bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanopore sequencing identifies a higher frequency and expanded spectrum of mitochondrial DNA deletion mutations in human aging
Authors: Vandiver Amy R. , Hoang Austin N. , Herbst Allen , Lee Cathy C. , Aiken Judd M. , McKenzie Debbie , Teitell Michael A. , Timp Winston , Wanagat Jonathan
Published: May 2023

Mitochondrial DNA (mtDNA) deletion mutations cause many human diseases and are linked to age‐induced mitochondrial dysfunction. Mapping the mutation spectrum and quantifying mtDNA deletion mutation frequency is challenging with next‐generation sequencing methods. We hypothesized that long‐read sequencing of human mtDNA across the lifespan would detect a broader spectrum of mtDNA rearrangements and provide a more accurate measurement of their frequency. We employed nanopore Cas9‐targeted sequencing (nCATS) to map and quantitate mtDNA deletion mutations and develop analyses that are fit‐for‐purpose. We analyzed total DNA from vastus lateralis muscle in 15 males ranging from 20 to 81 years of age and substantia nigra from three 20‐year‐old and three 79‐year‐old men. We found that mtDNA deletion mutations detected by nCATS increased exponentially with age and mapped to a wider region of the mitochondrial genome than previously reported. Using simulated data, we observed that large deletions are often reported as chimeric alignments. To address this, we developed two algorithms for deletion identification which yield consistent deletion mapping and identify both previously reported and novel mtDNA deletion breakpoints. The identified mtDNA deletion frequency measured by nCATS correlates strongly with chronological age and predicts the deletion frequency as measured by digital PCR approaches. In substantia nigra, we observed a similar frequency of age‐related mtDNA deletions to those observed in muscle samples, but noted a distinct spectrum of deletion breakpoints. NCATS‐mtDNA sequencing allows the identification of mtDNA deletions on a single‐molecule level, characterizing the strong relationship between mtDNA deletion frequency and chronological aging.
Identification of fecal microbiome signatures associated with familial longevity and candidate metabolites for healthy aging
Authors: Gong Junli , Liu Sanxin , Wang Shisi , Ruan Hengfang , Mou Qianqian , Fan Ping , Chen Tao , Cai Wei , Lu Yongjun , Lu Zhengqi
Published: May 2023

Gut microbiota associated with longevity plays an important role in the adaptation to damaging stimuli accumulated during the aging process. The mechanism by which the longevity‐associated microbiota protects the senescent host remains unclear, while the metabolites of the gut bacteria are of particular interest. Here, an integrated analysis of untargeted metabolomics and 16S rRNA gene sequencing was used to characterize the metabolite and microbiota profiles of long‐lived individuals (aged ≥90 years) in comparison to old‐elderly (aged 75–89 years), young‐elderly (aged 60–74 years), and young to middle‐aged (aged ≤59 years) individuals. This novel study constructed both metabolite and microbiota trajectories across aging in populations from Jiaoling county (the seventh longevity town of the world) in China. We found that the long‐lived group exhibited remarkably differential metabolomic signatures, highlighting the existence of metabolic heterogeneity with aging. Importantly, we also discovered that long‐lived individuals from the familial longevity cohort harbored a microbiome distinguished from that of the general population. Specifically, we identified that the levels of a candidate metabolite, pinane thromboxane A2 (PTA2), which is positively associated with aging, were consistently higher in individuals with familial longevity and their younger descendants than in those of the general population. Furtherly, functional analysis revealed that PTA2 potentiated the efficiency of microglial phagocytosis of β‐amyloid 40 and enhanced an anti‐inflammatory phenotype, indicating a protective role of PTA2 toward host health. Collectively, our results improve the understanding of the role of the gut microbiome in longevity and may facilitate the development of strategies for healthy aging.
Delayed cortical thinning in children and adolescents with prenatal alcohol exposure
Authors: Gimbel Blake A. , Roediger Donovan J. , Ernst Abigail M. , Anthony Mary E. , de Water Erik , Mueller Bryon A. , Rockhold Madeline N. , Schumacher Moss J. , Mattson Sarah N. , Jones Kenneth L. , Lim Kelvin O. , Wozniak Jeffrey R.
Published: May 2023

Background

Prenatal alcohol exposure (PAE) is associated with abnormalities in cortical structure and maturation, including cortical thickness (CT), cortical volume, and surface area. This study provides a longitudinal context for the developmental trajectory and timing of abnormal cortical maturation in PAE.

Methods

We studied 35 children with PAE and 30 nonexposed typically developing children (Comparisons), aged 8–17 at enrollment, who were recruited from the University of Minnesota FASD Program. Participants were matched on age and sex. They underwent a formal evaluation of growth and dysmorphic facial features associated with PAE and completed cognitive testing. MRI data were collected on a Siemens Prisma 3T scanner. Two sessions, each including MRI scans and cognitive testing, were spaced approximately 15 months apart on average. Change in CT and performance on tests of executive function (EF) were examined.

