysis included all patients in the registry who had anterior circulation LVO, an Alberta Stroke Program Early CT Score of at least 6, and late onset to treatment (>6 hours from stroke onset to puncture).

Results

Of the 650 patients in the COMPLETE registry, 167 were included here. The rate of successful revascularization at the end of the procedure was 83.2% (139/167), the rate of good functional outcome (mRS 0-2) at 90 days was 55.4% (87/157), and the all-cause mortality rate at 90 days was 14.4% (24/167). No device-related serious adverse events (SAEs) occurred.

Procedure-related SAEs occurred in 9 patients (5.4%) within 24 hours and in 12 patients (7.2%) overall. No significant difference was detected between the outcomes of patients with an onset to puncture time of greater than 6 hours and less than or equal to 12 hours and the outcomes of patients with an onset to puncture time of greater than 12 hours.

Conclusions

For patients with AIS due to anterior circulation LVO and with late onset to treatment, aspiration thrombectomy with the Penumbra System appears to be safe and effective. The rates of good functional outcome and all-cause mortality from this study compared favorably with those rates from the medical management arms of the DAWN and DEFUSE-3 studies.

Registration

URL:https://www.clinicaltrials.gov; Unique identifier:NCT03464565.
Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response
Authors: de Cevins Camille , Delage Laure , Batignes Maxime , Riller Quentin , Luka Marine , Remaury Anne , Sorin Boris , Fali Tinhinane , Masson Cécile , Hoareau Bénédicte , Meunier Catherine , Parisot Mélanie , Zarhrate Mohammed , Pérot Brieuc P. , García-Paredes Víctor , Carbone Francesco , Canard Luc , Boussard Charlotte , Crickx Etienne , Guillemot Jean-Claude , Frémond Marie-Louise , Neven Bénédicte , Boldina Galina , Augé Franck , Alain Fischer , Didier Michel , Rieux-Laucat Frédéric , Ménager Mickael M.
Published: April 2023

Gain-of-function mutations inSTING1, which encodes the Stimulator of Interferon Gene (STING), result in a severe autoinflammatory disease termed STING-associated vasculopathy with onset in infancy (SAVI). Although elevated type I interferon (IFN) production is thought to be the leading cause of the symptoms observed in patients, STING can induce a set of pathways, which roles in the onset and severity of SAVI, remain to be elucidated. To address this point, we compared a single-cell RNA sequencing (scRNA-seq) dataset of peripheral blood mononuclear cells (PBMCs) from SAVI patients to a dataset of healthy PBMCs treated with recombinant IFN-β. We revealed a loss of mucosal associated invariant T cells and CD56brightnatural killer cells in SAVI patients, not observed in IFN-β-treated PBMC. Patients’ T cells present markers of early activation, associated with markers of senescence and apoptosis. Inferring cell-to-cell communication from scRNA-seq predicted monocytes as potential drivers of this T cell phenotype. Furthermore, scRNA-seq clustering identified a patient-specific subset of monocytes, expressing a strong integrated stress response (ISR), and highCCL3,CCL4andIL-6. It also pinpointed to a patient with lower ISR, allowing us to identify a secondary mutation in PERK, recently shown to be activated by STING to trigger the ISR. Finally, based on the identification of this patient-specific subset of monocytes and the exploration of IFN-β stimulated PBMCs from healthy donors, we developed a strategy to propose a transcriptomic signature specific of STING activation and independent of type I IFN response. Altogether, these results provide a deeper understanding of SAVI at the cellular and molecular levels.
Mapping of the gene network that regulates glycan clock of ageing
Authors: Frkatović-Hodžić Azra , Miškec Karlo , Mijakovac Anika , Nostaeva Arina , Sharapov Sodbo Z. , Landini Arianna , Haller Toomas , van den Akker Erik , Sharma Sapna , Cuadrat Rafael R. C. , Mangino Massimo , Li Yong , Keser Toma , Rudman Najda , Štambuk Tamara , Pučić-Baković Maja , Trbojević-Akmačić Irena , Gudelj Ivan , Štambuk Jerko , Pribić Tea , Radovani Barbara , Tominac Petra , Fischer Krista , Beekman Marian , Wuhrer Manfred , Gieger Christian , Schulze Matthias B. , Wittenbecher Clemens , Polasek Ozren , Hayward Caroline , Wilson James F. , Spector Tim D. , Köttgen Anna , Vučković Frano , Aulchenko Yurii S. , Vojta Aleksandar , Krištić Jasminka , Klarić Lucija , Zoldoš Vlatka , Lauc Gordan
Published: April 2023

