bluuebunny/crossref_metadata_2025 huggingface dataset:
High prevalence of fluoroquinolone‐resistant UTI among US emergency department patients diagnosed with urinary tract infection, 2018–2020
Authors: Faine Brett A. , Rech Megan A. , Vakkalanka Priyanka , Gross Alan , Brown Caitlin , Harding Stephanie J. , Slocum Giles , Zimmerman David , Zepeski Anne , Rewitzer Stacey , Howington Gavin T. , Campbell Matt , Dawson Jordan , Treu Cierra N. , Nelson Lucas , Jones Mandy , Flack Tara , Porter Blake , Sarangarm Preeyaporn , Mattson Alicia E. , Bailey Abby , Kelly Gregory , Talan David A.
Published: June 2022

Background

Uropathogen resistance, fluoroquinolone‐resistance (FQR), and extended spectrum beta‐lactamase (ESBL), has been observed to be emerging worldwide with prevalences above recommended thresholds for routine empirical treatment. The primary aim of our study was to determine the prevalence of FQR from a geographically diverse sample of United States emergency departments (EDs).

Methods

We conducted a multi‐center, observational cohort study using a network of 15 geographically diverse US EDs. All patients ≥18 years of age with the primary or secondary diagnosis of urinary tract infection (UTI) in the ED identified using International Classification of Diseases (ICD‐10) diagnosis code of cystitis, pyelonephritis, or UTI from 2018 to 2020 were included. We calculated descriptive statistics for uropathogens and susceptibilities. Logistic regression analysis was used to identify antimicrobial resistance risk factors associated with FQR Escherichia coli.

Results

Among 3779 patients who met inclusion criteria, median age was 62.9 years (interquartile range [IQR]: 41–77.6) and 76.3% were female. The most common diagnoses were complicated (41.2%) and uncomplicated cystitis (40.3%). E. coli was the most common pathogen (63.2%), followed by Klebsiella pneumoniae (13.2%) and Enterococcus species (5.8%). Across all sites, overall E. coli FQ‐resistance prevalence was 22.1%, ranging from 10.5 to 29.7% by site. The prevalence of ESBL‐producing uropathogen was 7.4%, ranging from 3.6% to 11.6% by site. Previous IV or oral antimicrobial use in the past 90‐days and history of a multi‐drug resistant pathogen were associated with FQ‐resistant E. coli (odds ratio [OR] 2.68, 95% confidence interval [CI]: 2.04–3.51, and OR 6.93, 95% CI: 4.95–9.70, respectively). Of the patients who had FQ‐resistant E. coli or an ESBL‐producing uropathogen isolated, 116 (37.1%) and 61 (36.7%) did not have any documented risk factors for resistance.

Conclusion

FQ‐resistant E. coli is widely prevalent across US sites highlighting the need for ongoing monitoring of antimicrobial resistance and, at some locations, modification of empirical treatments.
The SCF/KIT axis in human mast cells: Capicua acts as potent KIT repressor and ERK predominates PI3K
Authors: Franke Kristin , Kirchner Marieluise , Mertins Philipp , Zuberbier Torsten , Babina Magda
Published: June 2022

Background

The SCF/KIT axis regulates nearly all aspects of mast cell (MC) biology. A comprehensive view of SCF‐triggered phosphorylation dynamics is lacking. The relationship between signaling modules and SCF‐supported functions likewise remains ill‐defined.

Methods

Mast cells were isolated from human skin; upon stimulation by SCF, global phosphoproteomic changes were analyzed by LC–MS/MS and selectively validated by immunoblotting. MC survival was inspected by YoPro; BrdU incorporation served to monitor proliferation. Gene expression was quantified by RT‐qPCR and cytokines by ELISA. Pharmacological inhibitors were supplemented by ERK1 and/or ERK2 knockdown. CIC translocation and degradation were studied in nuclear and cytoplasmic fractions. CIC's impact on KIT signaling and function was assessed following RNA interference.

Results

≈5400 out of ≈10,500 phosphosites experienced regulation by SCF. The MEK/ERK cascade was strongly induced surpassing STAT5 > PI3K/Akt > p38 > JNK. Comparison between MEK/ERK's and PI3K's support of basic programs (apoptosis, proliferation) revealed equipotency between modules. In functional outputs (gene expression, cytokines), ERK was the most influential kinase. OSM and LIF production was identified in skin MCs. Strikingly, SCF triggered massive phosphorylation of a protein not associated with KIT previously: CIC. Phosphorylation was followed by CIC's cytoplasmic appearance and degradation, the latter sensitive to protease but not preoteasome inhibition. Both shuttling and degradation were ERK‐dependent. Conversely, CIC‐siRNA facilitated KIT signaling, functional outputs, and survival.

Conclusion

The SCF/KIT axis shows notable strength in MCs, and MEK/ERK as most prominent module. An inhibitory circuit exists between KIT and CIC. CIC stabilization in MCs may turn out as a therapeutic option to interfere with allergic and MC‐driven diseases.
Comparison of ciprofol (HSK3486) versus propofol for the induction of deep sedation during gastroscopy and colonoscopy procedures: A multi‐centre, non‐inferiority, randomized, controlled phase 3 clinical trial
Authors: Li Junxiang , Wang Xiao , Liu Jin , Wang Xia , Li Xiangkui , Wang Yaping , Ouyang Wen , Li Jun , Yao Shanglong , Zhu Zhaoqiong , Guo Qulian , Yu Yonghao , Meng Jinhai , Zuo Yunxia
Published: June 2022

