bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning models for identifying pre-frailty in community dwelling older adults
Authors: Sajeev Shelda , Champion Stephanie , Maeder Anthony , Gordon Susan
Published: October 2022

Background

There is increasing evidence that pre-frailty manifests as early as middle age. Understanding the factors contributing to an early trajectory from good health to pre-frailty in middle aged and older adults is needed to inform timely preventive primary care interventions to mitigate early decline and future frailty.

Methods

A cohort of 656 independent community dwelling adults, aged 40–75 years, living in South Australia, undertook a comprehensive health assessment as part of the Inspiring Health cross-sectional observational study. Secondary analysis was completed using machine learning models to identify factors common amongst participants identified as not frail or pre-frail using the Clinical Frailty Scale (CFS) and Fried Frailty Phenotype (FFP). A correlation-based feature selection was used to identify factors associated with pre-frailty classification. Four machine learning models were used to derive the prediction models for classification of not frail and pre-frail. The class discrimination capability of the machine learning algorithms was evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, F1-score and accuracy.

Results

Two stages of feature selection were performed. The first stage included 78 physiologic, anthropometric, environmental, social and lifestyle variables. A follow-up analysis with a narrower set of 63 variables was then conducted with physiologic factors associated with the FFP associated features removed, to uncover indirect indicators connected with pre-frailty. In addition to the expected physiologic measures, a range of anthropometric, environmental, social and lifestyle variables were found to be associated with pre-frailty outcomes for the cohort. With FFP variables removed, machine learning (ML) models found higher BMI and lower muscle mass, poorer grip strength and balance, higher levels of distress, poor quality sleep, shortness of breath and incontinence were associated with being classified as pre-frail. The machine learning models achieved an AUC score up to 0.817 and 0.722 for FFP and CFS respectively for predicting pre-frailty. With feature selection, the performance of ML models improved by up to + 7.4% for FFP and up to + 7.9% for CFS.

Conclusions

The results of this study indicate that machine learning methods are well suited for predicting pre-frailty and indicate a range of factors that may be useful to include in targeted health assessments to identify pre-frailty in middle aged and older adults.
Simulation-based holistic education in physiotherapy interns to increase empathy toward older adults and individuals with disabilities
Authors: Lin I.-Hsien , Wang Chien-Yung , Lin Yen-Nung , Chen Hung-Chou , Lin Li-Fong
Published: October 2022

Background

The proportion of older adults and individuals with disabilities in the general population increases each year. Thus, clinical clerkships designed for physiotherapy interns should provide more than simply knowledge and skills. For such interns to be able to handle the requirements of their future jobs, clerkships must enable them to develop empathy and positive attitudes toward patients. This study investigated the effect of simulation-based, holistic health-care education on physiotherapy interns’ empathy, attitudes, and knowledge. 

Methods

A parallel-group design. Thirty physiotherapy interns from a medical institution were enrolled as participants, with experimental and control groups each comprising 15 participants. Both groups received standard clinical training. However, the experimental group received an additional 3.5 h of simulation-based holistic health-care education. The Jefferson Scale of Empathy, Kogan’s Attitudes Toward Old People Scale, the Attitudes Towards the Elderly Scale, the Knowledge About Aging Scale, Knowledge of the Situation of Older People Scale, Perceptions of Working with Older People Scale, and Care Willingness Scale were used in a pretest and posttest.

Results

After the intervention period, we observed substantial between-group differences of 6.4 points on the Jefferson Scale of Empathy (p = 0.001), 7.7 points on Kogan’s Attitudes Toward Old People Scale (p = 0.002), 3.5 points on the Attitudes Toward the Elderly Scale (p = 0.002), 2.5 points on Knowledge About Aging (p = 0.055), 4.5 points on the Knowledge of the Situation of Older People Scale (p < 0.001), and 2.1 points on Perceptions of Working with Older People Scale (p = 0.046).

Conclusion

Simulation-based, holistic health-care education can significantly improve the empathy, knowledge, and attitudes of physiotherapy interns.
How acceptable do parents experiencing mental health challenges find e-Health interventions for mental health in the postnatal period: a systematic review
Authors: Attard Rosie , Iles Jane , Satherley Rose-Marie
Published: October 2022

Poor mental health in the postnatal period is experienced by high numbers of parents, with a high associated cost to society, however accessing therapeutic support during this time is complicated by parenting commitments. This has been further compounded by the covid-19 pandemic, where access to traditional therapy has been impacted. A lack of access to support for poor mental health in this period can have long term impacts on both the parents and their child. E-Health provides a potential solution to parents accessing support during this period by providing a convenient and flexible intervention which overcomes the barriers of traditional face-to-face therapy. However, without investigating the acceptability of such support for parents, it is not possible to predict uptake and consequent effectiveness. The current review synthesizes data available on acceptability of e-Health interventions in the post-natal period, finding that parents valued e-Health interventions however considerations must be made to certain, key areas impacting the acceptability of these interventions for parents. An element of therapist support and individualised content was preferred, along with a smooth user experience. Parents valued that e-Health fit into their routines and provided anonymity in their interactions. Further research needs to be completed into acceptability for minority social and ethnic groups where access and preference may differ.
#Fitmom: an experimental investigation of the effect of social media on body dissatisfaction and eating and physical activity intentions, attitudes, and behaviours among postpartum mothers
Authors: Tang Lisa , Tiggemann Marika , Haines Jess
Published: October 2022