Glycans are an essential structural component of Immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation). We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in thein vitroIgG expression system. Up- and downregulation of three genes,EEF1A1, MANBAandTNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in thisin vitroexpression system.
Non-obese lipedema patients show a distinctly altered Quantitative Sensory Testing profile with high diagnostic potential
Authors: Dinnendahl Rebecca , Tschimmel Dominik , Löw Vanessa , Cornely Manuel , Hucho Tim
Published: April 2023

Background

Lipedema is a widespread severe chronic disease affecting mostly women. Characterized by painful bilateral fat accumulation in extremities sparing hands and feet, objective measurement-based diagnosis is currently missing. We tested for characteristic psychometric and/or sensory alterations including pain and for their potential for medical routine diagnostic.

Methods

Pain-psychometry were assessed using the German Pain Questionnaire. Sensory sensitivity toward painful and non-painful stimuli was characterized in non-obese lipedema patients and matched controls using the validated QST-protocol of the German Research Network on Neuropathic Pain.

Results

Lipedema patients showed no overt psychometric abnormalities. Pain was reported as somatic rather than psychosomatic-aversive. All QST measurements were normal, but the pressure pain threshold (PPT) was twofold reduced and the vibration detection threshold (VDT) was two and a half times increased. Both thresholds were selectively altered at the affected thigh but not the unaffected hand. ROC-analysis of the combination of PPT and VDT of thigh versus hand into a PVTH-score shows high sensitivity and specificity, categorizing correctly 96.5% of the participants as lipedema patients or healthy controls. Bayesian inference analysis corroborated the diagnostic potential of a combined PVTH score.

Conclusion

We propose to assess PPT and VDT at the painful thigh and the pain-free hand. Combination in a PVTH-score may allow a convenient lipedema diagnosis early during disease development.

Trial Registration

German Clinical Trials Register (DRKS00030509)

Funding

The project was funded by the DFG (459479161).
Complete genome sequences of the species type strainsSinorhizobium garamanticumLMG 24692TandSinorhizobium numidicumLMG 27395Tand CIP 109850T
Authors: Kaur Sabhjeet , Espinosa-Sáiz Daniel , Velázquez Encarna , Menéndez Esther , diCenzo George C
Published: April 2023

The genusSinorhizobiumcomprises rhizobia that fix nitrogen in symbiosis with legumes. To support taxonomic studies of this genus and of rhizobia more broadly, we report complete genome sequences and annotations for the species type strainsSinorhizobium garamanticumLMG 24692TandSinorhizobium numidicumLMG 27395Tand CIP 109850T. Average nucleotide identity and core-genome phylogenetic analyses confirm thatS. garamanticumandS. numidicumrepresent distinct species.
Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market
Authors: Bloom Jesse D.
Published: April 2023

The role of the Huanan Seafood Market in the early SARS-CoV-2 outbreak remains unclear. Recently the Chinese CDC released data from deep sequencing of environmental samples collected from the market after it was closed on January-1-2020 (Liu et al. 2023a). Prior to this release, Crits-Christophet al. (2023) analyzed data from a subset of the samples. Both studies concurred that the samples contained genetic material from a variety of species, including some like raccoon dogs that are susceptible to SARS-CoV-2. However, neither study systematically analyzed the relationship between the amount of genetic material from SARS-CoV-2 and different animal species. Here I implement a fully reproducible computational pipeline that jointly analyzes the number of reads mapping to SARS-CoV-2 and the mitochondrial genomes of chordate species across the full set of samples. I validate the presence of genetic material from numerous species, and calculate mammalian mitochondrial compositions similar to those reported by Crits-Christophet al. (2023). However, the number of SARS-CoV-2 reads is not consistently correlated with reads mapping to non-human susceptible species. For instance, 14 samples have >20% of their chordate mitochondrial material from raccoon dogs, but only one of these samples contains any SARS-CoV-2 reads, and that sample only has 1 of∼200,000,000 reads mapping to SARS-CoV-2. Instead, SARS-CoV-2 reads are most correlated with reads mapping to various fish, such as catfish and largemouth bass. These results suggest that while metagenomic analysis of the environmental samples is useful for identifying animals or animal products sold at the market, co-mingling of animal and viral genetic material is unlikely to reliably indicate whether any animals were infected by SARS-CoV-2.
Capsular polysaccharide-mediated protein loading onto extracellular membrane vesicles of a fish intestinal bacterium,Shewanella vesiculosaHM13
Authors: Kamasaka Kouhei , Kawamoto Jun , Tsudzuki Taiku , Liu Yuying , Imai Tomoya , Ogawa Takuya , Kurihara Tatsuo
Published: April 2023