Results

Significant age‐by‐group (PAE vs. Comparison) linear interaction effects in CT were observed in the parietal, temporal, occipital, and insular cortices suggesting altered developmental trajectories in the PAE vs. Comparison groups. Results suggest a pattern of delayed cortical thinning in PAE, with the Comparison group showing more rapid thinning at younger ages and those with PAE showing accelerated thinning at older ages. Overall, children in the PAE group showed reduced cortical thinning across time relative to the Comparison participants. Symmetrized percent change (SPC) in CT in several regions was significantly correlated with EF performance at 15‐month follow‐up for the Comparison group but not the group with PAE.

Conclusions

Regional differences were seen longitudinally in the trajectory and timing of CT change in children with PAE, suggesting delayed cortical maturation and an atypical pattern of development compared with typically developing individuals. In addition, exploratory correlation analyses of SPC and EF performance suggest the presence of atypical brain–behavior relationships in PAE. The findings highlight the potential role of altered developmental timing of cortical maturation in contributing to long‐term functional impairment in PAE.
Estimating the true effectiveness of smoking cessation interventions under variable comparator conditions: A systematic review and meta‐regression
Authors: Kraiss Jannis , Viechtbauer Wolfgang , Black Nicola , Johnston Marie , Hartmann‐Boyce Jamie , Eisma Maarten , Javornik Neza , Bricca Alessio , Michie Susan , West Robert , de Bruin Marijn
Published: May 2023

Background and aims

Behavioural smoking cessation trials have used comparators that vary considerably between trials. Although some previous meta‐analyses made attempts to account for variability in comparators, these relied on subsets of trials and incomplete data on comparators. This study aimed to estimate the relative effectiveness of (individual) smoking cessation interventions while accounting for variability in comparators using comprehensive data on experimental and comparator interventions.

Methods

A systematic review and meta‐regression was conducted including 172 randomised controlled trials with at least 6 months follow‐up and biochemically verified smoking cessation. Authors were contacted to obtain unpublished information. This information was coded in terms of active content and attributes of the study population and methods. Meta‐regression was used to create a model predicting smoking cessation outcomes. This model was used to re‐estimate intervention effects, as if all interventions have been evaluated against the same comparators. Outcome measures included log odds of smoking cessation for the meta‐regression models and smoking cessation differences and ratios to compare relative effectiveness.

Results

The meta‐regression model predicted smoking cessation rates well (pseudo R2 = 0.44). Standardising the comparator had substantial impact on conclusions regarding the (relative) effectiveness of trials and types of intervention. Compared with a ‘no support comparator’, self‐help was 1.33 times (95% CI = 1.16–1.49), brief physician advice 1.61 times (95% CI = 1.31–1.90), nurse individual counselling 1.76 times (95% CI = 1.62–1.90), psychologist individual counselling 2.04 times (95% CI = 1.95–2.15) and group psychologist interventions 2.06 times (95% CI = 1.92–2.20) more effective. Notably, more elaborate experimental interventions (e.g. psychologist counselling) were typically compared with more elaborate comparators, masking their effectiveness.

Conclusions

Comparator variability and underreporting of comparators obscures the interpretation, comparison and generalisability of behavioural smoking cessation trials. Comparator variability should, therefore, be taken into account when interpreting and synthesising evidence from trials. Otherwise, policymakers, practitioners and researchers may draw incorrect conclusions about the (cost) effectiveness of smoking cessation interventions and their constituent components.
Cost‐effectiveness analysis of human papillomavirus vaccines for the prevention of cervical cancer in India
Authors: Arora Shiksha , Tuffaha Haitham
Published: May 2023

Background

Human papillomavirus (HPV) vaccines represent an important strategic opportunity to prevent cervical cancer in low‐middle income countries, such as India. The economic evaluation of HPV vaccines is crucial to inform public‐health decisions; however, the scarce economic evaluations from India have focused on the value for money of bivalent vaccines and took a healthcare perspective. The aim of this study is to conduct a cost‐effectiveness analysis of all available HPV vaccines in India.

Material and methods

The Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model was used to evaluate the cost‐effectiveness of HPV vaccination of 12‐year‐old girls in India, from both healthcare and societal perspectives. Cervical cancer cases, deaths averted and the incremental cost per Disability Adjusted Life Years (DALY) averted were reported as primary outcomes. Sensitivity analysis was undertaken to handle any uncertainty or variability in the results.

Results

Compared with no vaccination, the incremental cost per DALY averted was USD 362.78 for nonavalent vaccine, USD 393.16 for quadrivalent vaccine and USD 432.24 for bivalent vaccine from a healthcare perspective. From a societal perspective, the incremental cost per DALY averted was USD 334.28 for nonavalent vaccine, USD 364.67 for quadrivalent vaccine and USD 403.75 for bivalent vaccine. Assuming constant prices per dose for all vaccines, the nonavalent vaccine dominated both quadrivalent and bivalent vaccines, indicating that it is the more cost‐effective strategy.