Ciprofol is a propofol analogue with improved pharmacokinetic properties. A multi‐centre, non‐inferiority trial was conducted to compare the deep sedation properties of ciprofol and propofol with a non‐inferiority margin of 8% in patients undergoing gastroscopy and colonoscopy. In total, 289 patients were randomly allocated for surgery (259 colonoscopy and 30 gastroscopy) at a 1:1 ratio to be given intravenous injections of ciprofol (0.4 mg/kg) or propofol (1.5 mg/kg). The primary outcome was the success rate of colonoscopy defined as colonoscopy completion with no need for an alternative sedative or >5 ciprofol or propofol top up doses within any 15‐min time period. The success rate of colonoscopy was 100% in the ciprofol group vs. 99.2% in the propofol group (mean difference 0.8%, 95% CI: −2.2% to 4.2%). Except for the gastrointestinal lesions found during the gastroscopy and colonoscopy procedures, the occurrence rates of adverse drug reactions in the ciprofol and propofol groups were 31.3% and 62.8%, respectively (P < 0.001). Pain on injection was less common in the ciprofol group (4.9% vs. 52.4%, P < 0.001). The outcomes demonstrated that ciprofol was non‐inferior to propofol with regard to successful sedation for gastroscopy or colonoscopy procedures and no obvious important adverse events occurred.
Stakeholder theory: A process‐ontological perspective
Authors: Valentinov Vladislav , Chia Robert
Published: June 2022

Advocates of stakeholder theory have long known that grasping its key insights requires a specific worldview that is, unfortunately, still not prevalent within the community of strategic management scholars. We argue that this worldview encompasses a process ontology that is radically different from the substance‐ontological outlook typical of the mainstream approaches to strategic management. The unquestioned commitment of strategic management scholarship to a substance ontology leads to the viewing of corporations as macro‐entities comprising aggregations of discrete autonomous actors each relying on individual choice and instrumental rationality. In contrast, within a process‐ontological worldview, corporations and their stakeholders are seen to be sustained and attenuated through social practices and relationships involving interlocking chains of coping actions taken in everyday interactions. We show that adopting a process‐ontological worldview presents a much‐needed step that may help strategic management scholars reach a better understanding of how stakeholder theory deals with three problems of today's capitalism, those value creation and trade, ethics of capitalism, and managerial mindsets. On this basis, we discuss how to process ontology may lead stakeholder theory to further refine its understanding of business strategy, corporate social responsibility, and the common ground between the firm and stakeholders.
Establishing repellent effects of aromatic companion plants on Dysaphis plantaginea, using a new dynamic tubular olfactometer
Authors: Dieudonné Emma , Gautier Hélène , Dardouri Tarek , Staudt Michael , Costagliola Guy , Gomez Laurent
Published: June 2022

The repellent properties of volatile organic compounds (VOCs) emitted by several companion plant species (CPs) were tested on the rosy apple aphid, Dysaphis plantaginea (Passerini) (Hemiptera: Aphididae), in a new dynamic tubular olfactometer connected to a dynamic plant chamber. This device allows a rapid and direct measurement of the repellency of whole plants on an aphid population. The VOC production, correlated to the number of plants in the chamber, was determined, and the VOC concentration in the emitted blend was evaluated to establish a causal link with the aphid response. Three species showed strong repellency properties to D. plantaginea: peppermint, Mentha piperita L., lavandin, Lavandula × intermedia Emeric ex Loisel., and rosemary, Salvia rosmarinus Schleid. (all Lamiaceae). In addition, tests on various rosemary chemotypes showed that the repellency could vary within the chemotype. The developed device revealed a classification of the tested CPs according to the analyzed VOCs and a link between the repellency index (RI) and the presence of certain VOCs. Thus, eucalyptol, β‐ocimene, allo‐ocimene, piperitone, l‐menthone‐1, and l‐menthone‐2 were associated with the highest RIs, although not all of them were identified as repellents. Thus, the repellent effect of a CP results primarily from the produced olfactory mixture in which the presence and quantity of particular VOCs would modulate the repellent efficiency.
Use of antihypertensive medication and formation of de novo intracranial aneurysms
Authors: Räisänen Sari , Huttunen Jukka , Huuskonen Terhi J. , von und zu Fraunberg Mikael , Koivisto Timo , Jääskeläinen Juha E. , Frösen Juhana , Lindgren Antti
Published: June 2022

Background and purpose

Hypertension is a risk factor for subarachnoid hemorrhage and is also considered a risk factor for saccular intracranial aneurysm (sIA) formation. However, there is little direct evidence that antihypertensive medication will reduce sIA formation.

Methods

The impact of antihypertensive medication on de novo sIA formation was studied in an angiographically followed cohort of 1419 patients. Patients were identified from our population‐based Kuopio Intracranial Aneurysm Database, and data on the purchases of antihypertensive medication were obtained from a national registry. Univariate and multivariate analyses were used to investigate the risk factors.

Results

Of the 966 sIA patients who were prescribed with antihypertensive medication, 841 patients used the medication regularly; 20 of them had de novo sIA. One hundred and twenty‐five patients used the medication irregularly and 12 of them developed de novo sIAs. Four hundred and fifty‐three patients did not use antihypertensive medication even though 27 of them had a diagnosis of hypertension, and 10 of them developed de novo sIAs. In the multivariate analysis antihypertensive medication did not significantly reduce de novo sIA formation (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.84–3.06). Age at primary diagnosis (HR: 0.95, 95%: CI 0.93–0.98) and smoking history (HR: 5.53, 95% CI: 2.77–11.05) were significant risk factors for de novo sIA formation. Also, irregular usage of antihypertensive medication was a significant risk factor (HR: 3.84, 95% CI: 1.59–9.29) for de novo sIA formation.