Bacterial extracellular membrane vesicles (EMVs) play various physiologically important roles mediated by cargo proteins. However, our understanding of the molecular mechanism underlying cargo loading onto EMVs is limited. In this study, we analyzed the mechanism of cargo protein loading onto EMVs from a fish intestinal Gram-negative bacterium,Shewanella vesiculosaHM13. This strain secretes EMVs carrying a major cargo protein, P49. Near the P49 gene, we found genes having homology to genes involved in protein secretion and surface polysaccharide-chain synthesis. Among them, the deletion of genes encoding homologs of a flippase involved in bacterial extracellular polysaccharide synthesis (HM3343), phosphoethanolamine transferase (HM3344), and glycerophosphodiester phosphodiesterase (HM3345) resulted in the loss of capsular polysaccharide (CPS) of EMVs. We conducted anin vitroP49 loading assay onto P49-free EMVs to examine whether P49 was loaded onto the EMVs via its interaction with the CPS of the EMVs. We found that purified P49 was loaded onto EMVs harboring CPSin vitro, whereas it was not loaded onto EMVs from the mutants lacking CPS production due to the loss of HM3343, HM3344, and HM3345. Transmission electron microscopy of EMVs loaded with P49in vitroandin vivoshowed spherical nanoparticles around the EMVs, whereas such particles were not observed for EMVs without loaded P49, implying that P49 constitutes those particles on the surface of EMVs. These results indicate that P49 is loaded onto EMVs via its interaction with the CPS of EMVs.

IMPORTANCE

Elucidating the mechanisms of cargo loading onto bacterial extracellular membrane vesicles (EMVs) is important to understand their biogenesis and to develop their applications. Here, we show that the major cargo protein of EMVs from a fish intestinal Gram-negative bacterium,Shewanella vesiculosaHM13, is loaded onto EMVs through its interaction with capsular polysaccharide (CPS) of EMVs. Genes involved in CPS synthesis were also identified. To our knowledge, there have been no reports describing the cargo protein-loading mechanism in which CPS serves as the protein-binding scaffold for EMVs. Thus, this study represents a new mode of protein loading onto EMVs. The results deepen our understanding of cargo loading onto EMVs and would contribute to development of their applications.
Regional Prevalence of Hypertension Among People Diagnosed with Diabetes in Africa, A Systematic Review and Meta-analysis
Authors: Hinneh Thomas , Akyirem Samuel , Bossman Irene Fosuhemaa , Lambongang Victor , Ofori-Aning Patriot , Ogungbe Oluwabunmi , Commodore Mensah Yvonne
Published: April 2023

Background

Hypertension and diabetes share common pathophysiological mechanisms and hence have a high likelihood of co-occurring. The co-existence of hypertension and diabetes increases cardiovascular disease risk and healthcare spending. This review aimed to estimate the burden of hypertension among people with diabetes in African countries.

Methods

This review was registered in the International Prospective Register of Systematic Reviews (CRD42021256221). We searched PubMed, Embase, and Hinari databases to identify peer-reviewed articles which provided data on the prevalence of hypertension in people diagnosed with diabetes in Africa. Studies included in the review used different diagnostic criteria and thresholds for hypertension and diabetes diagnosis. We quantified the prevalence of hypertension using random-effects models. We applied generalized linear mixed models with logit transformation to compute regional and overall pooled prevalence and estimate heterogeneity (I2).

Results

Out of 3810 studies retrieved from various sources, 41 met the inclusion criteria with sample sizes ranging from 80 - 116726. The mean age was 58 (± 11) years and 56% were women. The pooled prevalence of hypertension in people diagnosed with diabetes was 58.1% [95% CI: 52.0% - 63.2%]. By African region, Central Africa had the highest hypertension prevalence; 77.6% [95% CI: 53.0% - 91.4%], South Africa 69.1% [95% CI: 59.8% - 77.1%;], North Africa 63.4% [95% CI: 37.1% - 69.1%;], West Africa 51.5% [95% CI: 41.8% - 61.1%] and East Africa 53.0% [95% CI: 45.8% - 59.1%]. Increasing age, being overweight/obese, being employed, longer duration of diabetes, urban residence, and male sex were associated with a higher likelihood of hypertension diagnosis (p-values<0.005).