Background

Research has shown that body dissatisfaction is higher during the postpartum period compared to other periods of life, and strongly associated with disordered eating behaviours, which can lead to adverse health outcomes. While results from cross-sectional studies suggest that social media may play an important role in body dissatisfaction among postpartum mothers, causal inference is limited due to the observational nature of the existing research. The objective of this study is to experimentally test the effect of body-focused social media on the body dissatisfaction and eating and physical activity intentions, attitudes, and behaviours of postpartum mothers.

Methods

Postpartum mothers of infants 0–6 months (n = 132) were randomly assigned to view either body-focused social media posts (n = 65), or a control set of infant feeding tips (n = 67). ANCOVA was used to examine differences between the intervention and control group on levels of body dissatisfaction, eating and physical activity intentions, attitudes, and behaviours. There were two follow-up time points, immediately post intervention and 1-month post intervention to measure potential sustained effects of intervention.

Results

Exposure to body-focused social media posts resulted in higher levels of body dissatisfaction, mean difference 1.54 (p = 0.002); poorer body image, mean difference 0.41 (p = 0.007); eating attitudes, mean difference 2.26 (p = 0.025); and higher levels of restrained eating behaviours, mean difference 0.39 (p < 0.001) among the intervention group post intervention. Mothers in the intervention group also reported higher levels of inspiration to be active, mean difference 0.48 (p = 0.021) post intervention. A sustained effect was found for restrained eating, mean difference 2.03 (p < 0.001) and poorer eating attitude, mean difference 0.29 (p = 0.001) at 1-month follow-up. No sustained effects were found for any other outcomes at 1-month follow-up.

Conclusion

Social media exposure to body-focused social media posts negatively affect postpartum mothers’ body dissatisfaction and health behaviours. Further experimental research that includes an interactive social media component is needed among this population.

Trial Registration:

NCT05181280, Study ID Number: 054798. Registered 06/01/2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05181280.
NSMCE2, a novel super-enhancer-regulated gene, is linked to poor prognosis and therapy resistance in breast cancer
Authors: Di Benedetto Carolina , Oh Justin , Choudhery Zainab , Shi Weiquan , Valdes Gilmer , Betancur Paola
Published: October 2022

Background

Despite today’s advances in the treatment of cancer, breast cancer-related mortality remains high, in part due to the lack of effective targeted therapies against breast tumor types that do not respond to standard treatments. Therefore, identifying additional breast cancer molecular targets is urgently needed. Super-enhancers are large regions of open chromatin involved in the overactivation of oncogenes. Thus, inhibition of super-enhancers has become a focus in clinical trials for its therapeutic potential. Here, we aimed to identify novel super-enhancer dysregulated genes highly associated with breast cancer patients’ poor prognosis and negative response to treatment.

Methods

Using existing datasets containing super-enhancer-associated genes identified in breast tumors and public databases comprising genomic and clinical information for breast cancer patients, we investigated whether highly expressed super-enhancer-associated genes correlate to breast cancer patients’ poor prognosis and to patients’ poor response to therapy. Our computational findings were experimentally confirmed in breast cancer cells by pharmacological SE disruption and gene silencing techniques.

Results

We bioinformatically identified two novel super-enhancer-associated genes – NSMCE2 and MAL2 – highly upregulated in breast tumors, for which high RNA levels significantly and specifically correlate with breast cancer patients’ poor prognosis. Through in-vitro pharmacological super-enhancer disruption assays, we confirmed that super-enhancers upregulate NSMCE2 and MAL2 transcriptionally, and, through bioinformatics, we found that high levels of NSMCE2 strongly associate with patients’ poor response to chemotherapy, especially for patients diagnosed with aggressive triple negative and HER2 positive tumor types. Finally, we showed that decreasing NSMCE2 gene expression increases breast cancer cells’ sensitivity to chemotherapy treatment.

Conclusions

Our results indicate that moderating the transcript levels of NSMCE2 could improve patients’ response to standard chemotherapy consequently improving disease outcome. Our approach offers a new avenue to identify a signature of tumor specific genes that are not frequently mutated but dysregulated by super-enhancers. As a result, this strategy can lead to the discovery of potential and novel pharmacological targets for improving targeted therapy and the treatment of breast cancer.
Pilot evaluation to assess the effectiveness of youth peer community support via the Kooth online mental wellbeing website
Authors: Stevens Madeleine , Cartagena Farías Javiera , Mindel Charlotte , D’Amico Francesco , Evans-Lacko Sara
Published: October 2022

Background

Mental health problems among young people are of growing concern globally. UK adolescent mental health services are increasingly restricted to those with the most severe needs. Many young people turn to the internet for advice and support, but little is known about the effectiveness, and potential harms, of online support. Kooth is a widely-used, anonymised and moderated online platform offering access to professional and peer support. This pilot evaluation sought to assess changes in the wellbeing and mental health of Kooth users, and changes in their use of formal services, over one month. We explored how community aspects of the site were used, and we considered the economic implications for commissioners making Kooth available to young people.