Conclusions

Antihypertensive agents were not associated with a reduction of de novo sIA formation, but irregular use of antihypertensive agents was associated with an increased risk of de novo sIA formation.
Epigenetic regulation of Fructose‐1,6‐bisphosphatase 1 by host transcription factor Speckled 110 kDa during hepatitis B virus infection
Authors: Sengupta Isha , Mondal Payel , Sengupta Amrita , Mondal Atanu , Singh Vipin , Adhikari Swagata , Dhang Sinjini , Roy Siddhartha , Das Chandrima
Published: June 2022

Hepatitis B virus (HBV) is the leading cause of liver disease ranging from acute and chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Studies have revealed that HBV infection broadly reprogrammes the host cellular metabolic processes for viral pathogenesis. Previous reports have shown that glycolysis and gluconeogenesis are among the most deregulated pathways during HBV infection. We noted that despite being one of the rate‐limiting enzymes of gluconeogenesis, the role and regulation of Fructose‐1,6‐bisphosphatase 1 (FBP1) during HBV infection is not much explored. In this study, we report FBP1 upregulation upon HBV infection and unravel a novel mechanism of epigenetic reprogramming of FBP1 by HBV via utilizing host factor Speckled 110 kDa (Sp110). Here, we identified acetylated lysine 18 of histone H3 (H3K18Ac) as a selective interactor of Sp110 Bromodomain. Furthermore, we found that Sp110 gets recruited on H3K18Ac‐enriched FBP1 promoter, and facilitates recruitment of deacetylase Sirtuin 2 (SIRT2) on that site in the presence of HBV. SIRT2 in turn brings its interactor and transcriptional activator Hepatocyte nuclear factor 4‐alpha to the promoter, which ultimately leads to a loss of DNA methylation near the cognate site. Interestingly, this Sp110 driven FBP1 regulation during infection was found to promote viral‐borne HCC progression. Moreover, Sp110 can be used as a prognostic marker for the hepatitis‐mediated HCC patients, where high Sp110 expression significantly lowered their survival. Thus, the epigenetic reader protein Sp110 has potential to be a therapeutic target to challenge HBV‐induced HCCs.
Assessing the role of supplementation stocking: A perspective
Authors: Claussen Julie E. , Philipp David P.
Published: June 2022

Although it is widely accepted that stocking hatchery‐cultured fish can increase the number of fish, decades of scientific evidence have shown that most often those stocking efforts fail to provide the desired “demographic boost” to a naturally reproducing, self‐sustaining target population. Despite this evidence, fish stocking remains a mainstay of fisheries management programmes, even as the biodiversity of wild fish populations and other aquatic organisms are at serious risk due to habitat loss and/or overexploitation across the globe. In this perspective piece, we summarise the reasons why wild and hatchery‐produced fish are not equivalent and describe the genetic and ecological risks associated with stocking programmes. We then present our perspective on the institutional changes that need to occur to assess these risks and offer ways to transition fisheries management strategies to become more effective in conserving levels of aquatic biodiversity from populations to landscapes. We propose that a critical first step to control ill‐conceived fish stocking programmes is to have each country develop, implement, and enforce a scientifically sound National Fish Stocking Policy. To achieve the long‐term sustainability of native fish populations, it is imperative that ecological and evolutionary principles be better integrated into future conservation strategies and management actions.
Harvest and nitrogen effects on bioenergy feedstock quality of grass‐legume mixtures on Conservation Reserve Program grasslands
Authors: Lin Cheng‐Hsien , Namoi Nictor , Hoover Amber , Emerson Rachel , Cortez Marnie , Wolfrum Ed , Payne Courtney , Egenolf Josh , Harmoney Keith , Kallenbach Robert , Lee DoKyoung (D.K.)
Published: June 2022

Perennial grass mixtures established on Conservation Reserve Program (CRP) lands can be an important source of feedstock for bioenergy production. This study aimed to evaluate management practices for optimizing the quality of bioenergy feedstock and stand persistence of grass‐legume mixtures under diverse environments. A 5‐year field study (2008–2012) was conducted to assess the effects of two harvest timings (at anthesis vs after complete senescence) and three nitrogen (N) rates (0, 56, 112 kg N ha−1) on biomass chemical compositions (i.e., cell wall components, ash, volatiles, total carbon, and N contents) and the feedstock energy potential, examined by the theoretical ethanol yield (TEY) and the total TEY (i.e., the product of biomass yield and TEY, L ha−1), of cool‐season mixtures in Georgia and Missouri and a warm‐season mixture in Kansas. The canonical correlation analysis (CCA) was used to investigate the effect of vegetative species transitions on feedstock quality. Although environmental variations (mainly precipitation) greatly influenced the management effect on chemical compositions, the delayed harvest after senescence generally improved feedstock quality. In particular, the overall cell wall concentrations and TEY of the warm‐season mixtures increased by approximately 7%. Additional N supplies improved the total TEY of both mixtures by ~1.6–4.2 L ha−1 per 1.0 kg N ha−1 input but likely lowered the feedstock quality, particularly for the cool‐season mixture. The cell wall concentrations of cool‐season mixture reduced by approximately 3%–6%. The CCA results indicated that the increased legume compositions (under low N input) likely enhanced lignin but reduced ash concentrations. This field research demonstrated that with proper management, grass‐legume mixtures on CRP lands can provide high‐quality feedstock for bioenergy productions.
Leveraging the timing and frequency of patient decision aids in longitudinal shared decision‐making: A narrative review and applied model
Authors: LoBrutto Lara R. , Fix Gemmae , Wiener Renda S. , Linsky Amy M.
Published: June 2022

Introduction

Shared decision‐making (SDM) is intended to increase patient‐centredness of medical decision‐making for patients with acute and chronic conditions. Concurrently, patient decision aids (PtDAs) can supplement SDM by providing information to guide communication between patients and healthcare providers. Because of the prevalence of chronic conditions, where decisions may be extended or recurring, we sought to explore how effectively these tools have been leveraged in this context.