Conclusion

Vaccinating girls against HPV is a cost‐effective strategy to reduce the incidence of cervical cancer and mortality due to cervical cancer in India.
Five‐ and 10‐year survival in extramammary Paget's disease: A focus on wide local excision
Authors: Ha Dae‐Lyong , Ha Gi Ung , Kim Jun Young , Han Man‐Hoon , Lee Hyun Jung , Hong Dae Gy , Lee Jeong Eun , Chung Ho Yun , Lee Seok‐Jong
Published: May 2023

Aim

This study aimed to analyze extramammary Paget's disease (EMPD)‐specific survival, overall survival, and recurrence rate (RR) in patients with EMPD in South Korea, with a focus on wide local excision.

Methods

We retrospectively reviewed the medical records of patients with EMPD from 1993 to 2020 at Kyungpook National University Hospital. We determined the survival and RRs after wide local excision.

Results

A total of 95 patients (66 males and 29 females; mean age 67.4 years) were included. The 5‐year disease‐specific survival and overall survival were 91.8% and 79.3%, respectively, whereas the 10‐year rates were 81.6% and 64.7%, respectively. No significant sex differences were observed. Seventy‐five patients (78.9%) underwent wide local excision. Mucosal involvement and lymphadenopathy were identified as the significant prognostic factors of disease‐specific survival in multivariate analysis. The RR was 14.7% in patients who underwent wide local excision: seven local, two regional, and two distant metastases, with a mean recurrence‐free interval of 42.3 months.

Conclusion

Based on the survival and RRs obtained, surgical treatment of EMPD with wide local excision provides fair curative resection.

Practitioner points

Wide local excision can be a feasible treatment option for extramammary Paget's disease.
Diet composition and diurnal activity patterns of gelada baboon (Theropithecus gelada)
Authors: Gosheme Berhanu , Yihune Mesele
Published: May 2023

Gelada baboons (Theropithecus gelada) are the only surviving species of the genus Theropithecus and endemic to the highlands of Ethiopia. The present study deals with feeding ecology and diurnal activity patterns of gelada (T. gelada) in Wof‐Washa Forest, central Ethiopia. It was conducted from September 2016 to August 2017. Focal sampling technique for 10 min observation was employed to study the feeding ecology. Type of plant species consumed and parts eaten by gelada were recorded using binoculars during dry and wet seasons. On the other hand, data on diurnal activity patterns were collected using scan sampling technique. The activity patterns of bands under study were quantified by scanning at every 15‐min interval from 06:00 to 18:00 h. A total of 11 plant species that belong to 10 families were foraged by gelada during the wet and dry seasons. Grass was the main food source for geladas that contributed about 81% and 68% of their diet during the wet and dry seasons, respectively, while Thymus schimperi was the least consumed plant species during both wet (0.5%) and dry (1%) seasons. Grass blades were the most preferable food items by almost all age and sex categories. Daily activities of gelada were mainly dominated by feeding during both seasons. Geladas spent 58% of their time on foraging activity during the wet season and 67.2% of their time spent during the dry season. Geladas mainly depend on grasses for their diet in the study area. Therefore, to implement successful management and conservation of the species, the area needs to be properly protected.
Prevalence of vitreoschisis‐induced vitreous cortex remnants over the peripheral retinal surface in eyes undergoing vitrectomy for primary rhegmatogenous retinal detachment
Authors: van Overdam Koen A. , van Etten Peter G. , Accou Geraldine P.B.M. , Wubbels René J. , van Meurs Jan C. , Verhoekx Jennifer S.N.
Published: May 2023

Purpose

Unremoved vitreoschisis‐induced vitreous cortex remnants over the peripheral retinal surface posterior to the vitreous base (pVCR) may increase the risk of surgical failure after primary rhegmatogenous retinal detachment (RRD) repair. The purpose of this study was to validate our previous findings on pVCR prevalence during vitrectomy for RRD and to examine their association with proliferative vitreoretinopathy (PVR) and surgical failure.

Methods

Prospective observational multisurgeon study of 100 eyes of 100 consecutive patients who underwent vitrectomy for RRD by one of four vitreoretinal surgeons. Collected data included detected pVCR and known PVR risk factors. Pooled analysis with our previous retrospective study (251 eyes of 251 patients) was also performed.

Results

Initial PVR (≥C) was present and removed in 6/100 (6%) patients, pVCR were detected in 36/100 (36%) patients, pVCR were removed in 30/36 (83%) patients with pVCR, and 4/36 (11%) patients with pVCR were high myopes (≤−6D). Six per cent (6/100) developed a retinal redetachment, of which 3/6 (50%) had initial PVR (≥C). Surgical failure rates in eyes with and without pVCR were 17% (6/36) and 0% (0/64), respectively. In eyes with pVCR and surgical failure, pVCR were not or not completely removed during the first surgery. Overall analysis showed that pVCR were statistically significantly associated with PVR.

Conclusions

This study confirms our previous findings: a pVCR prevalence of around 35% and an association between pVCR, PVR formation and surgical failure in patients undergoing vitrectomy for RRD. More research is needed to determine which patients would benefit most from pVCR removal.
Ten‐year trends of immediate sequential bilateral cataract surgery (ISBCS) as reflected in the Swedish National Cataract Register
Authors: Lundström Mats , Kugelberg Maria , Zetterberg Madeleine , Nilsson Ingela , Viberg Andreas , Bro Tomas , Behndig Anders
Published: May 2023

Purpose

To analyse trends of ISBCS reported to the Swedish National Cataract Register (NCR) over a 10‐year period.