Conclusion

The high prevalence of hypertension among people with diabetes in Africa, highlights the critical need for an integrated differentiated service delivery to improve and strengthen primary care and prevent cardiovascular disease. Findings from this meta-analysis may inform the delivery of interventions to prevent premature cardiovascular disease deaths among persons in African countries.
Analysis of DNA transposition by DNA transposases in human cells
Authors: Bigot Yves , Yamada Makiko , Mueller Helen , Morell Victor , Alves Sabine , Lecomte Thierry , Kentsis Alex
Published: April 2023

This manuscript discusses the recent report “Cognate restriction of transposition bypiggyBac-like proteins” inNucleic Acids Researchby Beckermann et al and related recent publications about the inability to detect DNA transposition activity of human domesticated DNA transposase PGBD5. Measuring DNA transposition activity of transposases in human cells, where these enzymes can act on endogenous genomic substrates and induce DNA damage, is complicated by these and other cellular responses. Possible reasons for the discordant findings of Beckermann et al with prior independent reports of PGBD5 DNA transposition by Helou et al and Henssen et al and specific details of experimental methods in human cells are presented. In particular, by using independent experiments that reproduce PGBD5-mediated genomic integration, we demonstrate how supraphysiologic and ectopic overexpression of PGBD5 can cause DNA damage and cell death, and artifactual loss of apparent activity in clonogenic transposition reporter assays. While PGBD5 can support apparent DNA transposition, its cellular activity predominantly involves double-strand DNA breaks, deletions and other DNA rearrangements. We discuss the implications of this phenomenon for the interpretation of experimental assays and activities of domesticated DNA transposases.
The Sequence Basis for Selectivity of Ephrin-B2 Ligand for Eph Receptors and Pathogenic Henipavirus G Glycoproteins
Authors: Narayanan Krishna K. , Amaya Moushimi , Tsang Natalie , Yin Randy , Jays Alka , Broder Christopher C. , Shukla Diwakar , Procko Erik
Published: April 2023

Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and functions as a cell entry receptor for several henipaviruses including Nipah virus (NiV), a pathogenic zoonotic virus with pandemic potential. To understand the sequence basis of promiscuity for EFNB2 binding to the attachment glycoprotein of NiV (NiV-G) and Eph receptors, we performed deep mutagenesis on EFNB2 to identify mutations that enhance binding to NiV-G over EphB2, one of the highest affinity Eph receptors. The mutations highlight how different EFNB2 conformations are selected by NiV-G versus EphB2. Specificity mutations are enriched at the base of the G-H binding loop of EFNB2, especially surrounding a phenylalanine hinge upon which the G-H loop pivots, and at a phenylalanine hook that rotates away from the EFNB2 core to engage Eph receptors. One EFNB2 mutant, D62Q, possesses pan-specificity to the attachment glycoproteins of closely related henipaviruses and has markedly diminished binding to the six Eph receptors. However, EFNB2-D62Q has high residual binding to EphB3 and EphB4. A second deep mutational scan of EFNB2 identified combinatorial mutations to further enhance specificity to NiV-G. A triple mutant of soluble EFNB2, D62Q-Q130L-V167L, has minimal binding to Eph receptors but maintains binding, albeit reduced, to NiV-G. Soluble EFNB2 decoy receptors carrying the specificity mutations were potent neutralizers of chimeric henipaviruses. These findings demonstrate how specific residue changes at the shared binding interface of a promiscuous ligand (EFNB2) can influence selectivity for multiple receptors, and may also offer insight towards the development of henipavirus therapeutics and diagnostics.