Methods

We surveyed young people when they first accessed Kooth and again one month later (n = 302). Respondents completed measures of mental health and wellbeing, including family relationships and pandemic-related anxiety, and reported on their use of services and, at follow-up, their perceptions of whether and how they had benefitted. We carried out qualitative interviews with ten participants, exploring perceptions of the Kooth community and its impact.

Results

We found improvements across nearly all measures, including reductions in psychological distress, suicidal ideation and loneliness. Subsample analyses suggested similar benefits for those who used only the community/peer parts of Kooth as for those who engaged with Kooth’s counsellors. Participants reported learning from peers’ suggestions and experiences, described as different from the advice given by professionals. Helping others gave users a sense of purpose; participants learnt self-help strategies and became more confident in social interactions. Service use and opinion data suggested Kooth experiences may help users make more appropriate and effective use of formal services.

Conclusion

This pilot evaluation suggests that Kooth is likely to be a cost-effective way of providing preventative support to young people with concerns about their mental health, with possible benefits across a range of domains which could be investigated in a future controlled trial.
Pre-pandemic socio-economic status and changes in employment during the first lockdown (2020) on the health of middle-aged people in England: a longitudinal study
Authors: D’Angelo Stefania , Ntani Georgia , Bloom Ilse , Walker-Bone Karen
Published: October 2022

Background

The COVID-19 pandemic markedly disrupted people’s lives. It caused higher mortality and morbidity amongst individuals from poorer socio-economic position (SEP). It is well-recognised that job loss has a negative impact on health. We hypothesised that health effects of the pandemic on middle-aged people might be different depending on SEP and changes in employment.

Methods

Data are from the Health and Employment After Fifty (HEAF), a cohort recruited 2013–2014 when aged 50–64 through 24 English general practices. At baseline and annually since, participants completed a questionnaire reporting about demographics, employment, health, lifestyle, and finances. In 2021 we sent an e-survey to all contactable HEAF participants, asking about effects of the first lockdown (March-July 2020). Outcomes were participants’ perception of worsening of mental, physical health, and self-rated health (SRH) since lockdown. Associations between SEP, COVID-19 related employment changes and health were explored with Poisson regression with robust standard error, with adjustment for age, sex, and pre-pandemic SRH.

Results

In total, 2,469 (53%) returned a usable questionnaire, amongst whom 2,344 provided complete information for these analyses (44% men, mean age 65.7 years). Worsening of mental, physical or SRH since lockdown was reported by 21%, 27% and 17% respectively. Mutually adjusted models showed that reporting struggling financially pre-pandemic (versus living comfortably) was associated with an increased risk of deterioration in: mental (RR = 2.0, 95%CI 1.7–2.5), physical health (RR = 2.0, 95%CI 1.6–2.3), and SRH (RR = 1.6, 95%CI 1.2–2.1). Participants working from home during lockdown and those who lost their job (as opposed to those with unchanged employment) were at increased risk of reporting deterioration in mental health and SRH.

Conclusion

In a cohort of older workers, working from home, job loss and poorer pre-pandemic SEP were all associated with worsening of mental health and SRH since lockdown.
A co-created nurse-driven catheterisation protocol can reduce bladder distension in acute hip fracture patients - results from a longitudinal observational study
Authors: Frödin Maria , Nellgård Bengt , Rogmark Cecilia , Gillespie Brigid M. , Wikström Ewa , Andersson Annette Erichsen
Published: October 2022

Background

Urinary retention is common in elderly patients undergoing acute hip fracture surgery. Avoiding overfilling the urinary bladder is important to avoid detrusor muscle damage and associated motility problems. The aim of this study was to analyse associations between the co-creation of a nurse-driven urinary catheterisation protocol and the incidence of bladder distension in patients undergoing hip fracture surgery.

Methods

This is a single-centre implementation intervention with a retrospective longitudinal observation design, using five measures points, spanning from June 2015 to March 2020. The intervention was theory driven and the participants, together with the facilitators and researcher, co-created a nurse-driven urinary catheterisation protocol. Data were retrieved from the hip fracture register. Uni- and multivariable logistic regressions were used for analyses of changes in bladder distension and urinary volume of ≥500 ml over the years.

Results

A total of 3078 patients were included over a five-year period. The implementation intervention was associated with a reduction in the proportion of patients with bladder distension of 31.5% (95% confidence interval 26.0–37.0), from year 1 to year 5. The multivariable analysis indicated a 39% yearly reduction in bladder distension, OR 0.61 (95% confidence interval 0.57–0.64, p <  0001). There was a reduction in the proportion of patients with a bladder volume of ≥500 ml of 42.8% (95% confidence interval 36.2–49.4), from year 1 to year 5. The multivariable analysis found a 41% yearly reduction in patients with a bladder volume of ≥500 ml, OR 0.59 (95% confidence interval 0.55–0.64, p <  0.0001). The intervention was associated with improved documentation of both catheter indications and removal plans.