Methods

Since 2010 the NCR contains social security number of all individuals in the list of parameters reported to NCR after each cataract procedure. Bilateral surgeries were mapped out using social security numbers. When dates of both‐eye surgeries are identical for an individual it is classified as an immediate sequential bilateral cataract surgery (ISBCS). This study includes all data reported during the period 1st of January 2010 to 31st of December 2019. During the study period 113 cataract surgery clinics affiliated to the NCR reported their data on consecutive cataract cases.

Results

For the whole period 54 194 ISBCS were reported. The total number of bilateral cataract extractions was 422 300. There was a significant trend of increasing ISBCS over time with linear regression (Beta = 1.75, p < 0.001). In ISBCS the occurrence of an ocular comorbidity decreased over time. The use of a capsular tension ring was significantly more common in ISBCS than in delayed sequential bilateral cataract surgery (DSBCS). All other measures taken during surgery were more common in DSBCS. The use of multifocal IOL was significantly more frequent in ISBCS compared to DSBCS (p < 0.001).

Conclusions

The use of ISBCS has increased over the study period. The operated eyes have less risk factors than eyes going through a DSBCS, but both ocular comorbidities and surgical complications occur in ISBCS eyes.
The boundary problem: Defining and delineating the community in field trials with gene drive organisms
Authors: de Graeff Nienke , Pirson Isabelle , van der Graaf Rieke , Bredenoord Annelien L. , Jongsma Karin R.
Published: May 2023

Despite widespread and worldwide efforts to eradicate vector‐borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision‐making about their design and launch. It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this “community” should be defined and delineated. In this paper, we shed light on this “boundary problem”: the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision‐making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies.
Do AI chatbots improve students learning outcomes? Evidence from a meta‐analysis
Authors: Wu Rong , Yu Zhonggen
Published: May 2023

Artificial intelligence (AI) chatbots are gaining increasing popularity in education. Due to their increasing popularity, many empirical studies have been devoted to exploring the effects of AI chatbots on students' learning outcomes. The proliferation of experimental studies has highlighted the need to summarize and synthesize the inconsistent findings about the effects of AI chatbots on students' learning outcomes. However, few reviews focused on the meta‐analysis of the effects of AI chatbots on students' learning outcomes. The present study performed a meta‐analysis of 24 randomized studies utilizing Stata software (version 14). The main goal of the current study was to meta‐analytically examine the effects of AI chatbots on students' learning outcomes and the moderating effects of educational levels and intervention duration. The results indicated that AI chatbots had a large effect on students' learning outcomes. Moreover, AI chatbots had a greater effect on students in higher education, compared to those in primary education and secondary education. In addition, short interventions were found to have a stronger effect on students' learning outcomes than long interventions. It could be explained by the argument that the novelty effects of AI chatbots could improve learning outcomes in short interventions, but it has worn off in the long interventions. Future designers and educators should make attempt to increase students' learning outcomes by equipping AI chatbots with human‐like avatars, gamification elements and emotional intelligence.

Practitioner notes

What is already known about this topic

In recent years, artificial intelligence (AI) chatbots have been gaining increasing popularity in education.

Studies undertaken so far have provided conflicting evidence concerning the effects of AI chatbots on students' learning outcomes.

There has remained a paucity of meta‐analyses synthesizing the contradictory findings about the effects of AI chatbots on students' learning outcomes.

What this paper adds

This study, through meta‐analysis, synthesized these recent findings about the effects of AI chatbots on students' learning outcomes.

This study found that AI chatbots could have a large effect on students' learning outcomes.

This study found that the effects of AI chatbots were moderated by educational levels and intervention duration.

Implications for practice and/or policy

AI chatbot designers could make AI chatbots better by equipping AI chatbots with human‐like avatars, gamification elements and emotional intelligence

Practitioners and/or teachers should draw attention to the positive and negative effects of AI chatbots on students.

Considering the importance of ChatGPT, more research is required to develop a better understanding of the effects of ChatGPT in education.

More research is needed to examine the mechanisms underlying the effects of AI chatbots on students' learning outcomes.
Mutation profiling, tumour burden assessment, outcome prediction and disease monitoring by circulating tumour DNA in peripheral T‐cell lymphoma
Authors: Wei Chong , Wang Wei , Zhang Yan , Zhao Danqing , Zhang Wei , Zhou Daobin
Published: May 2023