IMPORTANCE

Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and regulates multiple cell developmental and signaling processes. It also functions as the cell entry receptor for Nipah virus and Hendra virus, zoonotic viruses that can cause respiratory and/or neurological symptoms in humans with high mortality. Here, we investigate the sequence basis of EFNB2 specificity for binding the Nipah virus attachment G glycoprotein over Eph receptors. We then use this information to engineer EFNB2 as a soluble decoy receptor that specifically binds the attachment glycoproteins of Nipah virus and other related henipaviruses to neutralize infection. These findings further mechanistic understanding of protein selectivity and may facilitate the development of diagnostics or therapeutics against henipavirus infection.
Quantifying cell viability through organelle ratiometric probing
Authors: Chen Rui , Qiu Kangqiang , Han Guanqun , Kundu Bidyut Kumar , Ding Guodong , Sun Yujie , Diao Jiajie
Published: April 2023

Detecting cell viability is crucial in research involving the precancerous discovery of abnormal cells, the evaluation of treatments, and drug toxicity testing. Although conventional methods afford cumulative results regarding cell viability based on a great number of cells, they do not permit investigating cell viability at the single-cell level. In response, we rationally designed and synthesized a fluorescent probe, PCV-1, to visualize cell viability under the super-resolution technology of structured illumination microscopy. Given its sensitivity to mitochondrial membrane potential and affinity to DNA, PCV-1’s ability to stain mitochondria and nucleoli was observed in live and dead cells, respectively. During cell injury induced by drug treatment, PCV-1’s migration from mitochondria to the nucleolus was dynamically visualized at the single-cell level. By extension, harnessing PCV-1’s excellent photostability and signal-to-noise ratio and by comparing the fluorescence intensity of the two organelles, mitochondria and nucleoli, we developed a powerful analytical assay namedorganelle ratiometric probing(ORP) that we applied to quantitatively analyze and efficiently assess the viability of individual cells, thereby enabling deeper insights into the potential mechanisms of cell death. In ORP analysis with PCV-1, we identified 0.3 as the cutoff point for assessing whether adding a given drug will cause apparent cytotoxicity, which greatly expands the probe’s applicability. To the best of our knowledge, PCV-1 is the first probe to allow visualizing cell death and cell injury under super-resolution imaging, and our proposed analytical assay using it paves the way for quantifying cell viability at the single-cell level.
A Rapid Inducible RNA Decay system reveals fast mRNA decay in P-bodies
Authors: Blake Lauren A. , Liu Yang , Inoue Takanari , Wu Bin
Published: April 2023

RNA decay plays a crucial role in regulating mRNA abundance and gene expression. Modulation of RNA degradation is imperative to investigate an RNA’s function. However, information regarding where and how RNA decay occurs remains scarce, partially because existing technologies fail to initiate RNA decay with the spatiotemporal precision or transcript specificity required to capture this stochastic and transient process. Here, we devised a general method that employs inducible tethering of regulatory protein factors to target RNAs and modulate their metabolism. Specifically, we established a Rapid Inducible Decay of RNA (RIDR) technology to degrade target mRNA within minutes. The fast and synchronous induction enabled direct visualization of mRNA decay dynamics in cells with spatiotemporal precision previously unattainable. When applying RIDR to endogenousACTBmRNA, we observed rapid formation and disappearance of RNA granules, which coincided with pre-existing processing bodies (P-bodies). We measured the time-resolved RNA distribution in P-bodies and cytoplasm after induction, and compared different models of P-body function. We determined that mRNAs rapidly decayed in P-bodies upon induction. Additionally, we validated the functional role of P-bodies by knocking down specific a P-body constituent protein and RNA degradation enzyme. This study determined compartmentalized RNA decay kinetics for the first time. Together, RIDR provides a valuable and generalizable tool to study the spatial and temporal RNA metabolism in cells.
Development of constrained peptide inhibitors targeting an oncogenic E3 ubiquitin ligase
Authors: Zenkevičiūtė Grasilda , Xu Wenshu , Iegre Jessica , Seki Hikaru , Tan Yaw Sing , Rowling Pamela J.E. , Ferrer Fernando , Verma Chandra , Spring David R. , Laman Heike , Itzhaki Laura S.
Published: April 2023