Conclusion

The use of predefined catheter indications and a tighter bladder scanning schedule were associated with a reduction in the incidence of both bladder distension and urine volume ≥ 500 ml in hip fracture patients. Registered nurses can play an active role in the facilitation of timely and appropriate catheter treatment in patients with hip fractures.

Trial registration

Clinical Trial Registry ISRCTN 17022695 registered retrospectively on 23 December 2021, in the end of the study, after data collection.
STING pathway contributes to the prognosis of hepatocellular carcinoma and identification of prognostic gene signatures correlated to tumor microenvironment
Authors: Pu Zhangya , Liu Jinghua , Liu Zelong , Peng Fang , Zhu Yuanyuan , Wang Xiaofang , He Jiayan , Yi Panpan , Hu Xingwang , Fan Xuegong , Chen Jiang
Published: October 2022

Background

Hepatocellular carcinoma (HCC) is one of the most malignant solid tumors worldwide. Recent evidence shows that the stimulator of interferon genes (STING) pathway is essential for anti-tumor immunity via inducing the production of downstream inflammatory cytokines. However, its impact on the prognosis and tumor microenvironment of HCC was still limited known.

Methods

We obtained gene expression profiles of HCC from GEO, TCGA, and ICGC databases, and immune-related genes (IRGs) from the ImmPort database. Multivariate Cox regression was performed to identify independent prognostic factors. Nomogram was established to predict survival probability for individual patients. Kaplan–Meier curve was used to evaluate the survival difference. Afterward, ESTIMATE, TISCH, and TIMER databases were combined to assess the immune cell infiltration. Furthermore, the qPCR, western blotting, and immunohistochemistry were done to evaluate gene expression, and in vitro cell models were built to determine cell migratory ability.

Results

We found that gene markers of NLRC3, STING1, TBK1, TRIM21, and XRCC6 within STING pathway were independent prognostic factors in HCC patients. Underlying the finding, a predictive nomogram was constructed in TCGA-training cohort and further validated in TCGA-all and ICGC datasets, showing credible performance. Experimentally, up-regulated TBK1 promotes the ability of HCC cell migration. Next, the survival-related immune-related co-expressed gene signatures (IRCGS) (VAV1, RHOA, and ZC3HAV1) were determined in HCC cohorts and their expression was verified in human HCC cells and clinical samples. Furthermore, survival-related IRCGS was associated with the infiltration of various immune cell subtypes in HCC, the transcriptional expression of prominent immune checkpoints, and immunotherapeutic response.

Conclusion

Collectively, we constructed a novel prognostic nomogram model for predicting the survival probability of individual HCC patients. Moreover, an immune-related prognostic gene signature was determined. Both might function as potential therapeutic targets for HCC treatment in the future.
Midazolam exhibits antitumour and enhances the efficiency of Anti-PD-1 immunotherapy in hepatocellular carcinoma
Authors: Kang Junwei , Zheng Zhiying , Li Xian , Huang Tian , Rong Dawei , Liu Xinyang , Qin Miaomiao , Wang Yuliang , Kong Xiangyi , Song Jinhua , Lv Chengyu , Pan Xiongxiong
Published: October 2022

Background

Midazolam (MDZ) is an anaesthetic that is widely used for anxiolysis and sedation. More recently, MDZ has also been described to be related to the outcome of various types of carcinomas. However, how MDZ influences the progression of hepatocellular carcinoma (HCC) and its effects on the biological function and tumour immune microenvironment of this type of tumour remain unknown.

Methods

The effects of MDZ on the proliferation, invasion, and migration of HCC cell lines were examined in vitro using the Cell Counting Kit 8 (CCK8), 5-ethynyl-2ʹ-deoxyuridine (EdU), Transwell, and wound healing assays. Additionally, western blotting was employed to confirm that PD-L1 was expressed. Chromatin immunoprecipitation-seq (ChIP-seq) analysis was used to pinpoint the transcriptional regulation regions of NF-κB and programmed death-ligand 1 (PD-L1). A C57BL/6 mouse model was used to produce subcutaneous HCC tumors in order to evaluate the in vivo performance of MDZ. Mass spectrometry was also used to assess changes in the tumour immunological microenvironment following MDZ injection.

Results

The HCC-LM3 and Hep-3B cell lines’ proliferation, invasion, and migration were controlled by MDZ, according to the results of the CCK8, EdU, Transwell, and wound healing assays. PD-L1 expression was shown by ChIP-seq analysis to be boosted by NF-κB, and by Western blotting analysis, it was shown that MDZ downregulated the expression of NF-κB. Additionally, in vivo tests revealed that intraperitoneal MDZ injections reduced HCC tumor development and enhanced the effectiveness of anti-PD-1 therapy. The CD45+ immune cell proportions were higher in the MDZ group than in the PBS group, according to the mass spectrometry results. Injection of MDZ resulted in a decrease in the proportions of CD4+ T cells, CD8+ T cells, natural killer (NK) cells, monocytes, Tregs, and M2 macrophages and a rise in the proportion of dendritic cells. Additionally, the concentrations of the cytokines IFN-g and TNF-a were noticeably raised whereas the concentrations of the CD8+ T-cell fatigue markers ICOS, TIGIT, and TIM3 were noticeably lowered.