Methods

We conducted a narrative review of the literature on both SDM and PtDAs, searching PubMed and Boston University's library database search tool for English‐language articles published from January 2005 until March 2021. Additional search terms focused on temporality. Drawing from our findings, we developed a combined framework to highlight areas for future research using the discussion of end‐of‐life decisions as an exemplar to illustrate its relevance to chronic care contexts.

Results

After screening 57 articles, we identified 25 articles that fulfilled the inclusion criteria on SDM, PtDA use and temporality for chronic care. The literature on SDM highlighted time outside of the medical visit and opportunity to include outside decision partners as important elements of the process. PtDAs were commonly evaluated for process‐related and proximal outcomes, but less often for distal outcomes. Early evidence points to the value of comparative outcome evaluation based on the timing of PtDA distribution.

Conclusion

Our review of the literature on SDM and PtDAs reveals less attention to the timing of PtDAs relative to that of SDM. We highlight the need for further study of timing in PtDA use to improve longitudinal SDM for chronic care. The model that we propose in our discussion provides a starting point for future research on PtDA efficacy.

Patient or Public Contribution

Five patient consultants provided input and feedback on the development and utility of our model.
Preparation and evaluation of a new combined conjugated vaccine against Klebsiella pneumonia and Pseudomonas aeruginosa
Authors: Bahy Rehab , Fatyan Eman , Saafan Amal E. , El-Gebaly Eman Abd El Aziz
Published: June 2022

Aims

Lower respiratory tract infections (LRTIs) have been identified by the World Health Organization as the most deadly infectious diseases and a pervasive public health problem, causing increased hospital admissions, mortality and antibiotic use. This study aims to determine the most common and resistant bacteria that cause LRTIs and prepare an appropriate vaccine to reduce and prevent potential future infections.

Methods and Results

Our survey was conducted by collecting respiratory exudate specimens. The most predominant and resistant types were Klebsiella pneumonia and Pseudomonas aeruginosa. The lipopolysaccharides (LPS) were extracted using a modified hot phenol method to prepare the vaccine. The LPS were then activated and conjugated. The immunogenicity of the prepared singles and combined vaccines was determined through an in vivo assay using BALB/c mice. The prepared vaccine provided high protection against the lethal dose of both bacteria in mice. The combined vaccine shows a significant value in achieving high immunization.

Conclusion

These findings demonstrate the potential of the bacterial LPS molecules to be used as effective vaccines.

Significance and Impact of Study

Developing an effective single and combined vaccine against P. aeruginosa and K. pneumonia can protect and reduce LRTI incidence.
Bacteriophage-antibiotic combination therapy for multidrug-resistant Pseudomonas aeruginosa: In vitro synergy testing
Authors: Holger Dana J. , Lev Katherine L. , Kebriaei Razieh , Morrisette Taylor , Shah Rahi , Alexander Jose , Lehman Susan M. , Rybak Michael J.
Published: June 2022

Aims

Here, we investigate the impact of phage-antibiotic combinations (PAC) on bacterial killing, resistance development and outer membrane vesicle (OMV) production in multidrug-resistant (MDR) P. aeruginosa.

Methods and Results

After screening 10 well-characterized MDR P. aeruginosa strains against three P. aeruginosa phages, representative strains, R10266 and R9316, were selected for synergy testing based on high phage sensitivity and substantial antibiotic resistance patterns, while phage EM was chosen based on host range. To understand the impact of phage-antibiotic combinations (PAC) against MDR P. aeruginosa, time-kill analyses, OMV quantification and phage/antibiotic resistance testing were performed. Phage and meropenem demonstrated synergistic activity against both MDR strains. Triple combination regimens, phage-meropenem-colistin and phage-ciprofloxacin-colistin, resulted in the greatest CFU reduction for strains R9316 (3.50 log10 CFU ml−1) and R10266 (4.50 log10 CFU ml−1) respectively. PAC resulted in regained and improved antibiotic susceptibility to ciprofloxacin (MIC 2 to 0.0625) and meropenem (MIC 32 to 16), respectively, in R9316. Phage resistance was prevented or reduced in the presence of several classes of antibiotics and OMV production was reduced in the presence of phage for both strains, which was associated with significantly improved bacterial eradication.

Conclusions

These findings support the potential of phage-antibiotic synergy (PAS) to augment killing of MDR P. aeruginosa. Systematic in vitro and in vivo studies are needed to better understand phage interactions with antipseudomonal antibiotics, to define the role of OMV production in P. aeruginosa PAC therapy and to outline pharmacokinetic and pharmacodynamic parameters conducive to PAS.

Significance and Impact of Study

This study identifies novel bactericidal phage-antibiotic combinations capable of thwarting resistance development in MDR and XDR P. aeruginosa strains. Furthermore, phage-mediated OMV reduction is identified as a potential mechanism through which PAC potentiates bacterial killing.
Characterization of carbapenem-resistant Acinetobacter baumannii ST540 and Klebsiella pneumoniae ST2237 isolates in a pneumonia case from China
Authors: Zhang Dao-Feng , Zhang Zeng-Feng , Li Pan-Dong , Qu Ping-Hua
Published: June 2022

Aims

This study aimed to characterize the chromosome and plasmid sequences, and determine the transferability of plasmids in carbapenem-resistance Acinetobacter baumannii DD520 and Klebsiella pneumoniae DD521 isolates from the same patient who was co-infected in a hospital in China.