SCFSkp2/Cks1is an E3 ubiquitin ligase, whose substrate specificity is determined by the oncogenic F-box protein Skp2 and the adaptor protein Cks1. A principal target of SCFSkp2/Cks1is the cyclin-dependent kinase inhibitor p27. Elevated levels of Skp2 and reduced levels of p27 are common in a variety of cancers, and there is consequently a need to develop effective inhibitors of the Skp2-p27 interaction. However, conventional small-molecule approaches are challenging due to the extended bi-molecular interface that spans both Skp2 and Cks1, the lack of suitable binding pockets on this surface, and the intrinsically disordered nature of p27. Here, we develop macrocyclic peptides capable of binding to SCFSkp2/Cks1with nanomolar affinities, an enhancement of almost two orders of magnitude over the natural p27 peptide. We show that these macrocyclic peptides inhibit p27 ubiquitination in vitro, restore p27 levels in a breast cancer cell line, and reduce cell proliferation.
Arbitrium communication controls phage life-cycle through modulation of a bacterial anti-phage defense system
Authors: Guler Polina , Omer Bendori Shira , Aframian Nitzan , Kessel Amit , Eldar Avigdor
Published: April 2023

Bacterial temperate viruses (phages) have to decide between a quiescent (lysogenic) and virulent (lytic) lifestyle in the face of a variety of phage defense systems. MultipleBacilliphage families have been shown to use the arbitrium communication system, but the mechanism by which the arbitrium system exerts its function remains largely unknown. Here we study phage ɸ3T, in which arbitrium was originally identified, and find that arbitrium communication controls the phage life-cycle through interactions with a host-encoded defense system. Under lytic conditions, the arbitrium system expresses an anti-toxin, AimX, which blocks the RNA ribonuclease activity of MazF, part of the MazEF toxin-antitoxin system. When arbitrium signal concentration is high, AimX is not expressed and MazF remains active. We find that this activity is necessary for lysogenization. Finally, we show that MazEF acts as a defense system, and protects bacteria against a lytic ɸ3T mutant which lacks AimX and an additional later-expressed MazE-like antitoxin, YosL. Altogether, our results show how a bacterial defense system has been co-opted by phages to control their lysis/lysogeny decision-making.
Live-cell super-resolution nanoscopy reveals modulation of cristae dynamics in bioenergetically compromised mitochondria
Authors: Golombek Mathias , Tsigaras Thanos , Schaumkessel Yulia , Hänsch Sebastian , Weidtkamp-Peters Stefanie , Anand Ruchika , Reichert Andreas S. , Kondadi Arun Kumar
Published: April 2023

Cristae membranes have been recently shown to undergo intramitochondrial merging and splitting events. Yet, the metabolic and bioenergetic factors regulating them are unclear. Here we investigated whether and how cristae membrane remodelling is dependent on oxidative phosphorylation (OXPHOS) complexes, the mitochondrial membrane potential (ΔΨm), and the ADP/ATP nucleotide translocator. Advanced live-cell STED nanoscopy combined with in-depth quantification were employed to analyse cristae morphology and dynamics after treatment of mammalian cells with rotenone, antimycin A, oligomycin A and CCCP. This led to formation of enlarged mitochondria along with reduced cristae density but did not change the number of cristae remodelling events. CCCP treatment leading to ΔΨmabrogation even enhanced the cristae dynamics showing their ΔΨm-independent nature. Inhibition of OXPHOS complexes was accompanied by reduced ATP levels but did not affect cristae dynamics. However, inhibition of ADP/ATP exchange led to aberrant cristae morphology and impaired cristae dynamics in a mitochondrial subset. In sum, we provide quantitative data of cristae membrane remodelling under different conditions supporting an important interplay between OXPHOS, metabolite exchange and cristae membrane dynamics.

Summary Blurb

Cristae morphology and dynamics are intricately connected
Dynamics and Plasticity of Immune Cells within Tumor Microenvironment
Authors: Wei Chuijin , Dong Liaoliao , Xiong Shumin , Yu Ping , Zhou Ren , Cheng Lin
Published: April 2023