Conclusion

According to this study, MDZ inhibited the progression of HCC by inhibiting the NF-κB pathway and reducing the exhaustion of CD8+ T cells. In clinical practice, MDZ combined with anti-PD-1 therapy might contribute to synergistically improving the antitumor efficacy of HCC treatment.
Current understanding of epigenetics role in melanoma treatment and resistance
Authors: Karami Fath Mohsen , Azargoonjahromi Ali , Soofi Asma , Almasi Faezeh , Hosseinzadeh Shahnaz , Khalili Saeed , Sheikhi Kamran , Ferdousmakan Saeid , Owrangi Soroor , Fahimi Minoovash , Zalpoor Hamidreza , Nabi Afjadi Mohsen , Payandeh Zahra , Pourzardosht Navid
Published: October 2022

Melanoma is the most aggressive form of skin cancer resulting from genetic mutations in melanocytes. Several factors have been considered to be involved in melanoma progression, including genetic alteration, processes of damaged DNA repair, and changes in mechanisms of cell growth and proliferation. Epigenetics is the other factor with a crucial role in melanoma development. Epigenetic changes have become novel targets for treating patients suffering from melanoma. These changes can alter the expression of microRNAs and their interaction with target genes, which involves cell growth, differentiation, or even death. Given these circumstances, we conducted the present review to discuss the melanoma risk factors and represent the current knowledge about the factors related to its etiopathogenesis. Moreover, various epigenetic pathways, which are involved in melanoma progression, treatment, and chemo-resistance, as well as employed epigenetic factors as a solution to the problems, will be discussed in detail.
Assessing road criticality and loss of healthcare accessibility during floods: the case of Cyclone Idai, Mozambique 2019
Authors: Petricola Sami , Reinmuth Marcel , Lautenbach Sven , Hatfield Charles , Zipf Alexander
Published: October 2022

Background

The ability of disaster response, preparedness, and mitigation efforts to assess the loss of physical accessibility to health facilities and to identify impacted populations is key in reducing the humanitarian consequences of disasters. Recent studies use either network- or raster-based approaches to measure accessibility in respect to travel time. Our analysis compares a raster- and a network- based approach that both build on open data with respect to their ability to assess the loss of accessibility due to a severe flood event. As our analysis uses open access data, the approach should be transferable to other flood-prone sites to support decision-makers in the preparation of disaster mitigation and preparedness plans.

Methods

Our study is based on the flood events following Cyclone Idai in Mozambique in 2019 and uses both raster- and network-based approaches to compare accessibility to health sites under normal conditions to the aftermath of the cyclone to assess the loss of accessibility. Part of the assessment is a modified centrality indicator, which identifies the specific use of the road network for the population to reach health facilities.

Results

Results for the raster- and the network-based approaches differed by about 300,000 inhabitants (~ 800,000 to ~ 500,000) losing accessibility to healthcare sites. The discrepancy was related to the incomplete mapping of road networks and affected the network-based approach to a higher degree. The modified centrality indicator allowed us to identify road segments that were most likely to suffer from flooding and to highlight potential backup roads in disaster settings.

Conclusions

The different results obtained between the raster- and network-based methods indicate the importance of data quality assessments in addition to accessibility assessments as well as the importance of fostering mapping campaigns in large parts of the Global South. Data quality is therefore a key parameter when deciding which method is best suited for local conditions. Another important aspect is the required spatial resolution of the results. Identification of critical segments of the road network provides essential information to prepare for potential disasters.
Medical student medium-term skill retention following cardiac point-of-care ultrasound training based on the American Society of Echocardiography curriculum framework
Authors: Jujo Satoshi , Sakka Brandan I. , Lee-Jayaram Jannet J. , Kataoka Akihisa , Izumo Masaki , Kusunose Kenya , Nakahira Atsushi , Oikawa Sayaka , Kataoka Yuki , Berg Benjamin W.
Published: October 2022

Background

No studies have demonstrated medium- or long-term skill retention of cardiac point-of-care ultrasound (POCUS) curriculum for medical student. Based on the American Society of Echocardiography (ASE) curriculum framework, we developed a blended-learning cardiac POCUS curriculum with competency evaluation. The objective of this study was to investigate the curriculum impact on image acquisition skill retention 8 weeks after initial training.

Methods

This study was a prospective, pre-post education intervention study for first- and second-year medical students, with blinded outcome assessment. The curriculum included a pre-training ASE online module and healthy volunteer hands-on training to obtain 5 views: parasternal long-axis (PLAX), parasternal short-axis (PSAX), apical 4-chamber (A4C), subcostal 4-chamber (S4C), and subcostal inferior vena cava (SIVC) views. Students took 5-view image acquisition skill tests at pre-, immediate post-, and 8-week post-training, using a healthy volunteer. Three blinded assessors rated the image quality using a validated 10-point maximum scoring system. Students used a hand-held ultrasound probe (Butterfly iQ).