Methods and Results

Both isolates DD520 and DD521 exhibited multidrug resistance phenotype, especially the former isolate which was resistant to nine classes of antimicrobials including carbapenems, quinolones, penicillins, cephalosporins, tetracyclines, phenicols, fosfomycins, sulfanilamides and aminoglycosides. Carbapenem resistance genes of blaOXA-23 and blaOXA-66 were identified on the chromosome of A. baumannii DD520, and blaKPC-2 was found in the plasmid pDD521.2 from K. pneumoniae DD521. Phylogenetic analysis revealed that A. baumannii DD520 belonged to the ST540 clone, and K. pneumoniae DD521 belonged to the ST2237 clone. Plasmid analysis suggested that blaKPC-2 was embedded into plasmid pDD521.2, which might be resulted from IS26- and Tn1721-mediated transposition. Plasmid pDD521.2 carrying blaKPC-2 successfully transferred from K. pneumoniae DD521 into Escherichia coli C600, and carbapenems resistance also transferred in the conjugation.

Conclusions

To our knowledge, it was the first report of A. baumannii ST540 and K. pneumoniae ST2237 in the same patient in China. Both these two isolates exhibited resistance to carbapenem, which was likely to have resulted from carbapenem-resistance genes blaOXA-23-blaOXA-66 on the chromosome of A. baumannii ST540, and blaKPC-2 in the plasmid of K. pneumoniae ST2237.

Significance and Impact of the Study

Our study highlighted that effective measures were urgent to prevent and control the co-infection caused by two or more carbapenem-resistance pathogens in the same patient.
Sonographic evaluation of hypertension: Role of atrophic index and renal resistive index
Authors: Gigante Antonietta , Perrotta Adolfo Marco , De Marco Oriana , Rosato Edoardo , Lai Silvia , Cianci Rosario
Published: June 2022

Hypertension can cause structural and functional renal damage. Intrarenal ultrasound parameters have been extensively investigated in hypertensive patients and among the parameters introduced, the renal resistive index (RI) is associated with the progression of chronic kidney disease and hypertension. Atrophic index (AI) is an indirect anatomical ultrasound index that reports the atrophic changes of the renal parenchyma and it is mainly studied in chronic glomerular diseases. The present study aimed to evaluate renal RI and AI in hypertensive patients with normal renal function. AI showed correlations with all parameters associated with renal function reduction (age, creatinine, and intrarenal arterial stiffness). AI, in combination with RI, can represent in hypertensive patients an additional marker for renal damage progression.
Investigation of umbilical cord serum miRNAs associated with childhood obesity: A pilot study from a birth cohort study
Authors: Takatani Rieko , Yoshioka Yusuke , Takahashi Tomoko , Watanabe Masahiro , Hisada Aya , Yamamoto Midori , Sakurai Kenichi , Takatani Tomozumi , Shimojo Naoki , Hamada Hiromichi , Ochiya Takahiro , Mori Chisato
Published: June 2022

We investigated umbilical cord serum microRNA (miRNA) profiles to identify biomarkers of a risk for obesity later in life. Participating children were divided into high‐ and low‐risk groups of obesity based on the timing of adiposity rebound and the body mass index (BMI) at 5 years and randomly selected from each group for this study. 3D‐Gene® Human miRNA Oligo Chip was performed using cord serum in five children of both groups. The most relevant miRNAs were confirmed in 33 children of the groups using the TaqMan® microRNA assay. We detected five cord serum miRNAs differentially expressed in children at high risk of obesity compared with the levels in children at low risk, namely, miR‐516‐3p and miR‐130a‐3p with increased levels and miR‐1260b, miR‐4709‐3p, and miR194‐3p with decreased levels. This study provides the first identification of altered umbilical cord serum miRNAs in childhood obesity.
Facilitators and barriers to providing culinary nutrition, culinary medicine and behaviour change support: An online cross‐sectional survey of Australian health and education professionals
Authors: Asher Roberta C. , Bucher Tamara , Shrewsbury Vanessa A. , Clarke Erin D. , Herbert Jaimee , Roberts Steven , Meeder Annette , Collins Clare E.
Published: June 2022

Background

An Australia wide cross‐sectional online survey examined facilitators and barriers of health and education professionals to providing culinary nutrition (CN) and culinary medicine (CM) education and behaviour change support in usual practice, in addition to identifying continuing professional development (CPD) needs in this domain.

Methods

Survey items included socio‐demographic characteristics, cooking and food skills confidence, nutrition knowledge (PKB‐7), fruit and vegetable intake (FAVVA) and CPD needs. Data were summarised descriptively.

Results

Of 277 participants, 65% were likely/somewhat likely to participate in CN CPD. Mean (SD) cooking and food skill confidence scores were 73 (17.5) and 107.2 (24), out of 98 and 147, respectively. Mean PKB‐7 score was 3.7 (1.4), out of 7. Mean FAVVA score was 98 (29), out of 190.