In this prospective study, we aimed to evaluate the utility of circulating tumour DNA (ctDNA) in peripheral T‐cell lymphomas (PTCLs). Plasma cell‐free DNA (cfDNA) was obtained, and the mutational profile was assessed in 47 patients with newly diagnosed mature T‐ and NK‐cell lymphoma. To validate the mutations detected in cfDNA, paired tumour tissue samples were available for 36 patients. Targeted next‐generation sequencing was performed. A total of 279 somatic mutations involving 149 genes were identified in the 47 cfDNA samples. The overall sensitivity of plasma cfDNA in discovering biopsy‐confirmed mutations was 73.9% with a specificity of 99.6%. When we considered only mutations with variant allele frequency >5% in the tumour biopsy, the sensitivity increased to 81.9%. Pretreatment ctDNA concentration and the number of mutations were highly correlated with tumour burden indicators including lactate dehydrogenase, Ann Arbor stage and International Prognostic Index score. Patients with high ctDNA level (>1.9 log ng/mL) had significantly lower overall response rates, inferior 1‐year progression‐free survival and overall survival rates than those with low level. Longitudinal analysis of ctDNA showed a strong agreement between ctDNA dynamics and the radiographic response. In conclusion, our study demonstrates that ctDNA may serve as a promising tool for mutational profiling, tumour burden assessment, outcome prediction and disease monitoring in PTCLs.
Risk factors associated with loss of variable‐thread tapered implants: A retrospective observational study of 1–5 years
Authors: Xu Yangbo , Liu Tie , Lin Mengna , Xu Antian , Shen Xiaoting , He Fuming
Published: May 2023

Objectives

This study aimed to evaluate the survival rate of variable‐thread tapered implants (VTTIs) and identify risk factors for early/late implant loss.

Materials and Methods

From January 2016 to December 2019, patients who received VTTIs were included in this study. The cumulative survival rates (CSRs) at implant/patient levels were calculated by the life table method and presented via Kaplan–Meier survival curves. The relation between investigated variables and early/late implant loss was analyzed by the multivariate generalized estimating equation (GEE) regression model on the implant level.

Results

A total of 1528 patients with 2998 VTTIs were included. 95 implants from 76 patients were lost at the end of observation. At the implant level, the CSRs at 1, 3, and 5 years were 98.77%, 96.97%, and 95.39%, respectively, whereas they were 97.84%, 95.31%, and 92.96% at the patient level, respectively. The multivariate analysis revealed that non‐submerged implant healing (OR = 4.63, p = .037) was associated with the early loss of VTTIs. Besides, male gender (OR = 2.48, p = .002), periodontitis (OR = 3.25, p = .007), implant length <10 mm (OR = 2.63, p = .028), and overdenture (OR = 9.30, p = .004) could significantly increase the risk of late implant loss.

Conclusion

Variable‐thread tapered implants could reach an acceptable survival rate in clinical practice. Non‐submerged implant healing was associated with early implant loss; male gender, periodontitis, implant length <10 mm, and overdenture would significantly increase the risk of late implant loss.
Invasion history of Lycium ferocissimum in Australia: The impact of admixture on genetic diversity and differentiation
Authors: McCulloch Graham A. , Gurdasani Komal , Hereward James P. , Morin Louise , Walter Gimme H. , Raghu S.
Published: May 2023

Aim

We investigated the invasion history of Lycium ferocissimum, a spine‐covered shrub native to South Africa that was introduced to Australia in the mid‐1800s, and has since developed into a damaging invasive plant of undisturbed landscapes and pastures. In addition to identifying the provenance of the Australian plants, we tested for evidence of admixture, and contrasted genetic diversity and structuring across the native and introduced ranges.

Location

Samples were collected across South Africa (24 localities) and Australia (26 localities).

Methods

We used genotyping‐by‐sequencing (3117 SNPs across 381 individuals) to assess population genetic structuring in L. ferocissimum across Australia and South Africa. Coalescent analyses were used to explicitly test contrasting invasion scenarios.

Results

Clear geographic genetic structuring was detected across South Africa, with distinct clusters in the Eastern and Western Cape provinces. The L. ferocissimum plants in Australia form their own genetic cluster, with a similar level of genetic diversity as plants in South Africa. Coalescent analyses demonstrated that the lineage in Australia was formed by admixture between Eastern Cape and Western Cape plants, with most of the genetic material from the Australian lineage originating from the Western Cape. Our analyses suggest that L. ferocissimum plants were originally introduced to South Australia, though it is unclear whether admixture occurred before or after its introduction to Australia. We detected little evidence of geographic genetic structure across Australia, although many of the populations were genetically distinct from one another.

Main Conclusions

Our results illustrate how admixture can result in genetically diverse and distinct invasive populations. The complex invasion history of L. ferocissimum in Australia poses particular challenges for biological control. We suggest potential biological control agents should be screened against admixed plants (in addition to plants from the Eastern and Western Cape) to test whether they provide effective control of the genetically distinct invasive lineage.
Hospital admissions of school‐age children with an intellectual disability: A population‐based survey
Authors: Horridge Karen A. , Bretnall Grace , Fraser Lorna K.
Published: May 2023

Aim

To describe the profiles of hospital admissions of school‐age children identified with a learning disability (ICD‐11 intellectual developmental disorder) and/or safeguarding needs compared to children without learning disability, in a population where proactive identification of learning disabilities in children is embedded in practice.

Method

Data were collected about the reasons for and duration of hospital admissions of school‐age children living in the study catchment area between April 2017 and March 2019; the presence (or absence) of learning disability and/or safeguarding flags in the medical record was also noted. The impact of the presence of flags on the outcomes was explored using negative binomial regression modelling.