Results

Fifty-four students completed hands-on training, and pre- and immediate post-training skill tests. Twenty-seven students completed 8-week post-training skill tests. Skill test score improvement between pre- and 8-week post-training was 2.11 points (95% CI, 1.22–3.00; effect size, 1.13).

Conclusion

The cardiac POCUS curriculum demonstrated medium-term skill retention. The curriculum was sufficient for S4C and SIVC skill retention, but inadequate for PLAX, PSAX, and A4C. Therefore, instructional design modifications or re-training for PLAX, PSAX, and A4C are needed to make the curriculum more effective for clinically relevant skill retention.
Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice
Authors: Sams Kelly L. , Mukai Chinatsu , Marks Brooke A. , Mittal Chitvan , Demeter Elena Alina , Nelissen Sophie , Grenier Jennifer K. , Tate Ann E. , Ahmed Faraz , Coonrod Scott A.
Published: October 2022

Background

Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo.

Methods

Preliminary analysis ofPadi2andPadi4single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created aPadi2/Padi4double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects.

Results

Controlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO or WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis.

Conclusions

ThePadi2/Padi4DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.
Sexual dimorphism in the molecular mechanisms of insulin resistance during a critical developmental window in Wistar rats
Authors: Ortiz-Huidobro Rosa Isela , Larqué Carlos , Velasco Myrian , Chávez-Maldonado Juan Pablo , Sabido Jean , Sanchez-Zamora Yuriko Itzel , Hiriart Marcia
Published: October 2022

Background

Insulin resistance (IR) is a condition in which the response of organs to insulin is impaired. IR is an early marker of metabolic dysfunction. However, IR also appears in physiological contexts during critical developmental windows. The molecular mechanisms of physiological IR are largely unknown in both sexes. Sexual dimorphism in insulin sensitivity is observed since early stages of development. We propose that during periods of accelerated growth, such as around weaning, at postnatal day 20 (p20) in rats, the kinase S6K1 is overactivated and induces impairment of insulin signaling in its target organs. This work aimed to characterize IR at p20, determine its underlying mechanisms, and identify whether sexual dimorphism in physiological IR occurs during this stage.

Methods

We determined systemic insulin sensitivity through insulin tolerance tests, glucose tolerance tests, and blood glucose and insulin levels under fasting and fed conditions at p20 and adult male and femaleWistarrats. Furthermore, we quantified levels of S6K1 phosphorylated at threonine 389 (T389) (active form) and its target IRS1 phosphorylated at serine 1101 (S1101) (inhibited form). In addition, we assessed insulin signal transduction by measuring levels of Akt phosphorylated at serine 473 (S473) (active form) in white adipose tissue and skeletal muscle through western blot. Finally, we determined the presence and function of GLUT4 in the plasma membrane by measuring the glucose uptake of adipocytes. Results were compared using two-way ANOVA (With age and sex as factors) and one-way ANOVA with post hoc Tukey’s tests or t-student test in each corresponding case. Statistical significance was considered forPvalues < 0.05.

Results

We found that both male and female p20 rats have elevated levels of glucose and insulin, low systemic insulin sensitivity, and glucose intolerance. We identified sex- and tissue-related differences in the activation of insulin signaling proteins in p20 rats compared to adult rats.

Conclusions

Male and female p20 rats present physiological insulin resistance with differences in the protein activation of insulin signaling. This suggests that S6K1 overactivation and the resulting IRS1 inhibition by phosphorylation at S1101 may modulate to insulin sensitivity in a sex- and tissue-specific manner.
Tumor necrosis factor inhibitors for pediatric patients with SAPHO syndrome associated with acne conglobata
Authors: Liu Shengyan , Wu Xia , Cao Yihan , Li Zhaohui , Liu Yuchen , Ma Mingwei , Li Chen
Published: October 2022

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease with osteoarticular and cutaneous involvements as its main manifestations. Acne conglobata as a severe acne form may affect adolescent patients. Tumor necrosis factor inhibitors are usually used as a second-line therapy for refractory SAPHO syndrome and has been reported to treat acne conglobata successfully. We herein report three cases of adolescent patients with SAPHO syndrome associated with acne conglobata who were successfully treated with TNFi therapy.
Thymofibrolipoma: a case report and review of the literature
Authors: Jokoji Ryu , Tomita Emiko
Published: October 2022

Background

Thymofibrolipoma has been described as a variant of thymolipoma. To date, 3 cases have been reported, and the lesion have been described to consist of extensive areas of collagenous tissue interspersed with islands of mature adipose tissue and strands of thymic tissue.