Conclusions

Gaps in knowledge and limited time were the greatest modifiable barriers to providing CM/CN education and behaviour change support in practice. Health and education professionals are interested in CPD conducted by dietitians and culinary professionals to enhance their knowledge of CM/CN and behaviour change support.
The factors related to recovery time of diaper dermatitis in infants: A prospective observational study
Authors: Yokoyama Moeri , Yonezawa Kaori , Matsubara Manami , Hikita Naoko , Sasagawa Emi , Haruna Megumi
Published: June 2022

Aim

Prolonged diaper dermatitis may increase the risk of atopic dermatitis or infections. This prospective observational study aimed to investigate the prevalence, symptoms, areas, and recovery time of diaper dermatitis in infants aged 1 month and identify the factors related to recovery time.

Methods

Diaper dermatitis was defined as the presence of erythema, papules, dryness, erosion, or ulceration in the diapered area. Recovery time was days between infant's 1‐month medical check‐up and disappearance of symptoms. Survival analysis was performed using the Kaplan–Meier method, and the log‐rank test was used to identify the factors related to recovery time.

Results

Among 113 infants, 66 (58.4%) had diaper dermatitis, with erythema at the perianal area being the most common symptom. The median recovery time was 10 days. Four infants (6.1%) had diaper dermatitis for >5 weeks. Severity was not related to recovery time.

Conclusions

A frequency of diaper changing of ≤10 times per day was a risk factor for recovery time. Our data showed recovery in approximately 10 days, regardless of severity at study enrollment. Health care professionals could inform parents of recovery time and recommended diaper changing frequency.
Variations in temporal trends in non‐traumatic dental condition related emergencies
Authors: Nagarajan Radhakrishnan , Panny Aloksagar , Berg Richard , Acharya Amit , Nycz Greg
Published: June 2022

Objective

The objective of the study was to investigate temporal trends in non‐traumatic dental condition (NTDC) related emergency visits at Emergency Department (ED), urgent care (UC), and at a Federally Qualified Health Center (FQHC) that providing dental services to a mid‐sized rural community.

Methods

Temporal trends over a 9‐year period (2008–2016) in NTDC rates at ED, UC, FQHC and in a region around the FQHC were determined. Statistically significant changes (α = 0.05) in the proportion of NTDC visits between FQHC and UC across each of the time points were investigated.

Results

Proportion of NTDC ED visits was relatively stable over the study period; whereas those at FQHC exceeded those at UC site beginning 2012 and were significantly (α = 0.05) higher than that of UC subsequently (2015–2016).

Conclusions

NTDCs are preventable dental conditions and the care provided in treating NTDCs in emergency settings is palliative and does not address the underlying conditions resulting in poor outcomes. The results presented elucidate the critical role of FQHCs in significantly reducing NTDC visits. These might be precursors to a potential shift in NTDC care seeking behavior and expected to favorably impact oral health outcomes.
Pharmacokinetics of grapiprant and effects on TNF‐alpha concentrations following oral administration to horses
Authors: Hoffmann Silke L. , Seminoff Kelsey , McKemie Daniel S. , Kass Philip H. , Knych Heather K.
Published: June 2022

Grapiprant is a prostaglandin E2 receptor antagonist that has been found to be an effective anti‐inflammatory in dogs and that is devoid of some of the adverse effects associated with traditional NSAIDs that elicit their effects through inhibition of PGE2 production. Previously published reports have described the pharmacokinetics of this drug in horses when administered at 2 mg/kg; however, pharmacodynamic effects in this species have yet to be described. The objective of the current study was to describe the pharmacokinetics and pharmacodynamics of grapiprant at a higher dose. Eight horses received a single oral administration of 15 mg/kg. Plasma concentrations were determined for 96 h using liquid chromatography–tandem mass spectrometry. Non‐compartmental analysis was used to determine pharmacokinetic parameters. Pharmacodynamic effects were assessed ex vivo by stimulating blood samples with PGE2 and determining TNF‐ɑ concentrations. Maximum concentration, time to maximum concentration and area under the curve were 327.5 (188.4–663.0) ng/ml, 1 (0.75–2.0) hour and 831.8 (512.6–1421.6) h*ng/ml, respectively. The terminal half‐life was 11.1 (8.27–21.2) hr. Significant stimulation of TNF alpha was noted for 2–4 h post‐drug administration. Results of this study suggest a short duration of EP4 receptor engagement when administered at a dose of 15 mg/kg.
A systematic review of the effect of early mobilisation on length of stay for adults in the intensive care unit
Authors: Monsees Jonas , Moore Zena , Patton Declan , Watson Chanel , Nugent Linda , Avsar Pinar , O'Connor Tom
Published: June 2022

Background

EM has been hypothesized to help prevent the development of ICU acquired weakness and may therefore result in positive outcomes for ICU patients.

Aim

To establish the impact of Early mobilisation (EM) on adult Intensive Care Unit (ICU) patients in terms of ICU length of stay (LOS), as well as hospital LOS, duration of mechanical ventilation, mortality, and functional independence.

Study design

A Systematic Review. EMBASE, MEDLINE, CINAHL, and the Cochrane Library were searched on 24th November 2020. Included studies and other systematic reviews were hand‐searched for further includable studies. The primary outcome was ICU LOS whilst secondary outcomes were duration of MV, mortality, hospital LOS and functional independence. The PRISMA guidelines were utilized to perform the review. Ten randomized controlled trials with a combined total of 1291 patients met inclusion criteria and were scrutinized using the Joanna Briggs Institute (JBI) Checklist for Systematic Reviews. Revman 5.4.1 was used to conduct meta‐analysis were possible.

Results

Results were limited by the evidence available for inclusion, in particular small sample sizes. However, a trend towards a shorter duration of ICU LOS and duration of mechanical ventilation emerged. There was also a trend towards higher rates of functional independence for intervention groups. Mortality rates appeared unaffected and results of meta‐analysis were statistically non‐significant (p = 0.90).