Results

Of 46 295 children in the local population, 1171 (2.53%) had a learning disability flag. The admissions of 4057 children were analysed (1956 females; age range 5–16 years, mean 10 years 6 months, SD 3 years 8 months). Of these, 221 out of 4057 (5.5%) had a learning disability, 443 out of 4057 (10.9%) had safeguarding flags, 43 out of 4057 (1.1%) had both, and 3436 out of 4057 (84.7%) had neither. There was a significantly increased incidence of hospital admissions and length of stay in children with either or both flags, compared to children with neither.

Interpretation

Children with learning disabilities and/or safeguarding needs have higher rates of hospital admissions than children without. Robust identification of learning disabilities in childhood is required to make the needs of this group visible in routinely collected data as the first step towards needs being appropriately addressed.

What this paper adds

Children with learning disabilities must be consistently identified in populations so that their needs are made visible.

Information about these needs must be collected from educational, health, and social care sources and scrutinized systematically.

Children with learning disabilities and safeguarding needs have an increased incidence of hospital admissions and length of stay.
Twenty‐four hour pattern of childhood febrile seizures substantiated by time series meta‐analysis: Circadian medicine perspectives
Authors: Smolensky Michael H. , Shah Ami P. , Fernández José R. , Sackett‐Lundeen Linda , Hermida Ramon C.
Published: May 2023

Major objectives of this work were to: (1) substantiate the 24‐hour pattern in the occurrence of childhood febrile seizures (CFSs) by a novel time series meta‐analysis of past reported time‐of‐day data and (2) discuss its potential circadian rhythm‐dependencies. Comprehensive search of the published literature retrieved eight articles that met inclusion criteria. Three investigations were conducted in Iran, two in Japan, and one each in Finland, Italy, and South Korea, representing a total of 2461 mostly simple febrile seizures of children who were on average about 2 years of age. Population‐mean cosinor analysis validated (p < .001) a 24‐hour pattern in the onset of CFSs, with an approximate four‐fold difference in the proportion of children expressing seizures at its peak at 18:04 h (95% confidence interval: 16:40–19:07 h) vs trough at 06:00 h, in the absence of meaningful time‐of‐day differences in mean body temeprarure. The CFS time‐of‐day pattern likely derives from the actions of multiple circadian rhythms, particularly the cytokines that comprise the pyrogenic inflammatory pathway and melatonin that influences the excitation level of central neurons and helps regulate body temperature. Past laboratory animal and patient investigations document that the vulnerability to a seizure by a provoking trigger of the same intensity is not the same but different in a predictable‐in‐time manner during the 24 h as a circadian susceptibility/resistance rhythm. Knowledge of the marked disparity in the time‐of‐day risk of CFSs can be translated into improved prevention, particularly during the late afternoon and early evening when highest, through proper timing of prophylactic interventions.
Columbite SN3: A New Potential Reference Material for U‐Pb Dating by LA‐ICP‐MS
Authors: Xiang Lu , Wang Rucheng , Romer Rolf L. , Che Xudong , Hu Huan , Tang Zhimin
Published: May 2023

Columbite‐tantalite LA‐ICP‐MS U‐Pb dating is a fast and useful method to determine the age of rare‐metal deposits and fingerprint the provenance of columbite‐tantalite ore concentrates. Accurate LA‐ICP‐MS U‐Pb dating requires matrix‐matched reference materials. We analysed three columbite‐tantalite samples (SN3, HND and RL2) from China using ID‐TIMS and LA‐ICP‐MS to assess their potential as reference materials for in situ U‐Pb dating. Coltan 139 and these three columbite‐tantalite samples with variable compositions yielded internally consistent LA‐ICP‐MS U‐Pb ages when using each other for calibration and the weighted mean 206Pb/238U ages are comparable to respective ID‐TIMS ages. Composition‐dependent U‐Pb fractionation seems to be insignificant under the LA‐ICP‐MS conditions used. Sample SN3 has a low percentage of heterogeneity for 206Pb/238U ages (4%) with low common Pb contributions (f206 < 1%) and shows a good potential in calibrating unknown samples as primary reference material for LA‐ICP‐MS analysis. Samples RL2 and HND have altered sections characterised by high LREE contents, flat LREE patterns and old 206Pb/238U apparent ages, and are not suited as reference materials. The low 207Pb/206Pb intercepts for samples RL2 and HND lack geological meaning but provide strong evidence that the disturbed U‐Pb systematics with anomalous apparent 206Pb/238U ages is a secondary feature.
Research and development intensive clusters and regional competitiveness
Authors: Kosfeld Reinhold , Mitze Timo
Published: May 2023