Case presentation

A 43-year-old woman had an anterior mediastinal tumor. Macroscopically, the cut surface of the tumor was composed of a yellowish lipomatous component and a uniform whitish fibrous component with elastic stiffness. Microscopically, the tumor was composed of collagenous fibrous tissue with sparse spindle cells, mature adipocytes and strands or islands of thymic tissue. The spindle cells in the fibrous tissue had monoallelic deletion of the 13q14 region and corresponding loss of RB1 and FOXO1A protein expression.

Conclusions

This case report may strengthen the hypothesis that thymofibrolipoma is a neoplastic lesion and a variant of thymolipoma and that thymofibrolipoma and lipofibroadenoma are different names for the same lesion. The name “lipofibroadenoma” was given to the lesion because of its histological resemblance to fibroadenoma of the mammary gland. However, this name does not reflect the pathogenesis of this lesion, and the name “thymofibrolipoma” would be preferable. It will be necessary to discuss whether lipofibroadenoma should be listed as an independent entity in the WHO classification.
Establishment of a bipedal rat model of lumbar facet joint osteoarthritis using intraarticular injection of urinary plasminogen activator
Authors: Yang Di , Hu Wei , Li Hao , Shao Yin-chu , Shan Ji-chun , Xiong Xu , Shuang Feng
Published: October 2022

Background

Previous studies have demonstrated that by injecting uPA into the lumbar facet joints (LFJ) of normal rats, a rat LFJOA animal model can be successfully established. However, there is no evidence that intraarticular injection of uPA can induce or much serious osteoarthritis in bipedal rats, which biomechanics is much more similar to human than normal rats. To investigate whether intraarticular injection of urinary plasminogen activator (uPA) can induce LFJOA and low back pain symptoms in bipedal rats.

Methods

An experimental study on the construction of a modified animal model of lumbar facet joints osteoarthritis (LFJOA) which biomechanics is similar to human. Sprague–Dawley rats were treated with intraarticular injection of uPA in the L5–L6 facet joints (uPA group, n = 15) or saline (saline group, n = 15). The forelimbs of both two group rats were amputated. Mechanical and thermal hyperalgesia in the ipsilateral hind paws were evaluated using von Frey hairs and a thermoalgesia instrument, respectively. Toluidine blue staining, hematoxylin–eosin staining, and immunohistochemical examination of the LFJ was performed.

Results

The saline group rats have not demonstrated significant osteoarthritis in rats LFJ after surgery. The uPA group has not been induced significantly higher mechanical and thermal hyperalgesia in comparison with the saline group. But intraarticular injection of uPA in biped rats induced significantly stronger articular cartilage damage, synovitis, and proliferation of synovial cells in the LFJ. Inflammatory factors such as iNOS, IL-1β, and TNF-a were more significantly expressed in bipedal rat injected with uPA (p < 0.05).

Conclusions

Intraarticular injection of uPA can induce LFJOA in bipedal rats, while upright posture does not induce osteoarthritis in rats LFJ in the short term.
Transcriptomic profiling of sporadic Alzheimer’s disease patients
Authors: Caldwell Andrew B. , Anantharaman Balaji G. , Ramachandran Srinivasan , Nguyen Phuong , Liu Qing , Trinh Ivy , Galasko Douglas R. , Desplats Paula A. , Wagner Steven L. , Subramaniam Shankar
Published: October 2022

Alzheimer’s disease (AD) manifested before age 65 is commonly referred to as early-onset AD (EOAD) (Reitz et al. Neurol Genet. 2020;6:e512). While the majority (> 90%) of EOAD cases are not caused by autosomal-dominant mutations in PSEN1, PSEN2, and APP, they do have a higher heritability (92–100%) than sporadic late-onset AD (LOAD, 70%) (Wingo et al. Arch Neurol. 2012;69:59–64, Fulton-Howard et al. Neurobiol Aging. 2021;99:101.e1–101.e9). Although the endpoint clinicopathological changes, i.e., Aβ plaques, tau tangles, and cognitive decline, are common across EOAD and LOAD, the disease progression is highly heterogeneous (Neff et al. Sci Adv Am Assoc Adv Sci. 2021;7:eabb5398). This heterogeneity, leading to temporally distinct age at onset (AAO) and stages of cognitive decline, may be caused by myriad combinations of distinct disease-associated molecular mechanisms. We and others have used transcriptome profiling in AD patient-derived neuron models of autosomal-dominant EOAD and sporadic LOAD to identify disease endotypes (Caldwell et al. Sci Adv Am Assoc Adv Sci. 2020;6:eaba5933, Mertens et al. Cell Stem Cell. 2021;28:1533–1548.e6, Caldwell et al. Alzheimers Demen. 2022). Further, analyses of large postmortem brain cohorts demonstrate that only one-third of AD patients show hallmark disease endotypes like increased inflammation and decreased synaptic signaling (Neff et al. Sci Adv Am Assoc Adv Sci. 2021;7:eabb5398). Areas of the brain less affected by AD pathology at early disease stages—such as the primary visual cortex—exhibit similar transcriptomic dysregulation as those regions traditionally affected and, therefore, may offer a view into the molecular mechanisms of AD without the associated inflammatory changes and gliosis induced by pathology (Haroutunian et al. Neurobiol Aging. 2009;30:561–73). To this end, we analyzed AD patient samples from the primary visual cortex (19 EOAD, 20 LOAD) using transcriptomic signatures to identify patient clusters and disease endotypes. Interestingly, although the clusters showed distinct combinations and severity of endotypes, each patient cluster contained both EOAD and LOAD cases, suggesting that AAO may not directly correlate with the identity and severity of AD endotypes.
Parents, health professionals and footwear stakeholders' beliefs on the importance of different features of young children's footwear: a qualitative study
Authors: Williams Cylie M. , Banwell Helen A. , Paterson Kade L. , Gobbi Katherine , Burton Sam , Hill Matthew , Harber Emma , Morrison Stewart C.
Published: October 2022