Conclusion

By applying a stricter time limit than previous systematic reviews a trend emerged that the commencement of EM has a positive effect on patient outcomes, in particular ICU LOS.

Relevance to clinical practice

The evidence base surrounding EM remains poor; however on the balance of the available evidence the application of EM should not be delayed.
The Fng3 ING protein regulates H3 acetylation and H4 deacetylation by interacting with two distinct histone‐modifying complexes
Authors: Xu Huaijian , Ye Meng , Xia Aliang , Jiang Hang , Huang Panpan , Liu Huiquan , Hou Rui , Wang Qinhu , Li Dongao , Xu Jin‐Rong , Jiang Cong
Published: June 2022

The steady‐state level of histone acetylation is maintained by histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes. INhibitor of Growth (ING) proteins are key components of the HAT or HDAC complexes but their relationship with other components and roles in phytopathogenic fungi are not well‐characterized.

Here, the FNG3 ING gene was functionally characterized in the wheat head blight fungus Fusarium graminearum. Deletion of FNG3 results in defects in fungal development and pathogenesis. Unlike other ING proteins that are specifically associated with distinct complexes, Fng3 was associated with both NuA3 HAT and FgRpd3 HDAC complexes to regulate H3 acetylation and H4 deacetylation.

Whereas FgNto1 mediates the FgSas3–Fng3 interaction in the NuA3 complex, Fng3 interacted with the C‐terminal region of FgRpd3 that is present in Rpd3 orthologs from filamentous fungi but absent in yeast Rpd3. The intrinsically disordered regions in the C‐terminal tail of FgRpd3 underwent phase separation, which was important for its interaction with Fng3. Furthermore, the ING domain of Fng3 is responsible for its specificities in protein–protein interactions and functions.

Taken together, Fng3 is involved in the dynamic regulation of histone acetylation by interacting with two histone modification complexes, and is important for fungal development and pathogenicity.
Alarmins and innate lymphoid cells 2 activation: A common pathogenetic link connecting respiratory syncytial virus bronchiolitis and later wheezing/asthma?
Authors: Rossi Giovanni A. , Ballarini Stefania , Salvati Pietro , Sacco Oliviero , Colin Andrew A.
Published: June 2022

Severe respiratory syncytial virus (RSV) infection in infancy is associated with increased risk of recurrent wheezing in childhood. Both acute and long‐term alterations in airway functions are thought to be related to inefficient antiviral immune response. The airway epithelium, the first target of RSV, normally acts as an immunological barrier able to elicit an effective immune reaction but may also be programmed to directly promote a Th2 response, independently from Th2 lymphocyte involvement. Recognition of RSV transcripts and viral replication intermediates by bronchial epithelial cells brings about release of TSLP, IL‐33, HMGB1, and IL‐25, dubbed “alarmins.” These epithelial cell‐derived proteins are particularly effective in stimulating innate lymphoid cells 2 (ILC2) to release IL‐4, IL‐5, and IL‐13. ILC2, reflect the innate counterparts of Th2 cells and, when activate, are potent promoters of airway inflammation and hyperresponsiveness in RSV bronchiolitis and childhood wheezing/asthma. Long‐term epithelial progenitors or persistent epigenetic modifications of the airway epithelium following RSV infection may play a pathogenetic role in the short‐ and long‐term increased susceptibility to obstructive lung diseases in response to RSV in the young. Additionally, ILC2 function may be further regulated by RSV‐induced changes in gut microbiota community composition that can be associated with disease severity in infants. A better understanding of the alarmin‐ILC interactions in childhood might provide insights into the mechanisms characterizing these immune‐mediated diseases and indicate new targets for prevention and therapeutic interventions.
Dental care experiences and clinical phenotypes in children on the autism spectrum
Authors: Alvares Gail A. , Mekertichian Kareen , Rose Felicity , Vidler Sally , Whitehouse Andrew J. O.
Published: June 2022

Aims

Children diagnosed with autism spectrum disorder may be at higher likelihood of experiencing poorer oral health and difficulties accessing dental health care. However, identifying which children on the autism spectrum may be more vulnerable to experiencing dental care difficulties is still unknown. This study investigated parental reports of oral health and dental service needs of children diagnosed with autism and explored relationships with clinical phenotypes.

Methods and Results

Participants (n = 140) were parents of children on the autism spectrum who had participated in a large national biobank study, the Australian Autism Biobank, invited to complete additional surveys about oral health, service use, and barriers to care. One third of parents reported their child's oral health was worse than other children the same age, with 26% reporting untreated dental problems. A third of children were reported to have undergone general anaesthesia at least once for dental procedures. Children who had undergone general anaesthesia were more likely to have intellectual disability and greater functional difficulties. Parents of children with greater functional limitations and sensory challenges reported experiencing barriers to accessing dental care more frequently.