Modern cluster theory provides reasons for positive external effects that accrue from the interaction of spatially proximate firms operating in common and related fields of economic activity. In this paper, we examine the impact of R&D‐intensive clusters as a key factor of regional competitiveness on productivity growth. In relying on a hybrid approach of cluster identification, we examine effects of cluster specialization and diversity for a panel of German NUTS‐3 regions in 2003–2019. After controlling for regional characteristics and unobserved heterogeneity, a robust cluster strength effect (i.e., specialization) on productivity growth is found within the context of conditional convergence across German regions. With regard to the underlying mechanisms, we find that the presence of multiple R&D‐intensive clusters in specific technological fields is most strongly linked to higher levels of regional productivity growth. We also find that advantages from cluster specialization are strongest in key industrial sector such as automobile production, machinery, chemical and pharmaceutical products. Overall, our estimates particularly highlight the working of Marshallian externalities in productivity dynamics, while Jacobs‐type spillovers tend to be partially realized. These findings indicate that some but not all cluster‐based regional development strategies are promising policy tools to foster regional growth processes.
‘Getting the vaccine makes me a champion of it’: Exploring perceptions towards peer‐to‐peer communication about the COVID‐19 vaccines amongst Australian adults
Authors: Karras Joshua , Harrison Mia , Seale Holly
Published: May 2023

Objectives

Peer‐to‐peer communication approaches have been previously described as the ‘power of personal referral’. Rather than relying on official channels of information, peer‐to‐peer communication may have a role in supporting changes in understanding and possibly behaviours. However, in emergency or pandemic situations, there is currently limited understanding of whether community members feel comfortable speaking about their vaccine experiences or advocating to others. This study explored the perceptions of COVID‐19 vaccinated and unvaccinated Australian adults regarding their preferences and opinions about peer‐peer communication and other vaccine communication strategies.

Study Design

Qualitative interview research.

Methods

In‐depth interviews were conducted in September 2021 with 41 members of the Australian community. Thirty‐three participants self‐identified as being vaccinated against COVID‐19, while the remainder were not vaccinated at the time or did not intend on receiving a COVID vaccine.

Results

Amongst those who were vaccinated, participants spoke about being willing to promote the vaccine and correct misinformation and felt empowered following their vaccination. They highlighted the importance of peer‐to‐peer communication and community messaging, expressing the need for both strategies in an immunisation promotional campaign, with a slight emphasis on the persuasive power of communication between family and friends. However, those who were unvaccinated tended to dismiss the role of community messaging, commenting on a desire not to be like one of the many who listened to the advice of others.

Conclusion

During emergency situations, governments and other relevant community organisations should consider harnessing peer‐to‐peer communication amongst motivated individuals as a health communication intervention. However further work is needed to understand the support that this constituent‐involving strategy requires.

Patient or Public Contribution

Participants were invited to participate through a series of online promotional pathways including emails and social media posts. Those who completed the expression of interest and met the study criteria were contacted and sent the full study participant information documentation. A time for a 30 min semi‐structured interview was set and provided with a $50 gift voucher at the conclusion.
Highly stable and fast‐dissolving ascorbic acid‐loaded microneedles
Authors: Leelawattanachai Jeerapond , Panyasu Kedsara , Prasertsom Kornkanok , Manakasettharn Supone , Duangdaw Hathaiphat , Budthong Pitchaon , Thepphornbanchakit Naranya , Chetprayoon Paninee , Muangnapoh Kullachate , Srinives Sira , Waraho‐Zhmayev Dujduan , Triampo Darapond
Published: May 2023

Objectives

Ascorbic acid has many benefits to the skin. Numerous attempts to promote its topical delivery show great challenges since its chemical instability and poor skin impermeability. Microneedle delivery is a simple, safe, painless and effective means to deliver therapeutic or nourishing molecules into the skin. The purpose of this study was twofold: (a) to develop a new formulation of ascorbic acid‐loaded microneedles to enhance ascorbic acid stability by investigating an optimal amount of polyethyleneimine as an additive to the dextran‐based microneedle formulation and (b) to assess microneedle properties in terms of dissolving rate, skin penetration ability, biocompatibility and antimicrobial activity.

Methods

The microneedles formulated with ascorbic acid and varied polyethyleneimine concentrations were fabricated and subsequently tested for ascorbic acid stability using 2,2‐diphenyl‐1‐picrylhydrazyl assay. The dissolution rate and skin penetration depth were investigated in porcine skin and the reconstructed human full‐thickness skin model respectively. The skin irritation tests were done according to the Organisation for Economic Co‐operation and Development Test Guideline No. 439. An antimicrobial disc susceptibility test was performed against Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis.

Results

Among varied amounts of 0%, 1.5%, 3.0% and 4.5% (w/v), the 3.0% polyethyleneimine showed the most desirable characteristics, including well‐preserved shape integrity after demoulding, significantly improved stability of ascorbic acid (p < 0.001) from 33% to 96% antioxidant activity after 8 weeks of storage at 40°C, increased dissolving rate (p < 0.001) by being completely dissolved within 2 min after the skin insertion, passing skin penetration and biocompatibility tests as well as having a broad spectrum of antimicrobial property.