Background

A small but building pool of evidence of the impact of footwear on children's function means understanding the different beliefs of stakeholders about footwear key features and flexibility is critical for translation into recommendations and to support parents and caregivers in purchasing footwear for their children. Therefore, this research aimed to describe how different stakeholders (health professionals, parents, and footwear industry representatives) described the importance of flexibility and other footwear features for young children.

Methods

This qualitative study was nested within an international modified Delphi online survey. Participants responded to open‐ended questions about footwear component flexibility and asked if and why flexibility in these areas were important. Participants also described any other important footwear features. Inductive thematic analysis was used to generate themes.

Results

There were 121 responses from three stakeholder groups including health professionals (n = 90), parents of young children (n = 26) and footwear industry representatives (n = 5). Overarching themes described by participants included developmental impacts of footwear, therapeutic impact and how footwear may play a role in function.

Conclusion

There were key differences in how stakeholders viewed footwear and any perceived benefits of footwear components, much of which was not backed with empirical evidence. It was also identified that health professionals are using footwear within treatment recommendations. This work highlights the importance of understanding circumstances in which footwear may have a therapeutic impact or be the first line of treatment for children with complex foot needs. This is the first step in developing contemporary footwear recommendations for parents and caregivers.
A low-cost genomics workflow enables isolate screening and strain-level analyses within microbiomes
Authors: Sanders Jon G. , Yan Weiwei , Mjungu Deus , Lonsdorf Elizabeth V. , Hart John A. , Sanz Crickette M. , Morgan David B. , Peeters Martine , Hahn Beatrice H. , Moeller Andrew H.
Published: October 2022

Earth’s environments harbor complex consortia of microbes that affect processes ranging from host health to biogeochemical cycles. Understanding their evolution and function is limited by an inability to isolate genomes in a high-throughput manner. Here, we present a workflow for bacterial whole-genome sequencing using open-source labware and the OpenTrons robotics platform, reducing costs to approximately $10 per genome. We assess genomic diversity within 45 gut bacterial species from wild-living chimpanzees and bonobos. We quantify intraspecific genomic diversity and reveal divergence of homologous plasmids between hosts. This enables population genetic analyses of bacterial strains not currently possible with metagenomic data alone.
Enhanced mitochondrial DNA editing in mice using nuclear-exported TALE-linked deaminases and nucleases
Authors: Lee Seonghyun , Lee Hyunji , Baek Gayoung , Namgung Eunji , Park Joo Min , Kim Sanghun , Hong Seongho , Kim Jin-Soo
Published: October 2022

We present two methods for enhancing the efficiency of mitochondrial DNA (mtDNA) editing in mice with DddA-derived cytosine base editors (DdCBEs). First, we fused DdCBEs to a nuclear export signal (DdCBE-NES) to avoid off-target C-to-T conversions in the nuclear genome and improve editing efficiency in mtDNA. Second, mtDNA-targeted TALENs (mitoTALENs) are co-injected into mouse embryos to cleave unedited mtDNA. We generated a mouse model with the m.G12918A mutation in the MT-ND5 gene, associated with mitochondrial genetic disorders in humans. The mutant mice show hunched appearances, damaged mitochondria in kidney and brown adipose tissues, and hippocampal atrophy, resulting in premature death.
Effect of intermittent fasting 5:2 on body composition and nutritional intake among employees with obesity in Jakarta: a randomized clinical trial
Authors: Witjaksono Fiastuti , Prafiantini Erfi , Rahmawati Anni
Published: October 2022

Objective

This study aimed to determine the effect of intermittent fasting 5:2 on body composition in employees with obesity in Jakarta.

Results

Fifty participants were included; 25 were allocated to the fasting group and 25 to the control group. There was no significant change in fat mass, fat-free mass, skeletal muscle, and BMI (p > 0.05). Significant in-group changes were observed in body weight (p = 0.023) and BMI (p = 0.018) in the fasting group. Dietary intake was similar before and during the intervention. The reduction in macronutrient intake resulted in a statistically significant difference in carbohydrate, protein, and fat intake in the two groups (p < 0.05). Intermittent fasting 5:2 results in weight loss but does not affect fat mass and fat-free mass reductions. None of the between-group differences were clinically relevant.

Trial registration:

ClinicalTrials.gov with ID: NCT04319133 registered on 24 March 2020.