Conclusion

These results have important implications for paediatric dentists working with children diagnosed with autism with co‐occurring intellectual, functional, and sensory challenges. Findings may inform the development of more personalised autism‐specific supports.
The Karolinska KI/K COVID‐19 immune atlas: An open resource for immunological research and educational purposes
Authors: Ljunggren Hans‐Gustaf , Heggernes Ask Eivind , Cornillet Martin , Strunz Benedikt , Chen Puran , Rao Muvva Jagadeeswara , Akber Mira , Buggert Marcus , Chambers Benedict J. , Cuapio Gomez Angelica , Dzidic Majda , Filipovic Iva , Flodström‐Tullberg Malin , Garcia Marina , Gorin Jean‐Baptiste , Gredmark‐Russ Sara , Hertwig Laura , Klingström Jonas , Kokkinou Efthymia , Kvedaraite Egle , Lourda Magda , Mjösberg Jenny , Maucourant Christopher , Norrby‐Teglund Anna , Palma Medina Laura M. , Parrot Tiphaine , Perez‐Potti André , Ponzetta Andrea , Ringqvist Emma , Rivera‐Ballesteros Olga , Rooyackers Olav , Sandberg Johan K. , Sandberg John Tyler , Sekine Takuya , Svensson Mattias , Varnaite Renata , Wullimann David ,   Karolinska KI/K COVID‐19 Study Group, Eriksson Lars I. , Aleman Soo , Malmberg Karl‐Johan , Strålin Kristoffer , Björkström Niklas K.
Published: June 2022

The Karolinska KI/K COVID‐19 Immune Atlas project was conceptualized in March 2020 as a part of the academic research response to the developing SARS‐CoV‐2 pandemic. The aim was to rapidly provide a curated dataset covering the acute immune response towards SARS‐CoV‐2 infection in humans, as it occurred during the first wave. The Immune Atlas was built as an open resource for broad research and educational purposes. It contains a presentation of the response evoked by different immune and inflammatory cells in defined naïve patient‐groups as they presented with moderate and severe COVID‐19 disease. The present Resource Article describes how the Karolinska KI/K COVID‐19 Immune Atlas allows scientists, students, and other interested parties to freely explore the nature of the immune response towards human SARS‐CoV‐2 infection in an online setting.
Distributed Model Predictive Control for Connected and Automated Vehicles in the Presence of Uncertainty
Authors: HomChaudhuri Baisravan , Bhattacharyya Viranjan
Published: June 2022

This article focuses on the development of distributed robust model predictive control (MPC) methods for multiple connected and automated vehicles (CAVs) to ensure their safe operation in the presence of uncertainty. The proposed layered control framework includes reference trajectory generation, distributionally robust obstacle occupancy set computation, distributed state constraint set evaluation, data-driven linear model representation, and robust tube-based MPC design. To enable distributed operation among the CAVs, we present a method, which exploits sampling-based reference trajectory generation and distributed constraint set evaluation methods, that decouples the coupled collision avoidance constraint among the CAVs. This is followed by data-driven linear model representation of the nonlinear system to evaluate the convex equivalent of the nonlinear control problem. Finally, to ensure safe operation in the presence of uncertainty, this article employs a robust tube-based MPC method. For a multiple CAV lane change problem, simulation results show the efficacy of the proposed controller in terms of computational efficiency and the ability to generate safe and smooth CAV trajectories in a distributed fashion.
Toward High Energy Density Redox Targeting Flow Batteries With a Mushroom-Derived Electrolyte
Authors: Egitto Joseph , Gokoglan Tugba Ceren , Pahari Shyam K. , Bolibok Jennifer N. , Aravamuthan Sundar Rajan , Liu Fuqiang , Jin Xinfang , Cappillino Patrick J. , Agar Ertan
Published: June 2022

Among several types of redox flow batteries (RFBs) under development, non-aqueous redox flow batteries (NRFBs) have the potential to approach the energy density of lithium-ion batteries, while maintaining the advantages of flow systems, including ability to decouple power and energy ratings, and thermal stability. Despite their promise, NRFBs suffer from low energy densities because the solubility limitation of redox species in non-aqueous solvents remains relatively lower compared to water. One promising concept for drastically improving the energy density of NRFBs is the utilization of solid charge storage materials, which are reversibly oxidized or reduced in the electrolyte tanks upon interaction with the redox active species (mediators) dissolved in electrolyte (i.e., redox-targeting flow battery (RTFB)). Herein, we demonstrate a RTFB using a highly stable, bio-inspired mediator, vanadium(IV/V)bis-hydroxyiminodiacetate (VBH), coupled with cobalt hexacyanoferrate (CoHCF) as the solid charge storage material. Based on the charge/discharge cycling experiments, the energy capacity was found to be enhanced by ∼5x when CoHCF pellets were added into the tank compared to the case without CoHCF. With the pellet approach, up to ∼70% of the theoretical capacity of CoHCF were utilized at 10 mA cm−2 current density. Sufficient evidence has indicated that this concept utilizing redox-targeting reactions makes it possible to surpass the solubility limitations of the active material, allowing for unprecedented improvements to the energy density of RFBs.
Benchmark Buckling Solutions of Truncated Conical Shells by Multiplicative Perturbation With Precise Matrix Exponential Computation
Authors: Zhou Chao , Wang Zixuan , Chen Yiming , Xu Jie , Li Rui
Published: June 2022

The multiplicative perturbation method with precise matrix exponential computation is developed for the buckling analysis of axially compressed truncated conical shells (TCSs) that are commonly encountered in engineering. To overcome the limitation of conventional methods in terms of assuming solution forms, the multiplicative perturbation method is introduced to tackle the governing partial differential equations (PDEs) with variable coefficients. Specifically, the governing equation in matrix form for a buckled TCS is first formulated in the state space. The multiplicative perturbation method is then employed to convert the matrix differential equation with variable coefficients into the state transition equations with constant coefficients, in which the arisen matrix exponential is computed by the precise integral method. Finally, the state transition equations and the boundary conditions are integrated into an entire matrix equation, whose solution provides the buckling loads and buckling modes of the TCS. The convergence study and comprehensive numerical and graphic results are presented. Given the new solutions, the effects of some crucial size parameters as well as boundary conditions on the critical buckling loads are quantitatively studied. Due to the merits on solving PDEs with variable coefficients, the developed method may be extended to more intractable plate and shell problems.