Extensive research has been conducted on the heterogenicity of immune cells within the tumor microenvironment, like cancer cell heterogenicity, particularly with the emergence of single cell analysis. While inducing factors have been used to artificially alter immune cell fatein vitroand dynamic cancer cell plasticity has been recently discovered, it remains unknown whether tumor infiltrating immune cells acquire plasticity and dynamics that contribute to heterogenicity. In this study, we explored mitochondrial DNA mutation combining with chromosome single nucleotide polymorphism to construct phylogenetic trees of immune cells within multiple solid tumors, together with precise cell type and subtype definition based on single cell RNA sequencing data. Based on these lineage tracing landscapes, we systematically identified cell state transitions and fate changes among different immune cell subtypes and types within multiple solid tumors. Interestingly, immune cells demonstrated a high level of plasticity for transitioning between different states, transdifferentiating from one type to another or dedifferentiating to a progenitor stage, in varying frequencies across different cancers. Moreover, most of these cell state transitions and cell fate changes discovered here were previously unknown. The cell changes may arise from extrinsic growth factors and cytokines secreted by tumor microenvironment cells, but intrinsic genetic mutations, particularly those related to ribosomes, may also be involved. Our data reveal that immune cell complexity extends beyond heterogenicity and also encompasses plasticity similar to that of cancer cells. Understanding the underlying mechanism of these cell changes will help elucidate the role of immune cells in cancer development and manipulating the cell change direction may ultimately enhance the efficiency of current immunotherapy.
BFIP: an online tool to calculate the best fitted idealized polyhedron
Authors: Song Zhen , Li Zhengxiao , Zhang Jiahao , Chen Zeyao , Suescun Leopoldo , Liu Quanlin
Published: April 2023

Distortion of polyhedra is frequently used in the structure–property analysis of inorganic materials. The commonly used Baur distortion index (BDI) loses efficacy in dealing with equi-length polyhedra. This work provides an online calculator to characterize the polyhedral distortion on the basis of the best fitted idealized polyhedron (BFIP) method. This method can determine any subtle change between distorted and corresponding idealized polyhedra. It works by fitting an idealized oriented polyhedron of user-selected type to a collection of center and vertex coordinates on an orthonormal basis. The input only needs the coordinates of the center and ligand atoms. It can be accessed at http://bfip.crystalstructure.cn. The function is demonstrated using a distorted MgO6 octahedron. Examples of the application and comparison with the BDI are given, including a tetrahedron, octahedron, eight-vertex triangular dodecahedron/cube and cuboctahedron.
Full-field hard X-ray nano-tomography at SSRF
Authors: Tao Fen , Wang Jun , Du Guohao , Su Bo , Zhang Ling , Hou Chen , Deng Biao , Xiao Tiqiao
Published: April 2023

An in-house designed transmission X-ray microscopy (TXM) instrument has been developed and commissioned at beamline BL18B of the Shanghai Synchrotron Radiation Facility (SSRF). BL18B is a hard (5–14 keV) X-ray bending-magnet beamline recently built with sub-20 nm spatial resolution in TXM. There are two kinds of resolution mode: one based on using a high-resolution-based scintillator-lens-coupled camera, and the other on using a medium-resolution-based X-ray sCMOS camera. Here, a demonstration of full-field hard X-ray nano-tomography for high-Z material samples (e.g. Au particles, battery particles) and low-Z material samples (e.g. SiO2 powders) is presented for both resolution modes. Sub-50 nm to 100 nm resolution in three dimensions (3D) has been achieved. These results represent the ability of 3D non-destructive characterization with nano-scale spatial resolution for scientific applications in many research fields.
Integrating indigenous knowledge and state-of-the-art Earth observation solutions for the Sendai framework implementation
Authors: Pimprikar Milind , Cunningham Myrna , Ravan Shirish , Lambert Simon
Published: April 2023

Purpose

Indigenous peoples represent one of the most vulnerable groups and need access as well as hands-on experience in the use of emerging Earth observations (EO)-based DRR solutions at the community level, while balancing this learning with traditional indigenous knowledge (IK). However, complicating any engagement between EO and IK is the reality that IKs are diverse and dynamic, with location-specific relevance and accuracy. Additionally, the COVID-19 pandemic caused complex risks and cascading effects for which the world was not prepared. Thus, there is a need to examine the lessons learned and motivate emerging EO-based innovations and demonstrations related to DRR and climate change adaptation.

Design/methodology/approach

Hence, this study aims to undertake an in-depth assessment of IK related to DRR covering relevant UN instruments and provides state-of-the-art of opportunities presented by EO-based tools and solutions.

Findings

The overall research strategy was designed to integrate key components of IK for DRR in a coherent and logical way, with those offered by the EO technology developers and providers. There are several EO tools accessible that are relevant to integrate IK and complement DRR. The study examined and identified challenges and barriers to implement workable and replicable EO solutions in pursuit of resilience.

Originality/value

The key findings of this study will help create a balanced approach by acknowledging the importance of IK for DRR with co-development, co-creation and use of culturally relevant EO data and tools for sustainable innovation, capacity building and youth empowerment. The technological inequalities appear to be growing, and it would be challenging to meet the Sendai Framework indicators.