Conclusion

With a safety profile and enhanced properties, the new formulation of ascorbic acid‐loaded microneedles shows outstanding potential as commercially available cosmetics and healthcare products.
Sentinel cluster of locally acquired Japanese encephalitis in southern Australia
Authors: Thorburn Samuel , Friedman Deborah , Burston John , Kinsella Paul M. , Martin Genevieve E. , Williamson Deborah A. , Jackson Justin
Published: May 2023

Prior to January 2022, only a single case of infection with Japanese encephalitis virus (JEV) had been reported on the Australian mainland, acquired in the northern extremity on Cape York. We report the clinical characteristics of the sentinel cluster of cases that confirmed the local acquisition of JEV in southern Australia along the Murray River bordering New South Wales and Victoria.
Patient referral flow between physician and ophthalmologist visits for diabetic retinopathy screening among Japanese patients with diabetes: A retrospective cross‐sectional cohort study using the National Database
Authors: Ihana‐Sugiyama Noriko , Sugiyama Takehiro , Hirano Takao , Imai Kenjiro , Ohsugi Mitsuru , Kawasaki Ryo , Murata Toshinori , Ogura Youichiro , Ueki Kohjirou , Yamauchi Toshimasa , Kadowaki Takashi
Published: May 2023

Aims/Introduction

Regular screening for diabetic retinopathy is essential. This study aimed to show the process and current situation of diabetic retinopathy screening prescribed by physicians (internists) and ophthalmologists for Japanese patients with diabetes.

Materials and Methods

This retrospective cohort study used data from the Japanese National Database of Insurance Claims between April 2016 and March 2018. Ophthalmology visits and fundus examinations are defined using specific medical procedure codes. The proportion of ophthalmology visits for patients with diabetic medication and for fundus examination among those who visited ophthalmologists was calculated in the fiscal year 2017. A modified Poisson regression analysis was carried out to identify factors associated with retinopathy screening. Similarly, quality indicators by prefectures were also calculated.

Results

Among 4,408,585 patients receiving diabetic medications (57.8% men, 14.1% insulin use), 47.4% visited the ophthalmology department and 96.9% of those underwent fundus examination. Regression analysis showed that female sex, older age, insulin use, medical facilities with Japan Diabetes Society certification and large medical facilities were predictors of fundus examination. By prefecture, the ophthalmology consultation rate and the fundus examination ranged 38.5–51.0% and 92.1–98.7%, respectively.

Conclusions

Less than half of the patients who were prescribed antidiabetic medication by their physicians visited an ophthalmologist. However, most of the patients who visited an ophthalmologist had a fundus examination carried out. A similar tendency was noted for each prefecture. It is essential to reaffirm the necessity of recommending ophthalmologic examinations to physicians and healthcare professionals who care for patients with diabetes.
Maternal uric acid levels and risk of gestational diabetes mellitus: A systematic review and dose–response meta‐analysis of cohort studies including 105,380 participants
Authors: Nikparast Ali , Rahmani Jamal , Bagheri Reza , Mohammadpour Saba , Shadnoosh Mehdi , Wong Alexei , Ghanavati Matin
Published: May 2023

Aims/Introduction

Although the association between uric acid levels and adverse pregnancy outcomes has been investigated, the effects of higher uric acid levels on the risk of gestational diabetes mellitus (GDM) have yet to be established. Therefore, this systematic review and meta‐analysis aimed to investigate the relationship between uric acid levels during pregnancy and the risk of GDM.

Materials and Methods

PubMed/Medline, Scopus and Web of Science databases were searched up to April 2022 for relevant observational studies. A random effects model was used to estimate pooled odds ratios (OR) and 95% confidence intervals (95% CI). To assess the heterogeneity of included studies, the I2 index was used.

Results

Among the initial 262 studies that were recognized from the databases search, 23 studies including 105,380 participants were eligible. Pooled analysis showed that higher uric acid levels significantly affected the risk of GDM (OR 2.58, 95% CI 1.89–3.52, I2 = 90.8%, P < 0.001). Subgroup analyses based on the gestational week showed that higher uric acid levels before the 20th week of gestation were significantly associated with the risk of GDM (OR 3.26, 95% CI 2.26–4.71, I2 = 89.3%, P < 0.001). Based on the meta‐regression analysis, uric acid levels and odds of GDM were significantly correlated with the participants' age, and it was more significant in younger pregnant women.

Conclusions

This study showed a positive association between uric acid levels and the risk of GDM. Also, our results indicate that measuring uric acid levels before 20 weeks of gestation can potentially predict GDM, especially in younger women.
Gut as a source of new β‐cells and Segi's cap
Authors: Yagihashi Soroku
Published: May 2023

A deficit of β‐cells is a salient feature in both type 1 and type 2 diabetes mellitus. Due to the absolute lack of supplying β‐cells for organ or cell transplantation, there is an urgent need to explore the efficient method to generate insulin‐producing cells. Cell conversion of intestinal cryptic epithelial cells to insulin‐producing β‐like cells is a novel and promising therapeutic target. Activation of β‐cell differentiation factors or modulation of terminally differentiated factors with forkhead homeobox O1 effectively induced such conversion, and suppressed hyperglycemia in streptozotocin‐induced and non‐obese diabetic (NOD) mice. Segi's cap, which was discovered >80 years ago, is composed of an aggregation of primitive granulated enteroendocrine cells, enterochromaffin cells, Paneth cells and goblet cells in the intestinal villi, and is only detected at the fetal stage. Its role has long been unknown, but the present study disclosed that it likely provides an underpin of newly generated β‐like cells.